Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

Abstract

A deoxygenative difluoromethylenation of carbonyl compounds has been developed by using readily available, inexpensive trifluoromethyltrimethylsilane, LiI, and PPh3. The presence of the Li+ ion prevents the unproductive exhaustion of trifluoromethyltrimethylsilane (TMSCF3) by keeping the soluble free fluoride concentration in the reaction medium under control. The strategy of combining solvents to increase the reactivity and thereby reduce the reaction temperature and time is disclosed.

Base Catalysis Enables Access to α,α-Difluoroalkylthioethers

“…The catalytic reaction enables access to a variety of functionalized α,α-difluoroalkylthioethers in high yield and selectivity versus the α-fluorovinylthioether. Combined with direct preparations of β,β-difluorostyrenes 2 by olefination 18 and cross coupling 19 chemistry, the present reaction should facilitate access to this underutilized functional group in medicinal and agrichemistry.…”

Stereoselective Synthesis of Z Fluoroalkenes through Copper‐Catalyzed Hydrodefluorination of gem‐Difluoroalkenes with Water

“…We suspected that the generated hydrogen atom in the product may come from residual water in the solvent. Under these conditions, B 2 nep 2 proved to be better than B 2 Pin 2 ,improving the yield of 2ato 90 %( [12][13][14]. To improve the result, we evaluated several copper salts and observed more promising results (Table 1, entries 3-6).…”

“…We were also pleased to observe that this method can be applied to some more challenging substrates.F or example, this approach allowed the CÀFactivation of 1,1-difluorobuta-1,3-dienes 5a-5c in 64-78 %y ields,t hus providing a method to synthesize conjugated terminal Z fluoroalkenes (Scheme 1). Moreover,k etone-derived difluoroalkene 7, [13] which bear a para-bromo atom, was successfully transformed into trisubstituted Zfluoroalkene 8 in moderate yield with complete stereoselectivity (Scheme 2).…”

“…Thelargest increase in reaction efficacyw as found with catalytic CuTc, which furnished the desired HDF product in 81 %y ield. Under these conditions, B 2 nep 2 proved to be better than B 2 Pin 2 ,improving the yield of 2ato 90 %( [12][13][14].…”

Pd‐Catalyzed Selective Carbonylation of gem‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters

“…[22] To the best of our knowledge,t he direct alkoxycarbonylation of such functionalized olefins to give difluoromethylated esters has not been reported yet. [24] Based on our continuous interest in carbonylations,herein we present the first examples of alkoxycarbonylations to construct a-difluoromethylated esters.I nterestingly,u sing Scheme 1. [23] Advantageously,t here are many methods and reagents developed for the synthesis of gem-difluoroalkenes from aldehydes and ketones.…”