Michael reaction in organocascade catalysis: A powerful tool for creating architectural complexity in the construction of medicinally privileged heterocyclic scaffolds

ABSTRACT

Cascade reactions are versatile tools in synthetic organic chemistry, allowing the creation of complex structures from simple building blocks in a consistent one-pot procedure. Recently, there has been renewed interest in the development of synthetic protocols using organocascade catalysis. This innovative approach combines two modes of catalyst activation into a single mechanism, enabling the rapid conversion of simple achiral starting materials into stereo-chemically complex single enantiomeric products. The utilization of enantiopure organic molecules as catalysts to enhance chemical transformations in the asymmetric synthesis of optically active compounds with the desired chirality has emerged as an extremely attractive synthetic approach in the field of modern chemistry. The organocatalytic cascade approach is a rapidly growing field in chemical science, spanning academia and industry. It offers promising solutions for achieving atom-efficient, time-efficient, and cost-efficient methods that often mimic biosynthetic pathways. As a result, it enjoys great popularity and is widely regarded as a wonderful protocol among the scientific community. Remarkable advances in the field of organocascade catalysis have been made over the past two decades, revolutionizing the catalytic regime. This review focuses on the early and recent advances in amino catalytic organocatalyzed Michael reactions, which serve as a powerful tool in the rational design and synthesis of chiral homo- and heterocyclic architectures found in various bioactive natural products and pharmaceuticals. Further, this review delves into the detailed investigation of their mechanisms and explores the synthetic transformations of Michael cascade adducts as precursors for the synthesis of drugs, natural products, and molecular analogs of diverse interest.

Graphical Abstract

KEYWORDS:

• Organocatalysis
• cascade reaction
• enamine-iminium activation
• Michael reaction
• hydrogen bonding
• covalent
• non-covalent catalysis
• aldol condensation
• dehydration

Acknowledgments

RNY and AKS acknowledges the Department of Chemistry and Mathematics, Faculty of Engineering & Technology for support and infrastructural facilities. BKB is grateful for financial supports from US NIH, US NCI, and Kleberg Foundation for financial assistance. MFH acknowledges the support received from SERB SURE project (file no.: SUR/2022/000342). The authors acknowledge the contributions of all those whose work is cited in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).