Controllable Single and Double Difluoromethylene Insertions into C–Cu Bonds: Copper-Mediated Tetrafluoroethylation and Hexafluoropropylation of Aryl Iodides with TMSCF₂H and TMSCF₂Br

Abstract

The selective difluoromethylene insertion into a C–Cu bond is a challenging task and is currently limited to either a single CF2 insertion into CuCF3 or double CF2 insertions into CuC6F5 (or (Z)-CF3CF = CFCu). Achieving both selective single and double CF2 insertions into the same C–Cu bond is even more difficult. Herein, highly controllable single and double CF2 insertions into CuCF2H species with a TMSCF2Br reagent have been described, affording two previously unknown fluoroalkylcopper species “Cu­(CF2)nCF2H” (n = 1 and 2) independently under different reaction conditions. This work represents the first example of both single and double CF2 insertions into the same C–Cu bond in a highly selective manner. The synthetic value of the obtained “Cu­(CF2) n CF2H” (n = 1 and 2) species is demonstrated by their reactions with aryl iodides, halogenation agents, and cinnamyl chloride, which enables the direct transfer of HCF2CF2 and HCF2CF2CF2 moieties into organic molecules. The key to controllable fluorocarbon chain elongation from C1 to C2 and from C1 to C3 is presumably attributed to the different reactivities of “Cu­(CF2) n CF2H” species (n = 0, 1, 2 and 3) and the loading of the TMSCF2Br reagent.

From intramolecular cyclization to intermolecular hydrolysis: TMSCF2Br-enabled carbonylation of aldehydes/ketones and amines to α-hydroxyamides

“…To some degree, these failures emphasized the uniqueness of the commercially available TMSCF 2 Br, which was initially developed by us as a difluorocarbene reagent. 16…”

[Ph4P]+[Cu(CF2H)2]−: A Powerful Difluoromethylating Reagent Inspired by Mechanistic Investigation

“…However, attempts towards the isolation of these copper(I) species failed. [14] To gain some fundamental information about the structure of the difluoromethylated Cu I species, Sanford and co-workers tried to utilize a sterically bulky N-heterocyclic carbene to stabilize the complex. They succeeded in the isolation of two stable Cu I complexes [(IPr)CuCF 2 H] (IPr = 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) and [(SIPr)CuCF 2 H], with a chemical shift at À 119.27 ppm ( 2 J HF = 42.1 Hz in CD 2 Cl 2 ) and À 119.67 ppm ( 2 J HF = 44.2 Hz in CD 2 Cl 2 ), respectively (Figure 1, bottom).…”

“…The former species was assigned as [XCu(CF 2 H)] − (X=SCN or other anions) and the latter was assigned as [Cu(CF 2 H) 2 ] − based on the observation that the species at −114.5 ppm could further react with TMSCF 2 H/CsF to generate the second difluoromethylated copper species. However, attempts towards the isolation of these copper(I) species failed [14] . To gain some fundamental information about the structure of the difluoromethylated Cu I species, Sanford and co‐workers tried to utilize a sterically bulky N ‐heterocyclic carbene to stabilize the complex.…”

Direct 1,6-Difluoromethylation of 3-Methyl-4-nitro-5-styryl Isoxazoles by Photoredox-Promoted Radical Addition

“…Nucleophilic difluoromethylation represents one of the most efficient means to introduce CF 2 H into the organic skeleton. However, the reaction often suffers from limited substrate scope and narrow functional group tolerance since the “ – CF 2 H” anion is a hard base. On the other hand, the radical difluoromethylation reaction is alternatively a convenient method to construct the CF 2 H-containing compounds .…”