Recent Advances in Photoredox Methods for Ketone Synthesis

Abstract

Synthesis of ketones is one of the most addressed problems in organic chemistry owing to their presence in a diverse array of drugs, pharmaceuticals, natural products and photosensitizers. Many of the limitations associated with the traditional approaches enabling the synthesis of ketones like creation of high energy acylating reagents, poor functional group tolerance, pre-activation of starting materials have been largely addressed with the advent of photoredox chemistry. This review summarizes the recent advances made in the photoredox catalyzed synthesis of ketones. 2 3 4 5 6 7 8

C(sp3)–H Bond Acylation with N-Acyl Imides under Photoredox/ Nickel Dual Catalysis

“…Over the last decade, dual visible-light photoredox and nickel catalysis has emerged as a powerful but operationally simple strategy for achieving, under very mild reaction conditions, challenging C(sp 2 )-C(sp 3 ) bond disconnections that are beyond the reach of classical cross-coupling approaches. 2,3 Hence, this method brings prospects for innovation in the area of catalytic acylation reactions of C(sp 3 )hybridized substrates, 4 and thereby offers a new paradigm for the synthesis of structurally diverse and highly func-tionalized alkyl ketones. Within this context, resonance-destabilized N-acyl imides stand amongst other carbonyl-type compounds as promising acyl electrophiles 5 owing to their remarkable stability and their documented capability to engage in nickel-catalyzed cross-coupling reactions through C-N bond activation to forge C(acyl)-C(sp 3 ) bonds.…”

“…Over the last decade, dual visible-light photoredox and nickel catalysis has emerged as a powerful but operationally simple strategy for achieving, under very mild reaction conditions, challenging C(sp 2 )-C(sp 3 ) bond disconnections that are beyond the reach of classical cross-coupling approaches. 2,3 Hence, this method brings prospects for innovation in the area of catalytic acylation reactions of C(sp 3 )hybridized substrates, 4 and thereby offers a new paradigm for the synthesis of structurally diverse and highly func-tionalized alkyl ketones.…”

“…The process was designed to follow a radical relay pathway where a silyl radical is generated photocatalytically and serves as an abstracting agent to activate the alkyl bromide through homolytic C-Br bond cleavage (Scheme 1A). 10 Another exciting challenge that we subsequently considered was the design of an alternative strategy that would rely on the selective C(sp 3 )-H bond activation of simple alkanes through a radical hydrogen-atom transfer (HAT) process. 11,12 The groups of Doyle and Molander independently demonstrated that organohalides could serve as both coupling partners and sources of halide radicals that act as potent H-abstracting agents in Ni/photoredox cross-coupling reactions with aliphatic substrates.…”

“…Further mechanistic studies are clearly necessary to confirm the specific behavior of these acyl substrates, which might be exploited to design complementary mechanistic sequences. 24 In summary, we have described a new acylation reaction of C(sp 3 )-H bonds by using bench-stable N-acyl imide substrates. The dual-catalytic process combines nickel-catalyzed C-N bond activation with photocatalytic HAT, and provides operationally simple access to valuable alkyl ketones.…”

Iodine-based reagents in photoredox-organocatalysis

“…The photochemical transformations have significantly impacted synthetic chemistry recently by the utilization of visible-light photocatalysts. [1][2][3] The frequently used visible-light photocatalysts are either organic dyes, 4 primarily pollutants in nature, or expensive transition-metal complexes. [5][6][7][8][9] Therefore the use of these photocatalysts in industrial, medicinal, and pharmaceutical applications are usually restricted.…”