Enantioselective Synthesis of Spiro Chroman‐Isoindolinones via Formal (4+2) Cycloaddition of In Situ‐Generated <i>ortho</i>‐Quinone Methides with 3‐Methylene Isoindolinones

Abstract

Abstract Using chiral phosphoric acids as organocatalysts, a formal asymmetric (4+2) cycloaddition of 3‐methylene isoindolinone and in situ‐generated ortho ‐quinone methide substrates is disclosed. This reaction exhibited a broad substrate scope with various substituted cyclic enamides and ortho ‐hydroxybenzyl alcohol derivatives to construct a series of spiro chroman‐isoindolinones containing spiro‐N,O‐heterocycles with 56 to 93% ee . This strategy demonstrates significant potential towards establishing a chiral spiro‐N,O‐aminal systems bearing two chiral carbon centers, including a tetrasubstituted carbon stereocenter. magnified image

Topics & Concepts