2.2.2- Trichloroethyl carbonate cleavage

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). 

Few examples have been described of nucleophilic cleavage of carbonate- or carbamate-linked alcohols from insoluble supports. A serine-based linker for phenols releases the phenol upon fluoride-induced intramolecular nucleophilic cleavage of an aryl carbamate (Entry 2, Table 3.36). A linker for oligonucleotides has been described, in which the carbohydrate is bound as a carbonate to resin-bound 2-(2-nitrophen-yl)ethanol, and which is cleaved by base-induced 3-elimination (Entry 3, Table 3.36). Trichloroethyl carbonates, which are susceptible to cleavage by reducing agents such as zinc or phosphines, have been successfully used to link aliphatic alcohols to silica gel (Entry 4, Table 3.36). These carbonates can also be cleaved by acidolysis (Table 3.22). 

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. 

Hydration with boranes proved difficult due to extensive reductive cleavage of the epoxide (Scheme 45). The best results (54%) were achieved with borane in THF. The subsequent oxidation with basic hydrogen peroxide led to the primary alcohol as well as to saponification of the acetate. Selective protection of the primary alcohol 397 as trichloroethyl carbonate was followed by oxidation with RuCl3/NaI04, thereby producing not only the y-lactone but also the cyclic ketone. 

Ireland utilized a sulfide ring contraction process for the ring-forming step of his synthesis of 47 (see Scheme 1.16) The diethyl acetal of 5-hydroxyhexanal (73) was converted to the trichloroethyl carbonate and the acetal hydrolized to produce aldehyde 74 in 86% yield. Addition of the zinc enolate of N,N-dimethylethanethioamide (75) to 74 then afforded an intennediate hydroxy thioamide which was subjected to acylation and reductive carbonate cleavage to yield 76 (53%). Acylation with chloroacetyl chloride was followed by ring closure to give the macrocycle 77 (24%). 

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