STEREOSELECTIVE SYNTHESIS OF (+/-)-VEADEIROIC ACID AND (+/-)-VEADEIROL BY CYCLIZATION OF A 2-(2-ARYLETHYL)-1,3,3-TRIMETHYLCYCLOHEXYL CATION - MECHANISM AND STEREOCHEMISTRY OF RELATED CYCLOALKYLATION REACTIONS

(+/-)-Veadeiroic acid 1 and (+/-)-veadeirol 2, two new cleistanthoid diterpenes, have been synthesized by stereoselective cyclisation of the carbocation 5 generated from the cyclohexanol 26. The latter is prepared from 2-ethyl-3-formylbenzoic acid (with CO2H masked as an oxazoline ring) by successive reaction with 3-methylbutan-2-one, Robinson annulation, and reduction of the styrylcyclohexenone 24. The stereochemistry of cycloalkylation of the carbocations A, which ranges from 100% trans to 50:50 cis-trans ring-fusion as a non-activated aryl ring becomes activated by substitution, has been rationalised on the basis of the shift of the rate-determining step from the formation of sigma-complexes to that of pi-complexes and the steric interactions therein.