Synthetic confirmation of the C(l ')-(S)-configuration of (+)-dihydropallescensin-2
(1) is reporled, the key reaction being a &iron-medialed asymmetric aza-Claisen rearrangement (6-7).
In 1982, Faulkner et.al.la reported the isolation of dihydropallescensin-2 from the nudibranch Cadlina luteomareinata and on the basis of both spectral and biogenetic considerations assigned structure 1 to this sesquiterpene. Three years later, Pietra et.al.lb reported the isolation of (+)-penlanpallescensin (1) from the marine sponge Dvsidea frapilis, but neither group reported compelling evidence for the C( I')-(S)-absolute configuration in 1. In planning an enantioselective total synthesis which would verify the C(l)-(S) configuration of (+)-1, it appeared to us that our recently developed asymmetric aza-Claisen protocol, which provides absolute stereocontrol in the preparation of C(a)-and/or C(P)-stereogenic pent-4encic acids,24 could give rise to non-racemic cyclohexaneacetic acid 8 (disconnection ii) from N-allylketene N,O-acetal6.
Subsequent coupling of iodide 9 with 3-lithiofuran (disconnection i) would give penlanpallescensin with the C(l)-@)-configuration.
Herein we report the realization of this strategy in what is the first synthetic application of our asymmetric aza-Claisen rearrangement.