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Catalyst and solvent screening in the Diels—Alder cycloaddition between anthrone (1a) and N-phenylmaleimide (13a)* * Experimental conditions: A mixture of 1a (0.25 mmol), 13a (0.30 mmol), and the catalyst (0.025 mmol) in the solvent specified in the table (1 mL) was stirred at rt during 14h. See Table 6 for the structures of catalysts VI and VII. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. 4 Preferential formation of ent-14a. Table 9 Table 10 Scope of the Diels—Alder cycloaddition between anthrone (1a) and maleimides (13a—e) catalyzed by V*

Table 6 Catalyst and solvent screening in the Diels—Alder cycloaddition between anthrone (1a) and N-phenylmaleimide (13a)* * Experimental conditions: A mixture of 1a (0.25 mmol), 13a (0.30 mmol), and the catalyst (0.025 mmol) in the solvent specified in the table (1 mL) was stirred at rt during 14h. See Table 6 for the structures of catalysts VI and VII. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. 4 Preferential formation of ent-14a. Table 9 Table 10 Scope of the Diels—Alder cycloaddition between anthrone (1a) and maleimides (13a—e) catalyzed by V*

Related Figures (19)

Fig. 1. Possible products of the addition of anthrone to enals.
Fig. 1. Possible products of the addition of anthrone to enals.
oy c Experimental conditions: A mixture of 1a (0.30 mmol), 2a (0.25 mmol), and the catalyst (0.05 mmol) in toluene (1 mL) was stirred at —20 °C during 48 h. Determined by 'H NMR analysis of the reaction mixture. Determined by HPLC analysis. Not determined. Catalyst screening in the reaction between anthrone (1a) and cinnamaldehyde (2a)* Table 1
oy c Experimental conditions: A mixture of 1a (0.30 mmol), 2a (0.25 mmol), and the catalyst (0.05 mmol) in toluene (1 mL) was stirred at —20 °C during 48 h. Determined by 'H NMR analysis of the reaction mixture. Determined by HPLC analysis. Not determined. Catalyst screening in the reaction between anthrone (1a) and cinnamaldehyde (2a)* Table 1
* Experimental conditions: A mixture of 1a (0.30 mmol), 2a (0.25 mmol), and catalyst II (0.05 mmol) in toluene or dichloromethane (1 mL) was stirred at the temperature pecified in the table. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. 4 Benzoic acid (0.2 mmol) was present in the reaction mixture. © Schreiner’s thiourea (0.2 mmol) was present in the reaction mixture. Solvent and temperature screening in the reaction between anthrone (1a) and cinnamaldehyde (2a) catalyzed by III" Table 2 Table 3
* Experimental conditions: A mixture of 1a (0.30 mmol), 2a (0.25 mmol), and catalyst II (0.05 mmol) in toluene or dichloromethane (1 mL) was stirred at the temperature pecified in the table. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. 4 Benzoic acid (0.2 mmol) was present in the reaction mixture. © Schreiner’s thiourea (0.2 mmol) was present in the reaction mixture. Solvent and temperature screening in the reaction between anthrone (1a) and cinnamaldehyde (2a) catalyzed by III" Table 2 Table 3
* Experimental conditions: A mixture of 1a (0.30 mmol), 2a—i (0.25 mmol), and catalyst II (0.06 mmol) in toluene (2 mL) was stirred at —40 °C for the time necessary t¢ achieve full conversion, as determined by 'H NMR analysis of the reaction mixture. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis of the reaction mixture. 4 Conversion was not complete. find that when dithranol was used in our reaction with aliphatic a,8-unsaturated aldehydes, the products of single Michael addition 4a—d were isolated with good yields and with very high enantio- selectivities after 10 days at —40 °C (Table 4). was treated with methylmagnesium bromide, affording the corre- sponding diastereomeric mixture of alcohols 5a and 5a’. Next, the oxidation of this mixture with pyridinium chlorochromate (PCC) gave the corresponding ketone 6a (Scheme 1). Comparison of its specific rotation with the literature data! revealed that the absolute configuration of this compound, and accordingly that of 3a, is (3R): [a]B° —1.8 (c 2.7, CH2Cly), (3S)-Ga, lit.: [a]6? +2.88 (c 1.0, CH2Cl)).
* Experimental conditions: A mixture of 1a (0.30 mmol), 2a—i (0.25 mmol), and catalyst II (0.06 mmol) in toluene (2 mL) was stirred at —40 °C for the time necessary t¢ achieve full conversion, as determined by 'H NMR analysis of the reaction mixture. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis of the reaction mixture. 4 Conversion was not complete. find that when dithranol was used in our reaction with aliphatic a,8-unsaturated aldehydes, the products of single Michael addition 4a—d were isolated with good yields and with very high enantio- selectivities after 10 days at —40 °C (Table 4). was treated with methylmagnesium bromide, affording the corre- sponding diastereomeric mixture of alcohols 5a and 5a’. Next, the oxidation of this mixture with pyridinium chlorochromate (PCC) gave the corresponding ketone 6a (Scheme 1). Comparison of its specific rotation with the literature data! revealed that the absolute configuration of this compound, and accordingly that of 3a, is (3R): [a]B° —1.8 (c 2.7, CH2Cly), (3S)-Ga, lit.: [a]6? +2.88 (c 1.0, CH2Cl)).
Scheme 1. Determination of the absolute configuration of 3a.
Scheme 1. Determination of the absolute configuration of 3a.
* Experimental conditions: A mixture of 1b (0.25 mmol), 2f—i (0.37 mmol), and catalyst II (0.05 mmol) in toluene (2 mL) was stirred at —40 °C during 10 day > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. Table 4
* Experimental conditions: A mixture of 1b (0.25 mmol), 2f—i (0.37 mmol), and catalyst II (0.05 mmol) in toluene (2 mL) was stirred at —40 °C during 10 day > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. Table 4
Scheme 2. Mechanistic proposal for the enantioselective addition of anthrones to enals.
Scheme 2. Mechanistic proposal for the enantioselective addition of anthrones to enals.
Catalyst screening in the reaction between anthrone (1a) and trans-B-nitrostyrene (10a) in toluene*
Catalyst screening in the reaction between anthrone (1a) and trans-B-nitrostyrene (10a) in toluene*
* Experimental conditions: A mixture of 1a (0.25 mmol), 10a (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in the solvent specified in the table (1 mL) was stirred at luring 14h. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. Solvent screening in the reaction between anthrone (1a) and trans-B-nitrostyrene (10a) catalyzed by V* Table 5
* Experimental conditions: A mixture of 1a (0.25 mmol), 10a (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in the solvent specified in the table (1 mL) was stirred at luring 14h. > Determined by 'H NMR analysis of the reaction mixture. © Determined by HPLC analysis. Solvent screening in the reaction between anthrone (1a) and trans-B-nitrostyrene (10a) catalyzed by V* Table 5
* Experimental conditions: A mixture of 1a (0.25 mmol), the nitroolefin (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) was stirred at rt during 14 h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. Table 7
* Experimental conditions: A mixture of 1a (0.25 mmol), the nitroolefin (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) was stirred at rt during 14 h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. Table 7
* Experimental conditions: A mixture of 1b (0.25 mmol), the nitroolefin (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) was stirred at the temperature specified in the table during 14 h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Not determined; 100% conversion by 'H NMR. Scope of the addition of dithranol (1b) to nitrostyrenes (10a-e) catalyzed by V* Table 8
* Experimental conditions: A mixture of 1b (0.25 mmol), the nitroolefin (0.28 mmol), and the catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) was stirred at the temperature specified in the table during 14 h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Not determined; 100% conversion by 'H NMR. Scope of the addition of dithranol (1b) to nitrostyrenes (10a-e) catalyzed by V* Table 8
Fig. 2. Transition state working models for the Michael addition of anthrones to nitroalkenes catalyzed by (R,R)-V.
Fig. 2. Transition state working models for the Michael addition of anthrones to nitroalkenes catalyzed by (R,R)-V.
* Experimental conditions: Maleimides 13a—g (0.30 mmol) were added to a solution of 1a (0.25 mmol) and of catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) and tk resulting mixture was stirred at rt for 14h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Only the Michael adduct 14’e was isolated.
* Experimental conditions: Maleimides 13a—g (0.30 mmol) were added to a solution of 1a (0.25 mmol) and of catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) and tk resulting mixture was stirred at rt for 14h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Only the Michael adduct 14’e was isolated.
Scheme 3. Amine-catalyzed Diels—Alder cycloaddition between anthrone (1a) and (R)-N-(1-phenylethyl)maleimide 13h.
Scheme 3. Amine-catalyzed Diels—Alder cycloaddition between anthrone (1a) and (R)-N-(1-phenylethyl)maleimide 13h.
Fig. 3. Rationalization of the enhanced thermodynamic stability of the Michael product in front of the Diels—Alder dithranol-maleimide cycloadducts.
Fig. 3. Rationalization of the enhanced thermodynamic stability of the Michael product in front of the Diels—Alder dithranol-maleimide cycloadducts.
* Experimental conditions: Maleimides 13a-d,f,g (0.30 mmol) were added to a solution of 1b (0.25 mmol) and of catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) and the resulting mixture was stirred at rt for 14h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Not determined. Scope of the reaction between dithranol (1b) and maleimides (13a-d,f,g) catalyzed by V* Table 11
* Experimental conditions: Maleimides 13a-d,f,g (0.30 mmol) were added to a solution of 1b (0.25 mmol) and of catalyst (R,R)-V (0.025 mmol) in toluene (1 mL) and the resulting mixture was stirred at rt for 14h. > Yield of isolated product after chromatographic purification. © Determined by HPLC analysis. 4 Not determined. Scope of the reaction between dithranol (1b) and maleimides (13a-d,f,g) catalyzed by V* Table 11
Fig. 4. Transition state working model for the Diels—Alder cycloaddition between anthrones and maleimides catalyzed by (R,R)-V. Scheme 4. Amine-catalyzed Michael addition between dithranol (1b) and (R)-N-(1-phenylethyl)maleimide 13e.
Fig. 4. Transition state working model for the Diels—Alder cycloaddition between anthrones and maleimides catalyzed by (R,R)-V. Scheme 4. Amine-catalyzed Michael addition between dithranol (1b) and (R)-N-(1-phenylethyl)maleimide 13e.
Fig. 5. Ball-and-stick representation of the proposed transition state for the Diels— Alder cycloaddition between anthrones and maleimides catalyzed by (R,R)-V.
Fig. 5. Ball-and-stick representation of the proposed transition state for the Diels— Alder cycloaddition between anthrones and maleimides catalyzed by (R,R)-V.
Related topics:
Organic ChemistryAsymmetric catalysisAsymmetric SynthesisMichael Addition
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