A General and Efficient Route for the Preparation of Phenyl-Substituted Vinyl Fluorides

Abstract

α-Fluorobenzyl phosphonate (EtO)2P(O)CFHPh (2) prepared from diethyl α-hydroxyphosphonate (EtO)2P(O)CH(OH)Ph (1) and diethylaminosulfur trifluoride (DAST), reacts with bases such as butyllithium, tert-butyllithium, lithium bis(trimethylsilyl)amide, or lithium diisopropylamide at −78° in THF to give the phosphonate carbanion [(EtO)2P(O)CFPh]−Li+ (3) which was detected by acylation with propionyl chloride or by addition of MeOD to the reaction mixture to give (EtO)2P(O)CF(COEt)Ph (4) and (EtO)2P(O)CFDPh (5), respectively. Addition of aldehydes or ketones to a THF solution of carbanion 3 led to moderate-to-good yields of phenyl-substituted vinyl fluorides RR′C=CFPh 6. The stereoselectivity of the products PhCH=CFPh (6a) and Ph(Me)C=CFPh (6i) formed in the reaction was examined. The presence of hexamethylphosphoric triamide or N,N′-dimethylpropyleneurea as cosolvent in the preparation of 6a and 6i increased the (Z)-stereoselectivity. However, the presence of LiCl in THF did not alter the (E)/(Z)-ratio of the product.