F-BUTYL AZIDOFORMATE

LA Carpino, BA Carpino, PJ Crowley, PH Terry. f-Butyl azidoformate. Org Syntheses 15, 1964. 

Isodrin (56) gives with f-butyl azidoformate an isolable triazoline (addition in position QQ) which decomposes into aziridine by chromatography over neutral alumina. 55 With tosyl azide, on the other hand, only the aziridine derivative could be isolated. Both aziridines undergo a series of transformations leading to a so-called bird-cage hydrocarbon 57. ... 

Isodrin, used for the synthesis of cagelike compounds, forms an exo adduct with f-butyl azidoformate (Scheme 16).134... 

Acylation, of amines with f-butyl azidoformate, 44, 17 of enamines by add halides, 43, 34 of ethyl acetoacetate by y-carbeth-oxybutyryl chloride, 42, 41 of mesitylene with oxalyl chloride, 44, 69... 

The reagent is prepared1 by the reaction of carbonyl chlorofluoride2 with /-butanol. Like f-butyl azidoformate, the reagent reacts with amino acids to give t-butyloxy-carbonylamino acids (BOC-amino acids).1... 

PEPTIDE SYNTHESIS r-Amyl chloro-formate. f-Butyl azidoformate. Diethyl methyleneraalonate. N-Ethoxycarbonyl-2-ethoxy-l,3-dihydroquinoline. Hexamethylphosphoric triamide. 1-Hydroxybenzo triazole. Triphenylphosphine—2,2 -Dipyridyl disulfide. Triphenyl phosphite. 

The functionalized allene, DIMETHYL 2,3-PENTADIENEDIOATE, the first in the series, is an intriguing substrate for various addition and cycloaddition reactions. Finally, a new reagent, DI-ferf-BUTYL DICARBONATE, for he formation of A-f-BOC derivatives which eliminates the use o the hazardous fert-BUTYL AZIDOFORMATE (WARNING) is intrqduced. 

OButyl azidoformate, a useful protective group for primary and secondary amino groups,4 0 has been prepared previously from f-butyl carbazate.3 The present procedure7 is a more convenient preparative method. 1 he intermediate carbonic phosphoric anhydride reacts with nucleophiles other than the azide ion in this preparation. Reaction of this anhydride with amines yields the t-butoxycarbonyl derivatives of amines.7 Other carbonic phosphoric anhydrides have been prepared by procedures analogous to the method described here.8... 

AMINO GROUP f-Amyl chloroformate. r-Butyl azidoformate. 9-Fluorenyl-methyl chloroformate. 

The f-butoxycarbonyl group (Boc, 7-box ) has been extensively used in peptide synthesis, and Boc derivatives of many amino acids are commercially available. The customary reagent for the preparation from the amine is t-butyl azidoformate in water, dioxane/water, DMSO, or DMF. The cleavage by acids of medium strength proceeds with concomitant loss Of isobutene and carbon dioxide (L.A. Carpino, 1957, 1973 see section 4.1.2.2). 

Although t-butyl azidoformate [373-375], t-butyl p-nitrophenyl carbonate [376], and f-butyl cyanoformate [375] have been recommended as t-butoxycarbonylating reagents, these cannot be synthesized as easily as benzyloxycarbonyl chloride. 

Sulfenamides. /er/-Butyl azidoformate added dropwise during 0.5 hr. at room temp, under Ng to a stirred mixture of 2-methyl-2-propanethiol and cuprous diloride, stirring continued 10 hrs. at room temp. N-/er -butoxycarbonyl-2-methyl-2-propanesulfenylamide. Y 77%. - Similarly with tert-hMiy azidoacetate N-fer/-butoxycarbonylmethyl-2-methyl-2-propanesulfenylamide. Y 64%. F. e. and products s. T. Saegusa, Y. Ito, and T. Shimizu, J. Org. Chem. 35, 2979 (1970). 

Related Reagents. t-Butyl Azidoformate f-Butyl Chloro-formate l-A(-(t-Butoxycarbonyl)-l//-benzotriazole 3-A-Oxide 1 -(t-Butoxycarbonyl)imidazole 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile A/ -(t-Butoxycarbonyloxy)phthalimide N-(7-Butoxycarbonyloxy)succinimide 1-r-Butoxycarbonyl-1,2,4-tri azole. 

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