Thomas Poisson

Recent Progress in Direct Introduction of Fluorinated Groups on Alkenes and Alkynes by means of CH Bond Functionalization

The direct introduction of fluorine and fluorinated building blocks has recently attracted a lot of attention and particularly the direct functionalization of alkenes and alkynes. This review will highlight the major progress recently made in that field, with a focus on photocatalyzed transformations, base-promoted processes, and transition metal-catalyzed functionalization of alkenes and alkynes. Special attention will be paid to explanations of the reaction mechanisms.

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

Fluorine chemistry is a field undergoing tremendous expansion. Although much attention has been paid to the introduction of the fluorine atom and the CF3 group, less interest has been devoted to the introduction of functionalized fluorinated building blocks, in sharp contrast with the high versatility of the fluorinated products. In this Minireview, the most relevant methods for the introduction of difluoromethylated building blocks are summarized. Access to difluoromethylated arenes, alkenes, and alkynes is highlighted and special attention is paid to explanation of the reaction mechanism.

Copper Catalyzed β-Difluoroacetylation of Dihydropyrans and Glycals by Means of Direct C–H Functionalization

A copper catalyzed direct functionalization of dihydropyrans and glycals has been developed. This method affords a new and straightforward access to C-2-CF2 dihydropyrans and glycosides in a single step starting from readily available starting materials. This new copper based catalytic system, probably involving a Cu(III) species as supported by experiments, allows the formation of the valuable fluorinated glycosides in good yields.

Catalytic asymmetric protonation of chiral calcium enolates via 1,4-addition of malonates.

Catalytic asymmetric protonation of chiral calcium enolates was performed. Chiral calcium enolates, prepared in situ from imides and malonates via 1,4-addition in the presence of catalytic amounts of Ca(OEt)(2), Ph-PyBox, and achiral phenol, were smoothly protonated to afford adducts bearing tertiary asymmetric carbons in high yields with high enantioselectivities. The adducts were readily converted to optically active 2-substituted 1,5-dicarboxylic acid derivatives.

Copper-catalyzed direct C-2 difluoromethylation of furans and benzofurans: access to C-2 CF2H derivatives.

We report herein the first copper-catalyzed C-2 difluoromethylation of furans and benzofurans. The developed methodology allows the selective introduction of the CF2CO2Et moiety at C-2 using CuI as a catalyst. This process was applied to a broad range of furans and benzofurans, giving the functionalized products in moderate to good yields. The resulting products were then decarboxylated to afford the highly valuable C-2-CF2H-substituted furans and benzofurans in good yields.

Copper-catalyzed direct arylation of cyclic enamides using diaryliodonium salts.

A convenient method for the copper(II)-catalyzed direct arylation of cyclic and nonaromatic enamides using diaryliodonium salts has been developed. The reaction demonstrates large functional group tolerance, good yields, and total regioselectivity with a C(3)-functionalization. The synthetic potential of this coupling was explored by using a range of readily accessible diaryliodonium salts and enamides.

Asymmetric Mannich Reaction of Malonates with Imines Catalyzed by a Chiral Calcium Complex

A chiral calcium complex was found to be effective for the Mannich reactions of malonates with N-Boc imines. The desired adducts were obtained in excellent yields (up to 95%) with moderate to good enantioselectivities (up to 77% ee).

New entries toward the synthesis of OCF3-containing molecules

The OCF3 group is of high interest in the quest for new drugs and agrochemicals, thanks to its atypical features. This Highlight article depicts the recent and impressive advances toward the synthesis of OCF3-containing molecules.

Copper‐Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics

A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in good to excellent yields. This method represents the first general synthetic route to this important class of fluorinated scaffolds, which are well-recognized as in vivo stable phosphate surrogates.

Indium-promoted Reformatsky reaction: a straightforward access to β-amino and β-hydroxy α,α-difluoro carbonyl compounds.

A versatile and practical methodology to access β-amino and β-hydroxy α,α-difluoro carbonyl compounds using indium metal is described. This methodology has been successfully applied to a broad range of substrates including aldehydes, ketones, and imines, affording the corresponding and highly valuable gem-difluoro esters. The wide substrate scope highlights the chemoselectivity of the process.