Photochemical activity of a key donor–acceptor complex can drive stereoselective catalytic α-alkylation of aldehydes

Abstract

Asymmetric catalytic variants of sunlight-driven photochemical processes hold extraordinary potential for the sustainable preparation of chiral molecules. However, the involvement of short-lived electronically excited states inherent to any photochemical reaction makes it challenging for a chiral catalyst to dictate the stereochemistry of the products. Here, we report that readily available chiral organic catalysts, with well-known utility in thermal asymmetric processes, can also confer a high level of stereocontrol in synthetically relevant intermolecular carbon-carbon bond-forming reactions driven by visible light. A unique mechanism of catalysis is proposed, wherein the catalyst is involved actively in both the photochemical activation of the substrates (by inducing the transient formation of chiral electron donor-acceptor complexes) and the stereoselectivity-defining event. We use this approach to enable transformations that are extremely difficult under thermal conditions, such as the asymmetric α-alkylation of aldehydes with alkyl halides, the formation of all-carbon quaternary stereocentres and the control of remote stereochemistry.

Photochemical activity of a key donor-acceptor complex can drive stereoselective catalytic a-alkylation of aldehydes

“…1 In this regard, our group developed a new protocol based on the formation of a chiral charge-transfer complex, formed between a catalytic generated enamine and an alkylating agent. 2 An electron transfer occurs between the two partners promoted by the visible light irradiation, followed by the fragmentation of the leaving group, thus originating a di-radical pair that combines in the solvent cage to afford the alkylated substrate (Scheme1). To the best of our knowledge, this activation mode has never been used before in asymmetric aminocatalysis.…”

Catalytic Supramolecular Photochirogenesis

“…[74] As illustrated in Scheme 15, aldehyde 61 first reacts with chiral amine 64 or 65 added as a catalyst (0.2 equivalent) to give the corresponding enamine, which forms a donor-acceptor complex with electron-deficient benzyl bromide 62 in the ground state. Selective photoexcitation of the charge-transfer band of the complex in the visible region induces electron transfer to give radical cationic enamine and 62 radical anion, the latter of which spontaneously decomposes to give a benzyl radical.…”

Enantioselektive Katalyse photochemischer Reaktionen

“…Dabei trifft man auf viele bekannte Gerüste, die sich bereits in nicht-photochemischen Arbeiten als privilegierte Strukturen herausgestellt haben, etwa die Pyrrolidine 61, [75] 64, [76] und 65, [77] die Imidazolidinone 62 [78] und 63, [79] sowie auf Chinin-Derivate wie 66 [80] (Abbildung 11). [82] Die intermediär erhaltenen a-Hydroperoxyaldehyde wurden sofort reduziert, und die entsprechenden Diole 67 wurden mit guter Enantioselektivität erhalten, wobei in der erwähnten Studie a-Methylprolin (61) als Katalysator verwendet wurde.…”

“…[89] Mechanistisch (68) in enantioselektiven a-Alkylierungen über-nehmen kçnnen. [92] In neueren Arbeiten haben Melchiorre und Mitarbeiter gezeigt, dass in vielen Fällen für die a-Alkylierung von Aldehyden [77] und Ketonen [93] kein zweiter Katalysator bençtigt wird. Vielmehr genügt eine direkte Anregung mit sichtbarem Licht, um derartige Alkylierungen durchzuführen.…”