Organocatalytic enantio- and diastereoselective 1,3-dipolar cycloaddition between alanine-derived ketonitrones and E-crotonaldehyde: efficiency and full stereochemical studies

Highly enantio- and exo-selective 1,3-dipolar cycloadditions of alanine-derived ketonitrones to E-crotonaldehyde could be realized in a good yield by the use of a chiral imidazolidinone salt without the addition of water. The origin of the stereoselectivity in the reaction was discussed and the absolute configuration of the cycloadduct determined unambiguously.

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(3R,4S,5R)-Ethyl 2-benzhydryl-4-formyl-3,5-dimethylisoxazolidine-3-carboxylateC22H25NO4[α]D20=+2.9 (c 0.85, CH2Cl2)Ee = 63% from HPLCSource of chirality: (2S,2′S)-N,N′-((S)-1,1′-Binaphthyl-2,2′-diyl)bis(2-amino-3-phenylpropanamide)Absolute configuration: (3R,4S,5R)

(3R,4S,5R)-Ethyl 2-benzyl-4-formyl-3,5-dimethylisoxazolidine-3-carboxylateC16H21NO4[α]D20=-82.8 (c 0.57, CH2Cl2)Ee = 95% from HPLCSource of chirality: (S)-5-Benzyl-2,2,3-trimethylimidazolidin-4-one hydrochloride saltAbsolute configuration: (3R,4S,5R)

(3R,4S,5R)-Ethyl 2-benzyl-3,5-dimethyl-4-(((S)-1-phenylethyl)carbamoyl) isoxazolidine-3-carboxylateC24H30N2O4[α]D20=-40.3 (c 0.53, CH2Cl2)Source of chirality: (S)-5-benzyl-2,2,3-trimethylimidazolidin-4-one hydrochloride salt and S-(−)-α-methyl benzylamineAbsolute configuration: (3R,4S,5R,7S)