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as CIX, affording the desired cycloadducts 402 in moderate yields and poor enantioselectivities, as it is Scheme 192: Asymmetric 1,3-dipolar cycloaddition of allenoates reported by Zhang. shown in Scheme 194.

Figure 210 as CIX, affording the desired cycloadducts 402 in moderate yields and poor enantioselectivities, as it is Scheme 192: Asymmetric 1,3-dipolar cycloaddition of allenoates reported by Zhang. shown in Scheme 194.

Related Figures (303)

The enantioselective step, the reaction of the enamine with the electrophile, can take place via two
The enantioselective step, the reaction of the enamine with the electrophile, can take place via two
Intramolecular aldol reactions discussed in sections 3.1 and 4.1 are representative examples of this
Intramolecular aldol reactions discussed in sections 3.1 and 4.1 are representative examples of this
protonation gives a saturated iminium ion. Hydrolysis of this intermediate releases both the product anc
protonation gives a saturated iminium ion. Hydrolysis of this intermediate releases both the product anc
has been recently forwarded by Seebach, Gilmour, Ebert and co-workers.[23] Figure 4. Stereochemical outcome of the amine-catalyzed Michael addition to enals. unsaturated iminium ion.[22] An alternative mechanistic explanation, based on stereoelectronic effects.
has been recently forwarded by Seebach, Gilmour, Ebert and co-workers.[23] Figure 4. Stereochemical outcome of the amine-catalyzed Michael addition to enals. unsaturated iminium ion.[22] An alternative mechanistic explanation, based on stereoelectronic effects.
Figure 5. MacMillan’s imidazolidinonium salt catalysts.
Figure 5. MacMillan’s imidazolidinonium salt catalysts.
Scheme 5. Basic processes in carbene catalysis.
Scheme 5. Basic processes in carbene catalysis.
Figure 6. Chiral triazolium salts used as precursors of NHC’s 2.2.7. Lewis base catalysis
Figure 6. Chiral triazolium salts used as precursors of NHC’s 2.2.7. Lewis base catalysis
hydrogen-bonding catalysts appearing in this review).[30] squaramides and chiral diols are the most widely used catalysts of this type (see Figure 8 for ch
hydrogen-bonding catalysts appearing in this review).[30] squaramides and chiral diols are the most widely used catalysts of this type (see Figure 8 for ch
Figure 9. Chiral BINOL-derived phosphoric acids and amides.
Figure 9. Chiral BINOL-derived phosphoric acids and amides.
Figure 11. Dual activation of electrophile and nucleophile by a bifunctional amine thiourea catalyst.
Figure 11. Dual activation of electrophile and nucleophile by a bifunctional amine thiourea catalyst.
Figure 14. Chiral phase-transfer organocatalysts
Figure 14. Chiral phase-transfer organocatalysts
The proline-catalyzed reactions of substrates related to 1 take generally place with useful yields and
The proline-catalyzed reactions of substrates related to 1 take generally place with useful yields and
Figure 15. Products from proline-catalyzed aldol cyclizations of compounds related to 1. It is worth noting here that the use of primary amino acids as catalysts can be sometimes
Figure 15. Products from proline-catalyzed aldol cyclizations of compounds related to 1. It is worth noting here that the use of primary amino acids as catalysts can be sometimes
Scheme 7. Proline-catalyzed synthesis of the Wieland-Miescher ketone 11. obtained in 49% yield and 76% ee (Scheme 8).[56] equiv) in DMSO at 35°C in the presence of (S)-proline I (35 mol%). After purification, (S)-11 w
Scheme 7. Proline-catalyzed synthesis of the Wieland-Miescher ketone 11. obtained in 49% yield and 76% ee (Scheme 8).[56] equiv) in DMSO at 35°C in the presence of (S)-proline I (35 mol%). After purification, (S)-11 w
Scheme 8. Proline-catalyzed single-step synthesis of the Wieland-Miescher ketone 11.
Scheme 8. Proline-catalyzed single-step synthesis of the Wieland-Miescher ketone 11.
compound 15 in only 32% ee. In a similar way, Davies and Smith[59] have found that the primary B-amino acid (1R,2S)-cispentacin
compound 15 in only 32% ee. In a similar way, Davies and Smith[59] have found that the primary B-amino acid (1R,2S)-cispentacin
(Sa)-binam-(S)-prolinamide VI[63] as efficient catalysts for the cyclization of 9 (Figure 16).
(Sa)-binam-(S)-prolinamide VI[63] as efficient catalysts for the cyclization of 9 (Figure 16).
Scheme 10. Proline-catalyzed asymmetric annelation of diketones.
Scheme 10. Proline-catalyzed asymmetric annelation of diketones.
intramolecular enolate addition to the more electron-defficient carbonyl group) as the sole product in unsymmetrical diketones. Thus, diketone 33 gave the cyclohexanone derivative 34 (resulting from th
intramolecular enolate addition to the more electron-defficient carbonyl group) as the sole product in unsymmetrical diketones. Thus, diketone 33 gave the cyclohexanone derivative 34 (resulting from th
Michael-aldol cyclizations will be discussed in section 6.1. Catalysts other than amino acids can also be used for the Hajos-Parrish-Eder-Sauer-Wiechert process.
Michael-aldol cyclizations will be discussed in section 6.1. Catalysts other than amino acids can also be used for the Hajos-Parrish-Eder-Sauer-Wiechert process.
purities comparable to those obtained with proline (Scheme 13).[70] Scheme 13. Bimorpholine-mediated enantioselective intramolecular aldol condensation. diketone (S)-3 and the Wieland-Miescher ketone (S)-11 were obtained in yields and enantiomeric
purities comparable to those obtained with proline (Scheme 13).[70] Scheme 13. Bimorpholine-mediated enantioselective intramolecular aldol condensation. diketone (S)-3 and the Wieland-Miescher ketone (S)-11 were obtained in yields and enantiomeric
energy difference for 37a, in agreement with the experimental results).[71] enol moieties, with preferred nucleophilic attack to the pro-(S) carbonyl of the indanone (1.3 kcal mol” The desymmetrization of 2-substituted-2-(3-formylpropyl)-1,3-cyclohexanediones 39a-c by means of
energy difference for 37a, in agreement with the experimental results).[71] enol moieties, with preferred nucleophilic attack to the pro-(S) carbonyl of the indanone (1.3 kcal mol” The desymmetrization of 2-substituted-2-(3-formylpropyl)-1,3-cyclohexanediones 39a-c by means of
Scheme 15. Chiral secondary amine-catalyzed desymmetrization of 1,3-diketones. purity (7% ee).[73a] The stereochemical outcome of the reaction fits with the Houk mechanism for the
Scheme 15. Chiral secondary amine-catalyzed desymmetrization of 1,3-diketones. purity (7% ee).[73a] The stereochemical outcome of the reaction fits with the Houk mechanism for the
obtained in excellent yields and enantioselectivities (Scheme 17) particularly powerful in this desymmetrization, and a variety of chiral cyclohexenones 42a-l were
obtained in excellent yields and enantioselectivities (Scheme 17) particularly powerful in this desymmetrization, and a variety of chiral cyclohexenones 42a-l were
Scheme 18. Organocatalytic enantioselective synthesis of (R)-celery ketone.
Scheme 18. Organocatalytic enantioselective synthesis of (R)-celery ketone.
(45) and (R,Z)-5-muscenone (46) without loss of enantiomeric purity (Scheme 19). Scheme 19. Enantioselective intramolecular aldol addition/dehydration reaction of a prochiral macrocyclic diketone. aldol intermediate. The final enone was subsequently transformed into the musk odorants (R)-muscon¢
(45) and (R,Z)-5-muscenone (46) without loss of enantiomeric purity (Scheme 19). Scheme 19. Enantioselective intramolecular aldol addition/dehydration reaction of a prochiral macrocyclic diketone. aldol intermediate. The final enone was subsequently transformed into the musk odorants (R)-muscon¢
Scheme 20. NHC-catalyzed desymmetrization of 1,3-diketones. from XIII) afforded the chiral o,a-disubstituted cyclopentenes 48a-h with high enantioselectivi
Scheme 20. NHC-catalyzed desymmetrization of 1,3-diketones. from XIII) afforded the chiral o,a-disubstituted cyclopentenes 48a-h with high enantioselectivi
Figure 18. Proposed transition state for the NHC-catalyzed desymmetrization of 1,3-diketones. through the model transition state depicted in Figure 18
Figure 18. Proposed transition state for the NHC-catalyzed desymmetrization of 1,3-diketones. through the model transition state depicted in Figure 18
Scheme 21. Proposed reaction pathway for the NHC-catalyzed desymmetrization of 1,3-diketones.
Scheme 21. Proposed reaction pathway for the NHC-catalyzed desymmetrization of 1,3-diketones.
furnished (15,5R,8R)-8-hydroxybicyclo[3.3.1]}nonan-2-one 51 with 94% ee. The enantiomer of 51 coul
furnished (15,5R,8R)-8-hydroxybicyclo[3.3.1]}nonan-2-one 51 with 94% ee. The enantiomer of 51 coul
The application of the intramolecular aldol reaction to the desymmetrization of meso-dialdehydes will
The application of the intramolecular aldol reaction to the desymmetrization of meso-dialdehydes will
Scheme 24. Asymmetric intramolecular Michael reaction of 4-substituted-4-(3- formylpropyl)cyclohexa-2,5-dien-1-ones. 4.2, this process can be applied to the asymmetric cyclization of acyclic formyl enones.
Scheme 24. Asymmetric intramolecular Michael reaction of 4-substituted-4-(3- formylpropyl)cyclohexa-2,5-dien-1-ones. 4.2, this process can be applied to the asymmetric cyclization of acyclic formyl enones.
Scheme 25. Catalytic enantioselective dearomatization of 4-substituted phenols. In the oxidative dearomatization step, nucleophiles other than methanol (water, acetonitrile, fluoride
Scheme 25. Catalytic enantioselective dearomatization of 4-substituted phenols. In the oxidative dearomatization step, nucleophiles other than methanol (water, acetonitrile, fluoride
carbonyl and the hydroxy groups, respectively (Figure 20).[84] a bifunctional catalyst, in which the acidic proton and the P=O moiety form hydrogen bonds with the proposed a catalytic working model for the desymmetrization process. The chiral phosphoric acid acts as
carbonyl and the hydroxy groups, respectively (Figure 20).[84] a bifunctional catalyst, in which the acidic proton and the P=O moiety form hydrogen bonds with the proposed a catalytic working model for the desymmetrization process. The chiral phosphoric acid acts as
Scheme 26. Enantioselective organocatalytic intramolecular oxa-Michael reaction.
Scheme 26. Enantioselective organocatalytic intramolecular oxa-Michael reaction.
Scheme 27. Asymmetric synthesis of cleroindicins. 3. 3. Desymmetrizing cyclizations via polarity inversion.
Scheme 27. Asymmetric synthesis of cleroindicins. 3. 3. Desymmetrizing cyclizations via polarity inversion.
[he process tolerates the presence of additional substituents in the cyclohexadienone moiety,
[he process tolerates the presence of additional substituents in the cyclohexadienone moiety,
evinced by the examples shown in Figure 21.
evinced by the examples shown in Figure 21.
obtained in 50% yield and with 78% ee. the base and dichloromethane as the solvent (Scheme 30). In this way, the cyclized product 67 w 3. 4. Desymmetrizing cyclizations via aza-Wittig reactions. for the desymmetrization of 66 involved the use of the chiral triazolium salt XX, cestum carbonate as
obtained in 50% yield and with 78% ee. the base and dichloromethane as the solvent (Scheme 30). In this way, the cyclized product 67 w 3. 4. Desymmetrizing cyclizations via aza-Wittig reactions. for the desymmetrization of 66 involved the use of the chiral triazolium salt XX, cestum carbonate as
cyclic (69a,b) diketo azides could be achieved with moderate enantioselectivities by using the chiral experimental actualization of this concept[92] revealed that the desymmetrization of acyclic (68a,b) o:
cyclic (69a,b) diketo azides could be achieved with moderate enantioselectivities by using the chiral experimental actualization of this concept[92] revealed that the desymmetrization of acyclic (68a,b) o:
hexanedial 76 took place with markedly lower stereoselectivity. the minor syn diastereomer of 75 was obtained in 95% ee. On the other hand, the aldolization of
hexanedial 76 took place with markedly lower stereoselectivity. the minor syn diastereomer of 75 was obtained in 95% ee. On the other hand, the aldolization of
Scheme 33. Proline-catalyzed intramolecular aldol reaction of 4-methylheptanedial. al. were able to reproduce qualitatively the experimental values.[95b] diastereomers 79a-e, with variable enantioselectivities (Scheme 33). The DFT calculations of Santos et
Scheme 33. Proline-catalyzed intramolecular aldol reaction of 4-methylheptanedial. al. were able to reproduce qualitatively the experimental values.[95b] diastereomers 79a-e, with variable enantioselectivities (Scheme 33). The DFT calculations of Santos et
Scheme 34. Proline-catalyzed aldol cyclization of meso-dialdehydes. Besides compound 74, other achiral ketoaldehydes have been submitted to intramolecular aldol
Scheme 34. Proline-catalyzed aldol cyclization of meso-dialdehydes. Besides compound 74, other achiral ketoaldehydes have been submitted to intramolecular aldol
acetate; the absolute configurations can be rationalized by an enol/exo transition state working model > 99:1 dr) and good enantioselectivity (from 76% to 87% ee). Enantiomerically pure 2,3-dihydro-3-
acetate; the absolute configurations can be rationalized by an enol/exo transition state working model > 99:1 dr) and good enantioselectivity (from 76% to 87% ee). Enantiomerically pure 2,3-dihydro-3-
the aldol cyclization of compounds 84.[98] major (or even the exclusive) product, suggesting a TS similar to that proposed by Enders in the case of
the aldol cyclization of compounds 84.[98] major (or even the exclusive) product, suggesting a TS similar to that proposed by Enders in the case of
aldol reaction of enones with aldehydes (Scheme 37).[101] Scheme 37. Lewis base-catalyzed reductive aldol reaction with trichlorosilane. organocatalysts promoting both the conjugate reduction of enones with trichlorosilane and the reductive
aldol reaction of enones with aldehydes (Scheme 37).[101] Scheme 37. Lewis base-catalyzed reductive aldol reaction with trichlorosilane. organocatalysts promoting both the conjugate reduction of enones with trichlorosilane and the reductive
XXIV gave ent-90 with 55% ee (Scheme 38). XXV produced the cyclic ketol 90 in good yield but in very low enantiomeric purity, and the use of XXvV leads to good diastereo- and enantioselectivities. In the cyclization of ketoenone 89, however
XXIV gave ent-90 with 55% ee (Scheme 38). XXV produced the cyclic ketol 90 in good yield but in very low enantiomeric purity, and the use of XXvV leads to good diastereo- and enantioselectivities. In the cyclization of ketoenone 89, however
Scheme 40. Scope of the Aza-aldol condensation / transfer hydrogenation route to 3-substituted cyclohexylamines.
Scheme 40. Scope of the Aza-aldol condensation / transfer hydrogenation route to 3-substituted cyclohexylamines.
Scheme 41. Asymmetric transannular aldol reaction of monocyclic diketones.
Scheme 41. Asymmetric transannular aldol reaction of monocyclic diketones.
Figure 23. Bicyclic 1,4-cyclooctanedones in transannular aldolizations. compounds, shown in Figure 23, were obtained with high diastereo- and enantioselectivity (90-96% ee).
Figure 23. Bicyclic 1,4-cyclooctanedones in transannular aldolizations. compounds, shown in Figure 23, were obtained with high diastereo- and enantioselectivity (90-96% ee).
Scheme 42. Organocatalytic kinetic resolution of 1.5-diketones via intramolecular aldol condensation. (Scheme 42). The transition states depicted in Figure 24 can account for the observed stereoselectivity.
Scheme 42. Organocatalytic kinetic resolution of 1.5-diketones via intramolecular aldol condensation. (Scheme 42). The transition states depicted in Figure 24 can account for the observed stereoselectivity.
4.2. Intramolecular Michael additions. The first intramolecular catalytic asymmetric Michael reaction of aldehydes was reported in 2004 by
4.2. Intramolecular Michael additions. The first intramolecular catalytic asymmetric Michael reaction of aldehydes was reported in 2004 by
thermodynamically more stable. Both isomers are formed with excellent enantioselectivity (Cf 99% ee different reaction times revealed that the cis-isomer is the kinetic product, while the trans-isomer is
thermodynamically more stable. Both isomers are formed with excellent enantioselectivity (Cf 99% ee different reaction times revealed that the cis-isomer is the kinetic product, while the trans-isomer is
Scheme 46. Reductive cyclization of aliphatic enals.
Scheme 46. Reductive cyclization of aliphatic enals.
Scheme 47. Chiral NHC-catalyzed asymmetric Michael cyclization of enals.
Scheme 47. Chiral NHC-catalyzed asymmetric Michael cyclization of enals.
leuconolam.[116] 51) for the syntheses of the alkaloids (-)-rhazinal, (-)-rhazinilam, (-)-leuconolam, and (+)-e
leuconolam.[116] 51) for the syntheses of the alkaloids (-)-rhazinal, (-)-rhazinilam, (-)-leuconolam, and (+)-e
outcome of the process is consistent with that observed for intermolecular conjugate additions to enals tetrahydroquinolines 128 could be prepared in high enantiopurity (Scheme 52). The stereochemical
outcome of the process is consistent with that observed for intermolecular conjugate additions to enals tetrahydroquinolines 128 could be prepared in high enantiopurity (Scheme 52). The stereochemical
enantioselectivity.
enantioselectivity.
Scheme 54. Enantioselective intramolecular Michael addition of nitronates onto conjugated esters.
Scheme 54. Enantioselective intramolecular Michael addition of nitronates onto conjugated esters.
A Cinchona alkaloid-derived thiourea catalyst (the quinine derivative XL, originally described by
A Cinchona alkaloid-derived thiourea catalyst (the quinine derivative XL, originally described by
Scheme 56. Catalytic enantioselective synthesis of chromanones by oxa-Michael cyclization / decarboxylation.
Scheme 56. Catalytic enantioselective synthesis of chromanones by oxa-Michael cyclization / decarboxylation.
80% ee after decarboxylation (Scheme 57).
80% ee after decarboxylation (Scheme 57).
Scheme 59. Asymmetric intramolecular aza-Michael addition of amides to enals.
Scheme 59. Asymmetric intramolecular aza-Michael addition of amides to enals.
a.,-unsaturated aldehydes took place with moderate to good yields (30-80%) and with good to excellent was used in the process. The starting materials 146 were easily accessed by a cross-metathesis reaction
a.,-unsaturated aldehydes took place with moderate to good yields (30-80%) and with good to excellent was used in the process. The starting materials 146 were easily accessed by a cross-metathesis reaction
Scheme 62. Organocatalytic intramolecular aza-Michael reaction of carbamates.
Scheme 62. Organocatalytic intramolecular aza-Michael reaction of carbamates.
Scheme 64. Alternative protocol for organocatalytic asymmetric aza-Michael cyclizations. cyclized by Carter et al. (including 149, that led to the indoline 150) are shown in Scheme 64. Subsequently, Fustero et a/.[133] extended their protocol, not only for the synthesis of indoline 150
Scheme 64. Alternative protocol for organocatalytic asymmetric aza-Michael cyclizations. cyclized by Carter et al. (including 149, that led to the indoline 150) are shown in Scheme 64. Subsequently, Fustero et a/.[133] extended their protocol, not only for the synthesis of indoline 150
4.3. Intramolecular Morita-Baylis-Hillman and Rauhut-Currier reactions.
4.3. Intramolecular Morita-Baylis-Hillman and Rauhut-Currier reactions.
Scheme 68. Inversion of enantioselectivity in the proline-catalyzed intramolecular MBH reaction. studied by Miller (Scheme 68). A mechanistic rationale for this inversion of the enantioselectivity was
Scheme 68. Inversion of enantioselectivity in the proline-catalyzed intramolecular MBH reaction. studied by Miller (Scheme 68). A mechanistic rationale for this inversion of the enantioselectivity was
Scheme 69. Enantioselective intramolecular MBH reaction catalyzed by amino acid-derived phosphinothiourea. In 2007, Aroyan and Miller[143] uncovered the first asymmetric organocatalytic intramolecular RC
Scheme 69. Enantioselective intramolecular MBH reaction catalyzed by amino acid-derived phosphinothiourea. In 2007, Aroyan and Miller[143] uncovered the first asymmetric organocatalytic intramolecular RC
A crossed intramolecular asymmetric organocatalytic RC-type reaction has been developed by
A crossed intramolecular asymmetric organocatalytic RC-type reaction has been developed by
Scheme 71. Asymmetric intramolecular crossed Rauhut-Currier-type reaction.
Scheme 71. Asymmetric intramolecular crossed Rauhut-Currier-type reaction.
Scheme 72. Dienamine mechanism for the intramolecular crossed Rauhut-Currier-type reaction.
Scheme 72. Dienamine mechanism for the intramolecular crossed Rauhut-Currier-type reaction.
74% ee). enantioselectivities (Cf product 167 in Figure 26 below, that was obtained by Enders in 95% yield and
74% ee). enantioselectivities (Cf product 167 in Figure 26 below, that was obtained by Enders in 95% yield and
the synthesis of the natural isoflavanone (+)-sappanone B.[148] Scheme 74. Alternative method for the chiral NHC-catalyzed intramolecular crossed benzoin reaction. group has been replaced by a N-(3,5-(CF3)2C6H3) moiety, and has applied this modified methodology to
the synthesis of the natural isoflavanone (+)-sappanone B.[148] Scheme 74. Alternative method for the chiral NHC-catalyzed intramolecular crossed benzoin reaction. group has been replaced by a N-(3,5-(CF3)2C6H3) moiety, and has applied this modified methodology to
Figure 26. Other compounds obtained by chiral NHC-catalyzed intramolecular crossed benzoin reaction.
Figure 26. Other compounds obtained by chiral NHC-catalyzed intramolecular crossed benzoin reaction.
Scheme 75. Enantioselective organocatalytic intramolecular Stetter reaction of salicyaldehyde-derived unsaturated esters.
Scheme 75. Enantioselective organocatalytic intramolecular Stetter reaction of salicyaldehyde-derived unsaturated esters.
Subsequently, the Rovis’ group has further explored the scope of this transformation. The introduction
Subsequently, the Rovis’ group has further explored the scope of this transformation. The introduction
A convenient method for the generation of the free NHC catalyst LII allowed the use of a,a-
A convenient method for the generation of the free NHC catalyst LII allowed the use of a,a-
Scheme 80. Enantio- and diastereoselective intramolecular Stetter reaction of aromatic substrates
Scheme 80. Enantio- and diastereoselective intramolecular Stetter reaction of aromatic substrates
Scheme 81. Enantio- and diastereoselective intramolecular Stetter reaction of aliphatic substrates.
Scheme 81. Enantio- and diastereoselective intramolecular Stetter reaction of aliphatic substrates.
More recently, Cullen and Rovis[152] have demonstrated that the chiral NHC derived from LIII can
More recently, Cullen and Rovis[152] have demonstrated that the chiral NHC derived from LIII can
Later on, Jacobsen’s group extended this approach to the enantioselective Pictet-Spengler-type
Later on, Jacobsen’s group extended this approach to the enantioselective Pictet-Spengler-type
Scheme 87. Enantioselective Bronsted acid-catalyzed N-acyliminium cyclization cascade. The first Bronsted acid-catalyzed asymmetric Pictet-Spengler reaction had been in fact reported in
Scheme 87. Enantioselective Bronsted acid-catalyzed N-acyliminium cyclization cascade. The first Bronsted acid-catalyzed asymmetric Pictet-Spengler reaction had been in fact reported in
The structural limitation imposed by the presence of the geminal bis(ethoxycarbonyl) substituent at
The structural limitation imposed by the presence of the geminal bis(ethoxycarbonyl) substituent at
Scheme 89. Catalytic asymmetric PS reactions via sulfenyliminium ions. obtained when (R)-LVIII was used as the catalyst.
Scheme 89. Catalytic asymmetric PS reactions via sulfenyliminium ions. obtained when (R)-LVIII was used as the catalyst.
orgensen and co-workers reported an organocatalytic diastereo- and enantioselective approach to the “2-symmetric 2,5-dibenzylpyrrolidine LX was found to catalyze the cyclization of several 2-(5
orgensen and co-workers reported an organocatalytic diastereo- and enantioselective approach to the “2-symmetric 2,5-dibenzylpyrrolidine LX was found to catalyze the cyclization of several 2-(5
Scheme 92. Mechanistic proposal for the chiral secondary amine-catalyzed synthesis of 1,2- dihydroisoquinolines from 2-(5-oxopentyl)isoquinolinium salts.
Scheme 92. Mechanistic proposal for the chiral secondary amine-catalyzed synthesis of 1,2- dihydroisoquinolines from 2-(5-oxopentyl)isoquinolinium salts.
Scheme 93. Organocatalytic asymmetric synthesis of a 1,2-dihydroisoquinoline derivative. formation from the cyclized product.
Scheme 93. Organocatalytic asymmetric synthesis of a 1,2-dihydroisoquinoline derivative. formation from the cyclized product.
transferred to the metal complex (See Scheme 96 for an example). Scheme 96. Catalytic asymmetric intramolecular Tsuji-Trost allylation. of asymmetric induction. Better results were obtained when the role of the asymmetric inductor was imidazolidinones, proline, prolinol derivatives) were unsuccessful, either for lack of catalytic activity, or Asymmetric intramolecular a-arylation of aldehydes were reported in 2009 first by Nicolaou et
transferred to the metal complex (See Scheme 96 for an example). Scheme 96. Catalytic asymmetric intramolecular Tsuji-Trost allylation. of asymmetric induction. Better results were obtained when the role of the asymmetric inductor was imidazolidinones, proline, prolinol derivatives) were unsuccessful, either for lack of catalytic activity, or Asymmetric intramolecular a-arylation of aldehydes were reported in 2009 first by Nicolaou et
derivatives, furnishing the cyclized products in good yields and in > 85% ee (Scheme 97).
derivatives, furnishing the cyclized products in good yields and in > 85% ee (Scheme 97).
shown in Scheme 98.
shown in Scheme 98.
radical cations resides mainly at the carbon atom. cyclization is depicted in Scheme 99, where it can be noted that the unpaired electron in the intermediate
radical cations resides mainly at the carbon atom. cyclization is depicted in Scheme 99, where it can be noted that the unpaired electron in the intermediate
230 were formed with total regioselectivity, when applicable with good cis-diastereoselectivity, and witl
230 were formed with total regioselectivity, when applicable with good cis-diastereoselectivity, and witl
(dichloromethane, room temperature, 24 h) resulted in its quantitative conversion to trans-230a without
(dichloromethane, room temperature, 24 h) resulted in its quantitative conversion to trans-230a without
crystallographically from its enol ester of (1.S)-camphanic acid. required reaction times were very long (5 to 8 days, yields from 11 to 66%), and stoichiometric amounts
crystallographically from its enol ester of (1.S)-camphanic acid. required reaction times were very long (5 to 8 days, yields from 11 to 66%), and stoichiometric amounts
Scheme 105. Chiral diamine-promoted enantioselective Nazarov cyclization of a-ketoenones.
Scheme 105. Chiral diamine-promoted enantioselective Nazarov cyclization of a-ketoenones.
Scheme 107. Organocatalytic asymmetric Nazarov cyclization mediated by a chiral amino-thiourea.
Scheme 107. Organocatalytic asymmetric Nazarov cyclization mediated by a chiral amino-thiourea.
The attempted cyclization of a,f-unsaturated alkyl hydrazones (one-pot procedure) took place with
The attempted cyclization of a,f-unsaturated alkyl hydrazones (one-pot procedure) took place with
Scheme 109. Proposed catalytic cycle for the cyclization of a,f-unsaturated aryl hydrazones On the other hand, Martin and co-workers have used a 2-azapentadienyl anion to explore the
Scheme 109. Proposed catalytic cycle for the cyclization of a,f-unsaturated aryl hydrazones On the other hand, Martin and co-workers have used a 2-azapentadienyl anion to explore the
Scheme 111. Mechanistic hypothesis and diastereo- and enantioselective cyclization. 4.8. Organocatalytic asymmetric polycyclizations.
Scheme 111. Mechanistic hypothesis and diastereo- and enantioselective cyclization. 4.8. Organocatalytic asymmetric polycyclizations.
enantioselectivity of the reaction (Scheme 115).
enantioselectivity of the reaction (Scheme 115).
At the beginning of 2009, Chung and Fu disclosed an asymmetric approach to this cyclization.[195]
At the beginning of 2009, Chung and Fu disclosed an asymmetric approach to this cyclization.[195]
Scheme 118. Catalytic enantioselective synthesis of dihydrobenzopyrans. Also in 2009, Sugiura, Kumahara, and Nakajima reported an asymmetric synthesis of 4H-1,3-oxazines
Scheme 118. Catalytic enantioselective synthesis of dihydrobenzopyrans. Also in 2009, Sugiura, Kumahara, and Nakajima reported an asymmetric synthesis of 4H-1,3-oxazines
hanced the formation rate of oxazines 260, as well as the enantioselectivity (Cf. 260e vs. 260d In this reaction, trichlorosilane acts not only as a reductant,[102] but also as a dehydrating agent. The
hanced the formation rate of oxazines 260, as well as the enantioselectivity (Cf. 260e vs. 260d In this reaction, trichlorosilane acts not only as a reductant,[102] but also as a dehydrating agent. The
Scheme 120. Synthetic utility of 44-1,3-oxazines.
Scheme 120. Synthetic utility of 44-1,3-oxazines.
Scheme 121. Organocatalytic asymmetric intramolecular allylic substitutions of MBH acetates.
Scheme 121. Organocatalytic asymmetric intramolecular allylic substitutions of MBH acetates.
Scheme 123. One-pot conversion a chlorolactone to a chiral epoxyalcohol. induced cyclization of the resulting chlorohydrin to the epoxy alcohol 268, without appreciable loss « Tang and co-workers have developed a similar approach to the enantioselective bromolactonization of
Scheme 123. One-pot conversion a chlorolactone to a chiral epoxyalcohol. induced cyclization of the resulting chlorohydrin to the epoxy alcohol 268, without appreciable loss « Tang and co-workers have developed a similar approach to the enantioselective bromolactonization of
deprotonation of the carboxylic acid and formation of hydrogen bonds with NBS. and the authors propose that this compound acts as a bifunctional catalyst, activating the system via the
deprotonation of the carboxylic acid and formation of hydrogen bonds with NBS. and the authors propose that this compound acts as a bifunctional catalyst, activating the system via the
Scheme 125. Enantioselective organocatalytic bromolactonization of aromatic cis-enynes.
Scheme 125. Enantioselective organocatalytic bromolactonization of aromatic cis-enynes.
alkoxy group of the acetal (C; Sy2-like pathway). Scheme 127. Mechanistic hypothesis for the asymmetric organocatalytic intramolecular transacetalization. intermediate (B; Syl-like pathway) or by intramolecular nucleophilic substitution of a hydrogen-bonded An organocatalytic asymmetric synthesis of planar chiral heterocycles has been reported very recently
alkoxy group of the acetal (C; Sy2-like pathway). Scheme 127. Mechanistic hypothesis for the asymmetric organocatalytic intramolecular transacetalization. intermediate (B; Syl-like pathway) or by intramolecular nucleophilic substitution of a hydrogen-bonded An organocatalytic asymmetric synthesis of planar chiral heterocycles has been reported very recently
Scheme 128. Enantioselective synthesis of planar chiral nitrogen heterocycles 8). The stereochemical outcome of this cyclization was rationalized by means of theoretical
Scheme 128. Enantioselective synthesis of planar chiral nitrogen heterocycles 8). The stereochemical outcome of this cyclization was rationalized by means of theoretical
imidazolidinone salt for a new catalytic cycle.[210] A, that after hydrolysis provides the enantioenriched Diels-Alder product 279, and regenerates ion B. This iminium ion is activated enough to react with the diene to furnish the saturated iminium ion
imidazolidinone salt for a new catalytic cycle.[210] A, that after hydrolysis provides the enantioenriched Diels-Alder product 279, and regenerates ion B. This iminium ion is activated enough to react with the diene to furnish the saturated iminium ion
alkyl, alkoxy, amino or aryl substituted cyclohexenyl ketones. Based in these results, MacMillan and coworkers applied this methodology to the synthesis of
alkyl, alkoxy, amino or aryl substituted cyclohexenyl ketones. Based in these results, MacMillan and coworkers applied this methodology to the synthesis of
intramolecular Diels-Alder reactions, as it is shown in Scheme 133. Moreover, in this report they showed that this methodology could be generally applied to
intramolecular Diels-Alder reactions, as it is shown in Scheme 133. Moreover, in this report they showed that this methodology could be generally applied to
MacMillan (Scheme 134). Scheme 134. Synthesis of amanimol A reported by Koskinen.
MacMillan (Scheme 134). Scheme 134. Synthesis of amanimol A reported by Koskinen.
Scheme 135. Synthesis of Eunicellin reported by Holmes. (Scheme 135). Alder reaction that furnished the tricyclic core of eunicellin in excellent yields and enantioselectivities
Scheme 135. Synthesis of Eunicellin reported by Holmes. (Scheme 135). Alder reaction that furnished the tricyclic core of eunicellin in excellent yields and enantioselectivities
snantioselectivities. However, the diastereoselectivity was rather low, affording a slight excess of exo Bonini and coworkers synthesized a new set of catalysts based on aziridin-2-yl-diphenylmethanol
snantioselectivities. However, the diastereoselectivity was rather low, affording a slight excess of exo Bonini and coworkers synthesized a new set of catalysts based on aziridin-2-yl-diphenylmethanol
cycloadducts in low enantioselectivities. Scheme 138: Diels-Alder reaction catalyzed by chiral aziridines
cycloadducts in low enantioselectivities. Scheme 138: Diels-Alder reaction catalyzed by chiral aziridines
Scheme 139: Diels-Alder reaction reported by Maruoka.
Scheme 139: Diels-Alder reaction reported by Maruoka.
Scheme 141: Diels-Alder reaction of 2-acetoxyacroleins reported by Ishihara In 2006, the same authors reported the use of BINAM (LXXXIV) as a catalyst for the Diels-Alder
Scheme 141: Diels-Alder reaction of 2-acetoxyacroleins reported by Ishihara In 2006, the same authors reported the use of BINAM (LXXXIV) as a catalyst for the Diels-Alder
carried out in the presence of trifluoromethanesulfonimide and it was extended to other dienes such as In order to explain the enantioselectivity of the reaction, and based both in 'H-NMR studies and in the
carried out in the presence of trifluoromethanesulfonimide and it was extended to other dienes such as In order to explain the enantioselectivity of the reaction, and based both in 'H-NMR studies and in the
should approach the Si face of the dienophile from the less hindered face to give the (2S)-exo adduct.
should approach the Si face of the dienophile from the less hindered face to give the (2S)-exo adduct.
The authors used this methodology for the preparation of norbornane-2-amino-2-methanol derivatives
The authors used this methodology for the preparation of norbornane-2-amino-2-methanol derivatives
Moreover, Zhao and coworkers applied this methodology to the synthesis of the core structure of
Moreover, Zhao and coworkers applied this methodology to the synthesis of the core structure of
was used as the ketone, an asymmetric aza-Diels-Alder reaction was observed (Scheme 146): dihydro-fB-carboline (314) using L-proline (I) as the chiral catalyst.[230] When 3-buten-2-one (284a)
was used as the ketone, an asymmetric aza-Diels-Alder reaction was observed (Scheme 146): dihydro-fB-carboline (314) using L-proline (I) as the chiral catalyst.[230] When 3-buten-2-one (284a)
Scheme 148: Tandem nitroso aldol/Michael reaction described by Yamamoto Cordova and co-workers performed the first complete study of the enantioselective organocatalytic Mannich/Michael reaction pathway and is catalyzed by L-proline (I) or by some of its derivatives with
Scheme 148: Tandem nitroso aldol/Michael reaction described by Yamamoto Cordova and co-workers performed the first complete study of the enantioselective organocatalytic Mannich/Michael reaction pathway and is catalyzed by L-proline (I) or by some of its derivatives with
observed. Two years later, Xu and co-workers reported the same reaction in seawater and in brine.[235 In 2009, Melchiorre and co-workers developed a similar Diels-Alder reaction overcoming the
observed. Two years later, Xu and co-workers reported the same reaction in seawater and in brine.[235 In 2009, Melchiorre and co-workers developed a similar Diels-Alder reaction overcoming the
Scheme 152: Diels-Alder reaction developed by Melchiorre. for the high stereoselectivity of the reaction (Scheme 152). and excellent enantioselectivities. The use of benzoic acid as a co-catalyst is of paramount importance
Scheme 152: Diels-Alder reaction developed by Melchiorre. for the high stereoselectivity of the reaction (Scheme 152). and excellent enantioselectivities. The use of benzoic acid as a co-catalyst is of paramount importance
ntramolecular hemiacetalization takes place, rendering the final adduct as it is shown in Scheme 153. Scheme 153: Inverse electron-demand hetero-Diels-Alder reaction via enamine activation In 2008, Liu and co-workers published an asymmetric inverse-electron-demand hetero-Diels-Alder
ntramolecular hemiacetalization takes place, rendering the final adduct as it is shown in Scheme 153. Scheme 153: Inverse electron-demand hetero-Diels-Alder reaction via enamine activation In 2008, Liu and co-workers published an asymmetric inverse-electron-demand hetero-Diels-Alder
as the diphenylprolinol derivative XLVIII, led to low yields. LXXXVIII (Scheme 155). The authors observed that the use of bulky C2-substituted pyrrolidines, such
as the diphenylprolinol derivative XLVIII, led to low yields. LXXXVIII (Scheme 155). The authors observed that the use of bulky C2-substituted pyrrolidines, such
strongest limitations of this methodology was its exclusive application to intramolecular reaction A similar approach was explored by Chen in 2010.[243] In this work, an inverse-electron-demand
strongest limitations of this methodology was its exclusive application to intramolecular reaction A similar approach was explored by Chen in 2010.[243] In this work, an inverse-electron-demand
respectively, in excellent enantioselectivities (Scheme 158). o-benzoquinone diimides,[248] affording the corresponding 1,4-benzoxazinones and quinoxalinones quinones.[246] The reaction was catalyzed by benzoylquinidine XC and rendered the corresponding
respectively, in excellent enantioselectivities (Scheme 158). o-benzoquinone diimides,[248] affording the corresponding 1,4-benzoxazinones and quinoxalinones quinones.[246] The reaction was catalyzed by benzoylquinidine XC and rendered the corresponding
Scheme 159: Diels-Alder reaction reported by Tan, catalyzed by chiral guanidines. easily converted into the N-hydroxy derivative (Scheme 159). reaction was also extended to N-acetoxymaleimide (346d), and the corresponding cycloadduct 347d was
Scheme 159: Diels-Alder reaction reported by Tan, catalyzed by chiral guanidines. easily converted into the N-hydroxy derivative (Scheme 159). reaction was also extended to N-acetoxymaleimide (346d), and the corresponding cycloadduct 347d was
from different amino acids. The reaction could be performed in a multigram scale.
from different amino acids. The reaction could be performed in a multigram scale.
moderate enantioselectivities in some instances (up to 74% ee; Scheme 162).[256] bond between a maleimide carbonyl and one hydroxyl group in the transition state (Figure 28), obtaining
moderate enantioselectivities in some instances (up to 74% ee; Scheme 162).[256] bond between a maleimide carbonyl and one hydroxyl group in the transition state (Figure 28), obtaining
afforded preferentially the exo adduct in good yields and good enantioselectivities. 163). The first catalyst was found to be endo selective, while the second one (a bifunctional catalyst) More recently, Bernardi, Ricci and co-workers hve reported a catalytic asymmetric Diels-Alder
afforded preferentially the exo adduct in good yields and good enantioselectivities. 163). The first catalyst was found to be endo selective, while the second one (a bifunctional catalyst) More recently, Bernardi, Ricci and co-workers hve reported a catalytic asymmetric Diels-Alder
en 3-hydroxy-2-pyrones (340) were used the enantioselectivities decreased down to a 30% ee.[259] maleimides catalyzed by Takemoto’s thiourea catalyst XLI, that afforded the cycloadducts 347 in good
en 3-hydroxy-2-pyrones (340) were used the enantioselectivities decreased down to a 30% ee.[259] maleimides catalyzed by Takemoto’s thiourea catalyst XLI, that afforded the cycloadducts 347 in good
Scheme 165: Diels-Alder reaction reported by Moyano and Rios
Scheme 165: Diels-Alder reaction reported by Moyano and Rios
stoichiometric amounts of the chiral amidinium ion and the low enantioselectivities achieved (Scheme In 2003, Rawal and coworkers made a significant advance in the use of Bronsted acids as catalysts, between aminodiene 360 and aldehydes.[264] The reaction took place with moderate to high yields and
stoichiometric amounts of the chiral amidinium ion and the low enantioselectivities achieved (Scheme In 2003, Rawal and coworkers made a significant advance in the use of Bronsted acids as catalysts, between aminodiene 360 and aldehydes.[264] The reaction took place with moderate to high yields and
bond interaction that is stabilized by an intramolecular hydrogen bond in the catalyst.
bond interaction that is stabilized by an intramolecular hydrogen bond in the catalyst.
Almost at the same time, Akiyama and coworkers reported the same reaction using Brassard’s diene
Almost at the same time, Akiyama and coworkers reported the same reaction using Brassard’s diene
170). The best catalyst was the anthryl-derived BINOL phosphoric acid LX VII. ind gave the corresponding cycloadducts with good yields and excellent enantioselectivities (Scheme limited to the use of aromatic or heteroaromatic aldimines (365) derived from 2-hydroxy-m-toluidine
170). The best catalyst was the anthryl-derived BINOL phosphoric acid LX VII. ind gave the corresponding cycloadducts with good yields and excellent enantioselectivities (Scheme limited to the use of aromatic or heteroaromatic aldimines (365) derived from 2-hydroxy-m-toluidine
Figure 29: Activation of imine proposed by Akiyama. attack the less-hindered Re face of the aldimine (Figure 29). the hydrogen atom of the hydroxy group. Under these conditions, the nucleophile should preferentially
Figure 29: Activation of imine proposed by Akiyama. attack the less-hindered Re face of the aldimine (Figure 29). the hydrogen atom of the hydroxy group. Under these conditions, the nucleophile should preferentially
cycloadditions with electron-rich alkenes (the Povarov reaction). leads to an attenuation of the reactivity of the iminium ion and allows high enantioselectivity ir the transition state through a non-covalent interaction network as depicted in Figure 30. This interaction
cycloadditions with electron-rich alkenes (the Povarov reaction). leads to an attenuation of the reactivity of the iminium ion and allows high enantioselectivity ir the transition state through a non-covalent interaction network as depicted in Figure 30. This interaction
Scheme 173: General concerted 1,3-dipolar cycloaddition. stereoconservative (suprafacial), and the reaction is therefore a [21s+42s] cycloaddition (Scheme 173). ylides, diazoalkenes, or azides. Two z-electrons of the dipolarophile and four z-electrons of the dipola
Scheme 173: General concerted 1,3-dipolar cycloaddition. stereoconservative (suprafacial), and the reaction is therefore a [21s+42s] cycloaddition (Scheme 173). ylides, diazoalkenes, or azides. Two z-electrons of the dipolarophile and four z-electrons of the dipola
crotonaldehyde were used as suitable dipolarophiles (Scheme 175). obtained, and that the scope of the reaction in terms of the enal was quite narrow, since only acroleine or A few years later, Karlsson and Hégberg reported the enantioselective 1,3-dipolar cycloaddition of
crotonaldehyde were used as suitable dipolarophiles (Scheme 175). obtained, and that the scope of the reaction in terms of the enal was quite narrow, since only acroleine or A few years later, Karlsson and Hégberg reported the enantioselective 1,3-dipolar cycloaddition of
after reduction of the formyl group with sodium borohydride, the isoxazolidines 376 in good yields and
after reduction of the formyl group with sodium borohydride, the isoxazolidines 376 in good yields and
Scheme 177: Synthesis of cycloheptanes reported by Cordova In 2007, Ogilvie and co-workers reported the use of chiral hydrazides in the 1,3-dipolar nitrone
Scheme 177: Synthesis of cycloheptanes reported by Cordova In 2007, Ogilvie and co-workers reported the use of chiral hydrazides in the 1,3-dipolar nitrone
Scheme 178. sycloadducts 379 in excellent yields and good to moderate enantioselectivities as it is depicted in
Scheme 178. sycloadducts 379 in excellent yields and good to moderate enantioselectivities as it is depicted in
at 0°C for 6 days, gave rise to chiral isoxazolidines in good chemical yields, high enantioselectivities and
at 0°C for 6 days, gave rise to chiral isoxazolidines in good chemical yields, high enantioselectivities and
deduced by computational calculations. explaines the elevated degree of stereocontrol is based on dominant secondary 1-orbital interactions
deduced by computational calculations. explaines the elevated degree of stereocontrol is based on dominant secondary 1-orbital interactions
(arylidene)iminomalonates by means of a multi-component reaction.[284] In this way, an aldehyde and
(arylidene)iminomalonates by means of a multi-component reaction.[284] In this way, an aldehyde and
Scheme 183: Asymmetric 1,3-dipolar cycloaddition of azomethyne ylides reported by Gong et al. excellent enantioselectivities (Scheme 183). catalyst CIII, rendering the endo cycloadducts 386 as the only diastereoisomers in good yields and with
Scheme 183: Asymmetric 1,3-dipolar cycloaddition of azomethyne ylides reported by Gong et al. excellent enantioselectivities (Scheme 183). catalyst CIII, rendering the endo cycloadducts 386 as the only diastereoisomers in good yields and with
In 2008, Gong and co-workers reported the first 1,3-dipolar cycloaddition between azomethyne ylides
In 2008, Gong and co-workers reported the first 1,3-dipolar cycloaddition between azomethyne ylides
vith good yields and diastereoselectivities, although with low enantioselectivities (Scheme 185) benzophenone imine derivative 389 and different nitroalkenes. The final cycloadducts 390 were isolated
vith good yields and diastereoselectivities, although with low enantioselectivities (Scheme 185) benzophenone imine derivative 389 and different nitroalkenes. The final cycloadducts 390 were isolated
Scheme 186: Proposed mechanism for the formal [3+2] cycloaddition. highly substituted pyrrolidine (391), as shown in Scheme 186.
Scheme 186: Proposed mechanism for the formal [3+2] cycloaddition. highly substituted pyrrolidine (391), as shown in Scheme 186.
Based in this methodology, Xie and co-workers developed in 2010 a powerful kinetic resolution of
Based in this methodology, Xie and co-workers developed in 2010 a powerful kinetic resolution of
good stereoselectivities. The reaction has some limitations in the scope of enals, only allowing the use of One year later, W. Chen’s research group reported the same reaction using cyclic enones instead of
good stereoselectivities. The reaction has some limitations in the scope of enals, only allowing the use of One year later, W. Chen’s research group reported the same reaction using cyclic enones instead of
snones. When acyclic enones were used no reaction was observed. In 2010, Gong and coworkers developed a [3+2] cycloaddition between quinones, amines, and 2-
snones. When acyclic enones were used no reaction was observed. In 2010, Gong and coworkers developed a [3+2] cycloaddition between quinones, amines, and 2-
the B-carbon of the alkyl allenoate generating a 1,3-dipole, which is an inner salt containing a
the B-carbon of the alkyl allenoate generating a 1,3-dipole, which is an inner salt containing a
Marinetti
Marinetti
the limitations of the work is the use of terminal allenic esters. adducts were obtained in good yields and excellent enantioselectivities as shown in Scheme 195. One of
the limitations of the work is the use of terminal allenic esters. adducts were obtained in good yields and excellent enantioselectivities as shown in Scheme 195. One of
subsequent intramolecular alkylation affords the dihydropyrrole (404) after protonation (Scheme 196). In 2008, Gong and co-workers reported an asymmetric [3+2] cycloaddition reaction of isocyanoesters
subsequent intramolecular alkylation affords the dihydropyrrole (404) after protonation (Scheme 196). In 2008, Gong and co-workers reported an asymmetric [3+2] cycloaddition reaction of isocyanoesters
catalyzed the process, which constituted a formal [3+3] cycloaddition of crotonaldehyde (Scheme 197 performed over the same substrate. Concretely, they described the synthesis of cis- and trans-4-methyl-
catalyzed the process, which constituted a formal [3+3] cycloaddition of crotonaldehyde (Scheme 197 performed over the same substrate. Concretely, they described the synthesis of cis- and trans-4-methyl-
Scheme 198: Proposed mechanism for the reaction depicted in Scheme 197. with a 50 mol% of catalyst I. The mechanism proposed by the authors is summarized in Scheme 198. As shown in Scheme 198, the authors proposed a Michael/Morita-Baylis-Hillman sequence. First of
Scheme 198: Proposed mechanism for the reaction depicted in Scheme 197. with a 50 mol% of catalyst I. The mechanism proposed by the authors is summarized in Scheme 198. As shown in Scheme 198, the authors proposed a Michael/Morita-Baylis-Hillman sequence. First of
corresponding Weinreb amides, affording the final compounds 406 in moderate to good yields anc of this reaction was extended to a variety of ketenes, generated in situ from acid chlorides (Scheme Cinchona-alkaloid derivatives on polystyrene support.[310] The reaction afforded the corresponding
corresponding Weinreb amides, affording the final compounds 406 in moderate to good yields anc of this reaction was extended to a variety of ketenes, generated in situ from acid chlorides (Scheme Cinchona-alkaloid derivatives on polystyrene support.[310] The reaction afforded the corresponding
complete reversal of enantioselectivity with identical levels of asymmetric induction. turned out to be highly stereoselective for this reaction, yielding the cycloadducts 408 in excellen Arguably, the most important [2+2] cycloaddition is the so-called Staudinger cycloaddition reaction.
complete reversal of enantioselectivity with identical levels of asymmetric induction. turned out to be highly stereoselective for this reaction, yielding the cycloadducts 408 in excellen Arguably, the most important [2+2] cycloaddition is the so-called Staudinger cycloaddition reaction.
enantioselectivities, as it is depicted in Scheme 201. Very recently, Zajac and Peters uncovered a procedure for the asymmetric synthesis of B-sultams
enantioselectivities, as it is depicted in Scheme 201. Very recently, Zajac and Peters uncovered a procedure for the asymmetric synthesis of B-sultams
In 2008, Smith and co-workers reported the first chiral N-heterocyclic carbene-catalyzed B-lactam
In 2008, Smith and co-workers reported the first chiral N-heterocyclic carbene-catalyzed B-lactam
benzoylmethyl sulfonium ylides (413) to afford the final cyclopropanes (Scheme 203).[321]
benzoylmethyl sulfonium ylides (413) to afford the final cyclopropanes (Scheme 203).[321]
Scheme 204: (a) Configurational equilibrium of iminium-ion derived from proline (1) populate both (£) and (Z) iminium isomers. This equilibrium led to a diminished enantiocontrol. ‘hey assumed that the zwitterion iminium-ion derived from proline (Scheme 204a) could readily n order overcome this limitation, MacMillan used dihydroindole 2-carboxylic acid (CXV) as the
Scheme 204: (a) Configurational equilibrium of iminium-ion derived from proline (1) populate both (£) and (Z) iminium isomers. This equilibrium led to a diminished enantiocontrol. ‘hey assumed that the zwitterion iminium-ion derived from proline (Scheme 204a) could readily n order overcome this limitation, MacMillan used dihydroindole 2-carboxylic acid (CXV) as the
one was the poor diastereoselectivities obtained (Scheme 208). benzylamide derivatives as starting materials in order to obtain good enantioselectivities, and another In 2006, Ley and co-workers reported an asymmetric organocatalytic intermolecular cyclopropanation ields and enantioselectivities. One of the limitations of this methodology was the need to use 2-fluorc
one was the poor diastereoselectivities obtained (Scheme 208). benzylamide derivatives as starting materials in order to obtain good enantioselectivities, and another In 2006, Ley and co-workers reported an asymmetric organocatalytic intermolecular cyclopropanation ields and enantioselectivities. One of the limitations of this methodology was the need to use 2-fluorc
the need of an excess of base, which is needed probably to trap the hydrobromic acid generated in the Very recently, Yan and co-workers have reported the same reaction under bifunctional catalysis by
the need of an excess of base, which is needed probably to trap the hydrobromic acid generated in the Very recently, Yan and co-workers have reported the same reaction under bifunctional catalysis by
the enone, so that when enones other than cyclohexenone were used the stetereoselectivities decreasec
the enone, so that when enones other than cyclohexenone were used the stetereoselectivities decreasec
(Scheme 211). Scheme 211: Connon’s asymmetric organocatalytic cyclopropanation. cyclopropanes. However, the enantioselectivity was only poor to moderate in all of the examples place first and a consequent intramolecular alkylation activated by base furnishes the corresponding
(Scheme 211). Scheme 211: Connon’s asymmetric organocatalytic cyclopropanation. cyclopropanes. However, the enantioselectivity was only poor to moderate in all of the examples place first and a consequent intramolecular alkylation activated by base furnishes the corresponding
Scheme 212: Asymmetric organocatalytic cyclopropanation reported by Yan. order to facilitate the final intramolecular alkylation after the first Michael addition (Scheme 212).
Scheme 212: Asymmetric organocatalytic cyclopropanation reported by Yan. order to facilitate the final intramolecular alkylation after the first Michael addition (Scheme 212).
Using 4-bromo-acetoacetate 427, under the effect of 20 mol % of catalyst XLVIII and 1 equivalent of potassium carbonate, cyclopentanones with three new stereocenters (428) were formed in good to high yields, 6:1-12:1 dr and 93-99% ee.
Using 4-bromo-acetoacetate 427, under the effect of 20 mol % of catalyst XLVIII and 1 equivalent of potassium carbonate, cyclopentanones with three new stereocenters (428) were formed in good to high yields, 6:1-12:1 dr and 93-99% ee.
(87-92%) as well as excellent diastereo- (9:1->20:1 dr) and enantioselectivities (84-99% ee). -yclopentanes (432) with three stereogenic centers. The final products were isolated with high yields The second contribution of W. Wang et al. was focused on the synthesis of cyclopentenes (433).[334]
(87-92%) as well as excellent diastereo- (9:1->20:1 dr) and enantioselectivities (84-99% ee). -yclopentanes (432) with three stereogenic centers. The final products were isolated with high yields The second contribution of W. Wang et al. was focused on the synthesis of cyclopentenes (433).[334]
reaction appears to be limited to aromatic nitroalkenes, since no examples of aliphatic nitroalkenes were good yields and in almost diastereo- and enantiopure form, as shown in Scheme 216. However, the
reaction appears to be limited to aromatic nitroalkenes, since no examples of aliphatic nitroalkenes were good yields and in almost diastereo- and enantiopure form, as shown in Scheme 216. However, the
previous one, given that only aromatic nitroalkenes were used. enantiopure form (Scheme 217). The limitations of this methodology seem to be the same that the again, the reaction furnished the cyclopentanes (437) in excellent yields and in almost diastereo- and Zhong and co-workers, in 2010, reported a similar reaction beween nitrostyrenes and cyclic
previous one, given that only aromatic nitroalkenes were used. enantiopure form (Scheme 217). The limitations of this methodology seem to be the same that the again, the reaction furnished the cyclopentanes (437) in excellent yields and in almost diastereo- and Zhong and co-workers, in 2010, reported a similar reaction beween nitrostyrenes and cyclic
imidazolium or chiral triazolium derived NHC catalysts were used. When imidazolium salts such as
imidazolium or chiral triazolium derived NHC catalysts were used. When imidazolium salts such as
Scheme 221: Synthesis of fused cyclopentanes reported by Bode.
Scheme 221: Synthesis of fused cyclopentanes reported by Bode.
inctionalized cyclohexanones (448) in high yields and enantioselectivities, as shown in Scheme 222. the skin of an equatorean frog. This compound presents analgesic properties (Scheme 223).
inctionalized cyclohexanones (448) in high yields and enantioselectivities, as shown in Scheme 222. the skin of an equatorean frog. This compound presents analgesic properties (Scheme 223).
The first example of an asymmetric domino reaction catalyzed by chiral primary amines was reported
The first example of an asymmetric domino reaction catalyzed by chiral primary amines was reported
Scheme 224: Michael-Michael-retro-Michael cascade reported by Chen and Deng
Scheme 224: Michael-Michael-retro-Michael cascade reported by Chen and Deng
decreased dramatically. stereogenic centres with high enantioselectivities under mild conditions (Scheme 225). However, when in 2008, Liu and co-workers disclosed the formation of B-hydroxy-B-trifluoromethyl cyclohexanones,
decreased dramatically. stereogenic centres with high enantioselectivities under mild conditions (Scheme 225). However, when in 2008, Liu and co-workers disclosed the formation of B-hydroxy-B-trifluoromethyl cyclohexanones,
The 3-hydroxy ketone 458 was obtained as a single diastereoisomer in high yields and with moderate
The 3-hydroxy ketone 458 was obtained as a single diastereoisomer in high yields and with moderate
broadened later on the scope this reaction by using phenylsulfonyl acetophenone instead of B-ketoesters,
broadened later on the scope this reaction by using phenylsulfonyl acetophenone instead of B-ketoesters,
corresponding cyclohexanes with good yields and stereoselectivities.[35 1] similar reaction using alkylidene malonates and 2,5-dihydroxy-3,4-dihydrofuran, obtaining the 463) in high yields and enantioselectivities (Scheme 228). In 2009, Cordova and coworkers reported < In 2006, Jorgensen developed a nice asymmetric synthesis of cyclohexenones (465).[352] The
corresponding cyclohexanes with good yields and stereoselectivities.[35 1] similar reaction using alkylidene malonates and 2,5-dihydroxy-3,4-dihydrofuran, obtaining the 463) in high yields and enantioselectivities (Scheme 228). In 2009, Cordova and coworkers reported < In 2006, Jorgensen developed a nice asymmetric synthesis of cyclohexenones (465).[352] The
yields, diastereo- and enantioselectivities, as illustrated in Scheme 230.
yields, diastereo- and enantioselectivities, as illustrated in Scheme 230.
the need to use aliphatic o,B-unsaturated aldehydes, due the poor reactivity showed by cinnamyl trimethylsilyl ether (XXXVI) and proceeds with moderate to low yields and with moderate diastereo-
the need to use aliphatic o,B-unsaturated aldehydes, due the poor reactivity showed by cinnamyl trimethylsilyl ether (XXXVI) and proceeds with moderate to low yields and with moderate diastereo-
Scheme 237: Synthesis of cyclohexanes reported by MacMillan. to the requirement of using only a-unsubstituted aldehydes and terminal alkenes (Scheme 237).
Scheme 237: Synthesis of cyclohexanes reported by MacMillan. to the requirement of using only a-unsubstituted aldehydes and terminal alkenes (Scheme 237).
enantioselectivities, as it is shown in Scheme 238. affords the corresponding cyclohexenes 482 in moderate yields, excellent diastereoselectivities and good
enantioselectivities, as it is shown in Scheme 238. affords the corresponding cyclohexenes 482 in moderate yields, excellent diastereoselectivities and good
imines were not reported by the authors. limitations of this methodology is the need to use aromatic imines, and examples concerning aliphatic (486) with excellent yields, diastereo- and enantioselectivities, as shown in Scheme 240. One of the
imines were not reported by the authors. limitations of this methodology is the need to use aromatic imines, and examples concerning aliphatic (486) with excellent yields, diastereo- and enantioselectivities, as shown in Scheme 240. One of the
tyransition stat,e as it is depicted in Figure 31. In 2009, Zhong and co-workers reported the same reaction using chiral phosphoric acid derivatives instead of dicarboxylic acids, obtaining the chiral trans-aziridines 486 in excellent yields and stereoselectivities (Scheme 241).[369] As in Maruoka’s work, only aromatic imines were reported
tyransition stat,e as it is depicted in Figure 31. In 2009, Zhong and co-workers reported the same reaction using chiral phosphoric acid derivatives instead of dicarboxylic acids, obtaining the chiral trans-aziridines 486 in excellent yields and stereoselectivities (Scheme 241).[369] As in Maruoka’s work, only aromatic imines were reported
cope of the method seems to be quite narrow; only aromatic glyoxals were used in this report.
cope of the method seems to be quite narrow; only aromatic glyoxals were used in this report.
Scheme 243: Aziridination of calchones reported by Shi.
Scheme 243: Aziridination of calchones reported by Shi.
Scheme 244: Aziridination reported by Armstrong. enantioselectivities, as it is shown in Scheme 244. chiral chiral amine like quinine (CXXXIID renders the trans-aziridines 490 in low yields and moderate
Scheme 244: Aziridination reported by Armstrong. enantioselectivities, as it is shown in Scheme 244. chiral chiral amine like quinine (CXXXIID renders the trans-aziridines 490 in low yields and moderate
efficiently catalyzed by simple diphenylprolinol derivatives (XLVIID) as illustrated in Scheme 248. The
efficiently catalyzed by simple diphenylprolinol derivatives (XLVIID) as illustrated in Scheme 248. The
Scheme 249: Synthesis of 1,2-dihydroquinolidines reported by Cordova. for the synthesis of 1,2-dihydroquinolines 499 (Scheme 249).
Scheme 249: Synthesis of 1,2-dihydroquinolidines reported by Cordova. for the synthesis of 1,2-dihydroquinolines 499 (Scheme 249).
the reaction is quite narrow, since again only aromatic enals could be used. corresponding imine that reacts with the heteroaromatic moiety rendering the final product. The scope of
the reaction is quite narrow, since again only aromatic enals could be used. corresponding imine that reacts with the heteroaromatic moiety rendering the final product. The scope of
(Scheme 254). Scheme 254: Tandem aza-ene type reaction/cyclization cascade described by Terada. controlling the formation of three stereogenic centres in a highly diastereo- and enantioselective manner
(Scheme 254). Scheme 254: Tandem aza-ene type reaction/cyclization cascade described by Terada. controlling the formation of three stereogenic centres in a highly diastereo- and enantioselective manner
tetrahydropyridines (513) from simple and readily available starting materials (Scheme 255). Scheme 255: Highly enantioselective cascade reported by Rueping. reaction.[388] This process was performed in the presence of a novel chiral triazolium salt (XX) based
tetrahydropyridines (513) from simple and readily available starting materials (Scheme 255). Scheme 255: Highly enantioselective cascade reported by Rueping. reaction.[388] This process was performed in the presence of a novel chiral triazolium salt (XX) based
Scheme 256: NHC-catalyzed aza-Diels—Alder reaction performed by Bode.
Scheme 256: NHC-catalyzed aza-Diels—Alder reaction performed by Bode.
Scheme 258: Stereochemical model for endo-Diels-Alder cycloaddition. Scheme 257: Postulated catalytic cycle for the NHC-promoted aza-Diels-A Ider reaction.
Scheme 258: Stereochemical model for endo-Diels-Alder cycloaddition. Scheme 257: Postulated catalytic cycle for the NHC-promoted aza-Diels-A Ider reaction.
Asymmetric Counteranion — Directed Catalysis (ACDC) (Scheme 260).[394] In 2008, Wang and List published a nice epoxidation of a,f-unsaturated aldehydes (277) by This asymmetric induction mode works as follows: the achiral secondary amine (CXXXVI) forms a
Asymmetric Counteranion — Directed Catalysis (ACDC) (Scheme 260).[394] In 2008, Wang and List published a nice epoxidation of a,f-unsaturated aldehydes (277) by This asymmetric induction mode works as follows: the achiral secondary amine (CXXXVI) forms a
261).[395] However, this methodology does not allow for the epoxidation of aromatic enals. In 2010, List and co-workers expanded the scope of the reaction by using a similar catalytic system
261).[395] However, this methodology does not allow for the epoxidation of aromatic enals. In 2010, List and co-workers expanded the scope of the reaction by using a similar catalytic system
Scheme 263: Catalytic synthesis of tetrahydroxanthenones disclosed by Cordova Very recently, D.-Q. Xu, Z.-Y. Xu and co-workers reported an improved protocol for the same
Scheme 263: Catalytic synthesis of tetrahydroxanthenones disclosed by Cordova Very recently, D.-Q. Xu, Z.-Y. Xu and co-workers reported an improved protocol for the same
(CX XX VII) and simple a—amino acids such as fert-leucine (CXXXVIII). As it is shown in Scheme 264,
(CX XX VII) and simple a—amino acids such as fert-leucine (CXXXVIII). As it is shown in Scheme 264,
it is shown in Scheme 265. Scheme 265: Catalytic synthesis of 2-amino-2-chromenes developed by Xie. phosphoric acids, rendering the corresponding chromenes in good yields and good enantioselectivities as
it is shown in Scheme 265. Scheme 265: Catalytic synthesis of 2-amino-2-chromenes developed by Xie. phosphoric acids, rendering the corresponding chromenes in good yields and good enantioselectivities as
In 2008, Xu and co-workers developed a novel catalytic tandem oxa-Michael-Henry reaction between
In 2008, Xu and co-workers developed a novel catalytic tandem oxa-Michael-Henry reaction between
aromatic nitroalkenes. enantioselectivities (Scheme 267). One of the limitations of this technology was the need to uss In the first step, the alcohol effects a nucleophilic attack to the B-position of the nitrostyrene, and a
aromatic nitroalkenes. enantioselectivities (Scheme 267). One of the limitations of this technology was the need to uss In the first step, the alcohol effects a nucleophilic attack to the B-position of the nitrostyrene, and a
Scheme 268: Proposed mechanism for the amine-catalyzed synthesis of 3-nitro-2H-chromenes.
Scheme 268: Proposed mechanism for the amine-catalyzed synthesis of 3-nitro-2H-chromenes.
use of l-naphthols, and when other aromatic alcohols such as phenols were used no reaction was stereoselectivities, as it is shown in Scheme 270. However, this methodology seems to be limited to the
use of l-naphthols, and when other aromatic alcohols such as phenols were used no reaction was stereoselectivities, as it is shown in Scheme 270. However, this methodology seems to be limited to the
yields and with excellent enantioselectivities (Scheme 272). -atalyzed by diphenylprolinol derivatives (CXXIV), affording the corresponding chromenes 540 in goo sequence between propargylic aldehydes 539 and 2-(£)-(2-nitrovinyl)phenols 538. The reaction is
yields and with excellent enantioselectivities (Scheme 272). -atalyzed by diphenylprolinol derivatives (CXXIV), affording the corresponding chromenes 540 in goo sequence between propargylic aldehydes 539 and 2-(£)-(2-nitrovinyl)phenols 538. The reaction is
acid additive no reaction was observed after 16 h. Scheme 273: Synthesis of hexahydrofuro[3,4-c]furanes reported by Vicario. acid additive such as benzoic acid is crucial for enhancing the rate of the reaction. Without the use of an
acid additive no reaction was observed after 16 h. Scheme 273: Synthesis of hexahydrofuro[3,4-c]furanes reported by Vicario. acid additive such as benzoic acid is crucial for enhancing the rate of the reaction. Without the use of an
Scheme 274: Synthesis of pyranones reported by Bode.
Scheme 274: Synthesis of pyranones reported by Bode.
good yields and moderate to good stereoselectivities (Scheme 275). Scheme 275: Synthesis of pyranones from propargylic aldehydes reported by Bode. aldehydes react with pyruvic esters, kojic acids or naphthols to afford the corresponding pyranones it
good yields and moderate to good stereoselectivities (Scheme 275). Scheme 275: Synthesis of pyranones from propargylic aldehydes reported by Bode. aldehydes react with pyruvic esters, kojic acids or naphthols to afford the corresponding pyranones it
Scheme 276: Synthesis of furanes reported by Calter.
Scheme 276: Synthesis of furanes reported by Calter.
yields and enantioselectivities (Scheme 277). bifunctional thiourea-tertiary amine catalysts such as CXLII affording the final compounds 550 in good in 2010, Zhao and Cao expanded the scope of the reaction by using cyclic 1,3-dicarbonyl compounc
yields and enantioselectivities (Scheme 277). bifunctional thiourea-tertiary amine catalysts such as CXLII affording the final compounds 550 in good in 2010, Zhao and Cao expanded the scope of the reaction by using cyclic 1,3-dicarbonyl compounc
Scheme 278: Synthesis of aminobenzopyranes reported by Rueping. affording the final benzopyranes 553 in good yields and excellent enantioselectivities (Scheme 278).
Scheme 278: Synthesis of aminobenzopyranes reported by Rueping. affording the final benzopyranes 553 in good yields and excellent enantioselectivities (Scheme 278).
organocatalytic asymmetric synthesis of chiral thiochromenes (554) via a sulfa-Michael/aldol tandem three contiguous estereocentres with excellent enantioselectivities (96-99% ee) and yields (71-98%), and
organocatalytic asymmetric synthesis of chiral thiochromenes (554) via a sulfa-Michael/aldol tandem three contiguous estereocentres with excellent enantioselectivities (96-99% ee) and yields (71-98%), and
(bicarbonate or benzoic acid) allowed the control of the regioselectivity of the reaction (aldol step)
(bicarbonate or benzoic acid) allowed the control of the regioselectivity of the reaction (aldol step)
(559) to obtain chiral tetrahydrothiophenes (560) under catalysis by diphenylprolinol trimethylsilyl ether particular, they developed a double Michael addition between enals (277) and 4-mercapto-2-butenoate After the first thio-Michael addition, the enamine intermediate undergoes a conjugate addition to the
(559) to obtain chiral tetrahydrothiophenes (560) under catalysis by diphenylprolinol trimethylsilyl ether particular, they developed a double Michael addition between enals (277) and 4-mercapto-2-butenoate After the first thio-Michael addition, the enamine intermediate undergoes a conjugate addition to the
affords the tetrahydrothioxanthenone (561) (Scheme 282). incoming thiol. Hydrolysis of the resulting iminium intermediate gives aldol 562. Elimination of water
affords the tetrahydrothioxanthenone (561) (Scheme 282). incoming thiol. Hydrolysis of the resulting iminium intermediate gives aldol 562. Elimination of water
Scheme 283: Zhang’s synthesis of 3-nitro-2H-thiochromenes.
Scheme 283: Zhang’s synthesis of 3-nitro-2H-thiochromenes.
shown in Scheme 284. hiochromenes (565) in high yields, and with excellent diastereomeric and enantiomeric excesses a:
shown in Scheme 284. hiochromenes (565) in high yields, and with excellent diastereomeric and enantiomeric excesses a:
diastereoselectivity and with excellent yields and enantioselectivities (Scheme 285). obtained by means of this procedure, with the formation of three stereogenic centres with total Soon after, the same group published another organocatalytic, enantioselective domino Michael-aldol
diastereoselectivity and with excellent yields and enantioselectivities (Scheme 285). obtained by means of this procedure, with the formation of three stereogenic centres with total Soon after, the same group published another organocatalytic, enantioselective domino Michael-aldol
such as N-benzyl maleimide, the enantioselectivities decreased dramatically. methodology is the need to use aromatic maleimides, since when N-aliphatic substituents were used,
such as N-benzyl maleimide, the enantioselectivities decreased dramatically. methodology is the need to use aromatic maleimides, since when N-aliphatic substituents were used,
furnishing tetrahydro-1,2-oxazines (571) with excellent yields and enantioselectivities (Scheme 288). nitroalkene moiety, and nitrosobenzene (322).[428] In the first step, O-alkylation took place at the a-
furnishing tetrahydro-1,2-oxazines (571) with excellent yields and enantioselectivities (Scheme 288). nitroalkene moiety, and nitrosobenzene (322).[428] In the first step, O-alkylation took place at the a-
Scheme 290: Synthesis of trifluoromethyl-isoxazolines described by Shibata. In 2010, Pitacco and coworkers reported the symthesis of chiral 1,4-dihydropyridazines (581) starting from enolizable aldehydes and 1,2-diaza,1,3-dienes (580).[431] The reaction was simply catalyzed by proline, affording the corresponding cycloadducts in low yields and with moderate enantioselectivities
Scheme 290: Synthesis of trifluoromethyl-isoxazolines described by Shibata. In 2010, Pitacco and coworkers reported the symthesis of chiral 1,4-dihydropyridazines (581) starting from enolizable aldehydes and 1,2-diaza,1,3-dienes (580).[431] The reaction was simply catalyzed by proline, affording the corresponding cycloadducts in low yields and with moderate enantioselectivities
synthesis of natural products and in medicinal chemistry (Scheme 292). concerted [4+2] cycloaddition with a 2-amino-1,3-butadiene generated in situ from the enone 284 and
synthesis of natural products and in medicinal chemistry (Scheme 292). concerted [4+2] cycloaddition with a 2-amino-1,3-butadiene generated in situ from the enone 284 and
for a triple cascade reaction. creation of three bonds by a high enantioselective combination of enamine-iminium-enamine catalysis This catalytic cascade is a three component reaction comprising a linear aldehyde (332), a nitroalkene
for a triple cascade reaction. creation of three bonds by a high enantioselective combination of enamine-iminium-enamine catalysis This catalytic cascade is a three component reaction comprising a linear aldehyde (332), a nitroalkene
scheme 294: Proposed catalytic cycle for the asymmetric organocatalytic triple cascade reaction developed by Enders.
scheme 294: Proposed catalytic cycle for the asymmetric organocatalytic triple cascade reaction developed by Enders.
enantioselectivities, albeit with low diastereoselectivities due the poor stereocontrol in the newly formed
enantioselectivities, albeit with low diastereoselectivities due the poor stereocontrol in the newly formed
Scheme 297: Reaction pathway for the synthesis of cyclohexanes reported by Dixon.
Scheme 297: Reaction pathway for the synthesis of cyclohexanes reported by Dixon.
final compounds in good yields and stereoselectivities (Scheme 299). same mixture of a diphenylprolinol catalyst (CX VIII) and a bifunctional catalyst (CXIX), rendering the
final compounds in good yields and stereoselectivities (Scheme 299). same mixture of a diphenylprolinol catalyst (CX VIII) and a bifunctional catalyst (CXIX), rendering the
oxindoles via a triple cascade reaction.[237] As it is shown in Scheme 301, the reaction between a- methyleneoxindoles (330), aldehydes (332) and enals (277) catalyzed by a diphenylprolinol derivative
oxindoles via a triple cascade reaction.[237] As it is shown in Scheme 301, the reaction between a- methyleneoxindoles (330), aldehydes (332) and enals (277) catalyzed by a diphenylprolinol derivative
In 2009, Enders and co-workers reported the asymmetric synthesis of cyclohexenes via a triple
In 2009, Enders and co-workers reported the asymmetric synthesis of cyclohexenes via a triple
Scheme 303: Triple cascade reaction reported by Enders. this methodology is the need to use aromatic enals, given that when aliphatic enals were used no domino
Scheme 303: Triple cascade reaction reported by Enders. this methodology is the need to use aromatic enals, given that when aliphatic enals were used no domino
in 2009, Gong and co-workers developed the first highly enantioselective Biginelli reaction catalyzed
in 2009, Gong and co-workers developed the first highly enantioselective Biginelli reaction catalyzed
Scheme 305: Enantioselective Biginelli condensation developed by Gong. In the same year, Chen and co-workers developed a similar reaction using this time ureas as starting
Scheme 305: Enantioselective Biginelli condensation developed by Gong. In the same year, Chen and co-workers developed a similar reaction using this time ureas as starting
Scheme 306: Mechanism of the quadruple domino reaction developed by Gong. trisubstituted cyclohexenecarbaldehyde 609 and regenerating the catalyst.
Scheme 306: Mechanism of the quadruple domino reaction developed by Gong. trisubstituted cyclohexenecarbaldehyde 609 and regenerating the catalyst.
XLVI and affords the polisubstituted cyclohexenes 611 in good yields and enantioselectivities The reaction, as in the methodology of Gong, is simply catalyzed by commercially available catalyst
XLVI and affords the polisubstituted cyclohexenes 611 in good yields and enantioselectivities The reaction, as in the methodology of Gong, is simply catalyzed by commercially available catalyst
dicarbonylic compounds and 2-oxobutanoates is a clear limitation of this methodology. 8. Conclusions
dicarbonylic compounds and 2-oxobutanoates is a clear limitation of this methodology. 8. Conclusions
Related topics:
Organic ChemistryCatalysisAsymmetric catalysisMichael Addition
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