Photo‐Organocatalytic Enantioselective Radical Cascade Enabled by Single‐Electron Transfer Activation of Allenes

Abstract

Allenes are commonly used in metalmediated transformations, cycloaddition reactions, and radical processes. However, their activation by single-electron transfer (SET) is largely underexplored. Herein, we report a visible light-driven enantioselective organocatalytic process that uses the excited-state reactivity of chiral iminium ions to activate allenes by SET oxidation. The ensuing allene cation radicals participate in stereocontrolled cascade reactions to deliver chiral bicyclic scaffolds with good enantioselectivity and exquisite diastereoselectivity. Density Functional Theory (DFT) calculations support a mechanism that combines the peculiar chemistry of allene radical cations with polar reactivity.

Construction of Chiral Cyclic Compounds Enabled by Enantioselective Photocatalysis

“…The proposed mechanism was conducted as follows. The α,β-unsaturated aldehydes (46) reacted with chiral amine catalyst to form eniminium ions (48), which could transform into the triplet intermediates (48a) through energy transfer from ruthenium catalyst at assistance of light. Subsequently, the addition of intermediates (48a) to olefins (47) generated 1,4-diradical intermediates (48b), which underwent intersystem crossing and hydrolysis to give the desired products ( 45) from (48c).…”

“…In 2019, Melchiorre et al reported an enantioselective photocatalysis which utilized chiral amine (172) as a photo-organocatalyst, and α,β-unsaturated aldehydes (173) reacted with allenes (174) to provide bicyclic lactones (175) upon the irradiation of single highpower (HP) LED light (λ = 420 nm) in good yields and enantioselectivity (up to 92% yield, up to 88% ee) (Scheme 38) [48]. Allenes bearing bulkier substituents showed better enantioselectivity.…”

Asymmetric Photocatalysis Enabled by Chiral Organocatalysts

“…developed the asymmetric β‐alkylation of enals with allenes followed by a subsequent cascade process to generate stereoenriched bicyclic lactones (Scheme 55). [135] Electron‐rich and electron‐deficient enals reacted with a variety of tri‐ and tetrasubstituted allenes bearing bulky alkyl chains, aromatic rings, and trimethylsilyl moieties, forming the desired products in 42–66 % yields with 57–83 % ee. High levels of diastereoselectivity were also observed and rationalized by DFT calculations.…”

“…The proposed mechanism proceeds as follows: photoexcited iminium ion 56.2* (* E 1/2 red =+2.4 V vs. Ag/Ag + in MeCN) [125] oxidizes an allene 56.1 ( E 1/2 ox =+1.76 V to +2.28 vs. Ag/Ag + in MeCN), [135] yielding radical cation 56.3 and enaminyl radical 56.4 (Scheme 56). Deprotonation of 56.3 followed by intramolecular nucleophilic cyclization on the central allene carbon forms a β,γ‐unsaturated lactone radical 56.5 , which couples with enaminyl radical 56.4 , affording enamine intermediate 56.6 .…”

Recent developments in enantioselective photocatalysis

“…Subsequent condensation releases the photocatalyst and the desired products 79 in good yields and excellent enantioselectivities (16 examples, up to 99:1 er). Recently, this process was extended to allenes 80 to give complex bicyclic products 81 in moderate yields and good enantioselectivities (20 examples, up to 92:8 er) ( Scheme 9 ) [ 47 ].…”