Thiocarbonyl compounds 5-esters

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). 

Bis-(4-methoxyphenyl)-[l,3,2,4]dithiadiphosphetane 2,4-disulfide, transforms the carbonyl groups of ketones, amides and esters into the corresponding thiocarbonyl compounds. Cf. Knorr thiophene synthesis. 

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). 

A facile route to isothiochromans involves the base-catalyzed reaction of a benzyl dibromide with an a-thiocarbonyl compound. The method has been extended to the synthesis of an anthraceno[2,3-f]thiopyran, a heterocyclic analogue of an anthracyclinone (Equation 169) <1994S363>. In like manner, alkylation of the 2-aryl-1-bromoethane 491 by thiourea and subsequent liberation of the thiol function creates an isothiochroman precursor. An intramolecular Michael addition to the cr, )-unsaturated ester side chain yields the 1-substituted heterocycle (Scheme 179) <1992JOC1727>. 

The enzymatic reduction of a thiocarbonyl compound has been investigated [159] for the first time, in order to provide a new route for enan-tiopure thiols, molecules which are currently needed for asymmetric synthesis. Reaction of easily available /1-thioxoesters with baker s yeast under classical conditions did furnish the expected thiols, but with lower enantiomeric purity and moderate conversion rate, due to the competitive hydrolysis of the thioxo group into a carbonyl leading to an alcohol. However, conditions (ethyl acrylate, dry yeast) were found to improve the production of (S)-ethyl 3-mercaptobutanoate. Cyclic thioxo esters led to high stereoselectivity of cis (1S,2S) products, but with moderate chemical yields. 

Preparations of acylpyrazines from methylpyrazines have been described in Sections IV.2A(2) (635) and IV.2A(3) (634, 642, 645-647, 650-651). Recently it has been shown that 2-hydroxy(or mercapto)-3-methylpyrazine with two equivalents of butyllithium in dry tetrahydrofuran gave the colored dilithium salt (71, X = 0 or S), which reacted with alkyl benzoates and gave 2-benzoylmethyl-3-hydroxy(or mercapto)pyrazines (72, X = O or S, Y = 0). Similar reactions occurred with thio esters to give the thiocarbonyl compounds (72, X = O or S, Y = S)(1446). 

In the last decade the methods of converting carbonyl to the corresponding thiocarbonyl compounds have been substantially improved. " Therefore, thioxo- as well as dithio-carboxylic esters are accessible from esters, thiol esters and even carboxylic acids by reacting them with phosphorus pentasul-fide or 1,3,2,4-dithiadiphosphetane 2,4-disulfides such as Lawesson s or Davy s reagent (equation 4 cf. Chapter 4.1, this volume). 

Olefinations. Reaction of carbonyl compounds with gem-dichlorides in the presence of Zn-MCjSiCl provides alkenes. Reformatsky reaction on thiocarbonyl compounds also gives conjugated esters. 

Electron-deficient thiocarbonyl compounds such as hexafluorothioacetone, metfiyl cyanodithiofor-mate " and thioglyoxylate esters are particularly reactive enophiles. Since these compounds react primarily or exclusively by pathway (b) to give allylic sulfides (264), rather than by pathway (a) to give homoallylic thiols (263), they are outside the scope of this chapter (Scheme 39). Thiobenzaldehyde, generated in situ, reacts with (3-pinene to give thiol in 38% yield and sulfide in 19% yield. ... 

Thiatioiij The reagent is one of the most efficient substances know to date for thiation of ketones, amides, and esters the yields of thiocarbonyl compounds are usually 90-1007 . The reaction is conducted in toluene or xylene at 110-140° with 0.6 eq. of 1. 

A second significant difference deals with the stereochemistry of the deprotonation [41]. The reaction of thiocarbonyl compounds leads to cis enethiolates (Sli and R groups are located on the same side of the C=C bond) predominantly with dithioesters [48] or exclusively with thioamides [47, 49] and thioketones [50]. Under similar (kinetic) conditions, analogous esters or ketones lead to the trans enolates. 

---