Visible-Light-Promoted Activation of Unactivated C(sp³)–H Bonds and Their Selective Trifluoromethylthiolation

Abstract

Selective functionalization of ubiquitous C(sp)-H bonds using visible light is a highly challenging yet desirable goal in organic synthesis. The development of such processes relies on both rational design and serendipitous discoveries from innovative tools such as screening technologies. Applying a mechanism-based screening strategy, we herein report photoredox-mediated hydrogen atom transfer catalysis for the selective activation of otherwise unactivated C(sp)-H bonds, followed by their trifluoromethylthiolation, which has high potential as a late-stage functionalization tool. The generality of this method is exhibited through incorporation of the trifluoromethylthio group in a large number of C(sp)-H bonds with high selectivity without the need for an excess of valuable substrate.

Photoredox-Mediated Routes to Radicals: The Value of Catalytic Radical Generation in Synthetic Methods Development

“…Toward this end, the ability to channel visible light energy selectively into synthetically useful C(sp 3 )–H activation reactions through elementary radical H atom transfer steps has already enabled a recent, rapid growth in methods for functionalization of unactivated C–H bonds at room temperature. 54 …”

Photoredox Imino Functionalizations of Olefins

“…Pleasingly, we were able to form the imines 5 h , i which incorporated S−CF 3 and S−Ph groups. In this case, CsOBz12h proved to be uniquely effective in promoting good conversions. The formation of 5 h is particularly relevant because the introduction of the S−CF 3 group in organic molecules is a significant but challenging task in medicinal chemistry 22.…”

Mild, visible light-mediated decarboxylation of aryl carboxylic acids to access aryl radicals

“…6 Additionally, our laboratory recently disclosed the use of I as a hydrogen atom transfer (HAT) catalyst for the functionalisation of unactivated C(sp 3 )–H bonds. 7 While the activation energy for the decarboxylation of I is only 8–9 kcal mol –1 , 8 a the rate of decarboxylation ( k = 1.4 × 10 6 s –1 ) is not competitive with nondecarboxylative pathways including addition to arenes ( k = 2.2 × 10 8 M –1 s –1 ) 8 a and HAT ( k = 1.2 × 10 7 M –1 s –1 ). 8a,9 As such, while the decarboxylation of I is theoretically possible its realisation is practically challenging.…”

“…5b,c Though generation of I via photoredox catalysis has been described, either via single electron reduction of benzoyl peroxide 6 a or single electron oxidation of benzoates, 6b,7 decarboxylation was not reported in these cases. Instead, I has been reported to add to arenes to provide benzoate esters (Scheme 1a).…”