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

摘要

Julia–Kocienski olefination reagents 1-fluoropropyl, (cyclopropyl)fluoromethyl, 1-fluoro-2-methy1-2-propenyl, and I -fluoro-5-hexenyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfones were prepared by metalationfollowed 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 fluoroPT-sulfones with aldehydes resulted in fluoroalkylidenes in high yields. Screening of olefination conditionsshowed that stereoselectivity depended on reagent and carbonyl structure and can in many cases be tunedeither toward E- or Z-selectivity. For example, LHMDS-mediated condensations of 1-fluoropropyl PT-sulfone in the presence of MgBr_2.OEt_2were Z-selective with electron-rich aromatic aldehydes, a hinderedaromatic aldehyde, and cinnamaldehyde. Low-temperature KHMDS-mediated condensations wereE-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.