Intramolecular [3 + 2] nitrone cycloaddition reaction: highly regio and diastereoselective synthesis of bicyclo[3.2.1]octane scaffolds

Abstract

Development of a regio- and a diastereoselective protocol for the synthesis of bicyclo[3.2.1]octane frameworks from vinylogous carbonates and N-substituted hydroxylamine hydrochlorides via intramolecular 1,3-dipolar nitrone cycloaddition reaction.

Unveiling the intramolecular [3 + 2] cycloaddition reactions ofC,N-disubstituted nitrones from the molecular electron density theory perspective

“…In 2004, Singha et al 15 used IM32CA reactions of nitrones for the synthesis of spironucleosides and spirobisnucleosides, while in 2011, Mazumder et al 16 used IM32CA reactions of nitrones for the synthesis of quinolones with antidepressant and antimalarial properties. In 2017, tricyclic fused isoxazolidines were synthesized regioselectively from the IM32CA reactions of 1,1,1,-trifluoromethyl styrene derived nitrones 17 and recently, in 2020, Bakthados and Mushaf 18 have reported the IM32CA reactions of nitrone 13 generated from substituted o-allyl salicylaldehyde 12 for the synthesis of complex bicyclo [3.2.1] scaffolds 14 (Scheme 2). The IM32CA reactions of nitrones have been experimentally studied by numerous synthetic chemists [7][8][9][10][11][12][13][14][15][16][17][18] as a well established synthetic strategy for fused isoxazolidines.…”

“…In 2017, tricyclic fused isoxazolidines were synthesized regioselectively from the IM32CA reactions of 1,1,1,-trifluoromethyl styrene derived nitrones 17 and recently, in 2020, Bakthados and Mushaf 18 have reported the IM32CA reactions of nitrone 13 generated from substituted o-allyl salicylaldehyde 12 for the synthesis of complex bicyclo [3.2.1] scaffolds 14 (Scheme 2). The IM32CA reactions of nitrones have been experimentally studied by numerous synthetic chemists [7][8][9][10][11][12][13][14][15][16][17][18] as a well established synthetic strategy for fused isoxazolidines. However, the theoretical implications of these reactions still remain a cornerstone relative to those addressing intermolecular 32CA reactions.…”

“…The IM32CA reactions of nitrones have been experimentally studied by numerous synthetic chemists 7–18 as a well established synthetic strategy for fused isoxazolidines. However, the theoretical implications of these reactions still remain a cornerstone relative to those addressing intermolecular 32CA reactions.…”

A theoretical study of the regioselectivity of the reaction of six-membered and five-membered nitrones with a series of substituted alkenes

“…Gunawardene et al [31] have rationalized the effects of N-and Cαsubstituent modifications at the nitrone on inverseelectron-demand strain-promoted alkyne-nitrone cycloaddition reaction kinetics and the overall rapid reactivity of pyridinium-delocalized nitrones by exploring density functional theory (DFT) and Xray crystallography. Recently, Bakthadoss et al [32] have developed a regio and diastereoselective strategy for the synthesis of complex bicyclo[3.2.1]octane scaffolds from the reaction of readily accessible vinylogous carbonates with N-substituted hydroxylamine hydrochlorides via intramolecular 1,3-dipolar nitrone cycloaddition reaction. They have synthesized a wide varieties of bicyclic isoxazolidines in high yields in the absence of any catalyst used.…”