General Method for Preparation of Allenic Zinc Reagents by Three-Carbon Homologation of Triorganozincates: Convergent Three-Component Coupling of Propargylic Substrates, Triorganozincates, and Electrophilic Reagents

Abstract

Allenic zinc reagents (R1R2CCC(R3)ZnL) are efficiently prepared by the reaction of propargylic substrates (R1R2C(X)C⋮CH, X = MeSO2O, Cl, R2NCO2) with a variety of triorganozincates ((R3)3ZnM; R3 = alkyl, alkenyl, aryl, M = Li, MgCl). Treatment of the allenic zinc reagents with D2O gives the corresponding deuteroallenes with high deuterium incorporation. The allenic zinc reagents thus prepared undergo a coupling reaction with a variety of electrophiles (aldehydes, acyl chlorides, I2, NCS, and chlorosilanes) regioselectively at the γ position to afford the corresponding propargylic derivatives (R1R2C(El)C⋮CR3, El = RCH(OH), RCO, I, Cl, R3Si) in high yields. Silicon containing allenic zinc reagents R1CHCC(CH2SiMe3)ZnL and R1CHCC(SiPhMe2)ZnL are readily prepared by the reaction of propargylic carbamates (R1CH(OCONPh2)C⋮CH) with (TMSCH2)3ZnLi and by the reaction of bromoproparglic mesylates R1CH(OSO2Me)C⋮CBr with (PhMe2Si)3ZnLi, respectively. Successive treatment of these reagents with electrophiles affords fu...