Enantioselective synthesis of 1-vinyltetrahydroisoquinolines through palladium-catalysed intramolecular allylic amidation with chiral PhthalaPhos ligands

The Phthalaphos ligands, a new class of chiral BINOL monophosphites endowed with a phthalamide group, were successfully used in rhodium-catalysed hydrogenation of olefins such as dehydroamino esters and enamides.1 Being capable of supramolecular hydrogen bonding interactions the ligands’ phthalamide moiety exerts a substrate orientation effect in the hydrogenation catalytic cycle, thus playing a role in determining high levels of enantioselectivity.1 These results prompted us to further explore the applicability of Phthalaphos ligands in enantioselective transformations promoted by other transition metal catalysts. Herein, we report the screening of the library in the enantioselective palladium-catalysed intramolecular amidation (AAA)2 of achiral amidocarbonates leading to the synthesis of pharmacologically interesting chiral 1-vinyltetrahydroisoquinolines.3 Identification of the best ligand followed by optimisation of the reaction conditions allowed for the obtainment of the desired product with up to 83% e.e.. Remarkably, the reaction is stereoconvergent, affording the same enantiomer of the desired product regardless the configuration of allylic carbonate’s double bond, which allows – in principle – the use of E/Z mixtures.