An approach to 2-cyanopyrrolidines bearing a chiral auxiliary

The reaction of 2-methyl-2-((1-phenylethyl)amino)propanenitrile with different γ-halocarbonyl compounds is investigated. The influence of different parameters such as the nature of the substrate and solvent, is discussed. The reaction is considered as a convenient route to 2-cyanopyrrolidines in the case of aliphatic γ-halocarbonyl compounds possessing a reasonably reactive carbonyl group. In many cases, the products can be obtained as single enantiomers. It is shown that cyclopropyl ketones can also react with 2-methyl-2-((1-phenylethyl)amino)propanenitrile to give 2-cyanopyrrolidines. A mechanistic scheme is proposed in order to explain the experimental facts observed.

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(2S,3R,5R)-3-(Chloromethyl)-5-isopropenyl-2-methylcyclohexanoneEe = 100%[α]D = −18.8 (c 0.41, MeOH)Source of chirality: (R)-carvoneAbsolute configuration: (2S,3R,5R)

(3aR,4S,9R,9aS)-2-(4-Methoxyphenyl)-10-[(1R)-1-phenylethyl]-3a,4,9,9a-tetrahydro-1H-4,9-epiminobenzo[f]isoindole-1,3-dioneEe = 100%[α]D = +88.5 (c 0.87, MeOH)Source of chirality: (R)-α-phenylethylamineAbsolute configuration: (3aR,4S,9R,9aS,1′R)