Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

Abstract

This review presents a comprehensive overview of transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes. These compounds are important synthons in organic synthesis, providing an important platform for the construction of biologically/medicinally significant compounds which bear multiple stereocenters. The review has been divided according to the metal used in the reaction. An overview of the substrate scope, reaction conditions, and their potential applications in organic synthesis is discussed. A comprehensive outlook on the reactivity paradigms of homo- and heterobicyclic alkenes is discussed and should shed light on future directions for further development in this field.

Nickel-Catalyzed Arylation/Lactonization Cascade Reactions for the Synthesis of Bicyclo[3.2.1]lactones

“…16 Interested in this result, we were prompted to investigate related methods for the synthesis of bicyclo[3.2.1]lactones through a cascade reaction on an oxabicyclic alkene. 17 We envisioned functionalization of the olefin through carbonickelation of 6, followed by β-oxygen elimination that would afford system 7, which could undergo transannular lactonization to afford the desired product (Scheme 1c). Herein, we report a Ni-catalyzed arylation/lactonization cascade reaction for the synthesis of the functionalized bicyclo[3.2.1]lactone scaffolds bearing 4-stereocenters in a single step.…”

“…When using exo dicarboxylate oxabicyclic alkene 4 , the anticipated reductively ring-opened cycohexanol product was not observed; instead, a bicyclo[3.2.1]lactone side product was isolated . Interested in this result, we were prompted to investigate related methods for the synthesis of bicyclo[3.2.1]lactones through a cascade reaction on an oxabicyclic alkene . We envisioned functionalization of the olefin through carbonickelation of 6 , followed by β-oxygen elimination that would afford system 7 , which could undergo transannular lactonization to afford the desired product (Scheme c).…”

Nickel-catalyzed arylative cyclization of 1,6-enynes: arylation of unactivated alkene moieties

“…Transition-metal-catalyzed domino reactions have become a powerful tool in synthetic chemistry, combining several catalytic steps into one process and providing a highly atom-and step-economical strategy for the synthesis of complex molecules. [1][2][3][4][5][6] Increasing attention has been focused on the development and use of Earth-abundant and sustainable elements, especially nickel catalysts, to replace the highly expensive and scarce metals of the second and third rows. The nickel(0)-catalyzed coupling of alkynes, activated alkenes, and organometallics via a nickel metallacycle intermediate offers a direct process for accessing complex olefins (Fig.…”

Catalytic multi-step domino and one-pot reactions

“…The Thematic Issue “Catalytic multi-step domino and one-pot reactions” in the Beilstein Journal of Organic Chemistry , which I had the pleasure to edit, covers the recent strategies of domino reactions and one-pot syntheses and presents the advances in the field. A Review article by Pounder, Tam, and co-authors summarizes new transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes highly useful for the construction of biologically significant compounds with multiple stereocenters [ 7 ]. In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [ 8 ].…”