Lithium triethylborohydride-promoted generation of α,α-difluoroenolates from 2-iodo-2,2-difluoroacetophenones: an unprecedented utilization of lithium triethylborohydride

Peng Peng,Jing-Jing Wu,Jin-Wen Huang,Jun-Qing Liang,Tian-Yu Zhang,Fan-Hong Wu

doi:10.1039/c7ra12130j

Abstract

Lithium triethylborohydride was found to promote the generation of α,α-difluoroenolates from 2-iodo-2,2-difluoroacetophenones, and applied to the synthesis of polyfluorinated β-hydroxy ketones via self-condensation or aldol reaction.

Highlights

Lithium triethylborohydride was found to promote the generation of a,a-difluoroenolates from 2-iodo-2,2difluoroacetophenones, and applied to the synthesis of polyfluorinated b-hydroxy ketones via selfcondensation or aldol reaction
The results showed that all these reduction reactions proceeded well leading to the formation of different reduction products, which demonstrates the speci c characteristic of substrate 2-iodo-2,2di uoroacetophenone owing to the adjacent uorine atoms of carbonyl group
A,a-Di uoro-b-hydroxy ketones are an important class of substructure in medicinal chemistry,[13] which could be obtained via aldol reaction with di uoroenolates.[14]

Summary

Introduction

Lithium triethylborohydride was found to promote the generation of a,a-difluoroenolates from 2-iodo-2,2difluoroacetophenones, and applied to the synthesis of polyfluorinated b-hydroxy ketones via selfcondensation or aldol reaction. Lithium triethylborohydride (LiEt3BH, a superhydride, 1 M in THF) is a powerful reducing agent and can efficiently reduce a wide range of functional groups, especially halogen atoms.[12] the reaction with 2-iodo-2,2-di uoroacetophenones and LiEt3BH result in the generation of di uoroenolates instead of reduction products. LiEt3BH-promoted in situ generation of di uoroenolates from 2iodo-2,2-di uoroacetophenones and their application in aldoltype self-condensation and aldol reactions to give various a,adi uoro-b-hydroxy ketones (Scheme 1).

Results

Conclusion