Asymmetric Propargylic Radical Cyanation Enabled by Dual Organophotoredox and Copper Catalysis

Abstract

The first asymmetric propargylic radical cyanation was realized through a dual photoredox and copper catalysis. An organic photocatalyst serves to both generate propargyl radicals and oxidize Cu(I) species to Cu(II) species. A chiral Cu complex functions as an efficient organometallic catalyst to resemble the propargyl radical and cyanide in an enantio-controlled manner. Thus, a diverse range of optically active propargyl cyanides were produced with high reaction efficiency and enantioselectivities (28 examples, 57−97% yields and 83−98% ee). Moreover, mechanistic investigations including experiments and density functional theory calculations were performed to illustrate on the reaction pathway and stereochemical results.

Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes

“…Both electron-rich (37) and electron-deficient alkenes (39-44) proved suitable substrates. In particular, hydrocyanation was achieved for cinnamoyl-type structures including esters (39,43,44), ketones (40,41), and nitriles (42). These results demonstrate that our reaction can serve as a more general alternative to the enantioselective Michael addition en route to similar products.…”

Copper-catalyzed enantioselective arylalkynylation of alkenes

“…Related examples of this so-called radical relay strategy have been extensively studied by Liu, 19,11f Liu 20 and Xiao. 21 Alternatively, the reaction might proceed through a electrophilic Cu(III)-Ph intermediate, although less likely, it cannot be ruled out. 7a-c In this study, beside the unusual BOPA ligand employed for enantioselective C-C bond formation, the observation of moderate 53% ee for 4bb suggests a possible interaction of phenyl radical species with chiral copper complex, which could potentially explain the selectivity when unsymmetrical diarylidonium salts were used.…”

Recent developments in enantioselective photocatalysis

“…Based on previous cyanation reactions [157], they propose an oxidative quenching cycle where benzyl radicals 396 • are formed from 396 after a reductive decarboxylation, [Ir] •+ then oxidises the Cu I catalyst to Cu II which accepts a second cyanide ion to A series of cyanation reactions have subsequently been developed using similar reactivity. For example, propargyl radicals were successfully used in concert with the more strongly reducing Ph-PTZ photocatalyst, and with a different leaving group to achieve the first enantioselective propargylic radical cyanation (Scheme 67a) [158]. Employing oxime esters 400 as radical precursors afforded enantioenriched dicyano alkanes 401 (Scheme 67b) [159].…”

“…A series of cyanation reactions have subsequently been developed using similar reactivity. For example, propargyl radicals were successfully used in concert with the more strongly reducing Ph-PTZ photocatalyst, and with a different leaving group to achieve the first enantioselective propargylic radical cyanation ( Scheme 67 ) [ 158 ]. Employing oxime esters 400 as radical precursors afforded enantioenriched dicyano alkanes 401 ( Scheme 67 ) [ 159 ].…”