Synthesis of model BC bicycles of taxol using C10–C11 ring-closing metathesis strategy

Ring‐Closing Metathesis in the Synthesis of BC Ring‐Systems of Taxol

“…Aldehyde 9 was prepared as a racemic mixture, according to our previous work 6. Ketone 10 was synthesized in an excellent overall yield by a Barbier reaction between prenyl bromide and valeraldehyde,7 followed by oxidation of the resulting alcohol with iodoxybenzoic acid 8.…”

“…In our preliminary study,6 ketone 14 was converted into the corresponding vinyl bromide in three steps, and the coupling reaction effected by lithium–halogen exchange to form the required vinyl lithium intermediate. Diols 15 a and 15 b were produced in 71 % combined yield after hydrolysis of the TMS ether.…”

“…The structure of diol 15 b was determined by X‐ray analysis;6 this diastereomer possesses the configuration found in taxol at the C1, C2, and C8 stereocenter. The structure of compound 15 a was secured by X‐ray analysis of its triol derivative 16 a (Scheme ) 6…”

“…Here, we wish to report the synthesis of models of compound 5 , with no alkoxy group at C7 and no ketal function at C13. In addition to our preliminary study,6 the influence of the group protecting the C1,C2‐diol moiety has been thoroughly studied.…”

Large‐Ring Carbocycles

“…156 However, in an effort to prepare the C10-C11 cyclooctene system using the same strategy, the authors observed that only diene 367 underwent ring-closing metathesis suggesting a higher energy barrier to preorganzation for these substrates. 157 The authors went on to demonstrate that catalysts 3 (30 mol %), 4 (10 mol%), and 5 (5 mol %) could be successfully employed to produce the desired C10-C11 cyclooctene system (not shown) in modest yields (65%, 69%, and 72% yield, respectively). Granja and co-workers employed a ring-closing metathesis strategy in their synthesis of a novel steroid-like polycycle incorporating a 6,8,6-fused carbocyclic system.…”