Fluorinated 1-Phenyl-1<i>H</i>-tetrazol-5-yl Sulfone Derivatives as General Reagents for Fluoroalkylidene Synthesis

Abstract

Julia-Kocienski olefination reagents 1-fluoropropyl, (cyclopropyl)fluoromethyl, 1-fluoro-2-methyl-2-propenyl, and 1-fluoro-5-hexenyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfones were prepared by metalation followed by electrophilic fluorination. Although metalation-fluorination of n-propyl, 5-hexenyl, and (cyclopropyl)methyl PT-sulfones proceeded under homogeneous conditions, fluorination of 2-methyl-2-propenyl PT-sulfone required heterogeneous fluorination conditions. Condensation reactions of fluoro PT-sulfones with aldehydes resulted in fluoroalkylidenes in high yields. Screening of olefination conditions showed that stereoselectivity depended on reagent and carbonyl structure and can in many cases be tuned either toward E- or Z-selectivity. For example, LHMDS-mediated condensations of 1-fluoropropyl PT-sulfone in the presence of MgBr(2) x OEt(2) were Z-selective with electron-rich aromatic aldehydes, a hindered aromatic aldehyde, and cinnamaldehyde. Low-temperature KHMDS-mediated condensations were E-selective with electron-rich and electron-deficient aromatic aldehydes and Z-selective with n-octanal. Dialkyl, aryl alkyl, and diaryl ketones reacted as well to give fluoro olefin products in 71-99% yields.