2,2,2-Trichloroethyl carbonate

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Alkyl 2,2,2-Trichloroethyl Carbonate (ROTroc) ROCO2CH2CCI3 (Chart 2)... 

Aiyl esters, prepared from the phenol and an acid chloride or anhydride in the presence of base, are readily cleaved by saponification. In general they are more readily cleaved than the related esters of alcohols, thus allowing selective removal of phenolic esters. 9-Fluorenecarboxylates and 9-xanthenecarboxylates are also cleaved by photolysis. To permit selective removal, a number of carbonate esters have been investigated aryl benzyl carbonates can be cleaved by hydrogenolysis aryl 2,2,2-trichloroethyl carbonates, by Zn/THF-H20. 

Aryl 2,2,2-Trichloroethyl Carbonate ArOCOOCH2CCl3 (Chart 4) Formation... 

Zn, THF-H2O, pH 4.2, 25°, 4 h. The authors suggest that selective cleavage should be possible by this method since at pH 4.2, 25°, 2,2,2-trichlo-roethyl esters are cleaved in 10 min, 2,2,2-trichloroethyl carbamates are cleaved in 30 min, and the 2,2,2-trichloroethyl carbonate of estrone, formed in 87% yield from estrone and the acid chloride, is cleaved in 4 h (97% yield). 

Trimethylbenzoate (Mesitoate) Ester 34. Methyl Carbonate 36. 2,2,2-Trichloroethyl Carbonate 39. Allyl Carbonate... 

Carbonates, like esters, can be cleaved by basic hydrolysis, but generally are much less susceptible to hydrolysis because of the resonance effect of the second oxygen. In general, carbonates are cleaved by taking advantage of the properties of the second alkyl substituent (e.g., zinc reduction of the 2,2,2-trichloroethyl carbonate). The reagents used to introduce the carbonate onto alcohols react readily with amines as well. As expected, basic hydrolysis of the resulting carbamate is considerably more difficult than basic hydrolysis of a carbonate. 

An excerpt from a synthesis of the phytosiderophore Nicotianamine illustrates the formation and cleavage of the 2,2,2-trichloroethyl carbonate protecting group [Scheme 4.357].676 Reaction of alcohol 357,1 with 2,2,2-trichloroethyl chloroformate and a catalytic amount of DMAP in pyridine gave the 2,2>2-tri-chloroethyl carbonate 357 2 in 98% yield. After oxidative destruction of the two p-methoxyphenyl rings to carboxylic acids and esterification, the 2224ri-chloroethyl carbonate 3573 was cleaved with zinc and acetic acid in 97% yield. 

Later work has shown that a dynamic kinetic asymmetric transformation could be obtained if the acetates were converted into carbonate groups. With the tetra(2,2,2-trichloroethyl) carbonate derivative, reactions with carbon and nitrogen nucleophiles gave exclusively the monosubstituted products in high yield (61-95%) and excellent enantiomeric excesses (95-99%). However, car-boxylate nucleophiles afforded the disubstituted products in high yield and enantiomeric excess (eq 7). This allowed an efficient synthesis of D-myo-inositol-l,4,5-trisphosphate to be devised. 

To a stirred soln of H-Met-OH (7.00 g, 46.9 mmol) in 1M NaOH (55 mL) in an ice bath was added Tboc-a (20.0 g, 94 mmol) and IM NaOH (12.5 mL) alternately in small portions over 7h under Nj. The mixture was stirred overnight, extracted with EtOAc (4 x 75 mL) to remove the bis(2,2,2-trichloroethyl) carbonate, the alkaline soln was chilled and acidified with HCl, which precipitated an oil. The oily... 

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