Synthesis of Hydroxysuccinimide Substituted Indolin-3-ones via One-Pot Cascade Reaction of o-Alkynylnitrobenzenes with Maleimides under Au(III)–Cu(II) Relay/Synergetic Catalysis

Abstract

Presented herein is a one-pot cascade reaction of o-alkynylnitrobenzenes with maleimides leading to the formation of hydroxysuccinimide substituted indolin-3-ones under Au­(III)–Cu­(II) relay/synergetic catalysis. Mechanistically, the formation of the title products involves an unprecedented cascade process including (1) nitro–alkyne cycloisomerization of o-alkynylnitrobenzene to give isatogen; (2) [3 + 2] dipolar cycloaddition of isatogen with maleimide; and (3) ring opening of the in situ formed isoxazolidine moiety under neutral conditions. Notably, a wide range of substrates bearing various functional groups are compatible with the reaction conditions to give a series of highly valuable hybrid compounds in good efficiency with excellent atom economy. In addition, the products thus obtained could be easily transformed into the corresponding maleimide substituted indolin-3-ones. Importantly, some products demonstrated significant antiproliferative activity in human cancer cell lines.

Recent Applications on Dual-Catalysis for C–C and C–X Cross-Coupling Reactions

“…34,37,[47][48][49] The use of dual-metal catalytic systems in the synthesis of new compounds has increased significantly during the past twenty years. [50][51][52] In addition to improving selectivity and reactivity, these novel methods can also greatly enhance the reaction processes that would not be feasible with a single metal catalyst, enabling the synthesis of novel compounds and molecular frameworks. Synergistic catalysis has often been studied by combining a transition metal catalyst with Lewis acids, 53,54 organocatalysts (e.g., Brønsted acids, N-heterocyclic carbenes, chiral amines, and Lewis bases), [55][56][57][58][59][60][61][62][63][64][65][66][67] or Lewis acids with N-heterocyclic carbenes.…”

Synthetic Applications of Ambiphilic C‐acylimines in Organic Synthesis

“…Fan and coworkers also utilized Au(III) to synthesize hydroxy‐succinimide substituted indolin‐3‐ones 89 via a one‐pot cascade reaction of o‐alkynylnitrobenzenes 35 with maleimides 88 (Scheme 31). [39] In this cascade, Au(III) works as a catalyst for the cycloisomerization of o ‐alkynylnitrobenzene, while Cu(II)/Au(III) works together to assist the ring‐opening of the in situ generated isoxazolidine molecule. The reaction conditions are generally compatible with a wide range of substrates with diverse functional groups.…”

Organocatalyzed Enantioselective Aza-Morita–Baylis–Hillman Reaction of Cyclic Ketimine with α,β-Unsaturated γ-Butyrolactam

“…As a subset, 2-alkenyl-2-phenyl-1,2-dihydro-3 H -indol-3-ones represent an attractive class of molecules bearing a quaternary carbon center. Notably, the diverse functionalities of the chiral 2-alkenyl-2-phenyl-indoline-3-ones provide potential possibilities for the synthesis of bioactive drugs . However, the universal and appropriate strategy suitable for the enantioselective construction of chiral 2-alkenyl-substituted indolin-3-one derivatives is still lacking.…”