2,2,2-Trichloro-t-butoxycarbonyl Chloride

[66270-36-8]  · C5H6Cl4O2  · 2,2,2-Trichloro-t-butoxycarbonyl Chloride  · (MW 239.91)

(easily removable acid- and base-stable protecting group for nitrogen, including amino acids1 and nucleosides;2 protecting group for alcohols3,4)

Alternate Name: TCBOC-Cl.

Physical Data: mp 30-32 °C; bp 77-81 °C/12 mmHg.

Form Supplied in: colorless solid; commercially available.

Preparative Method: from trichloro-t-butanol with Phosgene1 or triphosgene (Bis(trichloromethyl) Carbonate) (eq 1).5

Handling, Storage, and Precautions: moisture sensitive.

General Discussion.

As a protecting group for amines, the TCBOC group is stable to acid and base conditions normally used to remove Boc groups (e.g. TFA) or to hydrolyze methyl esters (NaOH-methanol).1 The TCBOC group is attached under standard Schotten-Baumann conditions (eq 2). In addition to the reductive conditions6 originally described for removal of the TCBOC group (eq 3), sodium-2-thiophenetellurolate7 and zinc-acetylacetone8 (neutral conditions) also deprotect in high yield. Nucleosides,2,8 indoles,7,9 indolines,7,10 and anilines7 have been N-protected with the TCBOC group.

The TCBOC group is useful as an alcohol protecting group (eq 4). Horner-Emmons reagent (3) is stable below 0 °C and can be used to prepare a-keto esters (eq 5).3 As an alcohol protecting group the TCBOC group is not stable to aqueous base,4 in contrast to its use as an amine protecting group.

1. Eckert, H.; Listl, M.; Ugi, I. AG(E) 1978, 17, 361.
2. Zhou, X.-X.; Ugi, I.; Chattopadhyaya, J. ACS 1985, 39B, 761.
3. Horne, D.; Guadino, J.; Thompson, W. J. TL 1984, 25, 3529.
4. Srivastava, R. P.; Hajdu, J. TL 1991, 32, 6525.
5. Eckert, H.; Forster, B. AG(E) 1987, 26, 894.
6. Eckert, H.; Kiesel, Y. S 1980, 947.
7. Lakshmikantham, M. V.; Jackson, Y. A.; Jones, R. J.; O'Malley, G. J.; Ravichandran, K.; Cava, M. P. TL 1986, 27, 4687.
8. Ueno, Y.; Mishima, T.; Hotoda, H.; Hata, T. CL 1992, 595.
9. Raucher, S.; Macdonald, J. E.; Lawrence, R. F. JACS 1981, 103, 2419.
10. Drost, K. J.; Jones, R. J.; Cava, M. P. JOC 1989, 54, 5985.

Scott McN. Sieburth & Elena Doval Santos

State University of New York at Stony Brook, NY, USA

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