Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas

Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.

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1-[(1R,2R)-2-Aminocyclohexyl]-3-benzylthioureaC14H21N3S[α]D24=-16.0 (c 1.0, CH3OH)Source of chirality: (1R, 2R)-cyclohexane-1,2-diamineAbsolute configuration: (1R,2R)

(R)-3-(3-Chlorophenyl)-2,2-dimethyl-4-nitrobutanalC12H14O3NClEe = 98%[α]D24=+10.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2,2-Dimethyl-3-(naphthalene-1-yl)-4-nitrobutanalC16H17O3NEe = 95%[α]D24=+87.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)