Benzyloxycarbonyl group protecting amines with

The benzyloxycarbonyl protecting group for amines is introduced in high yield using benzyl imidazole-carboxylate with a catalytic amount (5%) of dimethylamino-pyridine.[1953... 

The first procedure is the selective protection of an amine in the presence of an indole-NH group or an alcohol.14 Indole-NH (pKa = 17) shows a similar acidity to that of alcohols (pKa = 18). In the next step the benzyloxycarbonyl (CBZ) protected compound 26 is treated with di-fcrt-butyldicarbonate (B0C)20 and DMAP to form 27. Tert-butylchloroformate is unstable and therefore cannot be used for the preparation of BOC derivatives. Conversion of 10 with (B0C)20 in the presence of DMAP would lead to the double BOC protected compound 28. 

Another protecting group often employed for amines is the benzyloxycarbonyl group. The chemistry here is reminiscent of that of the BOC group in that the amine is protected by conversion to a carbamate. This time an acyl chloride derivative, car-bobenzoxy chloride, rather than an acid anhydride derivative, is reacted with the amine. 

Alternatively, compound 14 was oxidized with sodium periodate, followed by reduction with sodium borohydride in ethanol to afford 18 (Scheme 3). Hydrolysis of the isopropy-lidene group in 18 with 50% aqueous trifluoroacetic acid followed by hydrogenation of the azide group and then intramolecular reductive amination and protection of the imine group afforded 19. Selective mesylation of the primary hydroxyl group in 19 followed by silylation and subsequent removal of the benzyloxycarbonyl group and then cyclization with sodium acetate afforded 20. Deprotection of 20 led to me50-quinuclidine-3,5-diol (3). 

The best known group of this class is the t-butyloxycarbonyl(t-BOC) (45). Since its introduction as an amino-protecting group in peptide synthesis about seven years ago it became second in use only to the benzyloxycarbonyl group. Due to the instability of t-butylchloro-formate the /-butyloxycarbonyl derivatives are obtained by reaction of the corresponding isocyanate with t-butanoD or by the action of the amine with t-butyl-/ -nitrophenyl carbonate t-butylazido-formate , <-butylcyanoformate , t-butyl JV-hydroxysuccinimide... 

N-Acylation and 3-alkoxycarbonylation reactions may be achieved by conventional acylation procedures. A variety of 3-acyl derivatives 157 can be prepared most conveniently by the treatment of DPPOx 266 with carboxylic acids in the presence of a tertiary amine. tert-Butoxycarbonyl (Boc-Ox, 236) and benzyloxy carbonyl (Cbz-Ox, 267) (Cbz = benzyloxycarbonyl) compounds are of practical use for introduction of nitrogen protecting groups. ... 

However, most nucleophiles attack 5-oxazolones at the carbonyl group and the products are derivatives of a-amino acids formed by acyl-oxygen fission. Thus the action of alcohols, thiols, ammonia and amines leads, respectively, to esters, thioesters and amides orthophosphate anion gives acyl phosphates (Scheme 18). The use of a-amino acids in this reaction results in the establishment of a peptide link. Cysteine is acylated at the nitrogen atom in preference to the sulfur atom. Enzymes, e.g. a-chymotrypsin and papain, also readily combine with both saturated and unsaturated azlactones. A useful reagent for the introduction of an a-methylalanine residue is compound (202). Both the trifluoroacetamido and ester groups in the product are hydrolyzed by alkali to give a dipeptide. The alkaline hydrolyzate may be converted into the benzyloxycarbonyl derivative, which forms a new oxazolone on dehydration. Reaction with an ester of an amino acid then yields a protected tripeptide (equation 45). 

Butyl chloroformate reacts with cysteine to protect both the amine and thiol groups as with N,S-bis(benzyloxycarbonyl)cysteine, selective or simultaneous removal of the N- or S-protective groups can be effected.1... 

One of the syntheses mentioned there started with 3-pyrazolidinone 236, which was protected as the benzyloxycarbonyl derivative 237 in order to obtain selective N-alkylation at position 8 yielding compound 238 after removal of the protecting group. Addition of the resulting amine 238 to l-octyne-3-one 239 formed the enone 240 with the complete diazaprostanoid skeleton. Katalytic... 

For the reversible immobilization of amines to such linkers, the most frequently used strategy is conversion of the hydroxymethyl linkers into activated carbonic esters (Figure 14.7) [8, 39, 40]. These react with primary and secondary amines or hydrazines to form immobilized carbamates or carbazates analogous to the classical benzyloxycarbonyl protecting group. Amines and hydrazides attached by this strategy to Wang resin can be cleaved with TFA [8, 40]. 

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