Copper-Catalyzed Three-Component Photo-ATRA-Type Reaction for Asymmetric Intermolecular C–O Coupling

Abstract

Atom transfer radical addition (ATRA) reaction of alkenes has had a significant impact on the field of radical difunctionalization of alkenes. Particularly, in the three-component photo-ATRA-type processes, a rich chemical space and structural diversity could be achieved by smart combination of redox-active radical precursors and the third coupling components (e.g., halides, C-, N-, and O-nucleophiles) under mild conditions. However, the inherent complicated mechanisms involving radical chain or outer-sphere SET of the incipient radical intermediates have led to a dearth of general catalytic methods for highly enantioselective variants, especially those regarding asymmetric intermolecular C−O bond formation. Here, we report a visible-light-induced copper-catalyzed asymmetric three-component photo-ATRA-type reaction of alkenes with oxime esters and carboxylic acids. In this process, a highly enantioselective intermolecular C−O cross-coupling between incipient sp 3 -hybridized carbon radicals and carboxylic acids was enabled by the formation of an aryl π-bond-engaged [σ + π]-copper complex. This working hypothesis renders naphthyl or extended conjugation of alkenes to be suitable substrates and allows good stereocontrol. This three-component photo-ATRA-type reaction exhibits broad substrate scope and high functional group tolerance with respect to each component, giving the desired cross-coupling products with generally good yields and enantioselectivity (>70 examples; up to 97% ee). Preliminary experimental and computational studies are also performed to gain insight into the mechanism and stereoregulatory elements. This finding provides a promising platform for the development of other enantioselective benzylic-type radical-based cross-coupling reactions.

New insights into the mechanism of synergetic photoredox/copper(i)-catalyzed carbocyanation of 1,3-dienes: a DFT study

“…Obviously, the mechanism described above involves a Cu( i )/Cu( ii )/Cu( iii )/Cu( i ) cycle, which is similar to those found recently by Guan, 10,27,28 Lin, 29,30 and Lan 20 via density functional theory (DFT) calculations on the synergetic photoredox/copper( i )-catalyzed cyanations of alkenes and enynes. However, our calculations show that such a copper and photoredox catalytic cycle is not operative.…”

“…From our calculations, the allylcopper complex E is identied as a monovalent copper species rather than a trivalent species. Note that in the previous experimental and theoretical studies 10,20,21,26,[28][29][30] on the photoredox/copper(I)-catalyzed carbocyanation of alkenes or alkynes using trimethylsilyl cyanide (TMSCN) as the provider of the cyano group, the desilylation process was proposed to proceed via the reaction of a Cu(II) species with TMSCN. However, for the present system our calculations show that the involvement of Cu(II) in the desilylation process is expected to be energetically less favorable due to the higher barrier involved in the formation of the Cu(II) species, which requires an energy input of 31.7 kcal mol −1 (Fig.…”

Photoinduced copper-catalyzed enantioselective coupling reactions

“…Subsequently, the same group employed styrenes as radical acceptors, achieving the visible light-induced copper-catalyzed asymmetric intermolecular C(sp 3 )–O cross-coupling (Scheme 52). 62 With the aid of newly identified chiral BOX ligand L26 and the formation of aryl π-bond-engaged [σ + π]-copper complex, the enantioselective three-component reaction showed broad substrate scope, high yields and enantioselectivites. Besides cycloketone-derived oxime esters 182 , alkylsilyl peroxide 192 and lauroyl peroxide 193 could also act as alkyl radical precursors in this transformation, affording good yields and high enantioselectivites.…”

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis

“…Recently, asymmetric photoredox catalysis by a single catalyst has captivated much attention from the synthetics community due to its cost-effective and environmentally benign advantages. , In this aspect, chemists have developed dual-functional chiral transition-metal complex-induced asymmetric photoredox reactions , wherein the transition metal such as copper­(I)/(II), − nickel­(II), , and iridium­(III) served as photoredox catalysts (electron donor or acceptor) for electron transfer and enabled chirality induction concurrently. The merger of photocatalysis and organocatalysis with a single catalyst rendered an efficient alternative strategy for enantioselective photoredox transformations. , For instance, Melchiorre et al creatively took advantage of the electronically excited-state enamines , or iminium ions − intermediate generated from a chiral secondary amine and aldehyde to act as effective reductants or oxidants, triggering SET to undergo the ensuing stereoselective radical reactions.…”