Lipase catalyzed resolution of the quaternary stereogenic center in ketone-derived benzo-fused cyclic cyanohydrins

The enantioselective preparation of both enantiomers of the benzo-fused cyanohydrin derived from α-tetralone via lipase catalyzed processes is described. The (S)-enantiomer has been obtained as the remaining substrate in the CAL-A catalyzed aminolysis of the methoxyacetylated derivative, using a structurally related amine as the nucleophile. The (R)-enantiomer has been obtained as the product of CAL-A or PSL-C catalyzed hydrolysis of the methoxyacetylated derivative in organic solvents. The resolutions of several structural analogs of this cyanohydrin have been also tested under similar conditions.

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(S)-1-Cyano-1,2,3,4-tetrahydronaphtalen-1-yl metoxyacetateC14H15NO3Ee = 99%[α]D20=+22 (c 1, CH2Cl2)Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (S)

(R)-1-Trimethylsilyloxy-1,2,3,4-tetrahydronaphtalene-1-carbonitrileC14H19NOSiEe = 85%[α]D20=+11.5 (c 1, CH2Cl2)Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (R)

(R)-1-Trimethylsilyloxyindane-1-carbonitrileC13H17NOSiEe = 92%[α]D20=+10.4 (c 0.5, CH2Cl2)Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (R)