TCBoc

The TCBOC group is stable to the alkaline hydrolysis of methyl esters and to the acidic hydrolysis of r-butyl esters. It is rapidly cleaved by the supemucleophile lithium cobalt(I)phthalocyanine, by zinc in acetic acid, and by cobalt phthalocy-anine (0.1 eq., NaBH4, EtOH, 77-90% yield). 

Figure lZpl Total synthesis of (-)-Pateamine A.TBS, t-butyldimethylsilyl TIPS, triisopropyl silyl TCBoc, trichloro t-butoxycarbamate DIAD, diisopropyl azodicarboxylate. 

CBz = (benzyloxy)carbonyl, TCBoc = (2,2,2-trichloro-1,1 -dimethylethoxy)carbonyl, ... 

Scheme 5.4.4 Two approaches for the preparation of (-)-pateamine A (dba dibenzylideneacetone, TCBoc (3, (3, (3 -trichloro-tert-butoxycarbonyl)...

Protection of amino groups. Amino acids are converted to TCBpC-protected amino acids by reaction with 1 under the usual Schotten-Baumann conditions (80-95 7o yield). The products are nicely crystalline and are readily soluble in organic solvents. The TCBOC group is stable to N NaOH (40°, 2 hours) and to TFA (20°, 2 hours). The protecting group can be cleaved, as expected, with zinc in acetic acid or by reaction with lithium cobalt(I)-phthalocyanine. 

The Trichloro-tert.-butoxy-carbonyl (TCBOC) group survives the cleavage conditions of most other protective groups, and is cleaved under very mild conditions by PcCo a reagent that does not affect the other customary blocking groups (ref. 6). 

The use of TCB as the phosphite/phosphate protection and of TCBOC for the protection of the exocyclic amino functions of the bases enables an uniform deprotection strategy. Nevertheless care is necessary a study of the influence of the electron withdrawing properties of guanosine 2-N-protecting groups on the stability of guanosine revealed relative de-stabilisation by TCBOC vs. p-tert.-butyl benzoyl. 

H. Eckert, M. Listl and I. Ugi, Der 2,2,2-Trichlor-tert.-butyloxycarbonyl-(TCBOC)-Rest, eine saure- und basestabile, schonend abspaltbare Schutzgruppe, Angew. Chem. 90 (1978) 388-389 Angew. Chem. Int. Engl. 17 (1978) 361-362. 

X.X. Zhou, I. Ugi and J. Chattopadhyaya, A Convenient Preparation of N-protected Nucleosides with the 2,2,2-Trichloro-terrt-butyloxycarbonyl (TCBOC) Group. Structural Assignment of N,N-bis-TCBOC-Guanosine and its Deoxy Analogue, Acta Chem. Scand, B39 (1985) 761-765. 

The chloroformate of the tertiary alcohol l,l,l-trichloro-2-methylpropan-2-ol 90, 2,2,2-trichloro-tert-butyl chloroformate 91 (TCBoc-Cl), is a reagent that can be used to introduce the TCBoc protective group, and is stable under acidic and basic con-... 

Trichloro-t6rt-butoxycarbonyl TCBoc Zn in AcOH at room temp., or supemudeophiles such as li[Co Pc], Pc — phihalocyanine... 

The TCBoc group can be introduced by means of the stable and distillable chloroformate 564, which is readily accessible from 2,2,2-trichloro-tert-butanol (chloretone) 563 and phosgene in dichloromethane or pyridine. Chloretone itself is an inexpensive commerdally available reagent. 

Reaction of chloroformate 564 with amino acids or peptide esters can be accomplished under the usual Schotten-Baumann conditions. Thus, on treatment with 564, valine affords the TCBoc-protected amino acid in good yield [403]. 

Valine (11.7 g, 0.1 mol), dissolved in water (200 mL) and 1 n sodium hydroxide solution (250 mL), was treated with diethyl ether (100 mL) and then emulsified at 0 °C with TCBoc-Cl (33.8 g, 0.14 mol) in dioxane (140 mL) for 1 h. The aqueous phase was washed with diethyl ether, acidified with 5 n hydrochloric acid, and extracted with ethyl acetate. After washing the combined extracts with water, TCBoc-valine (26 g, 82%) crystallized from the ethyl acetate extract the product was recrystallized from hexane mp 102 °C. 

The use of triphosgene as an acid activator has been reported in several recent applications. Eckert and Seidel activated the N-protected amino acid Tcboc-valine 1351 (Tcboc = 2,2,2-trichloro-fert-butyloxycarbonyl [1022] for a preparation, see also Section 4.3.2.1) with triphosgene/DMF/TEA for racemization-free coupling with valine benzyl ester to afford Tcboc-Val-Val-OBn in 85% yield [1023, 1024]. 

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