Novel synthesis and application of γ-difluoromethylated prop-2-ynylic and allylic alcohols

Abstract

The reaction of chlorodifluoromethane with various acetylides derived from the corresponding prop-2-ynylic alcohols proceeds smoothly to afford difluoromethylated compounds in high yields; synthetic applications of the materials are also given.

Recent Progress toward the Introduction of Functionalized Difluoromethylated Building Blocks onto C(sp2) and C(sp) Centers

“…In 1996, Konno and Kitazume described a difluorocarbene‐based difluoromethylation of acetylides by using an excess of chlorodifluoromethane. Few alkynes were functionalized and, although this approach was mainly tested on alkyl‐substituted alkynes, it showcased the potential of such a transformation (Scheme ) 77. More than 10 years later, Hu and co‐workers astutely used the α‐difluoromethyl sulfoximine 162 as an electrophilic CF 2 H source, an emergent fluorinated group, avoiding the use of an excess of HCF 2 Cl.…”

Difluoromethylation of Terminal Alkynes by Fluoroform

“…Although many methods exist for the direct incorporation of a CF 2 H unit into target positions, 9 difluoromethylation of terminal alkynes is generally more challenging than that of O-, S-, and N-nucleophiles since C−H acidity is lower than heteroatom-H acidity. 10 There are only a few reported examples for the difluoromethylation of terminal alkynes. 11 In 1996, Kitazume and Konno succeeded in the difluoromethylation of terminal alkynes using chlorodifluoromethane (HCF 2 Cl) and lithium acetylides.…”

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF2Br

“…[6] Difluorocarbene,amoderately electrophilic species,i sa ni deal intermediate for difluoromethylation. [7a, [8][9][10][11][12][13][14] b-Ketoesters and malonates are the most studied CÀH nucleophiles, [7a, 8] and their efficient difluoromethylation with high C/O selectivity was reported very recently by the research groups led by Shibata, [9] Shen, [10] and Liu. [6,7] Most of these reactions are focused on the difluoromethylation of heteroatoms,such as O, S, N, P, and Se nucleophiles,a nd [2+ +1] cycloaddition with alkenes or alkynes.H owever,e xamples of the difluorome-thylation of C À Hnucleophiles are sparse,with limited success being reported.…”

“…[6,7] Most of these reactions are focused on the difluoromethylation of heteroatoms,such as O, S, N, P, and Se nucleophiles,a nd [2+ +1] cycloaddition with alkenes or alkynes.H owever,e xamples of the difluorome-thylation of C À Hnucleophiles are sparse,with limited success being reported. Chlorodifluoromethane, [12] N-tosyl-S-difluoromethyl-S-phenylsulfoximine, [13] and difluoromethyltri(n-butyl)ammonium chloride [14] were used for the difluoromethylation of alkynes (Scheme 1a), but these methods suffer from several drawbacks,s uch as low efficiency,n arrow substrate scope,a nd/or the requirement of ozone-depleting substances (ODSs). [11] However,t he reactivity of many other C À Hnucleophiles,s uch as common esters,a mides,f luorenes,a nd alkynes,t owards difluorocarbene is largely underexplored or unknown.…”

“…[6,7] Most of these reactions are focused on the difluoromethylation of heteroatoms,such as O, S, N, P, and Se nucleophiles,a nd [2+ +1] cycloaddition with alkenes or alkynes.H owever,e xamples of the difluorome-thylation of C À Hnucleophiles are sparse,with limited success being reported. [7a, [8][9][10][11][12][13][14] b-Ketoesters and malonates are the most studied CÀH nucleophiles, [7a, 8] and their efficient difluoromethylation with high C/O selectivity was reported very recently by the research groups led by Shibata, [9] Shen, [10] and Liu. [11] However,t he reactivity of many other C À Hnucleophiles,s uch as common esters,a mides,f luorenes,a nd alkynes,t owards difluorocarbene is largely underexplored or unknown.…”