Amines protection-deprotection

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

Finally, achiral phosphonium salts have been applied as Lewis acid catalysts in some other reactions. The examples will be listed here but not discussed in more detail. Phosphonium salts have been used as catalysts for the A,A-dimethylation of primary aromatic amines with methyl alkyl carbonates giving the products in good yields [123]. In addition acetonyltriphenylphosphonium bromide has been found to be a catalyst for the cyclotrimerization of aldehydes [124] and for the protection/ deprotection of alcohols with alkyl vinyl ethers [125, 126]. Since the pK of the salt is 6.6 [127-130], the authors proposed that, next to the activation of the phosphonium center, a Brpnsted acid catalyzed pathway is possible. 

The benzyne route to dibenzopyrrocoline alkaloids with the 1-benzyltetrahy-droisoquinolines (40) listed in Table II was investigated by Kametani et al. (28), Kessar et al. (29), and Gibson and Ahmed (31). Secondary amines protected as 7-0-benzyl ethers, affording unstable tetrahydro intermediates with benzyl ether functions difficult to deprotect, were less favored than the corresponding N-methyl-substituted analogs, affording the desired quartemary alkaloids directly. 

Initially, the Boc group was used for reversible a-amine protection and most side-chain functional groups were protected as benzyl derivatives, which are stable to Boc removal in HC1 or TFA. This Boc/Bzl strategy is still frequently used and is the method of choice in several laboratories. It has, however, been replaced in many laboratories by the base-labile Fmoc group, which allows weak acid deprotection of tert-butyl groups from the side chains. For short- and moderate-sized peptides both systems are effective. For protein synthesis, the relative merits have not yet been fully established. 

The ability of [18]crown-6 derivatives to complex primary alkylammonium ions has been elegantly exploited in the protection of primary amines (80CC300). In the presence of primary amines, secondary amines can be acylated selectively by adding [18]crown-6 and a proton source. This strategy has obvious advantages over normal amine protecting groups which require a deprotection step. 

Nitro- or 2,4-dinitrobenzenesulfonamides of primary or secondary amines can be hydrolyzed under mildly basic conditions, and are increasingly being used for amine protection (see Section 10.1.10.7 [123,139,140]). /V-(2-Nitrobenzenesulfonyl)amino acids can be used as an alternative to TV-Fmoc amino acids for the solid-phase synthesis of peptides [141]. Deprotection is achieved by treatment of the polystyrene-bound sulfonamide with a solution of PhSH (0.5 mol/L) and K2C03 (2 mol/L) in DMF for 10 min at room temperature [141], conditions that do not lead to cleavage of esters (e.g. of the Wang linker) or to racemization. The condensation of polystyrene-bound sulfinamides H2N-SO-Pol with aldehydes yields /V-sulfinylimines, which add... 

The 4-ethoxy-l-naphthyloxycarbonyl group is a valuable electrochemically labile protecting group for alcohols and amines. The deprotection of bomeol 105 and gerani-... 

A big improvement has been made in synthesis of cyclen. For a long time, the amine has been available mostly through classical so-called tosylamide synthesis <1974JA2268>. The method is atom noneffective , as most of molecular mass disappears by removal of the sulfonate group. Furthermore, harsh deprotection conditions can interfere with numerous functional groups. The method is time consuming when the protection-deprotection strategy is used. 

The second part deals with the grafting of amines or alcohols with protection/ deprotection methods and the third one presents the grafting of alkenes bearing free hydroxyl or acid functions. Finally, a table summarizing all experiments is also presented. 

In many cases, the electrochemical technique recently developed has been shown to be a fruitful alternative to chemical deprotection. Thus, organic chemistry functions that are mainly involved in protection/deprotection processes are mostly aldehydes and ketones, amines, alcohols, and thiols carboxylic acids can also be quoted, although their esterification as well as their ester hydrolyses are not straightforward. 

Method A An appropriate N-Fmoc-protected amino add resin (100 mg, 0.06 mmol for the Sasrin-support-immobilized amines) was deprotected by treatment with 20% piperidine in DMF for 30 min. The resin was then filtered off, washed Hberally with DMF, MeOH, and CH2CI2, and dried under... 

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