pi-facial diastereoselection in the 1,2-addition of allylmetal reagents to 2-methoxycyclohexanone and tetrahydrofuranspiro-(2-cyclohexanone)

The stereochemical course of the 1,2-addition of several allylmetal reagents and of the Normant Grignard [ClMgO(CH2)(3)MgCl] to 2-methoxycyclohexanone and tetrahydrofuranspiro-(2-cyclohexanone) has been determined. In four of the six substrates examined, a 4-tert-butyl group is present to serve as a conformational anchor. The neighboring methoxyl substituent is shown to be capable of engaging effectively in chelation, although special circumstances can dictate otherwise. Experiments involving the allylindium reagent as the nucleophile in aqueous solution reveal that the presence of water does not inhibit the operation of chelation control, which often exceeds that attainable with the corresponding magnesium, cerium, and chromium reagents in anhydrous media by significant margins. The extent to which cooperation between the alpha-oxygen atom and control of pi-facial nucleophilic attack reaches a maximum (>97:3) is when the system is conformationally rigid and the 2-methoxy and 4-tert-butyl groups are both oriented equatorially. As the steric bulk about the oxygen is increased, the ability of indium to anchor onto the heteroatom is significantly lessened. The results of competition experiments are detailed. The prospects for useful synthetic applications of indium catalysis in water or water/THF mixtures appear to be very promising.