Amine protecting group for

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

Scheme 8.5. Enzyme-triggered fragmentation of protective groups for amines, alcohols and carboxylic acids.

The electrochemical behavior of a series of nitrobenzenesulfonamides (48 and 49) were examined by cyclic voltammetry and other techniques in connection with the use of such arenesulfonyl groups as protecting groups for amines. Interestingly, the behavior of the 2-nitro derivative 48a and the iV.iV-dialkyl 4-nitro derivative 49 differed from that of the 3-nitro and 4-nitro monosulfonamides 48b and 48c62. Ortfco-derivative 48a and 49... 

An alternative approach is the cleavage of a UV-active protecting group from the resin, such as the widely used Fmoc Test. The quantitation of the 9-fluorenyl-methyloxycarbonyl (Fmoc) protecting group for amines is used in SPPS as an indirect method to determine the extent of a peptide coupling reaction. Similar approaches have also been recently reported for the quantitation of supported thiols [151, 154] and have also been the subject of an excellent review [148]. 

Amines are important synthetic intermediates, and numerous protective groups have been developed for temporarily preventing amines from being acylated or alkylated. The following sections cover protective groups for amines that can be introduced or removed on insoluble supports. The development of such protective groups was mainly driven by solid-phase peptide synthesis. A more detailed collection of protective groups can be found in [230],... 

Most carbamates used as protective groups for amines are either acid-labile or base-labile. Deprotection proceeds by the mechanisms outlined in Figure 10.8. During the deprotection of acid-labile carbamates, carbocations are formed, which can alkylate electron-rich structural elements in a given substrate (e.g. phenols, thiols, indoles,... 

Figure 10.14. 01igo(iV-alkyl glycines) as protective groups for amines [293]. 

Enamines derived from simple ketones and aliphatic amines are too acid-labile and nucleophilic to be useful as protective group for amines. Triacylmethanes, however, form less basic enamines, which are sufficiently stable to be of use as amine protection. 

Several types of imine have been used as protective groups for amines in solution [230]. Most are stable towards bases, but can be hydrolyzed by acids. Benzophenone-derived imines can be prepared by treating support-bound aliphatic primary amines with benzophenone imine [148,260], but usually not by treatment with benzophenone. Polystyrene-bound benzophenone imines of glycine are sufficiently C,H-acidic to enable C-alkylation with alkyl halides [260,313] or Michael acceptors [314], and have mainly been used for this purpose (see Section 13.4.4). 

Carbamates have mainly been used in solid-phase synthesis as linkers and protective groups for amines (see Sections 3.6.2 and 10.1.10.1). Carbamates are generally prepared by treating amines with aryl carbonates or chloroformates, which can be prepared from alcohols and phosgene or synthetic equivalents thereof. The alternative route, in which carbamates, isocyanates, or carbamoyl chlorides are reacted with alcohols, is less widely used, but can also lead to satisfactory results on insoluble supports (Tables 14.7 and 14.8). 

Another useful protecting group for amines has the structure R—O—... 

Yamashiro et al. 1972), boron trifluoride etherate in acetic acid (Schnabel et al. 1971), trimethylsylil triflate (Schmidt et al. 1987), trimethylsilyl perchlorate (Vorbrueggen Krolikiewicz 1975), and, most frequently, trifluoroacetic acid (Farowicki Kocienski 1995 and references therein). Deprotection of the /-HOC group under neutral conditions was not described until recently, yet it is highly desirable. Now it has been found that the tert-butoxycarbonyl protecting group for amines, alcohols, or thiols is removed efficiently (90-99% yield) with use of 0.2 equivalent of cerium ammonium nitrate in acetonitrile at 80°C (Hwu et al. 1996) ... 

The different reactivity of 1,2- and 1,1-acceptor/donor-substituted alkenes is paralleled by the readiness with which these compounds can be prepared. Thus, /3-amino acrylates are often spontaneously formed by mixing amines with /3-keto esters, and these derivatives have been used as protective groups for amines because of their low reactivity. a-Amino acrylates can, similarly, be prepared from a-keto esters [40], but this condensation reaction does not proceed spontaneously and requires chemical or azeotropic removal of water [41—43]. a-Amino acrylates are unstable compounds which must be stored at low temperatures [41] or N-acylated immediately after their generation [43]. 

The possibility of employing a wide range of nucleophilic radical sources, including alcohols, the choice of ideal protecting groups for amines, and the possibility of extending this process to ketimines by the development of a catalytic system in which TiCLt is associated with Zn, enables us to anticipate new frontiers for the synthesis of new structural types of a-amino acids and other amino-derivatives of crucial importance for chemistry, medicine, and life. 

Kammari, L., Plistil, L Wirz, J. and Klan, P. (2007) 2,5-Dimethylphenacyl carbamate a photoremovable protecting group for amines and amino acids. Photochemical cl Photobiological Sciences, 6, 50-56. 

Du, H. and Boyd, M.K. (2001) The 9-xanthenylmethyl group a novel photo-deavable protecting group for amines. Tetrahedron Letters, 42, 6645-6647. 

Wang, B. and Zheng, A. (1997) A photosensitive protecting group for amines based on coumarin chemistry. Chemical et Pharmaceutical Bulletin, 45, 715-718. 

You will see this Boc group used as a protecting group for amines in Chapter 24. 

The use of azidoformates as protecting groups deserves special comment. Increased importance has been attached to the <-butoxy-carbonyl (BOG) function as a protecting group for amines due to the ease with which it may be introduced and removed " ° . Acylation may be carried out under mild conditions with -butoxy-carbonyl azide and subsequent removal of the BOG group may be... 

The -nitrobenzyl ester of cephalosporin has been cleaved cathodically to yield cephalosporin [65]. The widely used benzyloxycarbonyl protecting group for amines is cathodically removed, giving free amine, CO2, and toluene [66] ... 

---