B Ring Elaboration
The second part of the B ring synthesis (Scheme 5) was concerned with correct chemistry for the newly formed ethylene bridge connecting the A and C rings. After Scheme 4, this bridge contained an exocyclic methylene group, but in the ultimate taxol molecule this bridge is an α-acylketone. The required conversion was accomplished in the next 10 steps.
The tert-butylsilyl protecting group in diene 39 was not compatible in later reactions and was replaced by a triethylsilyl. Epoxidation of diene 40 with meta-chloroperoxybenzoic acid gave the oxirane ring. This served solely as a protecting group in preparation for modifications of the exocyclic alkene. In the next two steps, the benzyl protecting group in compound 41 was replaced by an acetyl group. Carbonate ester 43 was opened by reaction with phenyllithium to give alcohol 44. The cleavage of the exocyclic double bond was difficult and accomplished only with forcing conditions (19 equivalents of osmium textroxide, 105 °C, 24 hours) by the putative osmate ester (45). Subsequent oxidative cleavage with lead tetraacetate gave ketone 46. The epoxide protecting group was removed with samarium (II) iodide to give α-ß-unsaturated ketone 47. The enolate was formed by the reaction of ketone 47 with potassium tert-butoxide, and subsequent reaction with phenylseleninic anhydride followed by acylation gave α-acylketone 49.
| Scheme 5 |
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Read more about this topic: Danishefsky Taxol Total Synthesis
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