Asymmetric Synthesis of Heterocyclic γ‐Amino‐Acid and Diamine Derivatives by Three‐Component Radical Cascade Reactions

Abstract

An enantioselective three-component radical reaction of quinolines or pyridines with enamides and a-bromo carbonyl compounds by dual photoredoxand chiral Brønsted acid catalysis is presented. Arange of valuable chiral g-aminoacid derivatives are accessible in high chemo-, regio-, and enantioselectivity from simple,readily available starting materials under mild reaction conditions.U sing the same strategy, the asymmetric synthesis of 1,2-diamine derivatives is also reported.

Intermolecular radical carboamination of alkenes

“…Recently, our group achieved an asymmetric radical aminoarylation of vinyl acetamides by merging chiral Brønsted acid catalysis and photoredox catalysis (Scheme 16). 66…”

Recent developments in enantioselective photocatalysis

“…Jiang et al developed a similar system for the enantioselective radical addition into 2-vinylazaarenes 122 using DPZ and either α-amino radicals [60] or ketyl radicals [61], with pyridines being well tolerated as substrates in this latter case (Scheme 17a). The same group also separately developed a Minisci-type reaction using phthalimide esters 123; however, their system did not extend past isoquinoline substrates 124 [63]. Interestingly, they found some of their examples required the more strongly reducing photocatalyst Ir(ppy) 3 to achieve high yields, although the reason for this is unclear.…”

“…The same group also separately developed a Minisci-type reaction using phthalimide esters 123 ; however, their system did not extend past isoquinoline substrates 124 ( Scheme 17 ) [ 62 ]. Zheng and Studer expanded the scope of this type of reactivity to a three-component cascade reaction with alkyl bromides 125 and enamides 126 ( Scheme 17 ) [ 63 ]. Interestingly, they found some of their examples required the more strongly reducing photocatalyst Ir(ppy) 3 to achieve high yields, although the reason for this is unclear.…”

Asymmetric Coupling of Carbon‐Centered Radicals Adjacent to Nitrogen: Copper‐Catalyzed Cyanation and Etherification of Enamides

“…[9] Later on, Studer and co-workers untilized this strategy to disclose the elegant asymmetric radical difunctionation of enamides (Scheme 1 a). [10] As our ongoing research interest in asymmetric radical transformations (ATRs), [11] our group has developed a series of copper-catalyzed asymmetric difunctionalizations of styrenes, such as cyanation, arylation and alkynylation reactions, where a benzylic radical intermedaite generated by radical addition across styrenes could be efficiently and enantioselectively trapped by the corresponding chiral (Box)Cu II species (Box = bisoxazoline), leading to the formation of a chiral CÀC bond (Scheme 1 b, i). [11a, 12] However, when aliphatic alkenes were employed as substrate, these reactions involving a non-benzylic radical intermediate furnished the corresponding products with low enantioselectivities.…”