Ultrasound in natural products synthesis: applications to the synthesis of histrionicotoxin via nitroalkanal acetals

Abstract

Ultrasound promoted the Kornblum reaction of silver nitrite or sodium nitrite with haloalkyl acetals to afford the corresponding C-nitro compounds. The acetalprotected nitro compounds were used as reactants in a ‘double Henry’ reaction to produce the key intermediate nitrocyclohexane diol with a masked aldehyde side chain. The nitrodiol was then subjected to an ultrasound-promoted one-pot/single operation sequence involving a reduction-deprotection followed by a cyclization-reduction. The entire sequence provided the core spiropiperidine substructure of the histrionicotoxins.