Electronic Tuning of Fischer Carbene Complexes in the Preparation of Bicyclo[3.1.1]heptanones as Taxane A-ring Synthons

✍ Scribed by Weiqin Jiang; Michael J Fuertes; William D Wulff

• Book ID: 104209845
• Publisher: Elsevier Science
• Year: 2000
• Tongue: French
• Weight: 334 KB
• Volume: 56
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(99)01101-1

✦ Synopsis

AbstractÐA synthetic route to taxol and other Taxus diterpenes is described which employs as a key step the reaction between a Fischer carbene complex and a 1,6 enyne to construct 1-substituted-7,7-dimethyl-2-methylenebicyclo[3.1.1]heptan-6-ones. It was found that the reaction between complex 2 and 7-methyl-3-methylene-6-octen-1-yne (dienyne 30) yielded a mixture of bicyclo[3.1.1]heptanone 35 and cyclobutenone 36, the latter possibly arising from the migration of the chromium fragment from an electron-rich alkene to a less electron-rich alkene in the vinyl carbene complex intermediate (i.e. 40±42). On this basis, it was expected that bicycloheptanone yields would increase with increasing electron de®ciency in the intermediate 40 since this should lead to more competitive CO insertion. This was observed with a series of electronically modi®ed carbene complexes (45 and 48a±d). The more electron de®cient complexes gave good yields of bicycloheptanones, thus providing an ef®cient means for preparing taxane A-ring synthons.