Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an α-Fluoroiodomethylzinc Carbenoid

Abstract

Chiral fluorocyclopropyl carbinols were synthesized in high diastereoselectivities via a zinc mediated cyclopropanation reaction, using sec-allylic alcohols as simple building blocks. An enantioselective version of this transformation was achieved through in situ formation of chiral allylic zinc sec-alkoxides from the requisite aldehydes using Walsh's protocol.

Synthesis and Applications of Fluorocyclopropanes

“…These reaction conditions were very effective for the conversion of chiral allylic alcohols and ethers into the corresponding chiral fluorocyclopropyl carbinols (Scheme 7). 22 The reactions proceed usually with high diastereoselectivities and yields.…”

Fluoro-bicyclo[1.1.1]pentanes

“…However, previously practical protocols for the addition of fluorocarbene to activated alkenes were developed. 18,19 These involved the use of freons CHF2I 18 and CH2FI. 19 We tried both literature protocols on the model substrate 5, but the formation of the needed product 6 was not observed (Table 1, entries 1-4).…”

“…Next, we studied the generality of the developed protocol. First, we synthesized representative starting compounds bearing simple methyl(13−15), fluorine(16, 17), and trifluoromethyl(18,19) substituents on the phenyl ring (Scheme 3). All bicyclo[1.1.0]butanes were prepared from ketoacid 10 analogously to the initial substrate 5 (Scheme 2, please see SI).…”

Optimized Monofluoromethylsulfonium Reagents for Fluoromethylene-Transfer Chemistry

“…One can distinguish two major approaches to accessing monofluorinated organic products: reactions that accommodate the formation of carbon–fluorine bonds or direct fluorination methodologies and the use of preformed fluorinated building blocks . Notably, significantly less investigated is the merger between these two approaches, an application of fluorocarbene precursors, the simplest of the fluoroorganic building blocks, allowing one fluorine and one carbon modification . Fluoromethylation has recently been investigated, offering a single attachment point for the target substrate .…”

“…However, fluoromethylene group transfer − formally offers two connection points, giving access to monofluorinated 3-membered rings . Along this line, we have recently reported on fluoromethylene transfer from S -monofluoromethyl- S -phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate ( 2a ) (Figure ) via ylide intermediate as an alternative to freon (CHFX 2 ) chemistry to access monofluorinated cyclopropane , and epoxide derivatives. Reagent 2a , originally developed for monofluoromethylation, turned out to be efficient; however, it was not an optimal reagent for fluoromethylene transfer chemistry…”