Sulfoxides carbanions from

III. REACTIONS OF ELECTROPHILES WITH a-SULFINYL CARBANIONS A. Carbanions from Alkyl Sulfoxides... 

No stereoselectivity was observed in the formation of a 1 1 diastereomeric mixture of 2-hydroxy-2-phenylethyl p-tolyl sulfoxide 145 from treatment of (R)-methyl p-tolyl sulfoxide 144 with lithium diethylamide . However, a considerable stereoselectivity was observed in the reaction of this carbanion with unsymmetrical, especially aromatic, ketones The carbanion derived from (R)-144 was found to add to N-benzylideneaniline stereoselectivity, affording only one diastereomer, i.e. (Rs,SJ-( + )-iV-phenyl-2-amino-2-phenyl p-tolyl sulfoxide, which upon treatment with Raney Ni afforded the corresponding optically pure amine . The reaction of the lithio-derivative of (-t-)-(S)-p-tolyl p-tolylthiomethyl sulfoxide 146 with benzaldehyde gave a mixture of 3 out of 4 possible isomers, i.e. (IS, 2S, 3R)-, (IS, 2R, 3R)- and (IS, 2S, 3S)-147 in a ratio of 55 30 15. Methylation of the diastereomeric mixture, reduction of the sulfinyl group and further hydrolysis gave (—)-(R)-2-methoxy-2-phenylacetaldehyde 148 in 70% e.e. This addition is considered to proceed through a six-membered cyclic transition state, formed by chelation with lithium, as shown below . ... 

An allylic sulfenate, like 199, is known to be in equilibrium with allylic sulfoxide, like 196, although its concentration is usually low . Various allylic sulfoxides can be prepared by treatment of allylic alcohols with arenesulfenyl chlorides . Evans and coworkers prepared various allylic alcohols by treating the corresponding allylic sulfoxides with trimethyl phosphite. For example, the carbanion from a cycloalkenyl sulfoxide 201 was readily alkylated at the a-position by treatment with alkyl halide. The resulting alkylated derivative 202 was then treated with trimethyl phosphite and 3-substituted cycloalkenol was obtained. Alkylation of acyclic allylic sulfoxide 204 gave... 

Intermolecular Nucleophilic Substitution with Heteroatom Nucleophiles. A patent issued in 1965 claims substitution for fluoride on fluorobenzene-Cr(CO)3 in dimethyl sulfoxide (DMSO) by a long list of nucleophiles including alkoxides (from simple alcohols, cholesterol, ethylene glycol, pinacol, and dihydroxyacetone), carboxylates, amines, and carbanions (from triphenyhnethane, indene, cyclohexanone, acetone, cyclopentadiene, phenylacetylene, acetic acid, and propiolic acid). In the reaction of methoxide with halobenzene-Cr(CO)3, the fluorobenzene complex is ca. 2000 times more reactive than the chlorobenzene complex. The difference is taken as evidence for a rate-limiting attack on the arene ligand followed by fast loss of halide the concentration of the cyclohexadienyl anion complex does not build up. In the reaction of fluorobenzene-Cr(CO)3 with amine nucleophiles, the coordinated aniline product appears rapidly at 25 °C, and a carefiil mechanistic study suggests that the loss of halide is now rate limiting. 

Unlike the carbanions from 1,3-dithians (see Chapter 3, p. 31 and Chapter 6, p. 90), the sulfinyl carbanions have the ability to undergo Michael additions (conjugate or 1,4-additions) with a,p-unsaturated carbonyl compounds. For instance, the secondary carbanion (44) from the ethyl ethylthiomethyl sulfoxide (45) may be sucessively reacted with ethyl iodide and 3-butene-2-one to give heptan-2,5-dione (46) via the tertiary carbanion (47), as shown in Scheme 23. The carbanion (47) may also be condensed with propyl bromide, and hydrolysis of the product yields ethyl propyl ketone (48) (Scheme 23). 

Nucleophilic substitution in electrophilic azine positions with nonstabi-lized carbanionic reagents is difficult. It has been found, however, that sulfoxides derived from an electrophilic azine position can react with a Grignard reagent with replacement of the sulfinyl group and carbosubstitu-tion [90AHC(48)1]. 

A sulfoxide derived from phenyl 3,4-0-isopropylidene-l-thio-P-L-fucoside, on treatment with MeLi followed by fcrt-BuLi, gave the glycosyl carbanion which added to iso-butanal to give p-C-glycosides as an epimeric pair, and the a-thioglycoside led to the a-C-glycosides. ... 

Recently developed trifluoromethylatmg agents capable of transferring the trifluoromethyl group as a cation to strongly nucleophilic compounds such as carbanions and sulfur and phosphorus nucleophiles are prepared from o-biphenyl trifluoromethyl sulfoxide [164] and are shown in equation 141... 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

A 1.5 to 2 M solution of methylsulfinyl carbanion in dimethyl sulfoxide is prepared under nitrogen as above from sodium hydride and dry dimethyl sulfoxide. An equal volume of dry tetrahydrofuran is added and the solution is cooled in an ice bath during the addition, with stirring, of the ester (0.5 equivalent for each 1 equivalent of carbanion neat if liquid, or dissolved in dry tetrahydrofuran if solid) over a period of several minutes. The ice bath is removed and stirring is continued for 30 minutes. The reaction mixture is then poured into three times its volume of water, acidified with aqueous hydrochloric acid to a pH of 3-4 (pH paper), and thoroughly extracted with chloroform. The combined extracts are washed three times with water, dried over anhydrous sodium sulfate, and evaporated to yield the jS-ketosulfoxide as a white or pale yellow crystalline solid. The crude product is triturated with cold ether or isopropyl ether and filtered to give the product in a good state of purity. 

Methylsulfinyl carbanion (dimsyl ion) is prepared from 0.10 mole of sodium hydride in 50 ml of dimethyl sulfoxide under a nitrogen atmosphere as described in Chapter 10, Section III. The solution is diluted by the addition of 50 ml of dry THF and a small amount (1-10 mg) of triphenylmethane is added to act as an indicator. (The red color produced by triphenylmethyl carbanion is discharged when the dimsylsodium is consumed.) Acetylene (purified as described in Chapter 14, Section I) is introduced into the system with stirring through a gas inlet tube until the formation of sodium acetylide is complete, as indicated by disappearance of the red color. The gas inlet tube is replaced by a dropping funnel and a solution of 0.10 mole of the substrate in 20 ml of dry THF is added with stirring at room temperature over a period of about 1 hour. In the case of ethynylation of carbonyl compounds (given below), the solution is then cautiously treated with 6 g (0.11 mole) of ammonium chloride. The reaction mixture is then diluted with 500 ml of water, and the aqueous solution is extracted three times with 150-ml portions of ether. The ether solution is dried (sodium sulfate), the ether is removed (rotary evaporator), and the residue is fractionally distilled under reduced pressure to yield the ethynyl alcohol. 

An a-phosphoryl sulfoxide (4) has also been prepared by the reaction of the appropriate carbanion with sulfinate ester 19 (see also Section II.A.l)18. Ugi and coworkers prepared (S, R, S)-65 by reaction of (R, R)-64 with ester 19. The (S, S, R) diastereomer was prepared from (S, S)-6496. 

Significantly, (a) a-sulfonyl carbanions of thiirane dioxides, generated from the latter in the presence of strong bases such as potassium t-butoxide19 and alkoxide ions99, do epimerize to relieve steric repulsion between substituents as in 42 above and (b) the a-hydrogen in aryl-substituted three-membered sulfoxides (e.g. 46c) are sufficiently acidic to... 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfinyl carbanion upon treatment with sodium hydride114 and that this conjugate base of DMSO reacts with various electrophiles115. This finding has opened up various reactions with a-sulfmyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfmyl carbanions have become versatile synthetically useful reagents. 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

Carbanions formed from methyl methylthiomethyl sulfoxide 94 and ethyl ethylthio-methyl sulfoxide 95 were shown to be alkylated in excellent yields126,127. Treatment of 94 with rc-BuLi or KH and subsequent reaction with 1, n-dihalo- or bis(tosyloxy)alkane gave 3-, 4-, 5- and 6-membered 1-methylsulfmyl-l-methylthiocycloalkanes128"130. Upon hydrolyses of these products, the corresponding aldehydes and ketones are obtained. 

Optically pure (S)-benzyl methyl sulfoxide 139 can be converted to the corresponding a-lithio-derivative, which upon reaction with acetone gave a diastereomeric mixture (15 1) of the /S-hydroxysulfoxide 140. This addition reaction gave preferentially the product in which the configuration of the original carbanion is maintained. By this reaction, an optically active epoxy compound 142 was prepared from the cyclohexanone adduct 141181. Johnson and Schroeck188,189 succeeded in obtaining optically active styrene oxide by recrystallization of the condensation product of (+ )-(S)-n-butyl methyl sulfoxide 143 with benzaldehyde. 

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