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Sulfur reagents in organic - Metzner P.

Metzner P., Thuiller A. Sulfur reagents in organic - Academic press, 1994. - 200 p.
Download (direct link): sulfarreagents1994.djvu
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4.2.8 Uses of sulfoxides
Most of the applications of sulfoxides in synthesis make use of the reactions of sulfur-stabilized carbanions with electrophiles [385, 386]. Thus the methylsulfinyl methylene carbanion, conveniently generated through the interaction of sodium hydride with DMSO [387], is a powerful nucleophile.
Me Me

CHjj Na
It is also a strong base and an excellent reagent for the generation of ylides (Wittig and related reagents, for example). It reacts with esters to yield anions of p-ketosulfoxides. As the methylsulfinyl group of these compounds is easily removed by an aluminum amalgam, a useful synthesis of ketones is at hand.
r1 OMe+Me''

ii) Al(Hg) /H2C
AI(Hg) /^
Many other uses of a-sulfinyl carbanions are found in the literature, and in the recent past the trend has been to take advantage of the chirality of the sulfoxide group in asymmetric synthesis. Various ways of preparation of enantiopure sulfoxides have been devised (see Section 2.6.2); the carbanions derived from these compounds were added to carbonyl compounds, nitriles, imines or Michael acceptors to yield, ultimately, with high e.e. values, optically active alcohols, amines, ethers, epoxides, lactones, after elimination at an appropriate stage of the sulfoxide group. Such an elimination could be achieved by pyrolysis, Raney nickel or nickel boride desulfurization, reduction, or displacement of the C-S bond, as in the lactone synthesis reported by Casey [388].
Natural products were often the target of such asymmetric bond formation mediated by optically active sulfoxides [86-95,389].
The experimental procedures given below for the synthesis of both enantiomers of 4-substituted butenolides [390] emphasize some aspects of the reactivity of chiral p-ketosulfoxides; their reduction with hydrides can
t-Bu '"S'4|
U) /T55t_^-COOMe THF. -78C iii) H20
i) LDA, THF. -78C
stereoselectivity >10:1
afford both epimeric alcohols with high enantioselectivity depending on the experimental conditions used [391]. For an interpretation of the stereochemical outcome of the hydride reduction, see [392].
0 LDA }
ATob'^s'------V J
R = t-Bu, CgH17, CgHn
(R,R)-( 3)
^4 la) i(R - t-Bu)
0 n-BuU ii) ICHjOOONa ffi) TsOH
iv) EtjN

(SHla) (R-t-Bu)
To a solution of LDA (16mmol) in THF (40ml) at -30C was added dropwise (+)-(/?)-methyl />-tolyl sulfoxide (8 mmol), prepared according to [91], in the THF (40ml). The temperature was allowed to reach 0C and then brought to -40C. A solution of ester (12 mmol) in THF (20 mmol) was added dropwise. The temperature was allowed to reach room temperature and then the reaction mixture was heated under reflux for 4h. The reaction mixture was treated with saturated ammonium chloride solution (20 ml). The organic layer was separated and the aqueous solution acidified with 10% HC1 to pH 3-4 and extracted with dichloromethane (3X20ml). After evaporation of the solvent, the residue was purified by chromatography on silica gel (ether/hexane 60:40), affording (2a) (R = t-Bu), yield 84%, m.p. 110-111C, [a]D = +181 ( 1 in CHC13).
From [390] with permission.
Reduction of ketosulfoxides with DIBAH
To a solution of p-ketosulfoxide (2 mmol) in THF (20mmol) at -78C was added dropwise a 1 solution of DIBAH in hexane (2.2 ml, 2.2 mmol). After lh at -78C the reaction mixture was quenched by adding methanol | (20 ml). The solvent was evaporated and the residue was diluted with
j water and extracted with dichloromethane. The organic layer was washed
with a 5% sodium hydroxide solution, dried and evaporated. Chromatography on silica gel (ether/hexane 60:40) afforded (,5)-() in an 80% yield, m.p. 124-126C, diastereoisomeric ratio (R,S)I(R,R)>95:5 (NMR).
From 390] with permission.
Reduction of ketosulfoxides with DIBAH in the presence ofZnCl2
To a solution of p-ketosulfoxide (2 mmol) in THF (20 ml) was added anhydrous zinc chloride (1.1 eq) in solution in THF (20ml). After lh at room temperature the reaction mixture was cooled at -78C, treated with DIBAH and then worked up as above. The 3-hydroxysulfoxide (/?,i?)-(3a) was obtained in an 80% yield, m.p. 99-102cC, (R,R)/(R,S) = 95:5.
From [390] with permission.
Oxidation of (RS)- and (RR)-(3-hydroxysulfoxides to fSJ- and (R)-sulfones
This step was necessary for the following metallation and alkylation.
To a solution of {3-hydroxysulfoxide () (1 mmol) in dichloromethane (20 ml) at room temperature was added m-CPBA (1.1 eq) in dichloromethane (20ml). After 6h at room temperature, the reaction mixture was washed with a 5% aqueous solution of sodium hydroxide (20 ml) and then dried over sodium sulfate. After evaporation of the solvent the crude sulfone obtained in a 56-58% yield was used without further purification (m.p. 69C).
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