A General Organocatalytic System for Enantioselective Radical Conjugate Additions to Enals

Abstract

Herein, we report ag eneral iminium ion-based catalytic method for the enantioselective conjugate addition of carbon-centered radicals to aliphatic and aromatic enals.T he process uses an organic photoredox catalyst, whicha bsorbs blue light to generate radicals from stable precursors,i n combination with ac hiral amine catalyst, which secures ac onsistently high level of stereoselectivity.T he generality of this catalytic platform is demonstrated by the stereoselective interception of aw ide variety of radicals,i ncluding nonstabilized primary ones whichare generally difficult to engage in asymmetric processes.T he system also served to develop organocatalytic cascade reactions that combine an iminiumion-based radical trap with an enamine-mediated step,affording stereochemically dense chiral products in one-step.

Acridinium Salts and Cyanoarenes as Powerful Photocatalysts: Opportunities in Organic Synthesis

“…Minireviews centered radicals to aliphatic and aromatic enals (Scheme 21). [37] Ther eactions were performed in MeCN under irradiation with blue LEDs in the presence of TFA (0.6 equiv) at À10 8 8C. Ther eaction exhibits al arge substrate scope,i ncluding various carbon radical precursors and enals (both aliphatic and aromatic).…”

A General Organocatalytic System for Enantioselective Radical Conjugate Additions to Enals

“…[24] Thestereochemistry of the major diastereoisomer of product 8c was established by single crystal X-ray crystallographic analysis. [25] We also implemented ad ifferent cascade (Figure 5b), where the Michael acceptor 9 was intercepted intermolecularly by the transient enamine.A fter completion of the conjugate radical addition, we added 9 along with aminocatalyst (S)-A (20 mol %), which assisted the enamine step of the cascade.This one-pot procedure granted access to the 2,3disubsitituted product 10 with high enantioselectivity and good anti diastereoselectivity.…”

Asymmetric Photocatalysis Enabled by Chiral Organocatalysts

“…reported chiral amine/photocatalytic asymmetric β‐functionalization of enals using TMS‐based radical precursors (Scheme 32). [114] A broad scope of aliphatic or (hetero)aromatic enals reacted with alkyl radicals generated from TMS precursors bearing protected amines, esters, ethers, thioethers, or fluorides, forming the desired product in 35–93 % yields with 62–98 % ee. The mechanism proposed by the authors was corroborated by Stern‐Volmer quenching experiments and quantum yield measurements (Φ=0.02).…”