Synthesis of (−)-pinidinone

The diastereoselective PdCl2/CuCl2-catalysed intramolecular methoxyaminocarbonylation of N-benzyl protected alkenyl amine 4 was used as a key step in the total synthesis of the naturally occurring piperidine alkaloid (−)-pinidinone. Commercially available (S)-propylene oxide was employed as starting material, delivering the key substrate 4 in three steps and 68% overall yield. Subsequently, the influence of various reaction parameters on the diastereoselectivity of the key cyclisation of 4 was scrutinised. Copper(II) chloride proved to be the optimum reagent and/or co-catalyst for the successful aminocyclisation-methoxycarbonylation tandem transformation of alkenyl amine 4 into the desired methyl esters 3 and 8. The latter were subsequently transformed into the title natural product.