Towards the synthesis of hyacinthacines

Abstract

The organocatalytic aldol reaction of tropinone with benzaldehyde using (S)-5-pyrrolidin-2-yl-1H-tetrazole as organocatalyst is described and it results in the formation of the dehydrated aldol adduct in moderate selectivity. The organocatalytic aldol reaction of CS and C2V-symmetrical dioxanones is also demonstrated and in most cases CS-symmetrical dioxanones offer a better stereoselectivity. A new approach towards synthesis of hyacinthacine alkaloids: 2-epihyacinthacine A2, 3-epihyacinthacine A2 and their enantiomers is illustrated. The key step involves an organocatalytic aldol reaction of dioxanones where proline is used both as the catalyst and as the precursor for the aldehyde building block.