1,3-Dithiane → 2-Bromo-2-methylcyclohexanone

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Aldehydes 4B and 4C were synthesized by a modification of the procedure reported by Corey and Erickson (Corey, E. J. and Erickson, B. W. (1971) “Oxidative hydrolysis of 1,3-dithiane derivatives to carbonyl compounds using N-halosuccimide reagent,” J. Org. Chem. 36(3):553-560) which is depicted in Scheme 4. Bromination of 2-methylcyclohexanone (7) with 1 equivalent of N-bromosuccinimide (Rinne, W. W. et al., “New methods of preparation of 2-methylcyclohexen-1-one,” J. Am. Chem. Soc. (1950) 72:5759-5760) in refluxing CCl4 for 12 hours gave quantitative yield of 2-bromo-2-methylcyclohexanone. Dehydrobromination of this bromide with three equivalents of Li2CO3 and three equivalents of LiBr in N,N-dimethylformamide (DMF) (Stotter, P. L. and Hill, K. A., “α Halocarbonyl Compounds. II. A Position-Specific Preparation of α-Bromo Ketones by Bromination of Lithium Enolates. A Position-Specific Introduction of α, β-Unsaturation into Unsymmetrical Ketones,” J. Org. Chem. (1973) 38:2576-2578) at 130° C. for 3 h provided a 72% yield of 2-methyl-2-cyclohexen-1-one (8). A 1,2-addition reaction of 8 with 1.5 equivalents of lithiated 1,3-dithiane [generated from 1,3-dithiane (9) with n-BuLi in THF] in THF at −10° C. to give a 96% yield of the 1,2-adduct 10. Rearrangement of 10 with 1% sulfuric acid in p-dioxane (52% yield) followed by removal of the dithiane protecting group of the resulting alcohol, 11, with N-chlorosuccinimide (NCS) and silver nitrate in acetonitrile-water gave aldehyde 4B (50% yield). Alcohol 4B is not a stable compound and decomposes upon standing at room temperature in a few days. A more stable material, 4C, was synthesized in a better yield from the rearrangement reaction of 10 in formic acid-THF in the presence of catalytic amount of p-toluenesulfonic acid (70% yield) followed by removal of the dithiane moiety with NCS-AgNO3 (59% yield) (Scheme 4). In the formic acid rearrangement reaction, besides the desired product, 1-[2-(1,3-dithianyl)]-3-formyloxy-2-methyl-1-cyclohexene, 9% yield of 3-[2-(1,3-dithianyl)]-2-methyl-2-cyclohexen-1-ol (11) was isolated.

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