Thiocarbonyl compounds, nucleophilic

As discussed in Section II, thiocarbonyl compounds differ from their carbonyl counterparts in at least two important characteristics. Because of the higher energy of the sulfur p orbitals, they are much more reactive as electron donors. On the other hand, the C=S bond is also much less polarized than the C=0 bond, due to the smaller difference in electronegativities between carbon and sulfur. The latter fact leads to the reactions of the thiocarbonyl group being less selective than those of the carbonyl group. This happens, for instance, in the case of nucleophilic additions (see Section IV.C), and an enhanced reactivity against dipoles has also been observed (see Section IV.E.3). 

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... 

Thiocarbonyl compounds are much more nucleophilic than carbonyl compounds because of the lower electronegativity of sulphur as compared to oxygen. 

The main feature of thiocarbonyl compounds is their high reactivity. For instance their strong electrophilicity, relative to carbonyl compounds, is related to their low lying LUMO which causes an important reduction of the gap with occupied orbitals of nucleophiles [119]. At the same time, they are more nucleophilic in relation to their high HOMO. A number of examples reported below illustrate this. 

The sulfur analogues of enolates have recently received attention in the context of synthetic applications. Thiocarbonyl compounds bear a-protons which are rather acidic. Kresge et al. [120] has shown that their pKas are 10 units less than those of carbonyl compounds. Thus enethiolates are easily formed with a variety of bases, and they exhibit thermal stability [1]. They are ambident nucleophiles and the sulfur vs carbon regiochemistry has been rationalised by Anh [119] using frontier orbital treatment. 

In the next section the formation of acyl anion equivalents by nucleophilic addition to thiocarbonyl compounds is discussed. A direct and non-classical route to thiocarbonyl anions has been achieved [141]. Treatment of a thiocarbamoyl chloride by lithium powder, in the presence of both naphthalene and the carbonyl compound to which the intermediate will be added, led to a-hydroxy thioamides. 

The thiophilic addition of carbon nucleophiles to thiocarbonyl compounds was a topic of intense investigation during the 1980s. 

A new class of nucleophiles have been introduced for sulfur addition. Degl Innocenti and his group [145, 146] have shown that allyl or benzylsi-lanes, in the presence of tetra-n-butylammonium fluoride, reacted in a thiophilic fashion and led to allyl sulfides or dithioacetals. It is remarkable that this selective reaction is general for a large variety of thiocarbonyl compounds thioketones [145], dithioesters [146], and even with the normally sluggish trithiocarbonates [145]. With substituted allyl silanes retention of configuration of the allyl chain is observed. It is noteworthy that the possible [2,3] sigmatropic shift of the intermediate anionic species was not observed. 

A variety of nucleophiles have been reacted with thiocarbonyl compounds, usually for synthetic purposes exploiting the enhanced reactivity of the 2p-3p double bond between carbon and sulfur atoms. In contrast to the preceding part, most nucleophilic additions reported took place on the carbon atom very few cases of thiophilic addition were evidenced. 

Bis(trifluoromethyl)diazomethane is a reactive, electrophilic compound. It forms adducts with nucleophiles such as amines and phosphines and adds to olefins, acetylenes, and thiocarbonyl compounds to form heterocycles. It has been used as a source of bis(trifluoromethyl) carbene in reactions with benzene, saturated hydrocarbons, carbon disulfld< , and transition metal (iompounds, and it nndergoe.s a uni< im radicuil chain n aidion with saturat d hydrocarbons l.o form addiict.s that are hydrazonc.s and azines. ... 

Condensation with thiocarbonyl compounds. Activation of the C=S bond with AgaO renders such compounds reactive toward nucleophiles. 

The common method involves deprotonation of a thiocarbonyl compound and reaction of the intermediate enethiolate with an allyl halide (Scheme 9.8). This actually relies on two noticeable features of the sulfur series. (1) The proton located a to a thiocarbonyl group is much more acidic, by 7-10 pKa units, than the one of a carbonyl moiety [39, 41]. This may be related to the strong ability of the sulfur atom (polarizability) to stabilize the negative charge of the enethiolate. Presently, the preferred conditions involve LDA as a base for optimum deprotonation [42-45]. (2) The resulting anionic species are soft ambident nucleophiles. The... 

Thiocarbonyl compounds are characterized by a C=S unit rather than a C=0 unit. Draw the structure of 2-pentanone and then draw the corresponding thioketone by replacing O with S. If this thioketone reacted with a nucleophile such as CHgC C , what is the expected product ... 

The sulfur atom of the thiocarbonyl group is a good nucleophile, and reaction between benzyl bromide and l-(2-thiazolyl)thiourea yields the isothiouronium salt (496). The sulfur atom may also be engaged in a chelate, as exemplified by the Cu chelate of 2-thioureido-4-methylthiazole (491). These chelates with metal ions were thoroughly studied in acidic, neutral, and alkaline media for 66 metal ions in order to define their analytical use. They are formed in the molar ratio of 1 2 for metal II compounds (498). 

Thiocarbonyl ylides are both nucleophilic and basic compounds (40,41,86). For example, adamantanethione (5)-methylide (52) is able to deprotonate its precursor, the corresponding 2,5-dihydro-1,3,4-thiadiazole, and a 1 1 adduct is formed in a multistep reaction (40,86). Thioxonium ion (56) (Scheme 5.22) was proposed as a reactive intermediate. On the other hand, thiofenchone (S)-methylide (48) is not able to deprotonate its precursor but instead undergoes electrocyclization to give a mixture of diastereoisomeric thiiranes (41,87,88). The addition of a trace of acetic acid changes the reaction course remarkably, and instead of an electrocyclization product, the new isomer 51 was isolated (41,87) (Scheme 5.18). The formation of 51 is the result of a Wagner-Meerwein rearrangement of thioxonium ion 49. 

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