N,S-Dimethyl-S-phenylsulfoximine1

(±)

[30004-67-2]  · C8H11NOS  · N,S-Dimethyl-S-phenylsulfoximine  · (MW 169.27) (R)-(-)

[80482-67-3] (S)-(+)

[33993-53-2]

(chiral sulfone analog useful in methylenation of carbonyl compounds1,2 and resolution of ketones1,3)

Physical Data: oil; [a]D 184° (c 3, acetone); pKa (DMSO) ~32.1

Solubility: sparingly sol water; sol dil acid, aq CuII; highly sol THF, alcohols, etc.

Preparative Methods: methyl phenyl sulfoxide is treated with Hydrazoic Acid (generated by addition of sulfuric acid to a slurry of sodium azide) in chloroform maintained at 45 °C to produce S-methyl-S-phenylsulfoximine.4,5 The latter can be readily resolved using 10-Camphorsulfonic Acid; from the (+)-acid the salt of (+)-(S)-S-methyl-S-phenylsulfoximine is obtained pure by recrystallization.6,7 The Clarke-Eschweiler procedure using Formaldehyde and Formic Acid provides an effective method for conversion of the N-H sulfoximine to the title compound.7

Handling, Storage, and Precautions: due care should be taken in the synthetic step using hydrazoic acid. N,S-Dimethyl-S-phenylsulfoximine is apparently of low toxicity. The compound, which is stable to acids and bases, as well as to most oxidizing and reducing conditions, maintains chemical and enantiopurity on long term storage.

N,S-Dimethyl-S-phenylsulfoximine is rapidly deprotonated with n-Butyllithium in THF at 0 °C; the deprotonation can be conveniently monitored by use of a trace of Ph3CH as an indicator. The lithio reagent is an excellent nucleophile, particularly with respect to addition to carbonyl compounds (eq 1). Addition occurs in high yields with a wide range of carbonyl compounds in the temperature range of -78 to 25 °C. The reaction is often reversible in the cases of hindered carbonyl compounds. The major side reaction is enolization. Both the enolization and reversibility problems can be circumvented by conducting the addition and subsequent quenching at low temperatures; in this manner, b-hydroxysulfoximines are obtained in high yield.3 b-Hydroxysulfoximines are thermally unstable and revert to starting carbonyl compounds and sulfoximine in the temperature range 80-120 °C; the reversion is the basis for a ketone resolution method. The addition of optically pure sulfoximine (as its lithio derivative) to (±)-ketones which exhibit very high or complete diastereofacial selectivity results in the formation of two diastereomers which are generally responsive to separation by silica gel chromatography. Thermolysis of the separated diastereomers results in resolution of the ketone (eq 2).3 Treatment of the separated diastereomers with Raney Nickel results in optically pure methyl carbinols (at the expense of destruction of the chiral S center).8 The ketone resolution technique has reciprocity and a number of optically pure ketones, particularly (-)-menthone, have been found useful to resolve N,S-dimethyl-S-phenylsulfoximine.3

b-Hydroxysulfoximines undergo reductive elimination to yield alkenes upon treatment with Aluminum Amalgam in a mixture of THF, water, and acetic acid. In the case of conjugated enones and dienones the addition of the lithiosulfoximine occurs at the carbonyl; when the resulting adducts are reduced, dienes and trienes, respectively, are produced (eq 3).9 The sulfoximine method often works where methylenation with triphenylphosphonium methylide fails10 (eq 4).11

The combination of the chromatographic separation of enantiopure b-hydroxysulfoximine diastereomers and reductive elimination results in a method of ketone methylenation with optical resolution. The technique is illustrated in the synthesis of the ginseng sesquiterpene (-)-b-panasinsene and its enantiomer (eq 5).12 The addition of the enantiopure lithiosulfoximine to prochiral enones or the diastereoface selective addition to racemic enones results in the formation of two diastereomeric adducts. The hydroxy group in these adducts can be used to direct the Simmons-Smith cyclopropanation (eqs 6 and 7).13 Catalytic osmylation of such adducts is directed by the anti effect of the hydroxy augmented by chelation by the methylimino group (eq 7).14

Ylides derived from the salts obtained by N,N-dialkylation of sulfoximines and anions derived from N-tosylsulfoximines are useful reagents for the synthesis of epoxides or cyclopropanes from aldehydes and ketones or enones.1

Related Reagents.

Dibromomethane-Zinc-Titanium(IV) Chloride; Methylenetriphenylphosphorane.


1. Johnson, C. R. Aldrichim. Acta 1985, 18, 2.
2. Johnson, C. R.; Kirchhoff, R. A. JACS 1979, 101, 3602.
3. Johnson, C. R.; Zeller, J. R. T 1984, 40, 1225.
4. Whitehead, J. K.; Bentley, H. R. JCS 1952, 1572.
5. Johnson, C. R.; Haake, M.; Schroeck, C. W. JACS 1970, 92, 6594.
6. Fusco, R.; Tenconi, F. Chim. Ind. (Milan) 1965, 47, 61 (CA 1965, 62, 10 357h).
7. Johnson, C. R.; Schroeck, C. W.; Shanklin, J. R. JACS 1973, 95, 7424.
8. Johnson, C. R.; Stark, C. J. JOC 1982, 47, 1193.
9. Johnson, C. R.; Shanklin, J. R.; Kirchhoff, R. A. JACS 1973, 95, 6462.
10. Ansell, M. F.; Mason, J. S.; Caton, M. P. L. JCS(PI) 1984, 1061.
11. Bundy, G. L. TL 1975, 1957.
12. Johnson, C. R.; Meanwell, N. A. JACS 1981, 103, 7667.
13. Johnson, C. R.; Barbachyn, M. R. JACS 1982, 104, 4290. (b) Barbachyn, M. R.; Johnson, C. R.; Glick, M. D. JOC 1984, 49, 2726.
14. Johnson, C. R.; Barbachyn, M. R. JACS 1984, 106, 2459.

Carl R. Johnson

Wayne State University, Detroit, MI, USA



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