In the Laboratory JChemEd.chem.wisc.edu • Vol. 76 No. 1 Ja nua ry 1 9 9 9 • Jo urna l o f Chemic a l Educ a tio n 77 A Simple Method for Determining W the Absolute Configuration of -Amino Acids María Dolores Díaz-de-Villegas Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain Esteban P. Urriolabeitia* Departamento de Química Inorgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain T he increasing interest in enantioselective synthesis (1) has led to a high demand for accurate and convenient methods of measuring both the enantiomeric purity of the resulting mixtures and the absolute configuration of each compound in the mixture. The development of NMR spectroscopy has provided a variety of valuable methods for determining enantiomeric purity (2). More recently, techniques such as gas chromatography (3) and high-performance liquid chroma- tography (4) have also been used. The determination of absolute configuration in enantio- merically pure compounds has, in the past, been achieved through chemical methods (5). However, the scope of these methods is limited because they rely on suppositions about the inversion or retention of configuration at stereocenters during the course of the synthetic procedure to or from a substrate of known configuration. NMR spectroscopy has also been extensively applied to the determination of the relative stereochemistry (6, 7 ) using nuclear O verhauser effect (NO E) measurements. Such measurements can be used to determine the pattern of relative interatomic interactions in molecules with a fixed geometry, although some degree of internal molecular motion can be tolerated (6 ). How- ever, these measurements require the existence of protons (or other nuclei) that are very close to one another, because NOE interactions depend on the inverse sixth power of the inter- nuclear distance. Chiroptical methods such as polarimetry, optical rotatory dispersion (ORD), and circular dichroism (CD) overcome this particular problem. Circular dichroism is especially attractive for the determination of absolute configuration, since the shape of the CD curve can provide information about the orientation of the groups around the stereogenic center ( 8). In accord with this, we propose here a simple experiment comprising two well-defined sections. T he first is a prepara- tive section, in which the students will synthesize a dinuclear C,N-cyclometallated compound [Pd(C 6 H 4 CH 2 NMe 2 -2)(μ -Cl)] 2 (1 ) (or [Pd(dmba)(μ -Cl)] 2 ) via carbon–hydrogen activation of N,N-dimethylbenzylamine (dmbaH, C 6 H 5 CH 2 NMe 2 ) by the complex Li 2 [PdCl 4 ] (Scheme I). NMe 2 - [PhCH 2 N(H)Me 2 ]Cl 2 Li 2 [PdCl 4 ] MeOH - 2 LiCl N Me 2 Pd Cl 2 Complex 1 1 / 2 + Scheme I T reatment of 1 with T l(acac) (acac = acetylacetonate) yields the starting compound [Pd(dmba)(acac)] (2 ) (Scheme II). N Me 2 Pd O O N Me 2 Pd Cl Complex 2 2 Tl(acac) 2 CH 2 Cl 2 - 2 TlCl 2 + Scheme II Further reactivity of 2 with selected enantiomerically pure ( R- or S-) α-amino acids results in the formation of the [Pd(dmba)(Aa)] complexes (Scheme III) (Aa = S-alaninate [3 ], S-2-amino butyrate [4 ], R-2-amino butyrate [5 ], (2S, 3S)- isoleucinate [6 ], ( 2S , 3R)-threoninate [7 ], S-asparaginate [8 ]), which will be studied spectroscopically. N Me 2 Pd O O N Me 2 Pd H 2 N O H 2 N HO O R 1 R 2 O R 1 R 2 MeOH -Hacac R 1 = Me, R 2 = H ( 3); R 1 = Et, R 2 = H ( 4 ) R 1 = H, R 2 = Et ( 5); R 1 = S-C(H)MeEt, R 2 = H ( 6 ) R 1 = R-C(H)Me(OH), R 2 = H ( 7 ); R 1 = CH 2 C(O)NH 2 , R 2 = H ( 8 ) + Scheme III T he second section is devoted to the spectroscopic char- acterization of these complexes, using three methods: infra- red, nuclear magnetic resonance, and circular dichroism. T he students will themselves measure the IR spectra, comparing them with those provided by the instructor, in order to check the purity of the compounds obtained. T he 1 H NMR spectra will be provided by the instructor, leaving the task of their interpretation for the students. Some additional information can also be provided (see online Lab Documentation W ) to complete the structural characterization. T hus, the preparative section W Supplementary materials for this article are available on JC E O nline at http:/ / jchemed.chem.wisc.edu/ Journal/ issues/ 1999/ Ja n/ a b s7 7 .html. * Ema il: esteban@posta.unizar.es.