Ring Expansion of Isatins via 1,2-Phospha-Brook Rearrangement: A Route to the Synthesis of 2-Quinolinone-Derived p-Quinone Methides

Abstract

A Lewis acid-mediated one-carbon homologation approach to installing a 2-quinolinone core embedded with paraquinone methides, in a high yield of up to 92%, and with high regioselectivity has been developed. Also, post-synthetic modifications, including C−P, C−S, and C−C bond formations, have been demonstrated by the 1,6-addition of suitable nucleophiles. Further, cyclopropanation of 2-quinolinone-embedded p-QM is also demonstrated affording a contiguous quaternary spiro center.

Stereoselective Reductive Coupling Reactions Utilizing [1,2]-Phospha-Brook Rearrangement: A Powerful Umpolung Approach

“…36 These adducts could further be efficiently transformed The above transformation involves 1,6-addition of isatins to p-QMs via [1,2]-phospha-Brook rearrangement, which further paved the way to the development of a fascinating Lewis-acidmediated one-pot, two-step homologation approach installing p-QM-embedded 2-quinolinone cores 81 in highly regioselective fashion (Scheme 19). 37 The domino reaction proceeds through regioselective opening of cyclopropane ring 85 formed through P(NMe 2 ) 3 -mediated [1,2]-phospha-Brook rearrangement of isatins 20 and p-QMs 77, followed by ring expansion of 86 through neighboring group participation. Furthermore, the quinolinone containing p-QMs have been successfully exploited for various diastereoselective C−C, C−S, and C−P bond forming strategies by addition of the corresponding nucleophiles, rendering this approach a powerful synthetic tool.…”

Phosphine-catalysed transformations of ortho- and para-quinone methides

“…In 2022, Singh and coworkers reported the synthesis of 2-quinolone derivatives 93 from isatins 92 and p -QM 91 (Scheme 32). 78 The activation of isatin as indole derivatives by XXVI allows an initial 1,6-addition to p -QM ( A ). The overall reaction is a two-step reaction involving an initial 1,2-phospha-Brook rearrangement.…”

An Expedient Approach to Access Phenalenones via Unconventional [1,2]-Phospha-Brook Rearrangement/Carbonyl Migration

“…Toward this, it is hypothesized that the ring expansion approach, considering its predictability and atom-economy, might become an attractive alternative for directly obtaining phenalenones . Recently, many quinolinones have been synthesized via ring expansion by exploiting [1,2]-phospha-Brook rearrangement . This uniquely identified reactivity prompted us to investigate the possibility of acenaphthoquinone to undergo a similar type of ring expansion in the presence para -quinone methides ( p -QMs) to afford phenalenones.…”