We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3 + 3]) promising the synthesis of a cyclohexane-1,3-dione derivatives from nonactivated simple ketones and enoates and evaluated its potential in modern organic synthesis. Twenty to thirty examples were demonstrated to be effective. The reactions exhibited remarkable regioselectivity with the Michael addition proceeding through nucleophilic attack by the more hindered site of the ketones without exception. The subsequent Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. The MC-[3 + 3] process described is useful for the synthesis of Taxol A-ring synthons in multigram quantities and for the synthesis of other six-membered carbocyclic compounds. A number of control experiments have been conducted to provide strong support for the mechanism of this MC-[3 + 3].

cyclohexane derivativescyclohexane derivatives Q 0040 -078Revisiting [3 + 3] Route to 1,3-Cyclohexanedione Frameworks: Hidden Aspect of Thermodynamically Controlled Enolates.-Traditional Michael-Claisen [3 + 3] process allows effective and regioselective formation of a wide variety of 1,3-cyclohexanediones from nonactivated simple ketones and α,β-unsaturated esters. This process can be applied to the synthesis of the Taxol A-ring synthon (IX) and other six-membered carbocyclic compounds. Additionally, preparation of cyclohexenone derivatives by aldol condensation/Michael addition/aldol condensation is described.