Thiocarbonates, reduction

A number of substances, such as the most commonly used sulfur dioxide, can reduce selenous acid solution to an elemental selenium precipitate. This precipitation separates the selenium from most elements and serves as a basis for gravimetry. In a solution containing both selenous and teUurous acids, the selenium may be quantitatively separated from the latter by performing the reduction in a solution which is 8 to 9.5 W with respect to hydrochloric acid. When selenic acid may also be present, the addition of hydroxylamine hydrochloride is recommended along with the sulfur dioxide. A simple method for the separation and deterrnination of selenium(IV) and molybdenum(VI) in mixtures, based on selective precipitation with potassium thiocarbonate, has been developed (69). 

The asymmetric reduction of the benzoxathiin is very appealing because of its simplicity (Scheme 5.3). It was envisioned that intermediate 16 could be prepared from thiol-phenol 7 and bro moke tone 17. Scheme 5.8 summarized the synthesis for 16. The l,3-benzoxathiol-2-one 35 was prepared from 1,4-benzoquinone and thiourea following a literature procedure with minor modifications. Benzylation of 35 with benzyl bromide in the presence of KI gave benzyl ether 36 as a crystalline solid. It was observed that the benzylation gave better results when the reaction was run under anaerobic conditions. Hydrolysis of thiocarbonate 36 gave free thiophenol 7 which was used directly in the next reaction. 

The reduction of 2,2/-dithiobis(l,3-dithiolanium) bis(tetrafluoroborate) to the thiocarbonate compound by triethylsilane takes place quantitatively (Eq. 343).565... 

A fused OZT was obtained in the course of the reduction of vicinal azido-thiocarbonates via formation of the intermediate amine, which attacks the thiocarbonyl group (Scheme 37). The condensation reaction proved faster than the deoxygenation process for the synthesis of 2 -amino-2, 3 -dideoxyuridine50 or methyl 3-amino-4,6-0-benzylidene-3-deoxy-2-0-phenoxythiocarbonyl-a-L-talopyranoside.51... 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

Because vicinal dibromides are usually made by bromination of alkenes, their utility for synthesis is limited, except for temporary masking of a double bond. Much more frequently, it is desirable to convert a diol to an alkene. Several useful procedures have been developed. The reductive deoxygenation of diols via thiocarbonates was developed by Corey and co-workers.210 Triethyl phosphite is useful for many cases, but the more reactive reductant l,3-dimethyl-2-phenyl-l,3,2-diazaphosphohdine can be used when milder conditions are required.211 The reaction presumably occurs by initial P—S bonding... 

The A ring is closed by a Ti-mediated reductive coupling (step H-5). The C(ll)-C(12) double bond is introduced from the diol by deoxygenation of the thiocarbonate [step I-... 

F-17(20)-dehydro-20-cyanopregnene, which may be isomerized in base to the Z-isomer. Elaboration of the side-chain by successive Grignard reaction, reduction, and removal of the 22-hydroxy-group followed. Key steps in two stereospecific syntheses of Z-20(22)-dehydrocholesterol (234) from pregnenolone were (a) stereospecific removal of the 20- and 22-oxygen atoms of (20i ,22S)-20,22-dihydroxycholesterol by conversion into the thiocarbonate (232) and treatment with triethyl phosphite and (b) selective epoxidation of iE -20(22)-dehydrocholes-teryl benzoate to the epoxides (233), which were allowed to react with hexamcthyIdisilane-KOMe in HMPA (see also ref. 179). Syntheses of the 24-... 

Cyclic thiocarbonates offer another class of substrates for radical deoxygenation (Scheme 3.9b). In particular, thiocarbonates formed from a diol derived from a primary and secondary hydroxyl are of particular interest, since they can be deoxygenated regioselectively with tributyltin hydride and AIBN.53 In these cases, the secondary position is deoxygenated owing to the higher stability of secondary over primary radicals. As expected, radical reduction of thiocarbonates derived from two secondary hydroxyls leads to a mixture of deoxygenated isomers.52b 53... 

Radical deoxygenation of alcohols is important, and the reduction of xanthates prepared from alcohols, with Bu3SnH in the presence of AIBN is called the Barton-McCombie reaction (eq. 2.13) [37-51]. The driving force for the reaction is the formation of a strong C=0 bond from the C=S bond, approximately 10 kcal/mol stronger. This reaction can be used for various types of substrates such as nucleosides and sugars. Though methyl xanthates, prepared from alcohols with carbon disulfide and methyl iodide under basic conditions are very frequently used, other thiocarbonates, as shown in eq. 2.14, can also be employed. 

Dihydro-5,10-disilanthracene and AIBN can reduce xanthates and thiocarbonates in refluxing cyclohexane solution. Reduction of xanthates with monosilanes such as PhSiH3 and Ph2SiH2 initiated by AIBN does not work effectively because of their strong Si-H bond dissociation energies. However, the same reactions using either dibenzoyl peroxide or triethylborane as an initiator do induce the effective reduction of xanthates. 

Deoxygenative reduction can be carried out at room temperature with Et3B as an initiator [19,20]. However, this reaction is limited to thiocarbonates derived from sec- and tert-alcohols, since the C-0 bond cleavage of thiocarbonates derived from pr/m-alcohols does not occur easily at room temperature. 

We explored other thiocarbonyl derivatives including xan-thates (e.g. 19), thionoimidazolides (e.g. 20) and thio-carbonates. The last convert a glycol such as 21a via the thiocarbonate 22 and subsequent tin hydride reduction to mainly the primary alcohol 21b. The intermediate opens in such a way as to afford the more stable radical. This reaction is readily applied to nucleosides.910... 

Synthesis of 7-deoxy-6a-hydroxypaclitaxel was realized through the regiospeci-fic reduction of 6,7-ot-thiocarbonate 83 as the key step. 2 -TES-7-deoxy-6oc-hydro-... 

Surprisingly, the reaction of diethyl carbonate and 0,0 -diethyl thiocarbonate with lithium bis(trimethylsilyl)phosphanide has been found to give ethoxy trimethylsilane and the phosphaalkynes (dme)2Li-0-CsP and [(dme)3Li] [S-CsP] respectively. As known so far, lithoxymethylidynephosphane shows a great tendency to undergo [2+2] cycloaddition and reduction reactions. The NMR parameters of the [S-C=P] -anion resemble much more the values of diorganylamino-phosphaalkynes than those of its oxygen homologue. 

A related procedure involves reduction of thiocarbonates or thiocarbamates of primary or secondary alcohols. The alcohols need not be hindered in this case. This ilcoxygcnation procedure is more convenient than many other existing methods and... 

The di-O-tosylates (prepared by action of tosyl chloride in pyridine) are reduced with zinc (Nal/Zn route e Tipson-Cohen reaction) [13]. Cyclic ortho-esters (prepared by reaction of the diol with ethyl orthoformate) are transformed into olefins by simple heating in the presence of acids (Eastwood reaction, route b) [14]. Cyclic thiocarbonates (obtained by reaction of a diol with thiophosgene or (V,(V -thiocarbonyl-di-imidazole) are reduced to olefin with trimethyl phosphite (Corey-Winter method, route c) [15]. Finally, reduction of vicinal di-xanthates with tri- -butyltin hydride according to the Barton procedure [16] affords olefins via a reductive elimination process route a). The Corey-Winter, Garegg, and Tipson-Cohen methods are most commonly applied for deoxygenation of sugar diols. 

Many deoxy-sugars are synthesized by conventional methods of dehalogenation or reduction of thiocarbonates tosylates, mesylates etc. One notable exception, involving dimerization of phenylselenyl 2-deoxy-D-glucopyranose in a concentrated solution and in the absence of trapping agents is worthy of mention as it is related to the chemical character of the free radical intermediate. The approach proceeds by the formation of the axial-axial coupling product as the major one and axial-equatorial as the minor product. 

Butenolides derived from ribonolactone (78) have been valuable in the construction of several bicyclic natural products (ref.78). D(+)-Ribonolactone as its trityl derivative was converted to the 0,0-thiocarbonate and thence by reduction to the butenolide shown which with various buta-1,3-dienes readily formed bicyclic structures. Scheme 39... 

Diol 164 was treated with l,l -thiocarbonyldiimidazole to produce the cyclic thiocarbonate (168) product in 67% yield over two steps from salvinorin A (Scheme 26) [49]. Unfortunately, these conditions were found to cause epimerization at C-8, the products of which were inseparable on silica gel. However, this meant that initial separation of the C-8 epimers of the c/s-diol starting material was not necessary. Radical reduction (tributyltin hydride, AIBN, toluene, 80 °C) of the epimeric thiocarbonate mixture afforded the separable C-l deoxy products in 47% combined yield. Subsequent acetylation of the C-2 hydroxyl under standard conditions (Ac20, pyridine) gave 1-deoxysalvinorin A (169) in 82% yield. 

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