Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 1355 149

S-transferase (GST), glutathione (GSH) being the cofactor. These heterocyclic systems are strong peroxidizing herbicides.

K. Organometallic Derivatives

Although due to limitations in space organometallic applications lie beyond the scope of this overview, their increasing use in recent years for the generation and stabilization of thiocarbonyls will be summarized briefly in this section and leading references will be given.

As mentioned at the beginning of Section III, free thioaldehydes tend to polymerize. They can be stabilized by coordination to metals, and several complexes with-bonded thioaldehydes have been prepared, but only a few in which the thioaldehyde is -bonded have been reported389. Aromatic and heteroaromatic thioaldehyde pentacarbonyltungsten(0) complexes have been prepared in good yields390 and, for instance, complex 93b is very stable. Grubbs and collaborators have reported the obtention of a titanocene 2-thioformaldehyde triphenylphosphine complex 94391. In related work, Ando and coworkers392 have prepared the first stable enethiolizable thioaldehydes 95 via the corresponding zirconocene 2-thioacyl complexes.

In addition, several metal-coordinated thials have been described in studies pertaining to hydrodesulfurization (HDS) reactions. This catalytic process is used to remove sulfur from organosulfur compounds present in fossil fuel feedstocks by reaction with hydrogen and a transition metal (Rh, Ir) and possesses both commercial and environmental importance393,394.

A different strategy has been the utilization of organometallics, such as acylferrocenes, as stabilizing groups in thionation reactions either with P4S10395 or with Lawesson reagent396 (equation 101).

(101)

IV. CHEMICAL PROPERTIES OF THIOCARBONYL COMPOUNDS

In general, thiocarbonyl compounds tend to dimerize or polymerize and this side-reaction must be considered even in the presence of other reagents1.

1436 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

In addition to the typical behavior exhibited in a wide array of reactions by the carbonyl group, attack by nucleophiles and reactions leading to C S single bonds are generally favored. The energetic reasons for this behavior have been discussed in Section II. Likewise, thiocarbonyl groups show a rich variety of cycloaddition reactions, ranging from 1,3-dipolar to [4 C 2] cycloadditions, and ˛, ˇ-unsaturated thiones may behave either as dienes or dienophiles226.

A. Oxidation. Synthesis of Sulfines

The oxidation of thiocarbonyl compounds to give thiocarbonyl S-oxides (sulfines) is a characteristic reaction. Sulfines are nonlinear sulfur-centered heterocumulenes with the general structure R1R2CDSDO and their synthesis and reactions have been reviewed by Zwanenburg and by Maccagnani397. These compounds are formally derived from sulfur dioxide by replacement of one oxygen atom by a carbon atom, and the name sulfines (also called thione S-oxides) was coined by Sheppard and Dieckmann398 in 1964 to indicate the structural relationship with thione-S,S-dioxides, which are known as sulfenes. Sulfines, in particular aliphatic sulfines, are in general less stable than their thiocarbonyl precursors, making their isolation sometimes difficult, and frequently they have been trapped with 1,3-dipoles or dienes1,226. An important structural property of sulfines is that they can exist as stable geometrical isomers in agreement with their nonlinear nature and, in the case of stable sulfines (such as chlorosulfines), E- and Z-isomers are known with different properties397,399 401.

The chemistry of sulfines has experienced steady growth in recent years and many synthetic applications have been described399 405. Among the different methods reported for the generation of sulfines399 406, still the most versatile and generally accepted is the oxidation of thiocarbonyl compounds (equation 102). Hydrogen peroxide and, in some special cases, ozone and singlet oxygen have been used as oxidation reagents, although peracids, and in particular mCPBA, are the oxidizing agents of choice397. Stable sulfines 96259 and 97289 were obtained in good yields by oxidation of the corresponding thiones with monoperphthalic acid.

The oxidation of a Diels-Alder adduct may be achieved with mCPBA and the resulting product affords, by thermal cleavage, the corresponding sulfine224,264,407 (equation 103)

1438 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

chemistry is not yet fully developed1. The primary product of attack by EC is a salt, and for enethiolizable thiones the electrophilic attack is regiospecific on the thiocarbonyl sulfur, leading to the formation of C S single bonds. It is never observed on the ˛-carbon, in sharp contrast with the behavior of the carbonyl group (equation 106)1,226.

E

The simplest electrophilic attack, protonation, has been studied in the case of ˛, ˇ- unsaturated 3-aminothiones413 and the reaction with common electrophiles, such as alkylation, takes place with methyl iodide in the case of activated thiones, such as diazulenyl thioketone259 and phenantridine systems381, yielding the corresponding thioethers. N-substituted thiopyridone 100 reacts with carbapenem chloride 101, leading to the corresponding quaternized compounds which exhibit good antibacterial properties414 (equation 107).

Et3 SiO

In the case of ˇ-thioxoesters, deprotonation with base followed by alkylation gives rise to reaction on the sulfur atom415 (equation 108).

N-Alkylpyridyl disulfides are potent sulfenylating agents and react smoothly at sulfur with thiones, the reaction being driven by extrusion of 1-alkyl-2-thiopyridone416. In this case an additional S S bond is formed. Another S-hetero bond is generated by halogenation. Xenon difluoride is a mild and selective electrophilic fluorinating agent which reacts with diaryl thioketones, yielding difluoro derivatives417 (equation 109).

(109)

Sodium ethenethiolate affords by reaction with a variety of dibromosulfides, a range of vinyl thiovinyl sulfides418. A new application has been reported which consists of the allylboration of thioketones, useful in the preparation of homoallyl mercaptans419 (equation 110) and other adducts420.

B

All All (110)

1. MeOH

2. NaOH

C3 H7

C3 H7

SH

C. Nucleophilic Additions

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.1) 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 electrondeficient carbonyl carbon, this being the cornerstone of the synthetic applications of oxo

1440 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

compounds1. Metzner has reviewed the reactions with nucleophiles226 and we will only highlight the major advances recorded in this area.

In the case of ˛, ˇ-unsaturated thioketones, nucleophiles attack at the ˇ-carbon and the mechanism of aminolysis of 3-alkoxy and 3-alkylthio enaminothiones has been studied421. Likewise, addition of amines to ˛-thioxoketones gives rise to enaminothiones422.

1. Addition to the thiocarbonyl carbon

The protons located ˛ to the thiocarbonyl group are quite acidic and therefore thiocarbonyl compounds are easy to deprotonate with a variety of bases, the most common being lithium diisopropylamide (LDA). As a consequence of the remarkable ability of sulfur to stabilize a negative charge, the resulting species of this deprotonation are generally written as enethiolates 102b rather than being metalated on the ˛-carbon226. In comparison with enolates, enethiolates are thermally and configurationally stable and behave as ambident nucleophiles. For instance, dimerization of thione 102a yielding 103 and 104 can be rationalized only in terms of a thiophilic and a carbophilic addition, respectively, of the enethiol form to another molecule of the thione250.

Me

(104)

Reactions of different organometallic species with thiocarbonyl compounds have been extensively investigated and been shown to proceed both in a carbophilic and a thiophilic fashion. However, other reactions can be observed simultaneously such as reduction, double addition, coupling, deprotonation and formation of enesulfides1,226,423. A complex pattern appears in the reactions of thioketones with lithium or Grignard reagents424. The first application of Reformatsky reagents in C C bond formation by reaction with

1442 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

undergoes nucleophilic attack on the carbonyl carbon.

The basic reaction pioneered by Beak’s group429 has been studied by many other groups and also silyl thioketones behave similarly249,250, yielding ˛-silyl sulfides in good yields. These thiophilic reactions are probably facilitated by the silyl group due to its stabilizing effect on the intermediate ˛-silyl carbanion. The silyl sulfides can be used for further synthetic purposes, especially by making use of fluorodesilyation in the presence of carbon electrophiles, such as aldehydes and enones249.

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.

(116)

This regiochemical outcome contrasts with previous observations and the inversion of regiochemistry at the thiocarbonyl group also occurs with benzylsilanes423. The dependence of the regiochemistry on the nature of the organometallic species used is illustrated thus when lithium organocuprates are used, instead of allylsilanes, a clean carbophilic addition occurs423. Related to this, treatment of di-tert-butyl thioketone with sodium or lithium organocuprates affords a substantial proportion of thiophilic addition along with the reduction product430 (equation 117).

(117)

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 ˛-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the ˛-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective.

D. Reduction

The reduction of thiocarbonyl groups may lead to a variety of products: thiols, methylene compounds, sulfides etc. The reactions to achieve S/O exchange, namely desulfurization reactions, will be summarized in Section IV.G. There is a short review dealing with the reduction of the thiocarbonyl group432. As mentioned earlier, sometimes concomitant reduction of the CDS bond takes place in the reactions of thiones with organolithium or organosodium reagents, and thiols along with the corresponding addition products are obtained430.

Reduction of diaryl thioketones with ytterbium metal affords a mixture of the corresponding thiols and diarylmethanes together with products arising from homocoupling reactions (equation 119)433.

The use of sodium telluride under aprotic conditions allows the transformation of aromatic thioketones into hydrocarbons in good yields434, as shown in equation 120. Interestingly, when this reaction is carried out with sodium telluride in aqueous media the original ketones are generated.

E. Cycloaddition Reactions

Thiocarbonyl compounds are excellent reaction partners in all types of cycloadditions, especially 1,3-dipolar (Section IV.E.3) and Diels-Alder reactions (Section IV.E.4). They have been frequently used in the trapping of unstable thiocarbonyl derivatives1.

1. [2+1] Cycloaddition

Carbenes add to the CS bond in diarylthiones to give thiiranes by way of a [2 C 1] cycloaddition1. The carbene species may be generated from diazo compounds, from organomercury compounds or from phenyliodonium bis (arylor alkyl-sulfonyl)

the yields reported were low435 and several side products, such as benzothiophenes, were found. Using haloallenes or haloalkynes as source of carbenes under phase

(105)Ar = p-Tol

1444 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

(106)R4

The thermal formation of a nitrene has been invoked to account for the result in the reaction between a sterically hindered thioketene and benzyl azide437 (equation 123). Although initially a 1,3-dipolar cycloaddition between the CDS bond and the azide was expected, the temperature of the reaction (138 °C) led to decomposition of benzyl azide into benzyl nitrene and the subsequent [2 C 1] cycloaddition.

In addition to carbenes and nitrenes, organometallic species such as germylenes 107 have been utilized in [2 C 1] cycloadditions and, upon reaction with thioketones, afforded the corresponding thiagermiranes which are very stable and do not decompose even when heated to their melting point438 (equation 124).

Germylenes can be generated either thermally or photochemically438 and, apart from thioketones, they have been reacted with thioketenes to afford initially