SUBSTRATE LEAVING GROUP CONTROL OF THE ENANTIOSELECTIVITY IN THE PALLADIUM-CATALYZED ASYMMETRIC ALLYLIC SUBSTITUTION OF 4-ALKYL-1-VINYLCYCLOHEXYL DERIVATIVES

The strong influence of the nature of the leaving group in allylic derivatives in their enantioselective Pd-catalyzed substitution by nucleophile is reported. Analysis of the stereochemical course of the Pd-catalyzed substitution of achiral trans-4-tert-butyl-l-vinylcyclohexyl derivatives with nucleophiles indicates the enantioselective step to be oxidative addition of the allylic substrate onto the chiral Pd complex. The asymmetric induction may be understood as the result of the selection by the chiral Pd catalyst between two reactive enantiomeric conformations of the allylic substrate and, hence, was shown to be strongly dependent upon reaction conditions and especially upon the nature of the substrate leaving group. Indeed, dimethyl 2-[(4-tert-butylcyclohexylidene)methyl]malonate (4) was synthesized with 27,48, and 78% ee through Pd-catalyzed reaction of sodium dimethyl malonate in THF with trans-4-tert-butyl-1-vinylcyclohexyl carbonate (1c), acetate (1a) and 4-methoxybenzoate (1h), respectively, in the presence of BINAP as the chiral ligand. In dioxane, 4 was produced from 4-methoxybenzoate 1h with 90% ee. © 1990, American Chemical Society. All rights reserved.