Chiral compounds, Amino acids pyrrolidine

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Simple L-alanine, L-valine, L-norvaline, L-isolecucine, L-serine and other linear amino acids [ 121 ] or chiral amino acids with a binaphthyl backbone [ 122] and peptides have also been used as asymmetric catalysts [123,124,125,126]. Solid-supported proline-terminated peptides have been used for heterogeneous catalysis of the asymmetric aldol reaction [ 127]. Apart from proline and derivatives, other cyclic compounds such as 5,5-dimethyl thiazolidinium-4-car-boxylate (DMTC) [128], 2-fert-butyl-4-benzyl imidazolidinones [129], (l/ ,25)-2-aminocy-clopentanecarboxylic acid [130], (5 -5-(pyrrolidin-2-yl)tetrazole, (5)-l,3-thiazolidine-4-car-boxylic acid, (5)-5,5-dimethyl-l,3-thiazolidine-4-carboxylic acid, and (5)-hydroxyproline are effective catalysts in asymmetric aldol reactions [126,131,132,133,134,135]. 

Proline is a stable, nontoxic, cyclic, secondary pyrrolidine-based amino acid with an increased pK value. Thus, proline is a chiral bidentate compound that can form catalytically active metal complexes (Melchiorre et al. 2008). Bidentate means that proline has not only one tooth but also a second one to bite and react. The greatest difference to other amino acids is a Lewis-base type catalysis that facilitates iminium and enamine-based reactions. It is especially noteworthy that cross-aldol condensations of unprotected glycoladehyde and racemic glyceralde-hyde in the presence of catalytic amounts of the Zn-(proline)2 gave a mixture of pentoses and hexoses (Kofoed et al. 2004). Again, proline seems to play the decisive role. The conditions are prebiotic the reaction proceeded in water for seven days at room temperature. It is remarkable that the pentose products contained ribose (34%), lyxose (32%), arabinose (21%), and xylose (12%) and that all are stable under the conditions. Thus, the diastereomeric and enantiomeric selection observed support the idea that amino acids have been the source of chirality for prebiotic sugar synthesis. 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

Cycloadditions of chiral A -acylnitroso compounds have been widely studied. These heterodienophiles are accessible e.g. by oxidation of hydroxamic acid derivatives with periodate. C2-symmetric pyrrolidines lead to high selectivities. 1,2-Oxazines are useful precursors of amino alcohols and aza sugars. 

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