Asymmetric Rh(II)/Pd(0) Relay Catalysis: Synthesis of α-Quaternary Chiral β-Lactams through Enantioselective C–H Insertion/Diastereoselective Allylation of Diazoamides

Abstract

A straightforward route toward construction of α-quaternary chiral β-lactam moiety via Rh(II)/Pd(0)catalyzed stereoselective relay catalytic reaction is reported. This asymmetric dual relay catalysis involves Rh(II)-catalyzed enantioselective intramoluecular C−H insertions of αdiazoamides, and sequential Pd(0)-catalyzed diastereoselective intermolecular allylic alkylation. Under mild reaction conditions, a broad range of α-quaternary allylated chiral βlactams have been synthesized in high yields (up to 99%) with excellent stereoselectivities [up to diastereomeric ratio (dr) >99:1, up to 98% enantiomeric excess (ee)].

Asymmetric Synthesis of β-Lactam via Palladium-Catalyzed Enantioselective Intramolecular C(sp3)–H Amidation

“…13,14 C−H functionalization strategy via metal-catalyzed intramolecular C−H carbene insertion has long been employed for synthesis of β-lactams. 15 In recent years, Pd-catalyzed intramolecular C(sp 3 )−H functionalization reactions including C−H alkylation, 16 carbonylative amination, 17 and the carbamoylation 18 process via Pd 0/II or Pd II/0 catalytic cycles have offered new ways to construct β-lactams. Among these reactions, enantioselective transformations based on C−H alkylation 16 and carbamoylation 18 have also been demonstrated using chiral phosphonite and phosphoramidite ligands, respectively.…”

“…In general, substituents on the meta and para positions of aryl groups were well tolerated (see 4, 8). Ortho-substituted or electron-deficient aryl groups gave a significantly lower yield and ee (14,11,15). As exemplified by 13, intramolecular amination of the unactivated C(sp 3 )−H bond gave very low yield and moderate ee under the standard conditions.…”

New Catalytic Radical Process Involving 1,4-Hydrogen Atom Abstraction: Asymmetric Construction of Cyclobutanones

“…Due to the high strain associated with four-membered ring structures, the catalytic process for 1,4-C–H alkylation has been largely underdeveloped. While there have been a few reports on the asymmetric synthesis of β-lactams and β-lactones from α-diazoamides and α-diazoesters, respectively, by Ru, Rh, and Ir-based catalytic systems, asymmetric synthesis of cyclobutanones via 1,4-C–H alkylation from α-diazoketones has not been previously realized . The absence of a catalytic system for cyclobutanone synthesis is presumably attributed to the augmented challenge of 1,4-C–H alkylation for α-diazoketones because of their relatively higher conformational flexibility than α-diazoamides and α-diazoesters.…”

Modular Synthesis of α‐Quaternary Chiral β‐Lactams by a Synergistic Copper/Palladium‐Catalyzed Multicomponent Reaction

“…Recently, Lee et al. reported a Rh II ‐catalyzed intramoluecular C−H insertion reaction of α‐diazo acetamides, followed by intermolecular AA, providing α‐quaternary chiral β‐lactams [9e] . In this context and with our continuing interests in bimetallic catalysis, [13] we speculated that a Cu/Pd‐catalyzed, IKAA achieved by integrating the two name reactions together could resolve this C−C bond formation problem (Scheme 1 c).…”