Trifluoromethylated amino alcohol as chiral auxiliary for highly diastereoselective and fast Simmons–Smith cyclopropanation of allylic amine

Three advantages of a trifluoromethylated amino alcohol auxiliary in the Simmons–Smith cyclopropanation of allylic amines are described. The trifluoromethylated amino alcohol auxiliary reduces unwanted side reactions induced by its acidic, and thus less nucleophilic, hydroxy group. The auxiliary accelerated the reaction rate by its electron-withdrawing effect, and promoted the reaction with excellent diastereoselectivity.

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(2S)-1-{Methyl-[(E)-3-phenyl-2-propenyl]amino}-3,3,3-trifluoropropan-2-olC13H16F3NO[α]D25=-13.7 (c 1.1, EtOH)Source of chirality: enantiomerically pure epoxideAbsolute configuration: 2S

(2S)-1-{Methyl-[(Z)-3-phenyl-2-propenyl]amino}-3,3,3-trifluoropropan-2-olC13H16F3NO[α]D25=-13.5 (c 1.5, EtOH)Source of chirality: enantiomerically pure epoxideAbsolute configuration: 2S

(2S)-1-{Methyl-[(1R,2R)-2-phenyl-cyclopropenyl](methyl)amino}-3,3,3-trifluoropropan-2-olC14H18F3NO[α]D25=-84.2 (c 1.3, EtOH)Source of chirality: diastereoselective synthesis (stereochemistry of the cyclopropane ring was confirmed by the specific rotation of the known final product without chiral auxiliary, Ref. 8)Absolute configuration: 2R,(1R,2R)

(2S)-1-{Methyl-[(1S,2R)-2-phenyl-cyclopropenyl](methyl)amino}-3,3,3-trifluoropropan-2-olC14H18F3NO[α]D25=-59.0 (c 1.2, EtOH)Source of chirality: diastereoselective synthesis [stereochemistry of the cyclopropane ring was confirmed by a X-ray crystallographic analysis (CCDC-602550)]Absolute configuration: 2R,(1S,2R)

N,N-Dimethyl-2-phenyl-(1R,2R)-cyclopropanemethanamineC12H17N[α]D25=-116 (c 1.5, CHCl3)Source of chirality: diastereoselective synthesis (stereochemistry of the compound was confirmed by the comparison of the specific rotation with that of the literature, Ref. 8)Absolute configuration: 1R,2R