Synthesis of Organofluorine Compounds with Acylsilanes†

Abstract

Comprehensive SummaryOrganofluorine compounds are central in synthetic chemistry, medicinal chemistry and material chemistry. In this review, we summarize the investigations on the synthesis of organofluorine compounds with acylsilanes. For the non‐fluorinated acylsilanes, the in situ generation of difluoroenoxysilanes from the reactions of the acylsilanes with trifluoromethylation reagents is the major pathway, leading to the facile preparation of various α,α‐difluoroketones. For the fluoroalkylacylsilanes, apart from the in situ generation of difluoroenoxysilanes through anion Brook rearrangement, radical Brook rearrangement of the photoexcited acylsilanes and the selective control of reactivities of the biradicals pave the way for the synthesis of a variety of organofluorine compounds. In general, most of these reactions gave racemic products, and the asymmetric synthesis of organofluorine compounds with acylsilanes is still rare, which would be a future direction of this field. Key ScientistsIn 1957, the first acylsilane compound, triphenylsilyl phenyl ketone was reported by Brook group. In 1991, Portella and coworkers reported the reaction of non‐fluorinated acylsilanes and perfluoroorganometallic reagents without Brook rearrangement, resulting in the formation of alcohols as the products. In 1992, Xu and coworkers carried out the first investigation on fluoroalkylacylsilanes for the preparation of difluoroenoxysilanes through anion Brook rearrangement. In 1994, Portella group reported the synthesis of difluoroenoxysilanes with non‐fluorinated acylsilanes and Ruppert‐Prakash reagent. In 2009, Otaka and coworkers reported a NHC‐mediated intramolecular redox reaction to prepare (Z)‐fluoroalkene dipeptide isosteres (FADIs) from γ,γ‐difluoro‐α,β‐ enoylsilane. Until 2022, the application of radical Brook rearrangement of fluoroalkylacylsilanes for the generation of fluoroalkylsiloxycarbenes was achieved by Shen group, enabling the synthesis of fluoroalkylated cyclopropenols. In 2022, Shen and coworkers successfully achieved the trapping of biradical intermediates generated from fluorine‐containing acylsilanes, leading to the facile preparation of fused gem‐difluorooxetanes. In the same year, Shen group reported the first asymetric reactions of fluoroalkylacylsilanes to prepare enantiomerically enriched fluoroalkyl alcohols and difluoroenoxysilanes.