Thiocarbonyl-substituted compound

An attempted synthesis of biotin using thiocarbonyl ylide cycloaddition was carried out (131,133,134). The crucial step involves the formation of the tetrahydrothiophene ring by [3 + 2] cycloaddition of a properly substituted thiocarbonyl ylide with a maleic or fumaric acid derivative (Scheme 5.27). As precursors of the thiocarbonyl ylides, compounds 25a, 72, and 73 were used. Further conversion of cycloadducts 74 into biotin (75) required several additional steps including a Curtius rearrangement to replace the carboxylic groups at C(3) and C(4) by amino moieties. 

The known nonclassical A,B-diheteropentalenes consist of compounds containing an annelated thiophene or selenophene ring, the only uncharged nonradical representations of which contain a tetravalent sulfur or selenium, while the charged structures represent carbonyl, azomethine, thiocarbonyl or selenocarbonyl ylides. The parent systems have not yet been synthesized, only substituted compounds being known. The properties of these substituted derivatives provide a good measure of understanding of the reactivities of the parent systems. 

The photocycloaddition of thiocarbonyl-containing compounds to alkenes provides an easy route to thietanes. 2,4,6-Tri-(t-butyl)thiobenzaldehyde (249) undergoes regiospecific addition to substituted allenes (250) to give the vinyl-thietanes (251). The formation of the ketones (252) by irradiation of the aryl... 

The synthesis of ylides which are a-substitued with a derivative of the caiboxy group can also be achieved via the addition of simple ylides to heteroallenes. The reaction with carbon oxysulfide gives rise to the formation of betaines from which alkylthiocarbonylalkylidenephosphoranes may be generated by alkylation and subsequent deprotonation (equation 78 X = O, Y = S). Carbon disulfrde reacts in a similar way yielding (alkylthio)thiocarbonyl-substituted ylides (equation 78 X = S, Y = S). These compounds are also available from the reaction of simple ylides with trithiocarbonates or dithiochloro-carbonates in analogy to the acylation of ylides (see equations 71 and 72). ... 

The reaction of thiocarbonyl compounds with diazoalkanes (alkyl, aryl substituted) frequently gives good to excellent yields of thiiranes. The mechanism may involve addition of a carbene across the thiocarbonyl group, especially in the presence of rhodium(II) acetate... 

A radical carboxyarylation approach was introduced as the key step in the total synthesis of several biologically important natural products (Scheme 27). Treatment of thiocarbonate derivatives 112 (R = Me or TBS) with 1.1 equiv of (TMS)3SiH in refluxing benzene and in the presence of AIBN (0.4 equiv added over 6h) as radical initiator, produced compound 113 in 44% yield. This remarkable transformation resulted from a radical cascade, involving (TMSlsSi radical addition to a thiocarbonyl function (112 114), 5-era cyclization (114->115) and intramolecular 1,5-ipso substitution (115 116) with the final ejection of (TMSlsSiS radical. 

Beside thioamides, dithioesters are the most stable and accessible thiocarbonyl compounds. Their specific reactivity, in particular towards nucleophiUc reagents and their apphcations to the formation of carbon-carbon bonds, have already been reviewed [8]. However, as shown below, the presence of a phosphonate function alpha or beta to the thiocarbonyl group in phosphonodithioformates and phosphonodithioacetates makes these difunctional compounds very versatile building blocks. Moreover, for the phosphonodithioacetates, the substitution of the methylenic hydrogen atoms by fluorine increases again their potential as intermediates for the synthesis of modified natural and bioactive phosphorylated structures. 

Reaction of lithium trimethylsilyldiazomethane (TMSC(Li)N2) with thiocarbonyl compounds has proved to be a convenient method for the preparation of 5-substituted 1,2,3-thiadiazoles. This reaction is very similar to the Pechmann-Nold reaction but probably does not proceed through a dipolar cycloaddition pathway. A number of examples of this type of reaction were described in CHEC-II(1996). More recently, it was reported that TMSCN2Li also reacts with diethylaminothiocarbonyl chloride to afford a mixture of 1,2,3-thiadiazoles 66 and 67 (Equation 19) <1997BSB533>. 

I.3.4.2.5. Carbonyl and Thiocarbonyl Compounds a-(Hydroxyimino)phenyl-acetonitrile oxide (generated in situ at room temperature from PhC( NOH)C ( NOH)Cl in the presence of NaHC03 or Et3N) reacts with simple aldehydes and ketones R1R2CO to give 1,4,2-dioxazoles 180 (347). Related dioxazoles, formed by cycloaddition of benzonitrile oxide to aromatic aldehydes, upon treatment with I-BuOK, undergo cyclo-reversion, allowing direct conversion to substituted benzoic acids or their esters (348). 

Treatment of Fischer-type carbene complexes with different oxidants can lead to the formation of carbonyl compounds [150,253]. Treatment with sulfur leads to the formation of complexed thiocarbonyl compounds [141]. Conversion of the carbene carbon atom into a methylene or acetal group can be achieved by treatment with reducing agents. Treatment of vinylcarbene complexes with diborane can also lead to demetallation and formation of diols [278]. The conversion of heteroatom-substituted carbene complexes to non-heteroatom-substituted carbene complexes... 

When planning reactions of thiocarbonyl compounds with electrophilic carbene complexes it should be taken into aceount that thiocarbonyl compounds can undergo uncatalyzed 1,3-dipolar cycloaddition with acceptor-substituted diazomethanes to yield 1,3,4-thiadiazoles. These can either be stable or eliminate nitrogen to yield thiiranes or other products similar to those resulting from thiocarbonyl ylides [1338]. 

Table 4.22. Reactions of thiocarbonyl compounds with acceptor-substituted carbene complexes.

Typically, thioxonium salts (32) are stable compounds, and the deprotonation is performed at low temperatures. This method has been used to synthesize reactive thiocarbonyl yhdes as well as stable and isolable ones (56-60). Arduengo and Burgess (3) prepared differently substituted thiocarbonyl ylides from thiourea derivatives, and in the case of 33, the structure has been established by X-ray crystallography. 

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

Numerous examples involving the preparation of tetrahydrothiophenes via [3 + 2] cycloaddition of thiocarbonyl ylides with electron-poor alkenes have been reported. Thiobenzophenone (5)-methylide (16), generated from 2,5-dihydro-1,3,4-thiadiazole (15) and analogous compounds, react with maleic anhydride, N-substituted maleic imide, maleates, fumarates, and fumaronitrile at —45°C (28,91,93,98,128,129). Similar reactions with adamantanethione (5)-methylide (52) and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (5)-methylide (69) occur at ca. +45°C and, generally, the products of type 70 were obtained in high yield (36,94,97,130) (Scheme 5.25). Reaction with ( )- and (Z)-configured dipolaro-philes stereospecifically afford trans and cis configured adducts. 

The desUylation strategy has been used for the cycloaddition of the parent thiocarbonyl yhde la with aldehydes and reactive ketones. The product obtained using A-methyl-3-oxoindolinone as the trapping agent corresponds to the spiro-cyclic compound 125 (168). Thioketene (5)-methylide (127) was reported to react with aromatic aldehydes and some ketones to furnish 2-methylene-substituted 1,3-oxathiolanes (128) (51) (Scheme 5.42). 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

When thiocarbonyl and ot-diazocarbonyl compounds are combined, acyl-substituted thiocarbonyl ylides 158 are generated from a nonisolable 3-acyl-1,2,4-thiadiazoline 157 (Scheme 8.36). In addition to giving acylthiiranes 159 and 1,3-dithiolanes 160, dipoles 158 can also 1,5-cyclize to produce 1,3-oxathioles 161. Acyl-thiocarbonyl ylides derived from diazoketones [e.g., HC(0)C(N2)R, R = Ph, f-Bu (219,220) 2-diazocyclohexanone (221)] produce 1,3-oxathioles [e.g., 162 (220), Scheme 8.36], while those derived from diazoesters (218,222,223) lead to thiiranes by 1,3-cyclization. Ylides derived from a-diazocarboxamides form 1,3-oxathioles (e.g., 163) and thiiranes (e.g., 159, R = f-Bu, R = NMePh, R = R" = Ph), depending on the nature of the substituents (220). A related 1,5-cyclization of an aminomethyl-thiocarbonyl ylide formed from dimethyl 3-anilino-2-diazobutanedioate was also reported (224). 

The intermediate cyclooctene complex appears to be more reactive with respect to CS coordination and more sensitive to oxidation when the arene ring bears electron-withdrawing groups (e.g., C02CH3). Dicarbonyl(methyl rj6-benzoate)-thiocarbonyl)chromium is air stable in the solid state and reasonably stable in solution.9 The infrared spectrum exhibits metal carbonyl absorptions at 1980 and 1935 cm"1 and a metal thiocarbonyl stretch at 1215 cm"1 (Nujol) (these occur at 1978, 1932, and 1912 cm"1 in CH2C12 solution).10 Irradiation of the compound in the presence of phosphite or phosphine leads to slow substitution of CO by these ligands, whereas the CS ligand remains inert to substitution. The crystal structure has been published."... 

Fluorine-substituted thiocarbonyl compounds have been studied even more intensively than thioformaldehyde and thioacetone. These compounds have a very rich chemistry of which polymerization is only a part. The simplest member of this class is fluorothiocarbonyl fluoride, CF2==S, which also forms the most interesting polymers. Other members that have been investigated include a variety of fluorothioacyl halides and a number of fluorothioketones. Because... 

The lithium derivatives described above react with electrophiles such as alkyl halides, carbonyl compounds, and thiocarbonyl compounds, resulting in the corresponding 3-substituted derivatives (190). Hydrolysis of these products by dilute acid as described in Section B,1 gives the new nonproteinogenic amino acid ester (191) along with the original amino acid ester used as the chiral auxiliary. The chemical yields are above 80% (83MI1). 

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