Science of Synthesis

Ogura, K., Science of Synthesis, (2007) 30, 462.

As mentioned in Section ‌30.3.6.1.8.1‌, 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 6 M 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, 2.2–2.8 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 2.0–2.5 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 = 2–4) 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 4.5 M 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].

‌Meeeee 88‌ Meeeeeeee ee Meeeee (Meeeeeeeeeeeee)eeeeee Meeeeeeee eeee α,ω-Meeeeeeeeeeeee ee α,ω-Mee(eeeeeeee)eeeeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 88‌

Meee (M)-8,8-eeeeeeeeeee-8-eee (‌88M‌) ee eeeeeee eeee 8.8 eeeeeeeeeee ee eee eeeeeee eeeeeeeeee ee eeeeee (eeeeeeeeeeeeee)eeeeee eeeeeeeee ee eeeeeeeeeeeeeee eeee eeeeeeeee ee −88°M eee eeee ee eeee eeeeeeeeeee (ee. Meeeee M ee ‌Meeeee 88‌), 8-(eeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeeeeeeeeeee (‌88‌) ee eeeeeeee ee 88% eeeee. Meeeeeeeee eeeeeeeeee ee eeee eeeeeeee eeeee eeeeeeeee-8-eeeee (‌88‌). Me eee eeeee eeee, eeeeeee eeeeeeeee ee (M)-8,8-eeeeeeeeeee-8-eee (‌88M‌) eeeee 8-(eeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)-8-eeeeeeeeeeeeeeeee (‌88‌) ee 88% eeeee (‌Meeeee 88‌). Meeeeeeee eeeeeeeeee ee eeeeeeeee eeeeeeeee eeeeeeee eee ee eeeeeeee ee eee eeee eeeeee. Mee eeee eeeeeeee, ee eeeee eee eeeeeee ‌88‌ eee ‌88‌ eee eeeeeeeee ee eeee-eeeeeee eeeeeeeeeee, eee eeee eeeee ee ‌Meeeee 88‌.[‌88‌–‌88‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeeeeeee eee Meeeeee Meeeeeeee[‌88‌–‌88‌]

Mee ee eee eeee eeeeeeeee eeeeeee eee eeeeeeeee eeeeeeeeeeeeee eeee eeeeeee e Meeeee M eeee eeeeeeeee (ee. ‌Meeeee 88‌) eeeeeeee eeee eeeeee (eeeeeeeeeeeeee)eeeeee eeeeeeeee (‌8‌). Meee, eeeeeee 8,8-eeeeeeeeeeeeee eee eeeeeee eeee eee eeeeeee eeeeeeeeee ee eee eeeeeeeee ‌8‌ ee eeeeeeeeeeeeeee, eeeee ee −88°M, eee eeee ee eeee eeeeeeeeeee, ee eeee eee eeeeeeeeeeeee 8-(eeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeeeeeeeeeee ‌88‌ ee eeee eeeeee. Meee eeeeeeeeee ee eeeee eeeeeeee eeeeeee eee eeeeeeeeeeeee eeeeeeeeeeeeee ‌88‌ (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

8-(Meeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeeeeeeeeee (‌88‌, e = 8); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeeeee eeeeeee eeeeeee ee eeeeeeee ee eee eee ee eeeeeee eeee eeeeeeee eee ee eeeeee eeeeeeeeeee ee eee eeeeeee.

Meeeee M: Meeeee (eeeeeeeeeeeeee)eeeeee eeeeeeeee (‌8‌; 8.88 e, 8.88 eeee) eee eeeee ee e eeeeeeeeee ee MM (8.88 e, 88.8 eeee) ee MMM (88 eM) eeeeeeeee eeeee ee eeeee eeeeeeeeee eee eee eeeeeeeee eeeeeee eee eeeeeee eee 8 e eeee eee eeeeeee. 8,8-Meeeeeeeeeeeee (8.88 e, 88.8 eeee) eee eeeee eeeeeeee eeee 88 eee eee eee eeeeeee eee eeeeeee eee eeeeeee 8 e eeee eee eeeeeee, eee eeee ee ee eee 88 e. MM8Me8 (888 eM) eee eeeee eee eee eeeeeeeee eeeee eeee eee eeeeeeeee eee eeeeeeee eee. Mee eeeeeeee eee eeeeeeeeee eee eee eeeeeee eee eeeeeeeeeeeeeee (eeeeee eee) ee eeee ee eee; eeeee: 8.88 e (88%).

8-(Meeeeeeee)-8-(eeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeeeeeeeeee (‌88‌, M8 = M; M8 = MMe); Meeeeee Meeeeeeee:[‌88‌]

8.88 M MeMe (88.8 eeee) ee eeeeee (88.8 eM) eee eeeee ee eeeeee (eeeeeeeeeeeeee)eeeeee eeeeeeeee (‌8‌; 8.88 e, 88.8 eeee) ee MMM (88 eM) ee −88°M eee eee eeeeeee eee eeeeeee eee 8 e. Me eee, eeee eeeeee ee −88°M, eee 8-(eeeeeeeee)-8,8-eeeeeeeeeeeeee (8.88 e, 88.8 eeee) eee eeeeeeeeee eeeeeeee eeeeee eee eeeeee ee 88 eee. Meeee eeeeeeee ee −88°M eee eeeeeeeeeeee ee ee eee 88.8 e, eee eeeeeee eee eeeeeee eeee MM8Me8 (888 eM). Me eee, eeee eeeeee eeee M8M, eeeee (MeMM8), eee eeeeeeeeee, eee eee eeeeeee eee eeeeeeeeeeeeeee (eeeeee eee) ee eeee eee eeeee eeeeeeee ee e eeeeeeeeeeeeee eeeeeee (8.8:8); eeeee: 8.88 e (88%).

8-(Meeeeeeee)eeeeeeeeeeeee (‌88‌, M8 = M; M8 = MMe); Meeeeee Meeeeeeee:[‌88‌]

Mee eeeeeeeeeeeeee eeeeeee (888 ee, 8.88 eeee) eeee eee eeeeeeeee eeeeeeeeee eee eeeeeeeee ee Me8M (88 eM) eee 88% MMM8 (8.88 eM) eee eeeee. Meeee eeeeeeee eeee eeeeeee ee ee eee 88 e, MeMMM8 eee MeMM8 eeee eeeee, eee eeeeeeee eee eeeeeeeee eee e eeeee. Mee eeeeeeeee eeeee eeee eee eeeeee eee eeeeeeee eee, eee eeeeeeee eee eeeeeeeeee, eee eee eeeeeee eee eeeeeeeeeeeeeee (eeeeee eee) ee eeee e eeeeeeeee eee; eeeee: 888 ee (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 88-8, 888.
• 8.Meeeee-Meee, (8888) M 88-8, 888.