| Research Abstract |
We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3+3]) promising for the synthesis of a cyclohexane-1, 3-dione derivatives from non-activated simple ketones and enoates, and evaluated its potential in modern organic synthesis. The reaction conditions employing the ketones (1.2 equiv), enoate (1.0 equiv), and t-BuOK (1.2 equiv) in THF as a solvent at temperature range of 0℃ to 40℃ have been established. Twenty to thirty examples were demonstrated to be effective under such conditions including the synthesis of a taxol A, C-ring synthons available in multi-gram quantities. The reactions exhibited remarkable regioselectivity that the Michael addition proceeded through nucleophilic attack by more hindered site of the ketones without exceptions, which, in turn, means that Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. In addition, taking advantages of the MC- [3+3] process, a few useful methods for the synthesis of six membered carbocyclic compounds have also been developed. A number of control experiments have been conducted to provide strong supporting information for the mechanism of this MC-[3+3] process.
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