Multicomponent Synthesis of Isoindolinones by Rh^III Relay Catalysis: Synthesis of Pagoclone and Pazinaclone from Benzaldehyde

Abstract

A practical one-pot isoindolinone synthesis enabled by Rh III catalysis was developed. The advantage of this protocol is that it does not require pre-preparation of amide substrates, because Rh III participates in two reactions independently. This mild, operationally multicomponent process transforms a wide variety of commercially available aldehydes into the corresponding γ-lactams in good yields, thereby demonstrating that N-pyridin-2-yl benzamide is an effective directing group. Notably, the anxiolytic drugs pagoclone and pazinaclone can be directly prepared by this methodology.Letter pubs.acs.org/OrgLett

An Overview of Rhodium‐Catalysed Multi‐Component Reactions

“…Isoindolinones, because of its remarkable biological properties, are an attractive class of heterocycles worth synthesizing. In 2018, Zhang and co‐workers successfully demonstrated a one‐pot multi‐component synthesis of isoindolinones via C−H olefination from readily available starting materials such as benzaldehydes, aryl amines and activated olefins using [Cp * RhCl 2 ] 2 as catalyst ( Scheme ) . In the same year, a similar work was carried out by Wang an co‐workers using benzoyl chlorides, o ‐amino phenol and activated olefins using the same catalyst for the synthesis of isoindoline frameworks ( Scheme ) …”

Recent Advances in the Synthesis of 5‐MemberedN‐Heterocycles via Rhodium Catalysed Cascade Reactions

“…Synthesis of isoindolinones by Rh-III relay catalysis. [94] Scheme 45. Enantioselective synthesis of dihydro-β-carbolines via insertion to CÀ H bond and aza-michael reaction.…”

Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions

“…Rh III -catalyzed three-component synthesis of isoindolinone frameworks was achieved by both Wang et al [50] and Zhang et al [51] Wang used ac ombination of benzoyl chloride derivative, 2-aminophenol and electron deficienta lkene derivatives to synthesize av ariety of substituted isoindolinones in as ingle step under air (Scheme 14 A). In comparison, Zhang utilized an aromatica ldehyde, 2-aminopyridines and similarly activated olefins under nitrogen atmosphere,a nd was able to synthesize pagoclone andp azinaclone in as ingle step, albeit in 15 %a nd 20 %i solated yields, respectively (Scheme 14 B).…”

“…Rh III ‐catalyzed three‐component synthesis of isoindolinone frameworks was achieved by both Wang et al [50] . and Zhang et al [51] . Wang used a combination of benzoyl chloride derivative, 2‐aminophenol and electron deficient alkene derivatives to synthesize a variety of substituted isoindolinones in a single step under air (Scheme 14 A).…”