β‐Lactams as Formal Dipoles through Amide‐Bond Activation

Abstract

Activation of β‐lactams can be achieved by simple Lewis‐base catalysis to trigger an unprecedented reaction based on the formal dipolar behaviour of a strained amide bond. A new synthetic route for 1,3‐oxazinan‐6‐ones is presented by reaction of β‐lactams with ethylglyoxylate, which after methodological optimizations identified 4‐pyrrolidinopyridine as the catalyst of choice in aprotic polar solvents. Mechanistic details are also discussed in light of the intrinsic limitations identified for this transformation.

Synthesis of Indole‐ and Pyrrole‐Fused Seven‐Membered Nitrogen Heterocycles via Acid‐Base Switchable Cyclization Involving Cleavage of Amide C−N Bonds

“…Moreover, David et al. used β‐lactams as formal dipoles to synthesize six‐membered‐ring compounds by activation of amide bonds using ring tension and a Lewis acid; however, the substrate scope of this method is relatively narrow [21] …”

“…[20] Moreover, David et al used β-lactams as formal dipoles to synthesize sixmembered-ring compounds by activation of amide bonds using ring tension and a Lewis acid; however, the substrate scope of this method is relatively narrow. [21] To date, use of the above-described amide-activation strategies for construction of nitrogen-containing heterocycles has rarely been studied. Herein, we report the development of a method for synthesizing indoleand pyrrole-fused polycyclic compounds from Nsulfonyl amides by means of intramolecular migration of an acryloyl group.…”

The N‐Hydroxymethyl Group as a Traceless Activating Group for the CAL‐B‐Catalysed Ring Cleavage of β‐Lactams: A Type of Two‐Step Cascade Reaction

“…These efforts revealed that the ring‐opening reaction is sensitive to the structure of the nitrogen‐protecting group 9. Very recent synthetic efforts involving 1,3‐oxazinan‐6‐one generation through the use of N ‐activated β‐lactams 10 have highlighted the utmost importance of activating groups (sulfonyl‐based groups, amide or tert ‐butoxycarbonyl, with different electron‐withdrawing abilities) in dictating amide bond activation towards hydrolytic scission.…”