Thionester

Some applications of the thio-Claisen rearrangement to the syntheses of thiocarbonyl compounds, particularly unsaturated dithiocstcrs and thionesters, and of its stereocontrol aspects are reviewed in [120]. A particularly high stereoselectivity was observed with S-allyl derivatives of P-hydroxydithioesters syn products were obtained exclusively, according to the accompanying scheme [495,496]. 

Allylic thionesters, dithiocarbamates and thionocarbamates are starting materials for various synthetic purposes [203, 492,493]. General synthetic routes, from Nakai et al. [492], to a,0-unsaturated esters and ketones via the [3,3] sigmatropic rearrangement of allylic thionocarbamates (1) are featured in the accompanying schemes. 

Applied to dialkenyl disulfides, the dihetero sigmatropic shift gives rise to 1,4-dithiocarbonyl derivatives. The precursors are easily obtained by oxidation of the enethiolates, and the reaction has been observed with thioketones [500]. thioamides [501], dithioesters [356, 502] and thionesters [503],... 

Although almost all kinds of thiocarbonyl compounds are good dienophiles, synthetic applications derived from the Diels-Alder adducts of thioketones, thionesters and dithioesters remain rather rare and focused on specific targets, as in the preparation of a fragment of the antibiotic erythronolide from the cycloadduct formed regioselectively from 2-methyl-l,3-pentadiene and an a-oxodithioester, a particularly efficient dienophile [524]. 

T4 lysozyme 33,497 helix stability of 528, 529 hydrophobic core stability of 533, 544 Tanford j8 value 544, 555, 578, 582-Temperature jump 137, 138, 541 protein folding 593 Terminal transferase 408,410 Ternary complex 120 Tertiary structure 22 Theorell-Chance mechanism 120 Thermodynamic cycles 125-131 acid denaturation 516,517 alchemical steps 129 double mutant cycles 129-131, 594 mutant cycles 129 specificity 381, 383 Thermolysin 22, 30,483-486 Thiamine pyrophosphate 62, 83 - 84 Thionesters 478 Thiol proteases 473,482 TNfn3 domain O-value analysis 594 folding kinetics 552 Torsion angle 16-18 Tbs-L-phenylalanine chloromethyl ketone (TPCK) 278, 475 Transaldolase 79 Tyransducin-o 315-317 Transit time 123-125 Transition state 47-49 definition 55... 

Thiocarbonyl compounds bearing a heteroatom substituent, such as thio-noesters, dithioesters or thioamides, are much less reactive. In the glycono-lactone series it was shown [67] that a thionester adds to Danishefsky s diene at 110°C (Table 2, entry 6). 

The rearrangement is negligible in thiolesters (McFadden et al., 1965) but is considerable in the probably thermally less stable thionesters (84), (Karjala and McElvain, 1933) with ethyl as the migrating group. A four-centre rearrangement of the thioncarbonate to the thiocarbonate (85) 8... 

Carbamic acid thionesters can be prepared by the reaction of amines, thiophosgene and alcohols. CP-43 797 (I), for example, can be synthesised by the... 

Lithiation of Thiolesters, Thionesters, and Dithioesters with LDA (General Procedure)... 

The rearrangement of alkyl thiobenzoates had also been reported in certain cases. An application of this reaction is the thermal conversion of thionesters of glycerol to esters of thioglycerol (85->8Q . 

O-Alkyl thionesters rearrange easily to thiolesters when the alkyl group can form relatively stable carbonium ions. Benzhydryl thioncarbonate (87) yields 88 on heating in ethanol and the suggested mechanism is a dissociation to a ion pair, the return of which occurs via the sulphur because of the greater nucleophility of the sulphur compared to the oxygen. 

This isomerization is very little influenced by the medium and occurs only ca. ten times faster in acetic acid than in cyclohexane. This low sensitivity to the ionizing power of the solvent indicates that allyl thionesters rearrange by a mechanism which involves very little change in charge separation between the ground state and the transition state. Thus a cyclic concerted mechanism is more probable than dissociation to ion pairs. This conclusion was confirmed by deuterium isotope elfect measurements . 

The dissociation, and hence the rearrangement, may be caused by neighbouring group participation in the formation of the cation. An example is the rearrangement of the thionester 91 . ... 

The first isolation of the primary product from the transposition was effected in the aliphatic series and launched many developments. A pioneer contribution came from the group of Brandsma in the Netherlands, which started with a paper in 1968 [19]. The substrates were prepared by deprotonation of thionesters, dithioesters and thioamides with potassium amide and reaction with a variety of allyl bromides (Scheme 9.5). In some cases the initial aUyl ketenethioacetal was observed and it was rearranged upon purification by distillation (b.p. range 66-152 °C). In most cases, the authors noted that the rearrangement had already taken place during work up at ambient temperature. 

On the other hand, the rearrangement leading to thiocarbonyl compounds, such as dithioesters, thionesters or thioamides, instead of thioketones, has been shown to be driven to the right side. The only exception was observed when the initial unsaturated sulfide exhibits an aromatic nature [35]. 

Though they are less popular, thionesters can serve as starting materials for kete-nethioacetals, which, despite their sensitivity towards water, could be rearranged [74, 75]. A synthetically useful report [76] includes access to 2-allyl thionolactones (Scheme 9.13). 

Further uses of the dimer of p-methoxyphenylthionophosphine sulphide (3, 250, 251) are the conversions of simple butyrolactones into the sulphur analogues (135) and of jS-keto-esters into 3H-l,2-dithiole-3-thiones (136) rather than the expected jS-keto-thionesters. ... 

The dimer of p-methoxyphenylthionophosphine (169) has been found to be a very useful reagent for the conversion of amides into thioamides ° as well as for preparing thionesters from esters and dithioesters from thioesters. The usual... 

The action of diazoalkanes on thiocarbonyl compounds provides a versatile route to thiirans 1,2,3-thiadiazole derivatives, which function as intermediates, are isolable in suitable cases. Thus, diazomethane reacts with thionesters (1) yielding 5-alkoxy-5-methyl-A -l,2,3-thiadiazolines (2) (ca. 60%) together with the next higher homologous thionester (3) (ca. 30%). Aromatic members (2 R = Ar) decompose readily to the alkenes (5). Ethyl thioformate (1 R = H, R = Et) gives rise, by methylation and aromatiza-tion, to (4), and to linear products. Comparable observations involving diazoethane and diazopropane are also on record. The formulation of the products as 1,2,3-thiadiazolines (2) in preference to the possible A -1,3,4-thiadiazoline structures (6) is supported by the results of n.m.r. studies. However, both isomers, (8) (20%) and (9) (45%), are obtained when diazomethane acts on methyl dithioacetate (7) at —70 C (compare also these Reports, Vol. 1. p. 450). ... 

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