Reductive Demercuration in Deprotection of Trityl Thioethers, Trityl Amines, and Trityl Ethers

A room-temperature deprotection method of trityl amines, -ethers, and -thioethers is presented, based on coupling of metal acid catalysis (HgX2, with X- = Cl- or OAc-) and sodium borohydride reduction. The results of its application to monotritylated compounds (ethanethiol, ethanol, and piperidine)...

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Published in:Journal of organic chemistry 2001-11, Vol.66 (23), p.7615-7625
Main Author: Maltese, M
Format: Article
Language:English
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Summary:A room-temperature deprotection method of trityl amines, -ethers, and -thioethers is presented, based on coupling of metal acid catalysis (HgX2, with X- = Cl- or OAc-) and sodium borohydride reduction. The results of its application to monotritylated compounds (ethanethiol, ethanol, and piperidine) and to mono- and ditritylated 1,2-bifunctional compounds (mercaptoethanol, aminoethanethiol, and ethanolamine) are compared with those obtained with early methods based on the use of strong Brønsted acids (pure TFA and MeCN solutions of HCl). Trityl thioethers of simple thiols and amino and hydroxy thiols are promptly cleaved by reductive detritylation, and one-pot procedures can be employed to produce free thiols. In contrast, dilution with water of these same compounds in solutions of strong Brønsted acids leaves them unaffected. O−Tr and N−Tr bonds are broken by this latter treatment. However, trityl ethers are rapidly cleaved by even dilute HCl solutions, while cleaving of trityl amines is modulated by HCl concentration. Addition of NaBH4 to solutions of monofunctional trityl ethers in HgCl2/MeCN leads to complete deprotection. Monofunctional trityl amines are partially deprotected only if the complexation reaction is allowed to reach equilibrium. Combination of H+- with HgX+-catalyzed detritylation methods allows selective deprotection of pertritylated amino and hydroxy thiols. The results appear to be due to the strong difference in the affinity of the donor atoms present in the pertritylated substrates for H+ and HgX+. Catalysis based on Brønsted acids leads to cleaving of the N- and O-trityl bonds with recovering of the S-trityl group; that based on mercury salts allows recovering of N- and O-trityl groups with deprotection of the −SH function. Selectivity in deprotection of pertritylated amino alcohols seems to be severely hampered by similarity in the affinity of N- and O-atoms for H+ and HgX+, and, taking advantage of the lower HgX+-complexation rate of the N-trityl with respect to the O-trityl group, only preservation of the N-trityl bond has been achieved.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo0156971