From Esters to Ketones via a Photoredox‐Assisted Reductive Acyl Cross‐Coupling Strategy

Abstract

A method was developed for ketone synthesis via a photoredox-assisted reductive acyl cross-coupling (PARAC) using a nickel/photoredox dual-catalyzed cross-electrophile coupling of two different carboxylic acid esters. A variety of aryl, 18, 28, 38-alkyl 2-pyridyl esters can act as acyl electrophiles while N-(acyloxy)phthalimides (NHPI esters) act as 18, 28, 38radical precursors. Our PARAC strategy provides an alternative and reliable way to synthesize various sterically congested 38-38, 38-28, and aryl-38 ketones under mild and highly unified conditions, which have been otherwise difficult to access. The combined experimental and computational studies identified a Ni 0 /Ni I /Ni III pathway for ketone formation.

Nickel-Catalyzed Three-Component Alkylacylation of Alkenes Enabled by a Photoactive Electron Donor–Acceptor Complex

“…To determine the valence state of the Ni intermediate, a stoichiometric reaction with Ni­(COD) 2 was performed, and no desired product was obtained either under purple light irradiation or in the dark (Scheme d). This result suggests that the acyl-Ni II intermediate is unlikely involved in the catalytic cycle, which is consistent with our previous conclusion …”

“…On the basis of the mechanistic studies presented above and our previous work as well as literature reports, we proposed a plausible mechanism (Scheme ). First, the catalytically active Ni(0) is generated by the reduction of a Ni­(II) precatalyst {[ E red (Ni II /Ni 0 )] = −1.2 V vs SCE} with the excited state of HE* {[ E red (HE*/HE •+ )] = −2.28 V vs SCE}.…”

“…After a careful evaluation of the reaction conditions (Table ; for more details, see Tables S1–S4), the highest yield was obtained when the reaction was conducted in the presence of catalytic NiCl 2 ·glyme/4,4′-di­(CO 2 Me)­bpy (10 mol %) and HE (2.0 equiv) in DMAc at room temperature under 1 W purple LED (390 nm) irradiation for 24 h (Table , entry 1). The reactivity of 2-pyridyl ester was superior to those of other acyl electrophiles, including the structurally analogous 3-pyridyl or 4-pyridyl ester, phenyl ester, thioester, and N -acyl-imide (see page S13 of the Supporting Information), probably due to its good leaving ability and coordinating ability . The electronic nature of the ligand has a significant effect on the reactivity as an electron-rich bipyridyl ligand, such as dtbbpy or 4,4′-di­(OMe)­bpy, resulted in a large decrease in yield (entry 2 or 3, respectively).…”

“…α-Oxy- and fluorine-containing radical as well as cyclic and bridged systems were well tolerated. Lower yields were observed for less sterically encumbered moieties ( 15 and 16 ), as in such cases, two-component cross-coupling was competitive . Unfortunately, primary and secondary radical precursors turned out to be unsuitable due to their high propensity to undergo a direct coupling with 2-pyridyl ester. , …”

Cooperative triple catalysis enables regioirregular formal Mizoroki–Heck reactions

“…On the other hand, recent developments in Ni-catalysed C−C bond formation have taken advantage of the unique characteristics of nickel as compared with palladium, such as sluggish β-hydride elimination and the tendency to engage in single-electron transfer processes, to enable otherwise inaccessible reactivity 31 . Along this line, dual photoredox and nickel catalysis has shown great potential in the design of co-catalysis strategies for the construction of challenging chemical bonds starting from inexpensive substrates under very mild conditions [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] . Inspired by elegant reports on nickel/photoredox dual catalysis [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] and our recent work 65 , we envisioned an unprecedented triple catalysis process comprising cooperative nickel, photoredox and sulfinate catalysis to accomplish the challenging intermolecular α-arylation of electron-deficient alkenes and styrenes using commercially available aryl bromides (Fig.…”