Bifunctional Monothiosquaramide-Catalyzed Enantioselective Addition of Masked Acyl Cyanide to Isatins: Umpolung Strategy for the Total Synthesis of ( S )-(−)-Dioxibrassinin and ( R )-(+)-Spirobrassinin

Organic Letters 2026 Open access

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Authors: Francisco A. A. Reis, Manda Sathish, Bárbara V. Silva, Roberta K. F. Marra, Letícia Oliveira Magalhães, Viresh H. Rawal, Fabiane M. Nachtigall, Leonardo S. Santos
DOI: 10.1021/acs.orglett.5c04818
Cited by: 1
References: 64

Abstract

Abstract The enantioselective addition of masked acyl cyanide (MAC) to isatin is a highly efficient strategy for synthesizing bioactive chiral spirooxindoles. Herein, we report the utility of this strategy in an asymmetric total synthesis of (S)-(−)-dioxibrassinin and (R)-(+)-spirobrassinin, which are well-known phytoalexin alkaloids present in Brassicaceae plants. We developed a bifunctional monothiosquaramide (9b)-catalyzed addition of MAC to isatin, affording chiral oxindole esters (11a–11j) with excellent enantioselectivities (>99% ee) under mild conditions and catalyst loadings around 10 mol %. We accomplished the total synthesis of (S)-(−)-dioxibrassinin (1) and (R)-(+)-spirobrassinin (2) from oxindole ester 11a in a few subsequent steps with high overall yields (65%) and selectivities (99% ee).

Fields of Study & Subjects

Sphingolipid Metabolism and Signaling Asymmetric Synthesis and Catalysis Axial and Atropisomeric Chirality Synthesis

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
18
Pages
5659–5665
Publication date
9 January 2026
Language
EN