Catalytic Generation of C1 Ammonium Enolates from Halides and CO for Asymmetric Cascade Reactions

Abstract

A general strategy for the design of asymmetric cascade reactions using readily available halides and carbon monoxide (CO) as substrates is developed. The key is the catalytic generation of C1‐ammonium enolates for the subsequent asymmetric cascade reactions through the combination of palladium‐catalyzed carbonylation and chiral Lewis base catalysis. Utilizing this strategy, we have established asymmetric formal [1+1+4] and [1+1+2] reactions to afford chiral dihydropyridones and β‐lactams with high yields and high enantio‐ and diastereoselectivities.

Copper(I)‐Catalyzed Asymmetric Interrupted Kinugasa Reaction: Synthesis of α‐Thiofunctional Chiral β‐Lactams

“…These lactams are derived from an antiproliferative agent [Eq. (2)] [7c, 18] . In a gram‐scale experiment, 4 a was isolated in 66 % yield with 96:4 er with only 5 mol % copper catalyst.…”

Generation and Reactivity of C(1)‐Ammonium Enolates by Using Isothiourea Catalysis

“…Gong and co‐workers have also reported the seminal catalytic generation of C(1)‐ammonium enolates from the simple feedstock chemicals alkyl halides and carbon monoxide (CO) [62] . The authors hypothesised that oxidative addition of the palladium catalyst into the C−X bond of an alkyl halide, followed by CO insertion would give an acyl palladium intermediate (Scheme 24 a).…”

Tertiary Amine Lewis Base Catalysis in Combination with Transition Metal Catalysis

“…One limitation concerned the poor oxidative stability of styrenyl motifs. However, this could be circumvented by straightforward [34]. Using a Pd-catalyzed carbonylation process in combination with a newly developed isothiourea catalyst (fused-BTM), 22 dihydropyridones and 6 β-lactams were prepared in good yields and control over diastereo-and enantioselectivity.…”