Esterification alkoxycarbonylation

Amino alcohols can be resolved by a number of pathways including hydrolysis, esterification, and transesterification. For example, hydrolysis of Ai,0-diacet5l-2-amino-l-butanol with PPL followed by recrystallization results in (80a) with 95% ee (108). Hydrolysis of racemic acetates or butyrates of 2-[(aLkoxycarbonyl)amino]-l-aLkanols with PFL gives (R)-alcohol (81) with 95% ee (109). (3)-(81) can be obtained by transesterification of the racemic (81) with ethyl acetate which also serves as the reaction medium (109). 

Oxidation of the iV-alkoxycarbonyl-2-azabicyclo[2.2.0]hex-5-ene 158 with ruthenium tetroxide followed by esterification with diazomethane affords the cis-2,3-diester of azetidine 159 (R = Me) in 67% overall yield. The N-protecting group can be easily removed from the diacid by acidic hydrolysis to give acidic amino acid 160 in 85% yield. Strangely, the 2,3-diester 159 (R = Me) upon acidic hydrolysis failed to give any of the amino acid. This approach to azetidines is useful because 158 is readily available from pyridine in three steps <2003CPB96>. 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

The most extensively studied derivatization procedures for amino acids are (a) esterification followed by acylation, and (b) cyclization of the a-aminocarboxylic acids to oxazolidinones, followed by acylation. Other significant procedures include (c) alkoxycarbonylation followed by esterification, and (d) trimethyl-silylation. Comments on all four procedures are given below... 

Alkoxycarbonylation followed by esterification provides an attractive alternative derivatization method for amino acid quantitation (Yamamoto et al., 1982 Makita et al., 1982). N-Alkoxycarbonyl methyl esters are prepared by a two-step procedure involving the use of an alkyl chloroformate in aqueous medium, followed by esterification with diazomethane. (Fig. 5) Alk-oxycarbonylahon is performed at room temperature for 10 min, whereas esterification is complete in 3 min at room temperature. 

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