Enantioselective Conjugate Additions of α-Amino Radicals via Cooperative Photoredox and Lewis Acid Catalysis

Abstract

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

Photoredox Catalysis in Organic Chemistry

“…Elegant work from the Yoon and Melchiorre groups has subsequently demonstrated that by using a chiral Lewis acid or organocatalyst respectively, these transformations can be rendered asymmetric (vide infra). 33,34 …”

“…149 Of particular note is a report by Yoon and co-workers demonstrating that conjugate additions of α-amino radicals can be rendered asymmetric through the use of a chiral i -BuPyBox-ligated Lewis acid catalyst (Scheme 31a). 33 Here, photoredox catalysis mediates generation of the α-amino radical and the Lewis acid complex controls stereoselectivity in the subsequent addition step. Recently, Meggers and co-workers reported a similar dual photoredox Lewis acid-catalyzed conjugate addition reaction that utilizes organotrifluoroborate salts as the source of the alkyl radical coupling partner (Scheme 31b).…”

α‐Arylation/Heteroarylation of Chiral α‐Aminomethyltrifluoroborates by Synergistic Iridium Photoredox/Nickel Cross‐Coupling Catalysis

“…The intermediacy of α-amino radicals to elaborate aryl- and heteroaryl substructures has recently been demonstrated in photoredox catalysis [6,25,28,36] from both unfunctionalized amines (toward the preparation of JAK2 inhibitor LY2784544), [6] and those with the TMS [35,37,38] and CO 2 H [2,39] activating groups (Scheme 1). …”

Direct Photoredox‐Catalyzed Reductive Difluoromethylation of Electron‐Deficient Alkenes

“…In somes uch reactions, the resulting electrophilicr adical intermediatesd imerize, rearrange, or cyclize. [12] In others they are able to be reduced to anions by reductive reagents,s uch as the photocatalyst, [13] or low-valent metals [14] to avoid dimerization or polymerization. Reductivep erfluoroalkylation of electron-deficienta lkenesu sing R F Io rR F Br could also be achieved by addition of H-atom donors to reactions initiatedb ya zobisisobutyronitrile( AIBN), Et 3 B/O 2 ,U Vi rradiation, or photocatalysis.…”