Reductive Cyclization and Petasis‐Like Reaction for the Synthesis of Functionalized γ‐Lactams

Abstract

An efficient reductive cyclization strategy was employed for the synthesis of N-substituted β,γ-dihydroxy-γ-lactams. A subsequent Petasislike reaction (PLR) through nucleophilic additions of boronic acids to intermediate N-acyliminium ions produced substituted γ-lactams. Overall, the application of this protocol provides β,γ-dihydroxy-γ-lactams and functionalized γ-lactams with potential interest for synthetic and bioorganic chemistry.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…In contrast, the use of electron-rich boronic acids resulted in γ-lactams 117 with no or poor diastereoselectivity owing to a possible pathway of the direct addition of boronic acids to cyclic N -acyliminium ions (Scheme 36). 142…”

Synthesis of (Arylamido)pyrrolidinone Libraries through Ritter‐Type Cascade Reactions of Dihydroxylactams

“…Dihydroxylactams 1a – 1f with different N ‐substituents, synthesized by a new reductive cyclization method developed in our laboratory,8a were then used to investigate the scope of the reaction under the optimal conditions (Scheme ). To our delight, good to excellent yields were obtained using only 1.1 equiv.…”

“…In our recent work on Petasis‐type reactions,8a we made the curious observation that the reaction of dihydroxylactam 1a and ( Z )‐prop‐1‐en‐1‐ylboronic acid in acetonitrile gave the expected product (i.e., 2a ) together with a by‐product, which was later characterized as Ritter product 3a (Scheme a). In the absence of boronic acid, compound 3a could be isolated in 54 % yield from 1a , while dimerized by‐product 4a was isolated in 24 % yield (Scheme b).…”

Generation of a Heteropolycyclic and sp3‐Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence

“…However, routine syntheses of such sp 3 ‐rich molecules with stereochemical control for use in screening library productions remains a significant challenge . The European Lead Factory initiative addresses this developing issue by targeting natural product‐like libraries, while providing production feasible routes from cheap and commercially available building blocks in order to access scaffolds that are sp 3 ‐rich with 3–5 functional group handles . These handles can be further functionalised to provide a large library of compounds to be screened for biological activity.…”