Multicomponent Synthesis of Isoindolinone Frameworks via Rh^III‐Catalysed in situ Directing Group‐Assisted Tandem Oxidative Olefination/Michael Addition

Abstract

A Rh -catalysed three-component synthesis of isoindolinone frameworks via direct assembly of benzoyl chlorides, o-aminophenols and activated alkenes has been developed. The process involves in situ generation of o-aminophenol (OAP)-based bidentate directing group (DG), Rh -catalysed tandem ortho C-H olefination and subsequent cyclization via aza-Michael addition. This protocol exhibits good chemoselectivity and functional group tolerance. Computational studies showed that the presence of hydroxyl group on the N-aryl ring could enhance the chemoselectivity of the reaction.

Tunable Single and Double γ‐C−H Arylation of Phenylacetamides Directed by o‐Aminophenols

“…Using Pd(TFA) 2 and PdCl 2 in parallel experiment gave inferior results, respectively (entries 4-5, Table 1). Subsequently, varying the additive species to AgOAc, KIO 3 and Cu(OAc) 2 suggested that KIO 3 was amongst the most favourable additive (entries 6-8, Table 1). Increasing the loading of additive did not improve the reaction (entry 9, Table 1), and decreasing the amount of base led to reduced yield of 3 a (entry 10, Table 1).…”

“…[2] Later on, this DG was found as effective fragment in assisting the tandem CÀ H olefination and intramolecular hydroamination for the synthesis of isoindolinones with Rh-/Cu-cocatalyst system. [3] Rather recently, Panda and Sahoo developed the tandem synthesis of alkenyl functionalized benzoxazoles via a key CÀ H alkenylation with palladium catalysis using OAP-functionalized benzamides. [4] In despite of these inspiring works, more different CÀ H bond activation reactions assisted by such DGs are yet to explore.…”

An Overview of Rhodium‐Catalysed Multi‐Component Reactions

“…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 ) …”

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] .…”