Metal-Free Direct Intramolecular Carbotrifluoromethylation of Alkenes to Functionalized Trifluoromethyl Azaheterocycles

Abstract

The first example of a metal-free direct carbotrifluoromethylation of alkenes using inexpensive TMSCF3 as the CF3 source is described. The methodology not only exhibits high chemoselectivity for this transformation but also expands the substrate scope that is difficult to access by known transition-metal-catalyzed methods.

Addition of CF3 across unsaturated moieties: a powerful functionalization tool

“…An alternative metal-free aryltrifluoromethylation of alkenes was also recently described using inexpensive TMSCF 3 , PhI(OAc) 2 and KF as additives likely involving radical intermediates. 35 …”

Enantioselective CH Bond Functionalization Triggered by Radical Trifluoromethylation of Unactivated Alkene

“…However, although the racemic transformations have been well documented, to our knowledge, the development of catalyst-controlled enantioselective C À H bond functionalization by potentially useful radical transposition processes remains an underdeveloped area. [12] As part of our continued interest in the area of trifluoromethylation [13] and asymmetric catalysis, [14] herein, we describe the first successful example of a highly enantioselective redox-neutral reaction through a C À CF 3 formation/1,5-H shift/C À H functionalization process in the presence of a copper/Brønsted acid catalytic system and without the need for an external oxidant. Such a reaction might be realized by using the inherently high reactivity of an a-CF 3 -alkyl radical intermediate, derived from a radical trifluoromethylation of unactivated alkenes, [7] to give valuable enantioenriched CF 3 -containing N,O-aminals using the appropriate cooperative catalytic systems (Scheme 1b).…”

“…[10] Because of their biological and pharmacological activity, [11] asymmetric N,O-aminal synthesis has been proven to be an attractive but underexploited strategy. [12] As part of our continued interest in the area of trifluoromethylation [13] and asymmetric catalysis, [14] herein, we describe the first successful example of a highly enantioselective redox-neutral reaction through a C À CF 3 formation/1,5-H shift/C À H functionalization process in the presence of a copper/Brønsted acid catalytic system and without the need for an external oxidant. Notably, the current process provides a convenient and economical route for facile access to valuable enantioenriched CF 3 -containing N,O-aminal motifs with excellent regio-, chemo-, and enantioselectivity under mild reaction conditions.…”

The Truce–Smiles rearrangement and related reactions: a review

“…Other examples of aryl migration reactions that are able to achieve similar resultant chemical transformations as the TruceSmiles rearrangement but have been suggested to proceed through a radical mechanism are dominated by substrates featuring organosulfur linkages to the migrating aryl ring such as sulfonates, 67,68 sulfonamides, 67,[69][70][71][72] sulfones, 73 sulfoxides, 73 sulfonium salts, 74 and thioethers. 73,[75][76][77] Additionally, examples of silyl ethers, 78 hydroxamate esters, 79 amides, [80][81][82] and ethers 83,84 have been reported.…”