Highly regiocontrolled and stereocontrolled syntheses of polysubstituted aminocyclohexanes: mild inverse-electron-demand Diels-Alder cycloadditions of electrophilic 2-pyridones

Strongly electrophilic N-arenesulfonyl-2-pyridone-3-carboxylate methyl esters complex with zinc dibromide and then react with nucleophilic benzyl vinyl ether or benzyloxyallene to achieve inverse-electron-demand Diels-Alder (IEDDA) cycloadditions. These cycloadducts are produced on gram scale and in 77-89% yields, importantly without the use of high pressure. These 4+2 cycloadditions strongly favor regioselective and stereoselective formation of endo bicyclic lactams as established by X-ray crystallography. These bicyclic lactams undergo useful reactions, including reductive cleavage of the N-sulfonyl group, exo-syn-dihydroxylations, and lactam ring-opening to produce a variety of aminocyclitols. (C) 2016 Elsevier Ltd. All rights reserved.