Optically pure secondary amines preparation

Scheme 7. Chemoenzymatic preparation of optically pure secondary amines via hydrolysis of an racemic oxalamic ester linker...

The preparation of optically pure secondary amines was accomplished via the resolution of oxalamic esters 43 to give acids 44 and ultimately amines 45 [22]. Excellent selectivities ( >200) were obtained using a variety of proteases. Back ground chemical hydrolysis was suppressed by keeping the pH between 7.0 and 7.5 (Figure 14.16). 

Since simple ketones typically coordinate more weakly to metals than olefins, many Rh-phosphane complexes may show poor activity for the hydrogenation of simple ketones. However, the catalytic properties of cyclometalated half-sandwich Rh(lII) complexes 99-101, isolated or prepared in situ firom metal precursors and optically pure secondary amines, were evaluated, among which the complex 100 showed the highest productivity in the reduction of acetophenone with a i-PrOH/t-BuOK reductant system (Fig. 26) [93]. The complex 99 afforded good yield of alcohol products from acetophenone, but the enantioselectivity was low, while the cyclometalated imine 101 was almost inactive. The rhodacycle 100, which was formed in situ, efficientiy catalysed the reduction of substrates 102 (92 % ee), 103 (93 % ee) and 104 (91 % ee), with substrate 103 showing total chemoselectivity. For substrates 105,106 and 107, however, lower ee values were observed (<85 %). 

This acylating agent has also been used in the resolution of indolines see Gotor-Fernandez, V., Rebolledo, F. and Gotor, V., Chemoenzymatic preparation of optically active secondary amines a new efficient route to enantiomerically pure indolines. Tetrahedron Lett., 2006,17, 2558. 

Polymers derived from natural sources such as proteins, DNA, and polyhy-droxyalkanoates are optically pure, making the biocatalysts responsible for their synthesis highly appealing for the preparation of chiral synthetic polymers. In recent years, enzymes have been explored successfully as catalysts for the preparation of polymers from natural or synthetic monomers. Moreover, the extraordinary enantioselectivity of lipases is exploited on an industrial scale for kinetic resolutions of secondary alcohols and amines, affording chiral intermediates for the pharmaceutical and agrochemical industry. It is therefore not surprising that more recent research has focused on the use of lipases for synthesis of chiral polymers from racemic monomers. 

Ridha, T., Ben Hassine, B. and Genet, J.P., Synthesis of optically pure imines using microwave activation and application to the preparation of new secondary amines, Compt. Rend. Acad. Sci. Ser. II Fas. C, 2000, 3, 35-42. 

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