Aminal esters synthesis

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

In the asymmetric total synthesis of the marine natural product, methyl sarcoate, the key step for the introduction of the chirality, was achieved by using an asymmetric Michael addition. Asymmetric addition of /-PrMgCl to aminal ester 93 in the presence of a catalytic amount of Cul, followed by acidic hydrolysis of the aminal function, afforded the chiral aldehyde 94 in 60% yield (Equation 10) <2005TL1263>. 

Uses Solvent for liquids, gases, vinyl resins, wire enamels polyacrylic fibers gas carrier catalyst in carboxylation reactions organic synthesis (manufacture of aldehydes, amides, amines, esters, heterocyclics). 

Amides contain an acid portion and an amine portion. However, unlike the formation of an ester, the reaction of a carboxylic acid with an cimine is not an efficient method for preparing an amide, because, as you see in this section, the simple reaction of an acid (carboxylic acid) with a base (amine) causes interference. Fortunately, methods similar to many of the other ester synthesis methods are useful in the synthesis of amides. 

Problem 21.2 Synthesize leucine, (CH,),CHCH,CH(NH,)COO, by (a) Hell-Volhard-Zelinsky reaction (Section 16.3) followed by ammonolysis. (b) Gabriel synthesis, (c) phthalimidomalonic ester synthesis, (d) reductive amination of a keto acid, (e) Strecker synthesis (addition of NH, HCN to RCH=0), (/) acetylaminomalonic ester. 

One of the best methods of amino acid synthesis is a combination of the Gabriel synthesis of amines (Section 19-20) with the malonic ester synthesis of carboxylic acids (Section 22-16). The conventional malonic ester synthesis involves alkylation of diethyl malonate, followed by hydrolysis and decarboxylation to give an alkylated acetic acid. 

The Gabriel-malonic ester synthesis is used to make many amino acids that cannot be formed by direct amination of haloacids. The following example shows the synthesis of methionine, which is formed in very poor yield by direct amination. 

Q Show how to make a given amino acid using one of the following syntheses Reductive amination, HVZ followed by ammonia, the Gabriel-malonic ester synthesis, and the Strecker synthesis. Problems 24-34, 35, 37, 38, and 39... 

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