Copper(II)-Catalyzed Asymmetric Photoredox Reactions: Enantioselective Alkylation of Imines Driven by Visible Light

Abstract

Asymmetric photoredox catalysis offers exciting opportunities to develop new synthetic approaches to chiral molecules through novel reaction pathways. Employing the first-row transition metal complexes as the chiral photoredox catalysts remains, however, a formidable challenge, although these complexes are economic, environmentally friendly, and often exhibit special reactivities. We report in this Article the development of one class of highly efficient asymmetric/photoredox bifunctional catalysts based on the copper­(II) bisoxazoline complexes (CuII–BOX) for the light-induced enantioselective alkylation of imines. The reactions proceed under very mild conditions and without a need for any other photosensitizer. The simple catalytic system and readily tunable chiral ligands enable a significantly high level of enantioselectivity for the formation of chiral amine products bearing a tetrasubstituted carbon stereocenter (36 examples, up to 98% ee). Overall, the CuII–BOX catalysts initiate the radical generation, and also govern the subsequent stereoselective transformations. This strategy utilizing chiral complexes comprised of a first-row transition metal and a flexible chiral ligand as the asymmetric photoredox catalysts provides an effective platform for the development of green asymmetric synthetic methods.

Catalytic Asymmetric Fluorination of Copper Carbene Complexes: Preparative Advances and a Mechanistic Rationale

“…The benzyls ubstituents are hence "forward" oriented in at least one averaged conformer on the NMR timescale;a ss uch, they (temporarily) reside in vicinity of the incipientc arbene, above and below the catalytically active Cu-center.T he crystal structure of ar elated BOX·Cuc omplex with pendant p-(tert-butyl)benzyls ubstituents corroborates the notion that these seemingly remote substituents actually shield the upper and lower face of the coordination plane. [31,35] If one takes the ligateda cetonitrile as ad ummy for the carbene to be formed upon reactiono ft he Cu-center with the adiazoester,a ttack onto the Re face of the electrophilic C-atom seems most plausible at first sight, which would entail formation of (R)-2b (compare Figures 5a nd 6). Since( S)-2b,h owever,h as been shown to be the major product, am ore involved scenario must be operative.…”

Development of tethered dual catalysts: synergy between photo- and transition metal catalysts for enhanced catalysis

“…[15][16][17][18][19][20][21][22][23][24][25][26] While dual catalysis has emerged as an excellent synthetic platform for discovering new reactivity, most reported dual catalytic systems feature individual catalysts added as independent species to the reaction mixture, with comparatively little focus on single compounds that feature two distinct catalytic sites. [27][28][29][30][31][32][33] Recent examples of these 'bifunctional' catalysts include a photo-palladium catalyst for Sonogashira cross coupling 27 and a chiral copper catalyst for enantioselective imine alkylation. 30 Chemically tethering different catalysts could permit unique synergy between the catalytic centres, with this approach anticipated to be particularly advantageous for photocatalysis, as 'heavy atom' (e.g.…”

“…[27][28][29][30][31][32][33] Recent examples of these 'bifunctional' catalysts include a photo-palladium catalyst for Sonogashira cross coupling 27 and a chiral copper catalyst for enantioselective imine alkylation. 30 Chemically tethering different catalysts could permit unique synergy between the catalytic centres, with this approach anticipated to be particularly advantageous for photocatalysis, as 'heavy atom' (e.g. halide or metal) incorporation can enhance photocatalytic activity.…”

Benzylation of Imines with Activated Boronate Nucleophiles

“…The reaction between allylboron reagents and carbonyls or imines with and without catalysts has provided access to homoallylic alcohols and amines in high enantioselectivity and has been a very successful way to perform this transformation . Despite the success of allylboron reagents in 1,2‐addition reactions, the use of benzylboron reagents and other alkylboron reagents in a similar reaction is less common …”