Carbanions sulphur-stabilized

A 1,3-dithiane is a weak proton acid (pKa = 32) which can be deprotonated by strong bases such as n-butyllithium. The resulting carbanion is stabilized by the electron withdrawing effect of the two sulphur atoms. 

Sulphur.- As in previous years a large component of the sulphur chemistry reported has involved the reactions of sulphur-stabilized carbanions, an area that has been covered in Section 1. There has, however, been a good deal of activity in the synthesis and reactions of organosulphur compounds. 

Reactions ofThietan 1-Oxides, Tkietan 1,1-Dioxides, and Thiet 1,1-Dioxides involving Sulphur-stabilized Carbanions. Current interest in the stereochemistry of sulphur-stabilized carbanions has extended to thietan derivatives. Determination of the relative rate of base-catalysed racemiza-tion and of deuterium exchange for the thiet 1,1-dioxide derivative (89) in t-butyl alcohol-benzene indicated exchange with complete racemization, in accord with the enforced planar configuration (Figure 1)... 

Two general studies of sulphur-stabilized carbanions, employing n.m.r. and other... 

Cyclopropyl sulphones are readily synthesized by Grignard addition to 3-bromo- or 3-hydroxy-prop-1-enyl sulphones (Scheme 1). Ethyl 4-bromo-crotonate (10) undergoes a similar reaction with sulphur-stabilized carbanions to generate cyclopropanes e.g. (11)]. 

Another example of the addition of sulphur-stabilized carbanions to carbonyl groups is shown in the synthesis of a-sulphenylated aldehydes (179) from ketones (RR CO) and PhSCHOMe, and of vinyl sulphides or thioacetals from ketones and R C(SR)2 or C(SR)3, respectively. a-Sulphenylated aldehydes are also formed by electrolysis of vinyl sulphides as in the conversion of PhC=CSR to PhCH(SR )CHO. The carbanion PhSCH2 adds specifically to the ketone in (180) to provide methylenecyclohexenes by further elaboration as shown in Scheme 33. °... 

Methods previously used in the D-arabino-serles (Vol. 22, p.17-18) have been applied to the synthesis of derivatives (21) of 3-deoxy-D-lyxo-heptulosonic acid.22 Treatment of thioglycoside (22), prepared by acylation of a sulphur-stabilized C-1 carbanion as described previously for similar systems (Vol. 21, p.131-132), as indicated in Scheme 8 gave rise to the 4-acetamido-4-deoxy derivative (23) related to DAHP a [2,3]-sigmatropic rearrangement of an allyl sulphoxide is the key to the synthesis, and similar chemistry applied to (24) gave 3-deoxy-D-xylo-heptulosonic acid systems,23... 

Yet another general synthesis which relies on sulphur stabilized carbanions is Seebach s method for converting ketones into a-haloesters with the addition of one carbon atom (Scheme 32). The reaction sequence with aldehydes affords aa-dihaloesters for the conversion of aldehydes to the monohaloesters, the disilyl-thio anion (111) must be used. 

The ubiquitous sulphur-stabilized carbanion has been used in a general a-hydroxy ester synthesis as well as a general route to esters (Scheme 35), " the modification to the standard 1,3-dithiane being a change in oxidation level by the addition of a 2-methylthio group. 

Sulphur.—Sulphur-stabilized carbanions have been dealt with under Group I elements in this section discussion is restricted to those new reagents which introduce sulphur itself into a molecule, or are dependent on sulphur for their synthetic use. 

Thiirans are obtained in good yields (61—78%) by treatment of aldehydes and ketones with the lithium salt of 4,4-dimethyl-2-(methylthio)-A -oxazoline (4). Other sulphur-stabilized carbanions may similarly be used, e.g. the lithium salts of 2-(alkylthio)thiazolidines, 2-(benzylthio)pyridine, and benzyl diethyl-dithiocarbamate. ... 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

Thioethers have also been prepared by the direct reaction of sulphur with stabilized carbanions in the presence of an alkylating agent (Scheme 4.9). The overall... 

Ethyl 4-bromocrotonate (273) reacts as a Michael acceptor with carbanions derived from 288 stabilized by a sulphur substituent (sulphone, sulphoxide, sulphide). The conjugated addition is followed by displacement of bromide affording various cyclopro-panecarboxylates (289) (equation Also the reaction of methyl 4-bromocrotonate... 

Stabilize carbanions a to the sulphur atom is significant in the readily accomplished lithiation of 1,3-dithianes. The preparation and reactions of 2-lithio-l,3-dithianes have been reviewed . ... 

Dithioacetals and related compounds have a number of uses in synthesis, both in Friedel-Crafts-type reactions and in reactions which exploit the high reactivity of carbanions stabilized by two or more sulphur atoms bonded at the carbanion centre. Benzyl orthothioformate, CH(SCH2Ph)3, may be used to introduce a — CH(SCH2Ph)2 group into 2- and 3-positions of an indole, with TiCU as catalyst at - 5 °C in CHQ3, and has been used in this way for 2-substitution of (79), giving (80) and (81), with further elaboration of (80) into 2-methyl-lysergic acid. Studies of ethyl dithio-... 

In contrast with the spate of activity in the area of theoretical calculations on sulphur carbanions and ylides reported in Volume 5, only a single, brief paper has been published in this area in the past two years. This interesting study predicts (and experimentally substantiates) the greater stability of cr-disulphide carbanions compared to cr-sulphenyl carbanions. 

Stabilize an adjacent carbanion less effectively than sulphur. Some p/iT, values that are relevant to the deprotonation of selenides have been discussed. Base-induced elimination of HBr from /5-bromo-selenides has been reported, and MeSeCHjLi was found not to react satisfactorily with an aldehyde group in a study that led to the synthesis of aphidicolin. 

The use of carbon nucleophiles stabilized by SR groups has been a feature of sulphur chemistry for many years now, and this year has seen additional uses for these versatile reagents. Thus the carbanion CH(SPh)2 adds in a 1,2-manner to 2-methylacrolein giving the allyl alcohol (175), which is then converted to the activated diene (176) by standard methodology. The latter has been used in studies towards the total synthesis of the Rubradirin antibiotics. The related anion ArC(SPh)2 also adds to a,/3-unsaturated systems however, in the case of lactone (177) conjugate addition is observed. If the initial ion from (177) is trapped with benzylic bromides then frans-butyrolactones (178) are obtained in good yield. ... 

The species (10) and (11), may be considered as synthons for HSCH2 and H0(CH2) CH2 respectively, whilst (12) reacts with aldehydes and ketones to give oxiranes. Selenium is capable of stabilizing an adjacent carbanion centre in the same way as sulphur, and reaction of diselenoketals with Bu"Li provides a convenient approach to reagents of type (13). After alkylation, hydroxyalkylation, or acylation of (13) the selenium can be removed reductively, by oxidative elimination, or, in the case of 2-hydroxy compounds, by elimination to form an oxirane, so the synthetic potential is clear. 

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