合成路线1

The intermediate chiral 2-bromovinyl cyclohexane (XVIII) has been obtained as follows: The asymmetric epoxidation of divinyl carbinol (I) by means of L-(+)-diisopropyl tartrate, Ti(O-iPr)4 and tBu-OOH gives the epoxy alcohol (II), which is protected with p-methoxybenzyl bromide and NaH in THF to yield the benzyl ether (III). The condensation of (III) with the lithium derivative of ethyl acetate (IV) by means of BF3/Et2O, followed by hydrolysis with LiOH affords the 6-heptenoic acid (V). The methylation of the OH group of (V) with methyl iodide and NaH provides the corresponding methoxy acid (VI), which is esterified with diazomethane to give the methyl ester (VII). The debenzylation of (VII) by means of DDQ in dichloromethane yields the hydroxyester (VIII), which is cyclized by means of Ts-OH in refluxing benzene to afford the chiral tetrahydropyranone (IX). The Claisen rearrangement of the lactone (IX) catalyzed by Tbdms-OTf in refluxing toluene provides the cyclohexane carboxylic acid (X), which is esterified with diazomethane to give the methyl ester (XI). The hydroboration of the double bond of (XI) with BH3/THF, followed by protection with Tips-OTf yield the silyl ether (XII). The reduction of the ester group of (XII) with LiAlH4 affords the carbinol (XIII), which is treated with the Swern oxidant to afford the carbaldehyde (XIV). The condensation of (XIV) with the diazophosphonate (XV) and tBuOK provides the ethynyl cyclohexane (XVI), which is methylated with methyl iodide and BuLi in THF to give the propynyl cyclohexane (XVII). Finally, this compound is brominated by means of NBS and Cp2ZrHCl to yield the target intermediate, the chiral 2-bromovinyl cyclohexane (XVIII).