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Synthesis 2009(21): 3633-3641  
DOI: 10.1055/s-0029-1216974
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

(2,6-Dichloro-4-alkoxyphenyl)-(2,4-dichlorophenyl)methyl Trichloroacet­imidates: Protection of Alcohols and Carboxylic Acids in Solution or on Polymer Support

Michio Kurosu*, Kai Li
Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523-1682, USA
Fax: +1(970)4911815; e-Mail: michio.kurosu@colosate.edu;
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Publication History

Received 24 April 2009
Publication Date:
28 August 2009 (online)

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Abstract

(2,6-Dichloro-4-methoxyphenyl)-(2,4-dichlorophenyl)­-methyl trichloroacetimidate can be efficiently activated by TMSOTf­ (10˜100 mol%) to react with alcohols and carboxylic acids­. Under these conditions a wide variety of alcohols can be transformed into the corresponding ethers in excellent yields with a slight excess of the trichloroacetimidate. The resulting ethers are not susceptible to typical deprotection conditions for benzyl and 4-methoxybenzyl ether groups, however, they can be conveniently deprotected by treatment with 30˜50% trifluoroacetic acid in dichloromethane. Polymer-bound (2,6-dichloro-4-alkoxyphenyl)-(2,4-dichlorophenyl)methyl trichloroacetimidate is useful for immobilization of alcohols and carboxylic acids.

Key words

protecting group - alcohols and carboxylic acids - diphen­ylmethyl ester derivative - polymer-bound - linker

    References

  • 1a Pearson AJ. Roush WR. Handbook of Reagents for Organic Synthesis: Activating Agents and Protecting Groups   Wiley; New York: 1999. 
  • 1b Greene TW. Wuts PGM. In Protective Groups in Organic Synthesis   3rd ed.:  John Wiley and Sons; New York: 1999. 
    Search in Google Scholar
  • 2 Nakajima N. Horiat K. Abe R. Yonemitsu O. Tetrahedron Lett.  1988,  29:  4139 
    CrossrefSearch in Google Scholar
  • 3a Hanessian S. Xie F. Tetrahedron Lett.  1998,  39:  733 
    Search in Google Scholar
  • 3b Yan LZ. Mayer JP. J. Org. Chem.  2003,  68:  1161 
    Search in Google Scholar
  • 4a Nwoye EO. Dudley GB. Chem. Commun.  2007,  1436 
  • 4b Robles J. Pedroso E. Grandas A. Int. J. Pept. Protein Res.  1996,  43:  359 
    Search in Google Scholar
  • 5 Kurosu M. Biswas K. Crick DC. Org. Lett.  2007,  9:  1141 
    CrossrefSearch in Google Scholar
  • 9 Ali IAI. Ashry ESHE. Scmidt RR. Eur. J. Org. Chem.  2003,  4121 
    Crossref
  • 11 For optimized conditions for the formation of ester linkages with Fmoc-protected amino acids, see: Colombo A. Figuera ND. Fernández JC. Fernández-Forner D. Albericio F. Forns P. Org. Lett.  2007,  9:  4319 
    CrossrefSearch in Google Scholar
6

The ether 6l (Table  [²] ) was stable under hydrogenation with 10% Pd/C in MeOH at 150 psi.

7

The imidate 4 did not react with tertiary alcohols under the same protection conditions for primary and secondary alcohols.

8

In our studies the free alcohol at the C2′-position of uridine derivatives are generally more reactive than those at the C3′-position. For example, tritylation (2 equiv) of 5t furnished the C2′,5′-ditritylated product.

10

The yield was determined by ¹H NMR analysis using an internal standard (1-bromo-4-methoxybenzene).

12

Selective ether formation with the primary alcohols of 5s, 5u, and 5v were confirmed by acetylation of the unreacted secondary alcohols (Ac2O, pyridine, CH2Cl2) and subsequent cleavage of the generated molecules on the polymer support.

13

We have synthesized a variety of ethers with optically active alcohols and 4. Signal separation for a diastereomeric mixture of the ethers was observed in ¹H NMR spectra. However, so far, no good separation of the diastereomers of 6 was observed on TLC except in the case of 6e.

14

Detailed procedures for the cleavage of esters formed on resin 9 are given in reference 5.