Epi-Cylindricine

As will be discussed, our pivotal intramolecular aza-[3+3] cycloaddition was remarkably efficient in providing the tricyclic scaffold of (—)-cylindricine C 384 and that of putative (—)-lepadiformine 389 (or (—)-4-deoxo-2-epi-cylindricine C) [170b,[198], yet this route could not be implemented in our synthesis of (—)-lepadiformine 385. To reconcile this, we devised a unified strategy to synthesize (—)-lepadiformine and (+)-cylindricines C-E (386-388) that... 

Removal of the Boc group in enone 418 with TFA resulted in a free amine that underwent an in situ Michael cyclization to provide the desired aza-tricycle 409, the common intermediate, in 72% yield (Scheme 12.105). Additionally, we isolated a second product, which after careful scrutiny, learned that the aza-tricycle underwent rapid epi-merization at C5 when exposed to silica gel, thereby giving the TBDPS-protected form of (-l-)-cylindricine C 386 as well as 387 in a 1 1 mixture. It turned out that TBAF-mediated deprotection of the silyl group in tran.r-azadecalin 409 concomitantly epimerized C5 of the aza-tricycle, providing (+)-cylindricine C 386 and importantly verified the link between cylindricines and lepadiformine. Subsequent chemical manipulations then afforded (-l-)-cylindricines D and E (387 and 388 in Scheme 12.106). 

---