Stereoselective Domino Reactions in the Synthesis of Spiro Compounds

Abstract

This review aims to summarize the latest developments in asymmetric domino reactions, with the emphasis on the preparation of spiro compounds. Discussions on the stereoselectivity of the transformations, the reaction mechanisms, the rationalization of the stereochemical outcome, and the applications of domino reactions to the synthesis of biologically active molecules and natural products are included when appropriate.

Electrochemical electrophilic bromination/spirocyclization of N-benzyl-acrylamides to brominated 2-azaspiro[4.5]decanes

“…1 Among them, azaspiro compounds have attracted much attention as unique building blocks. 2 In recent years, noble-metal-involved spirocyclization of phenol derivatives containing allylic carbonates, difluorobromides or α-diazoacetamides is an efficient route to 2-azaspiro[4.5]decanes (Scheme 1a). 3 The intramolecular radical dearomatizing spirocyclization could be accomplished under dilauroyl peroxide-mediated, Et 3 B/air-mediated or visible-light-induced iridium-catalysis conditions (Scheme 1b, top).…”

Adventures in the Chemistry of Multicomponent and Domino Reactions

“…Domino reactions represent a valuable tool for the synthesis of spirocyclic compounds. [11] The reaction of N-methylglycine (9) with ninhydrin (10 a) and 3-alkylidene-2-oxindoles 8 a-j, available by condensation of the corresponding oxindoles with aldehydes, afforded dispiro[indene-2,2'-pyrrolidine-3',3''-indole]-1,2'',3(1''H)-triones 11 a-j in good to excellent yields (Scheme 4). [12] The formation of the products can be explained by attack of the nitrogen atom of 9 to the central carbonyl group of 10 a and subsequent cyclization to give intermediate A. Extrusion of carbon dioxide afforded nitrogen ylide B which subsequently underwent [3 + 2] cycloaddition with the exocyclic double bond of 8 a-j via transition state C. The products, which contain two asymmetric carbon atoms, were formed with excellent 1,2-diastereoselectivity.…”

Recent Advances in the Domino Annulation Reaction of Quinone Imines

“…Among the numerous reported synthetic strategies, domino reactions have attracted considerable attention due to their potential to conserve resources, reduce waste generation during the synthesis process, and align with the principles of green chemistry [ 13 , 14 , 15 , 16 ]. Most importantly, they enable the rapid assembly of polycyclic structures from simple starting materials [ 17 , 18 , 19 , 20 , 21 , 22 ]. This strategy has been successfully applied in the synthesis of natural products and bioactive compounds, demonstrating its potential to streamline the construction of complex molecular architectures [ 23 , 24 , 25 , 26 ].…”