Carbophilic addition

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. 

The iminofluorenes 50 are attacked by butyllithium at the nitrogen atom ( azophilic attack ) to give the fluorenylamines 51, accompanied by products 52 of carbophilic addition. The proportion of the two types depends on the nature of the group R for R = Me or Bu there is almost exclusive azophilic reaction, for R = i-Pr 64% azophilic and 16% carbophilic attack and for R = Ph or 4-McC.fiI U 23% azophilic and 70% carbophilic reaction77. 

From a synthetic point of view, both thiophilic and carbophilic additions on dithioesters afford pathways for carbon-carbon bond formation, and as the dithioacetals formed in these reactions are easily converted into carbonyl or methylene groups the dithioesters are equivalent to the four synthons... 

The possibility of conversion of the dithioacctal into the corresponding ketone without reconjugation of the double bond is a noteworthy j feature of this synthetic scheme. The syntheses of iso-ar-turmerone and isoartemisia ketone mentioned above proceeded similarly via a carbophilic pathway. In the latter case a p-ethylenic dithioester was not isomerized during the following overall sequence carbophilic addition-methylation-dithioacetalization [343]. ... 

Only a few reports deal with the reaction of thionoesters with organometallic reagents, and carbophilic addition was observed as the usual mode. The reaction of O-ethyl thioesters with alkyllithiums afforded, after methylation, good yields of monothioacetals, which can be hydrolysed to ketones [353]. 

With thioamides few results are available. Only carbophilic additions have been reported [329, 358]. This mode of addition of organolithiums was used for novel syntheses of unsymmetrical ketones and a-alkylated amines. Although enethiolization of aliphatic thioamides by alkyllithiums limits the scope of these synthetic routes the yields are good and reactions simple to run [358]. 

Reformatsky reagents were shown to undergo carbophilic addition with a variety of thiocarbonyl compounds (thioketones, dithioesters, trithiocarbonates and xanthates). Elimination of sulfur (or of an alkylthio group) led to the formation of carbon-carbon double (or single) bonds [448]. Typically ... 

With allylic Grignard reagents, the carbophilic addition on the thiocarbonyl of phenylisothiocyanate occurred as expected exclusively with inversion of the allylic chain. From crotyl and prenyl magnesium halides the compounds (4f) and (4g) were obtained in yields of 77 and 72%, respectively. 

The reaction of organocuprates with dithioesters has been reported [350]. High yields of tertiary thiols were obtained via a novel sequence of a double-barrelled carbophilic addition, such as with lithiocuprates ... 

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. 

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... 

Further examples of thiophilic addition of methyllithium and carbophilic addition of allyl- or benzyllithium and allyl Grignard reagents with 1,3-thia-zole-5(4ff)-thiones were reported [143]. Perfluorodithioesters were reacted with alkylmagnesium bromides, providing a new entry to perfluoroketene... 

Exceptions to the carbophilic addition of heteronucleophiles to thiocarbonyl compounds were demonstrated with thiols and thioaldehydes [160] or dithioesters [36] bearing an a-electron withdrawing group, which undergo selective thiophilic addition. 

The reaction of alkoxides with thioaldehyde S-oxides, generated from sul-finates, was carefully examined by Baudin et al. [163]. A number of products were isolated, formation of which was explained by carbophilic addition of the alkoxide anions. 

Carbophilic Addition of Organomagnesium Compounds to Thiocarbonyl Groups... 

On the whole, reactions of thioketones with vinyl-, allyl-, propargyl-, benzyl-, and, sometimes, methylmagnesium halides proceed by carbophilic addition [1-3] (though subsequent rearrangements to the thiophilic product may occur [2]) ... 

Reactions of organomagnesium compounds with a,(3-unsaturated dithioesters are somewhat unpredictable, 1,2-, 1,4-carbophilic and thiophilic addition having been observed [6], With a,(3-unsaturated thioamides [7] and imidothioesters [6], however, 1,4-carbophilic addition appears to predominate. 

The product is a new organomagnesium compound, which may be used in situ for further reactions reactions with dithioesters are particularly useful, giving functionalized dithioketals [2], It is interesting to contrast the following example with the reaction involving carbophilic addition described in the same paper (see p. 148) [3]. 

The thiophilic addition D is preferential when the temperature is less than — 17°C and when R is an ethyl or an isopropyl group similar results are observed with other dithioesters [33]. With CHaMgBr or CH3MgI, carbophilic addition is preferential if the reaction is performed at 20°C or at reflux, leading to the thiol E. 

Carbophilic addition of prenylmagnesium bromide and other allylic Grignard reagents to the thiocarbonyl group of dithioesters occurs exclusively with rearrangement of the allylic... 

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