Progress towards the pyrrolizidine alkaloid xenovenine (223H) via hydroamination.
Many natural products, pharmaceuticals and fine chemicals possess carbon-nitrogen bonds and thus the formation of such bonds is of great importance. Pyrrolizidine, indolizidine, quinolizidine and lehmizidine alkaloid skeletons all contain C–N bonds and are potentially accessible via a general synthetic route utilising hydroamination. The synthesis of the biologically active nitrogen containing pyrrolizidine alkaloid xenovenine 4 isolated from Solenopsis cryptic thief ants and Dendrobates poison dart frogs was attempted. One of the key intermediates, ethyl 2-[(5R)-5-methyltetrahydro-2Hpyrrol- 2-ylidene]acetate 127, was successfully synthesised in 7 steps from (S)-pyroglutamic acid through a lactim ether intermediate. The pivotal ring forming ZnCl2 catalysed 5-exo-dig hydroamination was unfortunately not attempted after the failed C-propargylation of ethyl 2-[(5R)-5- methyltetrahydro-2H-pyrrol-2-ylidene]acetate 127.