Protection of a-amino groups

The protection of a-amino groups is usually effected with allyl chloroformate under Schotten-Baumann conditions,P but diallyl dicarbonate (AI0C2O) can also be used.P As with other chloroformates, a severe side reaction is the formation of A -Aloc-protected dipeptides. Since most A -Aloc amino adds are not crystalline compounds, they are preferentially isolated as the corresponding DCHA salts (for A -Aloc amino acids and their analytical characterization, see reff l). 

Aminopalladation and subsequent carbonylation are also facile reactions. The carbonylation of substituted 3-hydroxy-4-pentenylamine as a carbamate (254) proceeds smoothly via the aminopalladation product 255 in AcOH to give 256[228). The protection of the amino group of the carbamate as tosyl amide is important in the carbonylation of 257 to give 258[229],... 

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. 

In laboratory-scale homogeneous catalysis applications, in the last decade further investigations have been carried out in which a less soluble organo-metallic catalyst system was utilized for metathesis reactions [46]. Under RCM-conditions, it was possible to convert substrates with functional groups that were problematic due to their potential to inactivate the rutheniiun catalyst here, the conversion in supercritical carbon dioxide avoids the protection of critical amino groups as an additional synthetic step. Consequently, it was possible to synthesize a number of carbo- and heterocyclic products with varying ring size (C4 to Cie). 

Tertiary electrophiles alkylate bydroxylamines through the SatI mechanism. These reactions (e.g. equation 10) are practically feasible only for compounds forming highly stabilized carbocations such as trityl , or 2-(p-alkoxyphenyl)propyl. All these reactions proceed exclusively on the nitrogen atom and have been used for A-protection of the amino groups in bydroxylamines. 

Minisci and coworkers followed Ishii s procedure, and implemented it in the oxidation of benzyhc alcohols to benzaldehydes in almost quantitative yields" (Table 12). A,Af-dimethylbenzylamines were converted into aldehydes in good yields, by using catalytic amounts of either HPI or A-hydroxysuccinimide (HSI) for the formation of the corresponding aminoxyl radical intermediates. Because the attempted oxidation of primary and secondary amines caused the degradation of catalyst HPI, protection of the amino group in those substrates by acetylation was considered. This led one to develop... 

Similarly, very useful yields and diastereoselectivities were observed on alkylation of (5R)-2,3,5,6,-tetrahydro-5-phenyl-A-(ter/-butoxycarbonyl)-4/f-l,4-oxazin-2-one (7)92, The latter is available from (A)-phenylglycinol and phenyl 2-bromoacetate with subsequent protection of the amino group. The influence of the base, the counterion and the solvent was studied for this example. Sodium hexamethyldisilazanide in tetrahydrofuran/dimethoxyethane turned out to be by far the best conditions for deprotonation. Also, it seems to be essential that the base is added to the chilled solution of 7 and not vice versa. 

Thus, the 1,4-addition of the lactams 72 to nitroolefins provided access to the Michael adducts 73 with good stereoselectivities, which could be improved by recrystallization or chromatography. After reduction and protection of the amino group the y-butyrolactams 74 were converted to the corresponding a-substituted lactams 75 in good overall yields (37-65%) and excellent diastereo- and enantio-... 

The statine-like moiety in one of the first drugs, saquinovir (23-8), comprises a transition state mimic for the cleavage of phenylalanylprolyl and tyrosylprolyl sequences. Constmction starts with the protection of the amino group of phenylalanine as its phthaloyl derivative (Phth) by reaction with phthalic anhydride this is then converted to acid chloride. The chain is then extended by one carbon using a Friedel-Crafts-like reaction. The required reagent (21-2) is prepared by reaction of the enolate obtained from the /7A-silyl ether (21-3) of glyoxylic acid and lithio... 

Introducing the Tau residue into a peptide according to the first approach demands protection of the amino group, usually in the form of a Z-derivative and turning the sulfonic acid into sulfonyl chloride. Synthesis of (j-su Ifonamidopeptides via an iterative process, both in solution and in the solid phase, has been described.11201 Chiral methylene sulfinamide peptides can be synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions (DMAP catalysis and excess methyl trimethylsilyl dimethylketene acetal as a proton trap).11261... 

A few methods for the esterification of 1-aminoalkylphosphonic adds have been developed for use when diesters of 1-aminoalkylphosphonic acids are the preferred starting materials for peptide synthesis. 8 In general, 1-aminoalkylphosphonic acids cannot be esterified under conditions that work for amino acids, and protection of the amino group is absolutely essential. Diethyl 1-aminoethylphosphonate [9, Alap(OEt)2] is synthesized from Alap in two steps (Scheme 6). Orthoformates are highly recommended because esterification is almost quantitative. 24 ... 

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