Highly regiocontrolled and stereocontrolled syntheses of polysubstituted aminocyclohexanes: mild inverse-electron-demand Diels–Alder cycloadditions of electrophilic 2-pyridones. Issue 30 (27th July 2016)

• Record Type: Journal Article
• Authors: Conyers, Ryan C.; Mazzone, Jennifer R.; Siegler, Maxime A.; Posner, Gary H.
• Is Part Of: Tetrahedron letters. Volume 57:Issue 30(2016)
• Page Start: 3344
• Page End: 3348
• Publication Date: 2016-07-27
• Subjects: Gram scale 4+2 cycloadditions -- Inverse electron demand Diels–Alder cycloadditions -- Regiocontrolled and stereocontrolled cycloadditions; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.06.068
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Developed procedure for IEDDA cycloadditions under mild conditions and avoiding undesired N - to O -sulfonyl group migration. These [4+2] cycloadditions very strongly favor regioselective and stereoselective formation of endo bicyclic lactams. These IEDDA cycloadditions produce highly functionalized pentasubstituted and hexasubstituted cyclohexanes. Abstract: 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.