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metathesis since it undergoes a retro [2+2] reaction to yield an alkyne and a triaryloxytungsten alkylidyne complex. Compound 36 (Scheme 7) reacts with an alkyne to afford a five-coordinate trichlorotungstacyclobutadiene analogous to the triaryloxytungstacyclobutadiene shown in Equation (2), but the trichlorotungstacycle reacts further, and irreversibly, with another alkyne equivalent to generate a WY cyclo- pentadienyl complex.'! These studies confirmed that alk- oxide ligands promote metathesis-like reactions, while chlor- ides encourage side reactions that destroy the alkylidyne. On the basis of these studies it was suggested that the most successful tungsten-based olefin-metathesis catalyst might be a pseudotetrahedral species that contains sterically demand- ing alkoxide ligands. thesis reactions when bulky electron-withdrawing alkoxides were present, and were isolated and characterized. The structure of intermediate trigonal-bipyramidal (TBP) metal- lacyclobutadienes could be elucidated by crystallography as well. A representative example of an isolable metallacyclo- butadiene is the triaryloxytungstacyclobutadiene shown in Equation (2)."| This species can act as a catalyst for alkyne — Figure 13 metathesis since it undergoes a retro [2+2] reaction to yield an alkyne and a triaryloxytungsten alkylidyne complex. Compound 36 (Scheme 7) reacts with an alkyne to afford a five-coordinate trichlorotungstacyclobutadiene analogous to the triaryloxytungstacyclobutadiene shown in Equation (2), but the trichlorotungstacycle reacts further, and irreversibly, with another alkyne equivalent to generate a WY cyclo- pentadienyl complex.'! These studies confirmed that alk- oxide ligands promote metathesis-like reactions, while chlor- ides encourage side reactions that destroy the alkylidyne. On the basis of these studies it was suggested that the most successful tungsten-based olefin-metathesis catalyst might be a pseudotetrahedral species that contains sterically demand- ing alkoxide ligands. thesis reactions when bulky electron-withdrawing alkoxides were present, and were isolated and characterized. The structure of intermediate trigonal-bipyramidal (TBP) metal- lacyclobutadienes could be elucidated by crystallography as well. A representative example of an isolable metallacyclo- butadiene is the triaryloxytungstacyclobutadiene shown in Equation (2)."| This species can act as a catalyst for alkyne

Related Figures (76)

Figure 1. Tungsten-based olefin-metathesis catalysts. Metal-catalyzed olefin metathesis has had an enormous impact on organic synthesis. A myriad of small-, medium-, and large-ring carbo- and heterocycles, and a wide assortment of acyclic unsaturated molecules are now readily accessible through this important class of reactions.!"“*! Stereoselective methods that utilize catalytic metathesis and successful complex-molecule total syntheses that have strategically benefited from this remarkable transformation are being disclosed in increasing numbers. Reports of new metal complexes that promote selective metathesis reactions that were not feasible before, catalysts that can be applied to large-

Figure 2. Achiral molybdenum-based olefin-metathesis catalysts. [a] Isolated with an additional 2,4-dimethylpyridine ligand (see 8b). [b] Isolatec with an additional quinuclidine ligand.

Figure 3. Chiral molybdenum-based catalysts for olefin metathesis bearing a 2,6-diisopropylaryl imido ligand. Complexes 11q and 11r to date have not exhibited catalytic metathesis activity and are shown here only for the purpose of discussion. Ad=adamantyl, Ts =tosyl.

Scheme 1. A representative metal-catalyzed olefin-metathesis reaction. Metallacyclobutanes II and II’ and the propagating alkylidene com- plexes I and I’ are key intermediates for productive metathesis. (Only metathesis of a trans olefin to give trans products is shown.) Figure 4. Chiral molybdenum-based catalysts for olefin metathesis bearing various imido ligands.

Scheme 2. Formation of the first high-oxidation-state alkylidene complex by a-hydrogen abstraction. in vacuo. It is sensitive to oxygen, water, and a variety of functionalities, among them ketones and aldehydes, with which it reacts to yield polymeric [(tBuCH,);Ta=O],, and the expected olefin.'“! Therefore 18 is related to an alkylidene phosphorane,!! and may be viewed as a Ta(v) alkylidene species. Complex 18 differs sharply in several respects from Fischer-type complexes where a heteroatom is bound to the carbene ligand (see above).'! Among these differences are the polarities of the M=C bonds (e.g., (6 + )Ta=C(6—) as in Scheme 2 vs. (6—)W=C(6 +) in [(CO);W=CPh(OMe)]) and the number of electrons in metal-based orbitals (10 for the Ta species versus 18 for the W complex). Note that the 18- electron count in [(CO);W=CPh(OMe)] would require that one CO ligand be lost to give a 16-electron species before an olefin can react and form the required metallacyclobutane intermediate. In contrast, no (covalently bound) ligand could be lost from the 10-electron tantalum species under mild conditions, nor would any have to be.

Scheme 3. B-Hydride rearrangement of a tantalacyclobutane formed by reaction of a tantalum-based alkylidene complex with ethylene. shown in Scheme 3 for t he reaction between 21 and ethylene, the intermediate (unobservable) tantalacycle 22 rearranges in the presence of ethylene to yield cis- | and trans-4,4-dimethyl-2- pentene, 4,4-dimethyl-1-pen- tene, and tantalacyclopentane 23.'! It is presumed that: 1) the two observed olefin products are bound to Ta in a [CpTaCl,(olefin) complex immediately upon rearrangement of 22; 2) olefin products are displaced by ethylene to yield [CpTaCl,(ethylene)]; 3) [CpTaCl,- (ethylene)] subsequently reacts with ethylene to yield 3.°5| Olefin complexes and tantalacyclopentanes ultimately ere investigated more extensively in the analogous Cp* (1’- sMe;) system.!**! la The reactions shown in Scheme 3 suggested that although a metallacyclobutane forms when a Ta neopentylidene reacts with ethylene, it rearranges more rapidly than it converts into tert-butylethylene and a Ta methylene complex analogous to 21. It was subsequently shown that complexes such as [Cl;(PMe;),Ta=CHrBu] react with olefins in a similar fashion to afford olefinic products through rearrangement of unob- servable tantalacyclobutanes, and that even 20 [Eq. (1)] is a short-lived metathesis catalyst for cis-2-pentene.'! In an important contrast, however, it was demonstrated that [(PMe;)(OfBu),ClTa=CH Bu] (24) reacts with styrene in the presence of PMe; to provide the isolable benzylidene com- plex, [(PMe;),(OtBu),CITa=CHPh] (25; Scheme 4). In addi- tion, when treated with cis-2-pentene in the presence of PMes, Ta complex 24 or the analogous Nb system 26 promote the metathesis of cis-2-pentene (25-30 turnovers) at room tem- perature.'"! This was the first time that an alkylidene complex analogous to the initial alkylidene species could be isolated upon reaction with an olefin!) However, the ethylidene and propylidene intermediates which were formed in the metathesis of cis-2-pentene (Scheme 4), apparently rearranged readily to give ethylene and propylene, respectively, and therefore could not be observed. Rearrange- ment of ethylidene and propylidene intermediates to olefins is one reason why metathesis by 24 or 26 is not long-lived. It was demonstrated later that some tantalacyclobutane and alkyli- dene complexes derived from them could be observed if three bulky phenoxide ligands were bound to the Ta center.!”~”) Thus, it was clear that bulky alkoxide ligands are beneficial to sustained metathesis reactions involving Ta or Nb alkylidene complexes.

Scheme 4. The first example of an isolable high-oxidation-state metal alkylidene complex (25) formed in a reaction between a well-character- ized metal alkylidene catalyst (24) and an olefin, and catalytic metathe- sis with 24 and 26.

Scheme 5. Synthesis of tungsten-based oxo alkylidene complexes from a tantalum alkylidene complex. A tungsten-based complex believed to be a plausible target as a well-defined catalyst for olefin metathesis was five- coordinate [(tBuO),W=CHrBu]. (The advantages of a steri- cally crowded pseudotetrahedral coordination sphere were not appreciated at that time.) The first reaction shown in Scheme 5 (between 27 and 28) was an attempt to prepare

Scheme 6. Formation of metathesis-active cationic tungsten-based alkylidene complexes. Related advances were disclosed by Osborn and co- workers," who found that addition of various Lewis acids (such as AIBr;) to [(OCH,fBu),(CH,fBu),W=O] leads to the formation of metathesis catalysts.) Accordingly, it was found that oxo-free alkylidene complexes represented by {[(OCH,tBu),Br,W=CHtBu] (32, Scheme 6) could be iso-

Scheme 7. Synthesis of tungsten-based imido alkylidene complexes from alkylidyne complexes; TMS = Me;Si. The first practical synthesis of a high-oxidation-state alkylidyne complex of tungsten consists of the reaction between [W(OMe);Cl] and six equivalents of neopentyl magnesium chloride (Scheme 7). Sequential abstraction of

Scheme 8. The route for practical synthesis of molybdenum-based alkylidene complexes; OTf=[CF;SO3] .

Scheme 9. syn and anti Mo and W alkylidene complexes are intercon- vertible. The rate constant for syn to anti conversion (k,/,), and the reverse (k,/,), are influenced by electronic and steric factors that affect the energy of intermediate I.

Scheme 10. Hyperconjugative effect proposed to be present in the syn alkylidene complexes and representative structural consequences. Stereoelectronic factors are at least partially responsible for the fact that syn alkylidenes are energetically favored. As illustrated in IT in Scheme 10, and supported by theoretical studies," an agostic interaction! is proposed to exist between the C,—H, bond and the transition-metal center. Such a stabilizing hyperconjugation (6¢_4—0*y,_n) increases the a character of the C,— H,, bond, thereby lowering JQ, and increasing the triple-bond character of the Mo=C, bond. Crystallographic studies support the validity of such inter- actions. As an example, as illustrated in Scheme 10, the X-ray

Figure 5. Steric interactions in the square-pyramidal (SP) complex formed upon coordination of olefin substrate may be partly responsi- ble for lower reactivity of syn alkylidenes towards an olefin (ethylene used as example).

Scheme 11. syn and anti metal alkylidene complexes form adducts with various donor ligands (L). Interconversion between the two isomers, however, requires loss and reassociation of the donor ligand (G=CMe,Ph). donor ligands, such as THF, PMe;, pyridine, or quinuclidine (see Figures 3 and 4 and Scheme 10 for THF and pyridine adducts).!'"7l In all cases reported to date, the donor has been found to add to a CNO tetrahedral face (one of two pseudotetrahedral faces with the imido nitrogen, the alkyli- dene C,, and an alkoxide oxygen atom at the corners), to afford a trigonal bipyramidal complex in which the new ligand is bound in the axial position (Scheme 11). When the alkoxide groups are electron-withdrawing, as in 3d (Scheme 11), and the donor (L) is PMe;, then the initial adduct contains the alkylidene in the syn orientation (e.g., syn-3d-PMe;). This is because the phosphane ligand binds tightly to the perdomi- nating syn isomer (K,,+1400 for 3d). With time, as illustrated in Scheme 11, the syn adduct loses the phosphane to give a small concentration of the base-free species, the

Figure 6. Structure of the PMe; adduct of [(NAr) {OCMe(CF;).}.Mo= CH¢Bu].

readily polymerizes (o-TMS)phenylacetylene.!?! When the base is pyridine, the adduct is virtually inactive toward (o- TMS)phenylacetylene, while the 2,5-dimethylpyridine com- plex analogous to 8b is unstable as a consequence of the high concentration of the base-free species formed in solution which then decomposes bimolecularly.

Scheme 72. Bis(trimethylsilyl)tungstacyclobutane 50, isolated and characterized by X-ray crystallography, breaks up to afford silylalkylidene complex 51 (not TASHC=CHTMS), which suggests that not all metallacyclobutanes lead to productive metathesis.

Figure 7. Tungstacycobutanes have been isolated, characterized, and shown to exist as trigonal-bipyramidal (TBP; 48) or square-pyramidal (SP; 49) complexes.

Scheme 713. One pathway that results in decomposition of molybde- num-based metathesis catalysts leads to molybdenum(tv) olefin com- plexes, such as 53. Two main mechanistically elucidated routes lead to a depletion of catalyst concentration during a typical meta- thesis reaction; in each of these processes, reduced (Mo™ or WY) species are generated. Such decomposition pathways are the following: 1) Rearrangement of metallacyclobutanes to olefins. For example, the reaction shown in Scheme 13

Scheme 14. Pathways that lead to the generation of dimeric complexes, such as 56, also account for decomposition of molybdenum-based metathesis catalysts. pathway, which is fastest for methylene complexes, leads to the formation of olefins as a result of coupling of two alkylidenes (Scheme 14). The tert-butoxide complex 3a upon

Scheme 15. ROMP and cleavage of the polymer with benzaldehyde in a Wittig-like reaction.

Scheme 16. Different alkylidene isomers can lead to polymeric struc- tures with varying backbone olefin stereochemistry (G=CMe,Ph).

Scheme 17. In spite of predominance of the syn molybdenum-based alkylidene complexes, the substantially higher reactivity of the anti isomers leads to the formation of all-trans polymers (G=CMe,Ph).

Figure 8 The four possible regular structures of 2,3-disubstituted nor- bornadienes and the effect of enantiomerically pure auxiliary R* (from reactions of 57b) on the chemical environments of the inequivalent protons H, and H,; a) cis, isotactic (cc,mm), b) cis, syndiotactic (cc,rr), c) trans, syndiotactic (tt,rr), d) trans, isotactic (tt,mm). The ability to control cis/trans selectivity as well as the elative stereochemistry between monomer units (tacticity) re important features of ROMP with well-defined catalysts. n ROMP reactions of norbornenes or norbornadienes that ontain a mirror plane, four stereoregular polymers can be ormed, as shown in Figure 8 for a generic disubstituted

Scheme 18. Approach from the two diastereotopic faces of a chiral alkylidene intermediate determines the tacticity of the polymer prod- uct. A) monomer approaches one CNO diastereoface (a or b) in each step, B) monomer approaches alternating CNO diastereofaces a and b. The all-trans product derived from polymerization of NBDF, catalyzed by Mo complex 3a is highly tactic (accord- ing to °C NMR spectroscopy; see below).!"4l In contrast, the high cis polymer obtained from the reaction of NBDF, with 3d (G=?Bu) has been shown to be biased toward one tacticity (~75%, '"°CNMR spectroscopy). Any tacticity control under either set of conditions must arise through chain-end control. That is, the chirality of the 8 carbon atom in the first insertion product determines which diastereotopic face of the M=C bond is approached by the next equivalent of monomer. As summarized in Scheme 18, if the same CNO

Figure 9. The C(7) resonance(s) in the °C NMR spectra of cis poly- mers obtained from reactions of NBDF,, where molybdenum-based complexes 3d (G=CMe,Ph); spectrum a), 110 (spectrum b), and 12g (spectrum c) are used as the catalyst. (cc mr=cis,cis,meso,racemic; see text for explanation.)

Figure 10. The olefinic regions of the 300 MHz homonuclear COSY NMR spectra of all-cis, isotactic (left) and all-trans, syndiotactic (right) polymers obtained from polymerization of 57b (CDCI; at 25°C) with 12g and 3a as the catalysts, respectively.

Figure 11. Achiral ruthenium-based olefin-metathesis catalysts. Mes = 2,4,6-Me;C,H).

Scheme 19. Top: Molybdenum complex 3d used in some the first examples of effi- cient catalytic and stereoselective cross metathesis, bottom: proposed molybde- num-catalyzed cross-metathesis mechanism.

Scheme 20. A key step in the total synthesis of fluvirucin B, is the molybdenum-catalyzed RCM that forms a trisubstituted olefin 60 with > 98% Z selectivity and generates a fourteen- membered cyclic lactam.

recently developed Ru-based catalysts, such as 58b-d (Figure 11), in promoting the formation of such trisubstituted cyclic olefins. In general, the same question can be posed in connection to a number of olefin-metathesis processes discussed below. through chromatography on silica gel). Subsequent func- tional-group manipulations, including oxidation of the appro- priate alkene isomer, led to the isolation of the target molecule.

Scheme 21. Molybdenum-catalyzed RCM affords a macrocyclic lactone bearing the trisubstituted olefin used at a later stage to install the requisite epoxide in the total synthesis of (—)-epothilone B. PMB =p-methoxybenzyl.

Scheme 22. The molybdenum-catalyzed tandem CM/RCM reaction leads to a regioselective dimerization that serves as the foundation of a total synthesis of (—)-cylindrocyclophanes; control experiments indicate that the initial CM is reversible, which allows the predominant formation of the lower energy head-to-tail macrocycle.

4.2.2. Synthesis of Medium Rings by Molybdenum-Catalyzed RCM In the above examples, where catalytic metathesis is used to prepare complex macrocycles, experimental evidence points to the influence of ring size and substrate stereo- chemistry in reaction efficiency. In this vein, it should be noted that, in the context of the total synthesis of diazona- mide A, Nicolaou and co-workers attempted to effect the RCM transformation in Equation (5) with 3d (Figure 2, G= CMe,Ph), or various Ru-based catalysts to no avail. This lack of reactivity is likely to be a result of the ring strain associated with the desired target structure.!!*?!

In the course of studies towards the total synthesis of balanol [Eq. (8); Boc =1,1-dimethylethoxycarbonyl], RCM of diene 69 was effected at 70°C in the presence of Ru complex 58a (Figure 11), to give a thermally induced non- metathesis product.'”! However, in the presence of 10 mol %

Angew. Chem. Int. Ed. 2003, 42, 4592-4633

Scheme 24. Functionalities within a substrate and conformational preferences can be critical to the outcome of RCM reactions that afford medium rings.

<5% product formed with 20 mol % 58a (catalyst decomposition)

Scheme 25. Molybdenum-catalyzed RCM delivers medium-ring enol ethers that may be used as building blocks in the total synthesis of ichthyotoxins, such as brevetoxin A (3d, Figure 2, G=CMe,Ph). The discovery of medicinally significant and structurally complex molecules, such as marine neurotoxin brevetoxin A (Scheme 25), has given rise to a number of investigations aimed at the development of efficient syntheses of these polycyclic ethers. Given the remarkable ability of catalytic

Scheme 26. Molybdenum-catalyzed RCM affords eight- and nine-mem- bered-ring allylic ethers; reaction facility depends on the relative ster- eochemistry of substrate structures (3d, Figure 2, G=CMe,Ph).

Scheme 27. Molybdenum-catalyzed ROM/CM used to prepare functionalized chromenes en route to the total synthesis of antihypertensive agent nebivolol (34d, Figure 2, G=CMe,Ph).

Scheme 28. Reaction pathway for the molybdenum-catalyzed (or ruthenium-catalyzed) reactions of disubstituted styrenyl ethers in the presence of ethylene atmosphere.

Molybdenum complex 3d has been employed in the synthesis of highly functionalized smaller ring structures. One example is illustrated in Equation (11) (3d, catalyst loading and reaction temperature not specified), where catalytic RCM occurs efficiently between a 1,1-disubstituted olefin and

and a sterically encumbered terminal olefin adjacent to a quaternary carbon center undergo efficient ring-closure to deliver the desired compound.!*!!

and reaction temperature not specified). These studies were disclosed by Martin and co-workers in the context of the total synthesis of the ergot alkaloid lysergic acid."*! In contrast, use of the ruthenium-based catalyst 58a provided “small quanti- ties” of the desired product. (For studies regarding enantio- selective olefin metathesis involving tertiary amines, see Sec- tion 5).

Scheme 29. Cyclic vinylsilane obtained from molybdenum-catalyzed RCM is used in a subsequent palladium-catalyzed intramolecular cross-coupling to afford a nine-membered-ring structure en route to the total synthesis of brasilenyne.

Nelson et al. in a key diastereoselective C—C bond-forming reaction en route to the total synthesis of laulimalide.

Scheme 30. Molybdenum-catalyzed RCM can be used in target-oriented synthesis to access a variety of complex cyclic enol ethers; TAEDA=N,N,N’,N’-tetramethyl 1,2-ethanediamine. Compound 88 is also formed with 25 mol % 58b (added in portions under Ar).

Scheme 31. Molybdenum-catalyzed (3d Figure 2, G=CMe,Ph) ROM/RCM provides access to bis(dihydropyran) structures that may be used as intermediates in the total synthesis of halichondrin B. With 25 mol% of Ru complex 58a as the catalyst (80°C, CgH,) the two byproducts shown in the middle of the scheme are formed in 21% yield.

Figure 12. The first attempt at kinetic resolution through molybdenum- catalyzed ARCM. The preparation and utility of chiral complex 11p (Figure 3) in kinetic resolution of various dienes was disclosed in 1996 by Grubbs and Fujimura."'”*"™! As the case regarding the resolution of shown in Figure 12 indicates, levels of enantiodifferentiation proved to be low (k,., <3).

Catalytic kinetic resolution of various dienes through ARCM can be carried out efficiently at 22°C in the presence of 5mol% 11a." As the data in Scheme 32 illustrate, 1,6- Scheme 32. Effective molybdenum-catalyzed kinetic resolution of 1,6- dienes through ARCM promoted by 11a.

Enantiomerically pure chiral Mo complexes 11a and 12a were synthesized in 1997 and their ability to effect ARCM was probed.''*'*! It was established that these Mo catalysts initiate olefin metathesis with excellent asymmetric induction owing to their rigidity and the sterically based differentiation imposed on the binding pocket of the chiral complex. Complexes 11a and 12a are orange solids and indefinitely stable when kept under an atmosphere of N>.

Scheme 33. Molybdenum-catalyzed kinetic resolution of 1,7-dienes and the importance of structural modification of the chiral catalysts.

Scheme 34. Small structural changes within the substrate structure can alter the identity of the optimum chiral Mo catalyst.

Scheme 35. Chiral complex 13a is the catalyst of choice for asymmetric synthesis of acetals. Incorporation of electron-withdrawing groups within either the imido or diolate moieties of a chiral Mo complex can result in enhanced Lewis acidity of the metal center and higher catalyst activity. As the examples in Scheme 35 outline, such structural modifications can have an effect on enantio- selectivity as well. In the desymmetrization of the acetal substrate in Scheme 36, dichlorophenylimido complex 13a provides higher asymmetric induction than the biphen- or binol-based catalysts that carry 2,6-dialkylphenylimido ligands (e.g., 1la and 11j). Note that cyclic unsaturated ether moiety can be subsequently removed to deliver the derived carbinol. In this enantioselective desymmetrization, alkylidenes of both enantiotopic terminal alkenes are likely to be generated. Since alkylidene formation is reversible, the major product arises from the rapid RCM of the “matched” segment of the tetraene. If any of the “mismatched” , RCM takes place, a subsequent and more facile matched RCM leads to the formation of the meso-bicyclized product. Such a byproduct is absent from the unpurified mixture, which highlights the exceptionally high degree of stereodifferentia- tion induced by the chiral catalyst. As before, in contrast to 11j, Mo complex 11a is ineffective in facilitating the ARCM depicted in Equation (17).

Scheme 36. Molybdenum-catalyzed tandem ARCM can be used to synthesize enantioenriched seven-membered heterocycles in a practical and efficient manner; mCPBA=/m-chloro peroxybenzoic acid. acetals of this type retain their stereochemical integrity through various laboratory operations (such as chromatog- raphy on silica gel) and can be functionalized to deliver a range of chiral nonracemic functionalized heterocycles.

Scheme 37. Enantioselective synthesis of amines through molybdenum-catalyzed ARCM. The functional group tolerance of chiral molybdenum- based catalysts is underlined in ARCM reactions illustrated in Scheme 37. Acyclic and cyclic tertiary amines are synthesized with high enantiopurity through catalytic kinetic resolution or asymmetric synthesis.'*! The facility and selectivity with which medium-ring unsaturated amines are obtained is noteworthy. Catalytic enantioselective synthesis of the eight-membered-ring amine (Scheme 37) proceeds efficiently, with excellent enantioselectivity and in the absence of solvent.

selective approach of the more reactive cyclobutenyl alkene leads to the enantioselective formation of the observed dihydrofuran enantiomer. in Equation (19) can be converted into a chiral heterocyclic triene in 92% ee and 68% yield in the presence of 5 mol% da." Tt has been proposed that, as illustrated, stereo-

Scheme 38. Efficiency of catalytic AROM processes can depend on the stereochemical identity of the substrate. Another early example of AROM, shown in Scheme 38, involves the net rearrangement of meso-bicycle 91 to 92 in 92% ee. The reaction is promoted by 5mol% Ila and

Elevated temperatures are required for high enantioselectiv- ity; under conditions shown in Scheme 39, (50°C) the triene substrates are converted into the desired pyrans in signifi- cantly lower ee values. The nonracemic pyrans shown in Scheme 39 can be obtained by molybdenum-catalyzed ARCM of trienes as well. The example shown in Equation (20) is illustrative.

Scheme 39. Molybdenum-catalyzed enantioselective rearrangement of cyclopentenes to unsaturated pyrans. Cy =cyclohexyl. The molybdenum-catalyzed transformations shown in Scheme 39 might be viewed as examples of tandem AROM/ RCM."'] Tt is however possible that initiation occurs at the

Scheme 4o. Enantioselective synthesis of carbocyclic tertiary ethers and spirocycles through molybdenum-catalyzed asymmetric olefin metathesis. A related process to those discussed above is the asymmetric molybdenum-catalyzed synthesis of cyclohexenyl ethers (96-97, Scheme 40).!') An unusual attribute of this class of reactions is that higher levels of enantioselectivity are

Scheme 41. Molybdenum-catalyzed tandem AROM/CM proceeds with high enantioselectivity and olefin stereocontrol; MOM = methoxy- methyl.

Scheme 43. In situ preparation and utility of chiral metathesis catalyst 11 f. ~ “ Not only is Mo complex 11f easier to prepare than biphenolate 11a, it is also simpler to use. As outlined in Scheme 43, a solution of 11f, obtained by the reaction of bis(potassium salt) 101 (commercially available from Strem) and Mo triflate 102 (commercially available from Strem), can be used directly to promote enantioselective metathesis.” Similar reactivity and selectivity is observed with in situ 11 f as with isolated and purified 11a or 11f. Moreover, asymmetric

Scheme 42. Chiral complex 11 f represents a hybrid between biphen- and binol-based catalysts and provides a unique selectivity profile.

Scheme 44. The first recyclable and supported chiral catalyst for olefin meta- thesis delivers reaction products that contain significantly less metal impurity. The two dram vials show unpurified product from a reaction catalyzed by T1a (left) and 103 (right). Synthesis and catalytic activity of the first supported chiral catalyst for olefin metathesis was disclosed in 2002.""! As illustrated in Scheme 44, supported catalyst 103 efficiently

Early in 2002, the synthesis, characterization and catalytic activity of chiral ruthenium-based carbene 108 was disclosed (Scheme 46).?"! Catalyst 108 is stereogenic at the metal center, can be prepared in >98% diastereoselectivity and Angew. Chem. Int. Ed. 2003, 42, 4592-4633

Scheme 46. Air stable chiral ruthenium-based catalyst for olefin metathesis can be used to promote AROM/CM reactions. Scheme 45. The adamantylimido chiral catalyst 17 can offer levels of reactivity and selectivity that are not available by the corresponding aryl imido catalysts.