Enantioselective Palladium-Catalysed Allylation of 1,5-Dimethylbarbituric Acid

Abstract

Allylation of 1,5-dimethylbarbituric acid (BS) with allyl acetate using in situ catalysts of palladium(II) acetylacetonate and chiral phosphane imine ligands results in the enantioselective formation of 5-allyl-1,5-dimethylbarbituric acid (ABS) as the main product with up to 34% ee and 3,5-diallyl-1,5-dimethylbarbituric acid (AABS) as a possible by-product, also with up to 34% ee. This reaction is a type of allylic alkylation, the stereoselectivity of which is difficult to control because the new stereocenter is formed in the nucleophile attacking from the side opposite to the metal atom. Classical optically active ligands do not give any enantioselectivity in this palladium-catalysed reaction. Chiral phosphane imine ligands, however, are a successful class of compound, synthesized by Schiff base condensation of 2-formylphenyl(diphenyl)phosphane with optically active primary amines. An optimisation of this ligand type showed that the substituents at the stereogenic center in the imine part should be a hydroxymethyl group and a bulky alkyl group, with the best ligand being the L-tert-leucinol derivative. A screening of other types of chiral ligand, e.g. phosphane amines and phosphane trisimines, has also been performed. NMR experiments and a molecular modelling study of the cation [(η3-allyl)Pd(2a)2]+ were carried out (tripos force field). The enantioselectivity of the phosphane imine ligands is explained by an interaction of the chiral side arm of one of the ligands, which extends to about 3 A above the allyl plane, with the incoming nucleophile.