Asymmetric Access of γ-Amino Acids and γ-Amino Phosphonic Acid Derivatives via Copper-Catalyzed Enantioselective and Regioselective Hydroamination

Abstract

γ-Aminobutyric acid is a major inhibitory neurotransmitter in the mammalian central nervous system that plays a substantial role in brain disorders. γ-Amino phosphonic acid is an unique surrogate of both natural and unnatural γ-amino acid. Because of their unique biological activity, γ-Amino acid, as well as γ-amino phosphonic acid derivatives have attracted considerable attentions. However, efficient and straightforward method for constructing chiral γ-substituted-γ-amino acid and γ-amino phosphonic acid derivatives remains a longstanding challenge. Herein, a highly efficient, versatile and universal Cu-catalyzed asymmetric hydroamination of cinnamyl esters, cinnamyl phosphonates and cinnamyl phosphine oxides is presented for accessing γ-amino acid and γ-amino phosphonic acid derivatives in good yields with high level of enantiocontrollings and regioselectivities.

Catalyst‐Controlled Regiodivergent and Enantioselective Formal Hydroamination of N,N‐Disubstituted Acrylamides to α‐Tertiary‐α‐Aminolactam and β‐Aminoamide Derivatives

“…Based on the mechanistic results and literature precedents, [11, 12a, b, e–g] two tentative mechanistic pathways for Ni‐ and Cu‐catalyzed reactions were proposed and depicted in Figure 3. In the case of Cu‐catalyzed reactions (Figure 3, left), the L* Cu−H catalyst M1 generated in situ from Cu salt, chiral ligand, and silane underwent enantioselective hydrometallation with N,N‐ acrylamide 1 to generate alkyl copper intermediate M2 with high Markovnikov regioselectivity.…”

Catalytic asymmetric ring-opening of aminocyclopropanes with oxygen nucleophiles: access to chiral γ-amino acid derivatives

“…For the catalytic asymmetric synthesis of chiral γ-amino acid derivatives, typical approaches rely on Michael additions, 6 γ-amination of carbonyl compounds, 7 three-component radical cascade reactions, 8 and alkylation of γ-butyrolactam. 9 However, products from the above methods are limited to carbon substituents at the γ-position, and the catalytic asymmetric synthesis of γ-amino acid derivatives with oxygen substituents at the γ-position has not been reported (Scheme 1a).…”

Cobalt-catalyzed asymmetric phospha-Michael reaction of diarylphosphine oxides for the synthesis of chiral organophosphorus compounds

“…6 asymmetric phospha-Michael addition of secondary phosphine oxides to electron deficient alkenes have been well developed. Recently, Liu and coworkers 7 reported the first Cu( i )-catalyzed enantioselective phosphinocyanation of styrenes through a tandem radical relay strategy; in 2020, Fu et al 8 developed a nickel-catalyzed enantioconvergent reductive hydroalkylation of olefins with an α-phosphorus alkyl electrophile to construct chiral organophosphorus compounds; recently, Wang's group 9 reported an enantioselective palladium-catalyzed hydrophosphinylation of allenes and a copper-catalyzed hydroamination for the synthesis of chiral organophosphorus compounds, respectively. Shortly afterwards, Xu and coworkers 10 presented a Ni/photoredox-catalyzed enantioconvergent reductive cross-coupling between α-bromoalkylphosphates and aryl iodide for the synthesis of chiral α-aryl phosphorus compounds.…”