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Please login or sign up for a free trial to access the full content. Variation 2: Dialkylation with Alkyl Halides

DOI: 10.1055/sos-SD-030-00335

Ogura, K.Science of Synthesis, (200730462.

As mentioned in Section, methyl (methylsulfanyl)methyl sulfoxide (2) undergoes monoalkylation on treatment with an alkyl halide and sodium hydride. When 2 molar equivalents of an alkyl halide and 2 equivalents of sodium hydride are employed, dialkylation occurs, but the temperature of the reaction has to be raised above that required for monoalkylation. The dialkylated products 63 are sensitive to acids, so that the corresponding symmetrical ketones 64 are readily obtained from them by hydrolysis with 6M hydrochloric acid (Scheme 27).[‌52‌,‌53‌] This reaction sequence can be extended to the syntheses of cyclic ketones 67 through the reactions of α,ω-dibromoalkanes 65 (X=Br) or α,ω-bis(tosyloxy)alkanes 65 (X=OTs) with methyl (methylsulfanyl)methyl sulfoxide. 1-(Methylsulfanyl)-1-(methylsulfinyl)cycloalkanes 66 are formed initially, and then subjected to acid hydrolysis (Scheme 27).[‌54‌] For the first step, two procedures (Methods A or B) can be employed; in Method A, 2.22.8 equivalents of potassium hydride in tetrahydrofuran are used, starting at a temperature of between 15 and 0°C, and then at room temperature. Method B, on the other hand, uses 2.02.5 equivalents of the lithium derivative of (methylsulfanyl)methyl sulfoxide in tetrahydrofuran at between 60 and 0°C, before the mixture is allowed to warm to room temperature. Both procedures give the S,S-acetal S-oxides 66 (n=24) of cyclobutanone, cyclopentanone, and cyclohexanone in fair to good yields. However, 1-(methylsulfanyl)-1-(methylsulfinyl)cyclopropane (66, n=1) is produced in 78% yield only when Method B is applied to 1,2-bis(tosyloxy)ethane (65, n=1; X=OTs). As in the monoalkylated series, acid hydrolysis of the 1-(methylsulfanyl)-1-(methylsulfinyl)cycloalkanes 66 (n=3, 4) with a small amount of 4.5M sulfuric acid in diethyl ether, or ethanol, takes place smoothly at room temperature to give cyclopentanone (92%) or cyclohexanone (88%), respectively [examples of the hydrolyses of some 1-(methylsulfanyl)-1-(methylsulfinyl)cyclobutanes leading to cyclobutanones are shown in Scheme 27].

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