Chiral analysis by NMR spectroscopy

Abstract

The analysis of the enantiomeric purity of chiral carboxylic acids requires a reagent to give acceptable NMR chemical shift non-equivalence with a wide range of substrate acids. Extensive studies of the behaviour of N-mono- methyl, N,N-dimethyl and cyclic amines as chiral solvating agents led to the finding that 1,2 diphenyl-1,2-diaminoethane can induce substantial non- equivalence in the diastereomeric salts of chiral a-phenyl and a-halo carboxylic acids. The diastereoisomeric complexes of the diamine with primary carboxylic acids (RCH(_2)CO(_2)H) presents an unusual case in which the internally enantiotopic methylene protons are rendered internally diasteretopic by an external non-covalently bonded reagent. Investigations of the physical parameters determining non-equivalence (stoichiometry, concentration, temperature and substrate enantiomeric purity), combined with NOE observations of the diastereomeric pairs and the crystal structure of the mono- hydrobromide salt were used to suggest the structure for the conformation responsible for shift non-equivalence. The zero valent platinum complex, 3-0-isopropylidene-2,3-dihydroxy-1,4- bis(diphenyl-phosphino)butane-platinum(0)-ethene (DlOP-Pt-ethene) was shown to be a versatile chiral derivatising agent for electron poor and strained η(^2)-donors. This was demonstrated by the enantiomeric purity determinations for alkynes, enones and norbornene derivatives. The crystal structure of DIOP-Pt-ethene was determined and found to be similar to the palladium analogue. If the achiral rhodium complex rhodium(I)-acetylacetone-diethene undergoes a reaction with 2 equivalents of a suitable chiral η(^2)-donor, it will result in the formation of 4 stereoisomers, two meso forms and a pair of enantiomers. The diasteroisomers should display chemical shift non-equivalence in the NMR spectrum of the product, reflecting the enantiomeric purity of the η(^2)-donor (self recognition). The derivatisation of rhodium(l)-acetylacetone-diethene with chiral η(^2)-donors was attempted.