Carbanions a-sulfinyl

The a-sulfinyl carbanion attacks a-halocarboxylic acid esters at the carboxylic carbon atom, not at the a-carbon atom, and the corresponding ketones are obtained slereoselectively in high yield62. 

TABLE 11. Relative stabilities derived from H/D exchange reactions of a-sulfinyl carbanions... 

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. 

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of / -hydroxyketones from /J-sulfinylhydrazones 166211-214, of /3, /l -dihydroxyketones from 3-(p-tolylsulfinyl-methyl)-A2-methylisoxalinones 167215, of /1-hydroxyacids from 2-(p-tolylsulfinylmethyl)oxazolines 168216 and of /J-hydroxyesters from ethyl-p-tolylsulfinyl-W-methoxyacetamide 169217. 

Asymmetric synthesis using a-sulfinyl carbanions and / -unsaturated sulfoxides... 

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

Stable conformation for CHjSOH and CH3SOCH3 may be illustrated by the Newman projections of 32 and 33, while those of the carbanions are given by 34 and 35. This means that the a-sulfinyl carbanion is nonplanar and the Hj proton on the opposite side of the S—O bond is removed preferentially. The same calculation also indicated that conformer 32 is 16.5kcalmol and 17.2kcalmol" more stable than conformers 29 and 31, respectively . This new MO calculation thus contradicts the earlier suggestion that the most stable carbanionic conformer is 29 but emphasizes the importance of the contribution of 3d-orbitals for the stabilization of a-sulfinyl carbanions. 

Table 11 summarizes the relative conformation stabilities of various sulfinyl carbanions, based on the H/D exchange rates of the corresponding sulfinyl compounds 36-39. The results are in good agreement with the order of stabilities obtained from the MO calculations using the 3-21G basis set. This is remarkable, since the calculation did not take into consideration the solvent effect, despite the strong unsymmetrical solvation on the a-sulfinyl carbanion. 

Accordingly, there have been numerous studies on the stereochemistry of these a-sulfinyl carbanions . Representative data on the reactions of a-lithiosulfoxides derived from benzyl sulfoxides with some electrophiles are listed in Table 13. Although the stereochemistry depends on the substituent on the sulfinyl function, the diastereomeric ratio remains the same regardless of the electrophile used for each sulfoxide. 

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

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of -hydroxyketones from -sulfinylhydrazones of -dihydroxyketones from 3-(p-tolylsulfmyl-... 

The Michael addition of nucleophiles to a, -unsaturated sulfoxides creates initially a-sulfinyl carbanions by nucleophilic attack on the /S-carbon atom. Russell and Becker found that treatment of a mixture of diphenylmethane and anisaldehyde with potassium t-butoxide in DMSO gave at first the condensation product 170, which upon Michael addition afforded the final product 171. 

This chapter, however, does not deal with above-mentioned reactions of sulfoxides. Rather it is limited to asymmetric synthesis using a-sulfinyl carbanions and -unsaturated sulfoxides, specifically in which the stereogenic sulfoxide sulfur atom is enantiomerically pure. Therefore reactions of racemic sulfoxides are for the most part excluded from this review. For more general discussions, the reader is referred to other chapters in this volume and to other reviews on the chemistry of sulfoxides. Especially useful are the reviews by Johnson and Sharp and by Mislow in the late 1960s and by Oae and by Nudelman as well as a book by Block . A review by Cinquini, Cozzi and Montanari" through mid-1983 summarizes the chemistry and stereochemistry of optically active sulfoxides. This chapter emphasizes results reported from 1984 through mid-1986. 

Four-carbon annulation onto the caprolactam ring is accomplished by intramolecular nucleophilic addition of an a-sulfinyl carbanion to the carbonyl group in order to obtain sulfinoenamine 110 (03OBC3495). Moreover, thiocaprolactam (111a) and its Michael adduct 111b, via... 

Formation of a-Sulfinyl carbanions has been widely investigated17. Several bases were found to be suitable for the generation of these species, e.g., methyllithium and lithium diisopropyl-amide. Butyllithium and rm-butyllithium, however, must be used with caution since they can cause cleavage of the carbon sulfur bond, resulting in an exchange of the ligand at sulfur by a nucleophilic displacement28-29. This method has been used for the preparation of optically active alkyl methyl sulfoxides 28. 

Generation of a-sulfinyl carbanions can also occur in 1 -alkenyl sulfoxides and can be easily achieved by using such bases as lithium diisopropylamide30 32, /erf-butyllithium33 and butyl-lithium (for allenyl sulfoxides)34. 

The anion crystallizes as a dimer with bonding occurring via a Li20, four-membered ring. Two further coordination sites on each Li4 arc occupied by the TMF.DA N-atoms. This result is fully consistent with the four-center chelate structure which was proposed before for a-lithio sulfoxides 39- 40 and believed to be responsible for the planar configuration of the anionic carbon atom, This chelation discriminates between the two diastereotopic faces and for this reason a-sulfinyl carbanions react with electrophiles in a highly stereoselective manner (see the following section). 

Therefore, it is clear that protonation with retention will occur cis to oxygen but alkylation with inversion will place the new C-C bond trans to oxygen. Interestingly, when a second lithium cation is allowed to complex to the sulfinyl oxygen, the intermolecular Li—O bond has the dominant structural effect. In the presence of excess lithium ions, the stereochemical behavior of an a-lithio sulfoxide should, therefore, resemble that of an a-sulfinyl carbanion. 

The lithium salts of the a-sulfinyl carbanions have been alkylated by alkylating reagents other than iodomethane. For example, alkylation of ( + )-l-[( )-ethylsulfinyl]-4-methylbenzene with lithium bromoacetate in the presence of lithium diisopropylamide gave (5)-3-[(2 )-4-methylphen-ylsulfinyl]butanoic (7) acid as the major product (d.r. 8 2) which was isolated as a pure solid in 58% yield55. 

The choice of the base and the solvent is crucial for the yield of a-sulfinyl carbanion alkylation. A high diastereoselection (80%) was observed in the alkylation of an a-sulfinyl carbanion with a-bromoacrylate56. In this ease the choice of the base appears to be decisive the highest asymmetric induction is found when the metalation is carried out using highly hindered bases, e.g., lithium tetramethylpiperidide. An interesting asymmetric synthesis of chiral 5-alkyl(or phenyl)dihydro-3-methylene-2(3f/)-furanoncs is based on this reaction56. 

From the synthetic point of view, the most important a-sulfinyl carbanions appear to be those derived from dithioacetal S-oxides which are a synthon for acyl anions65. However, the yields of the alkylation reaction were found to be low. In spite of the fact that dithiane S-oxides have been intensively studied66 63, their synthetic applications are limited,... 

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