Synthesis of intermediates for the preparation of core analogs of esperamicin

Bicyclo[7.3.1]enediyne intermediates for the synthesis of analogs of BMY-46108 (5), a simple core analog of esperamicin, were prepared by two different routes. One involved fluoride-promoted cyclization of 1 followed by epoxide rearrangement. The other proceeded by a base-promoted cyclization of the aldehyde 8 and was subject to thermodynamic control. The stereochemistry of the C-12 asymmetric center in the favored cyclization product (9) was established by its conversion into 5 and its isomer, 14.