Glycinal, reaction with ester enolates

Ester enolates, much more sensitive and capricious than ketone and amide enolates, seemed to be unsuitable for palladium-catalyzed allylic alkylations. Thus, Hegedus and coworkers [24] reported on low yields and predominant side reactions in the allylation of the lithium enolate of methyl cyclohexanecarboxylate. It seems that so far the only reliable and efficient version of a Tsuji-Trost reaction with ester enolates is based on the chelated zinc enolates 41 derived from N-protected glycinates 40 - a procedure that was developed by Kazmaier s group. 

The chelated ester enolate Claisen rearrangement of allylic glycinates 9 is carried out with zinc(II) chloride, which is added to the enolate at — 78 C (Table 19). The rearrangement occurs as the reaction mixture is allowed to warm to room temperature over 1 hour. The 2-amino-3,3-difluoro-4-[(2-methoxyethoxy)methoxy] alk-4-enoic acids 10 arc converted directly into the corresponding methyl esters, which can be hydrolyzed to the methyl 2-amino-3,3-difluoro-4-oxoal-kanoates. 

Oxidation of arylmethyl ketoximes by phenyliodoso diacetate in glacial acetic acid was second order overall, first order each in substrate and oxidant.145 Iodine allowed the oxidative dimerization of glycine ester enolates with low to moderate diastereoselec-tivity that is consistent with kinetic control.146 Although malonic acid is not oxidized by iodate under acidic conditions, oxidation proceeds in the presence of catalytic ruthenium(III). A mechanism is put forward to account for the observed orders of reaction.147 The rate of periodate oxidation of m-toluidine in acetone-water increases with ionic strength.148... 

An ion-pair derived from the substrate and solid NaOH forms a cation-assisted dimeric hydrophobic complex with catalyst 39c, and the deprotonated substrate occupies the apical coordination site of one of the Cu(II) ions of the complexes. Alkylation proceeds preferentially on the re-face of the enolate to produce amino acid derivatives with high enantioselectivity. However, amino ester enolates derived from amino acids other than glycine and alanine with R1 side chains are likely to hinder the re-face of enolate, resulting in a diminishing reaction rate and enantioselectivity (Table 7.5). The salen-Cu(II) complex helps to transfer the ion-pair in organic solvents, and at the same time fixes the orientation of the coordinated carbanion in the transition state which, on alkylation, releases the catalyst to continue the cycle. 

Enolates from A-(diphenylmethylene)glycine esters (211) were also used as nucleophiles in Mannich reactions with chiral A-sulhnyl imines (212), as reported by Davis and coworkers (equation 56f. They found that the simple antUsyn selectivity of the formed 2,3-diamino esters 213 and 214 was strongly influenced by the water content in the THE solvent. In the absence of water both 2,3-diamino ester isomers were equally obtained (first entry of Table 18), but by changing the H2O/LDA ratio the formation of the... 

In an application to asymmetric monobactam synthesis. Overman and Osawa observe a high level of 1,4-diastereofacial selectivity in the reaction of (5)-cyanoamine (235) with the enolate of STABASE-protected glycine ester (234), affording diastereomeric 3-amino-2-azetidinones (236) and (237) in a 10 1 ratio, respectively, and in 65% yield (Scheme 49). Based on the (E)-enolate geometry of glycine ester (234), determined in trapping experiments with TMSCl, the authors postulate a chelated, chair-like transition state (238) that is consistent with the observed stereoselectivity. 

For the production of glycinamide ribonucleotide, an acyl phosphate (anhydride) intermediate is formed by reaction of ATP -with a carboxylic acid of an amino acid (glycine), whereas in the production of guanylate (GMP) a phosphoryl ester intermediate is formed by reaction of ATP with an enol alcohol on the purine ring of the nucleotide. 

A typical reaction that uses an amino acid derivative involves initial conversion to an enolate anion. This nucleophilic species is then reacted with an alkyl halide or a carbonyl derivative. An example that produces a new amino acid is the reaction of the ethyl ester of n-benzyl glycine with lithium diisopropylamide to give the enolate. Subsequent reaction with the mixed anhydride shown below proceeded with displacement of acetate to give /.22J.13 Acid hydrolysis generated a P-keto amino acid, which decarboxylated under the reaction conditions to give 4-oxo-5-aminopen-tanoic acid 1.156, also known as 5-aminolevulinic acid). 

The reaction of Cbz-protected glycinal (6.65) with the ester enolate of 6.66... 

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