Proline compounds, copper compound

The most widely used approach for the separation of enantiomers by TLC is based on a ligand exchange mechanism using commercially available reversed-phase plates impregnated with a solution of copper acetate and (2S,4R,2 RS)-4-hydroxy-l-(2-hydroxydodecyl)proline in optimized amounts. Figure 7.9 (10,97,98,107-109). Enantiomers are separated based on the differences in the stability of the diastereomeric complexes formed between the sample, copper, and the proline selector. As a consequence, a prime requirement for separation is that the seumple must be able to form complexes with copper. Such compounds include... 

As thus obtained, the proline is a mixture of the optically active and the racemic forms these are separated by conversion into their copper salts and treatment with absolute alcohol which dissolves that of the optically active proline. Their purification is easy, and a determination of the water of crystallisation and of the copper establishes the identity of the compound. The phenylhydantoine derivative may also be used for this purpose. 

As this compound contains two asymmetric carbon atoms, four stereoisomeric forms are possible by synthesis these must occur in two inactive forms. These forms Leuchs separated by crystallisation of the copper salts, the more insoluble acid being termed (a)-7-oxy-proline, the other (b)-7-oxyproline. 

Copper chelates of amino acid enantiomers such as proline or phenylalanine have been used to resolve enantiomers of amino acids and structurally related compounds [241,245]. Other metals such as zinc and cadmium have also been used. Metal chelates have been used to resolve a-amino-a-hydroxy carboxy acids and a-methyl-a-amino acid enantiomers [246]. One example of pharmaceutical interest is the resolution of D-penicillamine from the L-antipod [247] and resolution of L,D-thyroxine [248]. 

The cyclopropanation with diazo compounds via decomposition is amenable to asymmetric induction using chiral metal chelates. Rhodium complexes of 3(S)-phthalimido-2-piperidinone and Al-(arenesulfonyl)proline 44 are typical. The latter catalyst is suitable for generating alkenylcarbenoids. For intramolecular reactions, the cognate complex 45 and the semicorrin-copper 46 are effective. 

The D-enantiomer of such bidentate compounds was generally retained more than L-enantiomer. Mixtures of methanol/acetonitrile/water or dichloromethane/methanol were often used as eluents. Chiral recognition based on CLEC was also involved in the enantiomer separation of amino acids and (3-adrenergic blocking agents on silica gel plates coated with the copper(II) complex of enantiomeric amino acids (L-proline, L-arginine, and lR,3R,5R-2-azobicyclo [3.3.0]octan-3-carboxylic acid). 

A convenient synthesis of substituted prolines using a copper complex of jV-pyruvylideneglycine and acrylic compounds has been described (Scheme 72). "... 

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