Thiocarbonate derivative

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. 

Alcohols can readily be converted to carbonate and thiocarbonate derivatives. Under... 

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... 

Thiocarbonates derived from sec- and terUalcohols are more easily reduced than those of pnm-alcohols. This is because of the slightly stronger C-0 bond dissociation energy of thiocarbonates derived from pnm-alcohols than that of thiocarbonates derived from sec-and te/T-alcohols. This reaction can be carried out with Et3B at room temperature, instead of AIBN under refluxing conditions, as shown in eq. 2.15. 

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. 

The utility of thiol esters and carbonates as protecting groups is limited by their vulnerability to hydrolysis, The poor overlap between the non-bonded electrons on the sulfur atom (3p) and the n-system of the carbonyl (2p) precludes or diminishes resonance stabilisation of the type enjoyed by normal esters thereby raising their ground state energy, The carbonyl group of the thioester is more electrophilic than a normal ester and hence more reactive. Thiocarbonate derivatives are marginally more stable. The 5-benzoyl derivative of cysteine is 95% hydrolysed in 30 minutes with 2 M ammonia whereas the 5-benzyloxycarbonyl derivative is only 20% hydrolysed in 30 minutes under the same conditions.54... 

Tougheners for thermsettable polymers using polymeric thiocarbonate derivatives, (I), were previously prepared by the author [1]. 

Isopropenyl carbonates 236 were introduced by Sinay [363] and were used with TMSOTf as a promoter. Reactions of imidazole carbonate derivatives 237 were assisted by ZnBr2 [522], whereas for imidazole thiocarbonate derivatives 238, AgC104 was used as the promoter [523, 524]. These methods were used in the total synthesis of avermectin Bla 245 by Ley [523,524] (Scheme 4.47). 

Deoxygenation of alcohols. Thiocarbonate derivatives of alcohols are con veniently reduced to alkanes by potassium and 18-crown-6 in /-butylamine. 

Thiocarbonate derivatives of choline (262a, 262b) competitively inhibit acetylcholinesterase from various sources (332). 

The episulfides (82), (83), (84), and (87) react readily with potassium methylxanthate in methanol at room temperature to give crystalline tri-thiocarbonate derivatives. Assuming attack at the primary position,the reaction from (84) may be formulated as follows. 

A particular case is the use of a hydrogen sulfide salt instead of the thiol, to effect the fragmentation. Treatment of the thiocarbonate derived from cysteine with 2 equiv of potassium hydrogensulfide in methanol results in the formation of the potassium salt of thiocysteine in 85% yield (eq 2). ... 

Treatment of alkylsulfenyl methyl thiocarbonates derived from alkyl thiols and Scm-Cl with triphenylphosphine at 0 °C in benzene generates 5 alkyl methyl thiocarbonates in good yield (78% for alkyl = benzyl) (eq 13). Arylsulfenyl methyl thiocarbonates do not parallel this behavior vs. triphenylphosphine but they react cleanly with tributylphosphine (e.g., in dioxane-water) to generate the free arylthiol (see below).The reductive cleavage of alkylsulfenyl methyl thiocarbonates with trialkylphosphines (McsP, EtsP, BU3P) can be achieved with practically quantitative yields in protic solvents (THF-water) in the presence of acids... 

The 1-thio-D-glucose derivative (15) has been synthesised from the corresponding free sugar (12) by treatment with 5,5 -bis( 1-phenyl-l f-tetrazoI-5-yl)dithiocarbonate, As indicated in Scheme 3, a thiocarbonate derivative (14) was formed initially with concomitant liberation of thiol (13). Direct attack by this thiol at C-1 (path a) gave the main product (15) in 63% yield, whereas benzyloxy participation in the displacement at C-1 with attack by the nucleophile at C-6 (path b) gave its regio-isomer (16) which was isolated in 33% yield. The use of compound (15) in silver triflate promoted glycosylations is referred to in Chapter 3. 

Some cyclic thiocarbonates derived from carbohydrate 1,2-diols undergo O - ... 

The synthesis of deoxy-sugars from thiocarbonate derivatives is noted in Chapter 13. ... 

Similarly, anionic polymerization of six-membered cyclic thiocarbonate derivatives, 5,5-(bicyclo [2.2.1 ]hept-2-en-5,5-ylidene)-l,3-dioxane-2-thione and 5,5-(bicyclo[2.2.1]heptan-5,5-ylidene)-l,3-dioxane-2-thione, initiated by DBU afforded poly(MPOC) derivatives.It is worth mentioning that those... 

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