Stereoselective Construction of γ-Lactams via Copper-Catalyzed Borylacylation

Abstract

A versatile and highly stereoselective borylative cyclization to generate polyfunctionalized γ-lactams has been developed. The stereoselective synthesis of these key ring systems is crucial due to their ubiquity in natural products. We report the diastero- and enantioselective construction of di- and trisubstituted γ-lactam cores, with examples containing an enantioenriched quaternary carbon.

Nickel-Catalyzed Asymmetric Reductive Dicarbamoylation of Alkenes

“…In recent years, several examples of asymmetric two-component olefin carbamoylation have been developed, in which facially selective carbamoylmetalation is followed by interception of the resultant σ-alkylmetal species with either a nucleophile or an electrophile, providing various highly enantioenriched oxindoles or γ-lactams containing a quaternary stereocenter (Scheme A, eq 2). The recent work of Lautens allowed the use of diboron and iodide as the nucleophiles in the copper-catalyzed asymmetric olefin boryl-carbamoylation , and iodo-carbamoylation, respectively. Later on, Ye et al expanded the scope of the terminating nucleophile to aryl boronic acids via nickel catalysis under redox-neutral conditions .…”

Recent Advances in Nonprecious Metal Catalysis

“…A highly diastereoselective synthesis of 3,4-disubstituted γlactams through copper−boron addition to 1,2-disubstituted alkenes followed by trapping of the generated benzylcopper intermediates with the N-carbamoyl moiety was reported. 61 Cyclizations that furnished sterically hindered 3,4,5-trisubstituted γ-lactams were more sluggish, and a prolonged reaction time at 50 °C was necessary (Scheme 41a). The enantioselective variant was shown to be feasible, with the Josiphos ligand giving the most promising preliminary enantioselectivity.…”

Asymmetric Synthesis of α-Alkylated γ-Lactam via Nickel/8-Quinim-Catalyzed Reductive Alkyl-Carbamoylation of Unactivated Alkene

“…In 2014, Zhang and Ding group almost simultaneously developed an efficient asymmetric hydrogenation reaction of exocyclic ,-unsaturated amide with spiro P,N ligands and iridium(I) to afford chiral lactam with a tertiary stereo carbon center (Scheme 2a). 7 In addition, transition-metal-catalyzed asymmetric cyanocarbamoylation, 8 hydrocarbamoylation, 9 borylcarbamoylation, 10 and arylcarbamoylation 11 of alkene pendent to carbamoyl electrophiles via redox-neutral manner to form the corresponding chiral lactams were also reported in recent years (Scheme 2b). Nevertheless, for the tertiary chiral moiety, only 3-methylated -lactams were obtained in Cramer's work.…”