An asymmetric synthesis of hamigeran B via a Pd asymmetric allylic alkylation for enantiodiscrimination.
A protocol for the asymmetric allylic alkylation of a five-membered ring ketone derivative that employs the lithium enolate in the presence of lithium alkoxides gave high yields and enantioselectivities. This product serves as a versatile intermediate as demonstrated in a convergent total synthesis of the antiviral agent hamigeran B. The sequence involves two unusual observations. In the intramolecular Heck reaction which establishes the complete ring sytem, the beta-H elimination step occurs both endocyclic (as expected) and exocyclic, the latter most surprising since it creates an exocylic tetrasubstituted double bond. In the catalytic hydrogenation, use of Pd/C gives complete selectivity for net delivery of hydrogen to the most hindered face of the substrate, whereas use of Ir black gives complete selectivity for delivery of hydrogen to the least hindered face. Such unusual behavior speaks to the unusual chemical properties associated with hamigeran B which may be relevant to its biological activity.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
Pissot-Soldermann
Carole
C
Chen
Irwin
I
Schroeder
Gretchen M
GM
D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry*; D000818:Animals; D003500:Cyclization; D008958:Models, Molecular; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
D000498:Allyl Compounds; D009285:Naphthoquinones; C483756:hamigeran B; D010165:Palladium