Ketone, methyl cyclohexyl enolates

Ketones such as methyl cyclohexyl ketone 1284 react with DMSO/TCS 14, via their enol form, to give 21% of the chloroketone 1285 a and 63% of the a-methyl mercaptoketone 1286 [70]. Reaction of 1284 with DMSO/MesSiBr (TBS) 16 affords 85% of the bromo compound 1285 b and 12% hexahydrophenacyl bromide 1287 but no 1286 [71]. Whereas reaction of tra s-4-phenyl-3-buten-2-one (benzalacetone) 1288 with DMSO/TCS 14 gives 81% of the sulfonium salt 1289 [70], the y9-dicar-bonyl compound ethyl acetoacetate furnishes 69% of 1290 [70]. In contrast with DMSO/TCS 14, the combination DMSO/TBS 16 effects selective monobromina-tion of y9-dicarbonyl compounds [71] (Scheme 8.28). 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

A first hint comes from the fact that the carbonyl carbon of the acyl substituent in IV may be the a carbon of the enol ether moiety in I. In fact, the vinyl ether would be converted into a methyl ketone by breakage of the bond between the acetal carbon and the endocyclic oxygen. In that case, the resulting oxycarbenium ion would serve as a linking position for the carbocyclization that eventually affords the cyclohexyl ring of IV. 

Masamune and coworkers have examined the facial selectivity of the (Z)-lithium enolates of 3-penta-none and ethyl cyclohexyl ketone with a series of P-alkoxy aldehydes having stereocenters at both the a-and p-position (equation 110 Table 18). In the six-mernbered chelate, the methyl and R groups are on the same side of the ring, and it may be seen from the data in Table 18 that the nature of R influences the facial preference of the chiral aldehyde. Another example of this effect is seen in equation (54). 

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