Addition thiophilic

For a review of additions of organometallic compounds to C=S bonds, both to the sulfur (thiophilic addition) and to the carbon (carbophilic addition), see Warded, J.L. Paterson, E.S. in Hartley Patai The Chemistry of the Metal-Carbon Bond, vol. 2 Wiley NY, 1985, p. 219. See pp. 261-267. 

More recently, 2-thioxo-4-thiazolidinones 415 were reported to undergo facile thiophilic addition of a-phosphonyl carbanions and subsequent lactamization to generate bicyclic thiazolo [2,3-A thiazole-3,5-diones 416 (Equation 189) <2004PS1307>. 

The inner salt (93) is able to react with both electrophiles (RI) and nucleophiles (RM) to give (92) and (94), respectively. Radical combination following single electron transfer from the nucleophile is believed to account for the thiophilic addition whereby the negatively charged nucleophile fails to react at the positively charged carbenium carbon. 

Thiophilic versus carbophilk addition of organometallics to a C=S bond. Carbanions through thiophilic addition... 

Many examples of the nucleophilic attack of organometallic compounds at the sulfur atom of thiocarbonyl groups were reported in the 1970s by Beak, Vialle, Ohno, Schaumann and their co-workers [119, 120, 327-329]. This thiophilic addition opens the way for a new method of preparation of carbanions a to sulfur. 

The thiophilic addition of aliphatic Grignard reagents to dithioesters deserves some comment. Although they are less reactive than organolithium compounds, their reactions are selective. With enethiolizable dithioesters, enethiolization cannot be avoided with the organolithium species, and at low temperatures this can become exclusive [332]. Enethiolization does not interfere in the case of the less... 

The difference in reactivity between saturated and unsaturated organomagnesium compounds towards a thiocarbonyl group has been interpreted by Fukui [338], and the thiophilic addition mechanism has been discussed in terms of single-electron transfer processes [329, 339, 340],... 

During the pine saw-fly pheromone synthesis based on thiophilic addition it was shown that high enantio- and diastereoselectivity were observed in the reduction of p-ketodithioesters with baker s yeast, affording new and useful chiral synthons [346]. 

A number of functionalized dithioesters have been utilized for carbophilic and/or thiophilic additions [120]. We shall mention only the potentialities offered by the readily available enolizable p-oxodithioesters (for a review, see [349]) R COCH(R2)CS2Me. 

This "thiophilic" mode of reaction fits well with the other ionic and radical thiophilic additions on a thiocarbonyl group (see [120], and the Barton-McCombie radical thiophilic addition [227] previously discussed in Sections 4.2.2 and 3.2). With thioaldehydes, both C-C and C-S bonds were formed, as in the following case in which 0-pinene was used to trap thiobenzaldehyde [514] ... 

Thiophilic addition of Grignard reagents to methyl dithioates... 

The thiophilic addition of Grignard reagents was also carried out with S-allylic and propargylic dithioates. In these cases a [2, 3] sigmatropic rearrangement of the magnesiocarbanion occurred, and alkylation at sulfur yielded the dithioacetals of (i-unsaturated ketones [334] or of allenic ketones [335]. 

One case of thiophilic addition has been reported for a bisthionester [356] ... 

This fits with the general tendency for thiophilic addition to be favoured by a strong withdrawing group a to the thiocarbonyl function [328]. 

As mentioned before, it was with thioketones that the first cases of thiophilic addition were evidenced, but many other modes of reaction have been observed concurrently carbophilic addition, reduction, coupling, double addition, and enethiolization [357]. We will not discuss these reactions here, which have not been used much for synthetic purposes. 

Cycloaddition of diazoalkanes with thiocarbonyl compounds occurs usually in the regiochemistry derived from a thiophilic addition of the carbon end of the dipole to sulfur, yielding a 1,3,4-thiadiazoline (1). 

Carbon-sulphur double bonds also undergo nucleophilic attack in a similar fashion to carbon-oxygen double bonds except in the cases of thiophilic addition, where the nucleophile selectively attacks the sulphur56 (Scheme 9). 

It has already been mentioned that thiocarbonyl compounds are much more reactive than their carbonyl congeners, but, at the same time, due to the low polarity of the C—S unit, they also react much less selectively. Thus, nucleophilic additions may occur either at the carbon (carbophilic addition, Section IV.C.l) or at the sulfur atom (thiophilic addition, Section IV.C.2), as shown in equation 111. This feature is in striking contrast with the behavior of the carbonyl group, which only undergoes nucleophilic attack on the electron-deficient carbonyl carbon, this being the cornerstone of the synthetic applications of oxo... 

A major advance in this area is represented by the fluoride ion-promoted addition of allylsilanes to thioketones423 (equation 116) giving the compounds arising from a direct thiophilic addition, namely the corresponding allyl sulfides. 

Sodium cuprate yielded less reduction product and less thiophilic addition product than lithium cuprate at both —50 and 0 °C. In the case of silyl thiones chiral at silicon, the reactions with organolithium derivatives and Grignard reagents produce a-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the a-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective. 

Rule 3 correctly predicts the experimentally observed thiophilic addition. Simple thio-aldehydes and thioketones always have a greater LUMO coefficient at C than S. The results are opposite here and this reversal reflects the experimental results nicely. 

Keywords Thiocarbonyl compounds, Thiophilic addition, Cycloaddition reactions, Enethioli-sation, Eschenmoser reaction, Sigmatropic rearrangement. 

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