Highly enantioselective 1,2-additions of various organolithium reagents to aldehydes

Several asymmetric 1,2-additions of various organolithium reagents (methyllithium, n-butyllithium, phenyllithium, lithioacetonitrile, lithium n-propylacetylide, lithium phenylacetylide) to aldehydes are shown to result in decent to excellent enantiomeric excesses (65–98%) when performed in the presence of a chiral lithium amido sulfide. The chiral lithium amido sulfides invariably exhibited higher levels of enantioselectivity in all the reactions tested, compared to the structurally similar chiral lithium amido ethers and the chiral lithium amide without a chelating group.

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(R)-1-Isopropylamino-1-phenyl-2-thiomethylethaneC12H19NSEe = 99%[α]D20=-61.0 (c 1.05, CH2Cl2)Source of chirality: (R)-phenylglycineAbsolute configuration: (R)

(R)-1-Isopropylamino-1-phenyl-2-phenoxyethaneC17H21NOEe = 99%[α]D20=-51.5 (c 1.06, CH2Cl2)Source of chirality: (R)-phenylglycineAbsolute configuration: (R)