Amine protection carbamate

Amine protection. Carbamate formation from amines and the reagent 1 is facile,... 

Amine protection. Carbamates are formed at room temperature or below. The removal of the protecting group, is most expediently achieved by treatment with a polymer-bound secondary amine. The released fragment is trapped and the isolation of amines is uncomplicated. 

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

The cyanomethyl ether, formed from bromoacetonitrile (acetone, K2CO3, 97-100% yield), is cleaved by hydrogenation of the nitrile with Pt02 in EtOH, in 98% yield. The method has also been used for the protection of amines and carbamates. 

The procedure has been extended to the synthesis of 7V,7V -substituted diamines 166 from the diazides 164 and dichloroboranes 165177. Primary amines protected by the t-butoxycarbonyl group are obtained by the action of trialkylboranes R3B (R = Bu, s-Bu, CsHn or cyclohexyl) on the lithium or potassium salt of t-butyl 7V-(tosyloxy)carbamate (equation 62)178. 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

Notes An important functional group for protecting amines as carbamates and alcohols as benzyl carbonates. Notable for the protection of amino acids during peptide synthesis. 

Carbamates are by far the most common type of amine protection used in solid-phase synthesis. Various types of carbamate have been developed that can be cleaved under mild reaction conditions on solid phase. Less well developed, however, are techniques that enable the protection of support-bound amines as carbamates. Protection of amino acids as carbamates (Boc or Fmoc) is usually performed in solution using aqueous base (Schotten-Baumann conditions). These conditions enable the selective protection of amines without simultaneous formation of imides or acylation of hydroxyl groups. Unfortunately, however, Schotten-Baumann conditions are not compatible with insoluble, hydrophobic supports. Other bases and solvents have to be used in order to prepare carbamates on, for example, cross-linked polystyrene, and more side reactions are generally observed than in aqueous solution. 

Various functional groups can be protected and released in high yields, such as alcohols (as ethers), carboxylic acids (as esters), amides (as amides), and amines (as carbamates). In the latter case, however, two drawbacks must be noted ... 

Amines, protection of, 309-405 as amides, 348-362 Reactivity Chart 9, 445-449 as carbamates, 315-348 Reactivity Chart 8, 441-444 as special derivatives, 362-385 Reactivity Chart 10, 449-452 Amino acetal derivatives, to protect amines, 392-394... 

Benzyl groups are the second fiddles of the amine protection repertoire, and they are especially useful when a substrate is to be subjected to powerful orga-no metal lie reagents or metal hydrides which might attack a carbamate. Benzyl-amines are not generally cleaved by Lewis acids under preparatively useful conditions. The following discussion embraces benzylamines, diphenylmethylamines and their methoxy-substituted derivatives. 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Now the epoxide 41 was opened regioselectively and stereospecifically with azide ion to give the trans di-axial product 42 that was reduced to the amine 43. The synthesis of fortamine 44 was completed by the removal of the protecting carbamate.4... 

Rather unusually, a method has been developed for the photoprotection of amines using the N-benzyloxycarbonyl (iV-Cbz) and N-9-fluorenylmethoxycar-bonyl (iV-Fmoc) derivatives of 5,7-dinitroindoline (51) and (52). ° These reagents allow efficient protection of primary and secondary amines as carbamate (iV-Cbz or N-Fmoc) derivatives in neutral conditions, by UV irradiation (350 nm) of a mixture of the amine with either (51) or (52). It is possible, moreover, to premix the reagents and then photolytically trigger the acylation reaction later. The mechanism of the overall protection reaction does not appear to have been determined, but formally it involves photorelease of the Cbz or Fmoc moiety from the indoline. Bulky amines and anilines gave low yields or no product, and... 

Even though the efficiency of deprotection of a-substituted nitrobenzyl carbamates as an amine protecting group had been published by Schofield [2] (6) in 1966, and later by Woodward [18] (7), it took 20 years more for a-substituted nitrobenzyl linkers to be applied to solid phase synthesis to decrease photo-byproduct formation (Figure 17.3). 

Appending the quinoxaline ring system to benzazepine 6 required amine protection before the dinitration reaction. The fused bicyclic system imposes close proximity of the nitrogen atom to the aromatic ring. As a result, the amine and sp -protected forms (amides and carbamates) unexpectedly inhibited electrophilic aromatic substitution (equations a and b. Scheme 3.6). We suspected that interactions of electrophilic reagents with the amine or protected amines generated competing... 

Amine protection. Amino groups present in oligonucleotides are readily protected with this activated carbonate 1 in the form of carbamates. 

Amine protection. Compared to simple 0-(9-fluorenylmethyl) carbamates, the t-butyl substituents make them more soluble. On deprotection by treatment with 20%... 

Carbamates. The Boc group is suitable for amine protection in hydroboration eactions. Thus, amino alcohols are synthesized from unsaturated amines via the IV-Boc aerivatives. The cleavage is effected with basic hydrogen peroxide. 

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