Synthesis of Perfluoroalkyl‐Substituted Vinylcyclopropanes by Way of Enhanced Neighboring Group Participation

Abstract

A simple, high yielding, two‐step, one‐pot protocol for the preparation of trifluoromethyl‐substituted vinylcyclopropanes from α‐CF3 homoallyl alcohols is disclosed. Destabilization of the cationic intermediate by the electron‐withdrawing CF3 group greatly enhances neighboring group participation of the alkene, allowing ring closure to predominate. The reaction can be extended to the difluoromethyl and pentafluoroethyl group, enabling the preparation of a diverse array of fluoroalkyl‐substituted vinylcyclopropanes.

Asymmetric Organocatalytic Synthesis of Fluorinated β‐Hydroxy Diazenes

“…Unless otherwise noted, analytical grade solvents and commercially available reagents were used without further purification. Formaldehyde tert ‐butyl hydrazone 1a and not commercially available ketones 2f , 2g , 2h , 2i , 2k and squaramide organocatalysts ( I , III , IV , V , VI , VII ) were synthesized according to literature procedures.…”

Recent Progress Toward the Synthesis of Trifluoromethyl‐ and Difluoromethyl‐Substituted Cyclopropanes

“…Later in 2015, the authors extended the scope of the reaction to homoallylic alcohols 78 a – j for the synthesis of trifluoromethyl‐substituted vinyl cyclopropanes 80 a – j . The reaction was successfully performed with electron‐donating and electron‐withdrawing substituted arenes with good yields but poor diastereoselectivities (Scheme ).…”

“…In the course of the development of their trifluoromethylated cyclopropanation using 1,3‐γ‐silyl‐elimination, Tilley and Leadbeater extended their approach to the construction of difluoromethylated cyclopropanes (Scheme ). Noteworthy, they demonstrated that the substitution of the CF 3 moiety by a CF 2 H group on alkyl systems was compatible with the 1,3‐γ‐silyl‐elimination.…”

Catalytic Enantioselective Synthesis of Highly Functionalized Difluoromethylated Cyclopropanes

“…[9] Quite surprisingly and despite the potential of this motif, the synthetic access to difluoromethylated cyclopropanes remains scarce,and no asymmetric process has been reported to date. [12] Another approach, developed by the group of Leadbeater, [13] relying on ac yclopropanation reaction using a1,3-g-silyl elimination, gave birth to the difluoromethylated cyclopropyl skeleton, limited to two examples,ingood yields and poor diastereosomeric ratios.T he deoxofluorination reaction was used by de Meijere,R aev and co-workers to access am ethyl difluoromethyl cyclopropyl ester for the synthesis of hormaomycin analogues. In 1980, Huff and Savins described the thermal ring contraction of difluoromethylated D 1 -pyrazolines.…”