Nuclear magnetic resonance shift reagents in organic chemistry
The paper deals with the implications of shift reagents in organic chemistry in several broad areas. First, the relative binding affinities of common functional groups to shift reagents are considered, and it is shown that such knowledge aids the analysis of the shifted spectra of polyfunctional molecules and (by extension of the principles involved) isotopically substituted molecules. Secondly, the quantitative application of the pseudo-contact shift equation is considered, and the importance of considering the population of two or more energy minima associated with conformational mobility in the shift reagent/ substrate complex is emphasized. In the most adverse cases, observed shifts must be separated into (i) complex formation shifts (ii) contact shifts and (iii) pseudo-contact shifts. Thirdly, the potential of shift reagents in biology and n.m.r. is briefly outlined. Finally, some miscellaneous applications are given. INTRODUCTION Although it has long been recognized that paramagnetic ions can cause shifts of resonance signals in n.m.r. spectra, prior to 1969 the most spectacular results had been obtained in cases where the substrate was covalently bound to the paramagnetic metal'. However, in. 1969 a breakthrough occurred when Hinckley2 discovered that addition of the pyridine adduct of europium dipivaloylmethane [Eu(dpm)3, 1] to a carbon tetrachloride solution of cholesterol caused relatively large selective downfield shifts of some of the steroid proton resonances without adverse line broadening. It was soon shown3 that Eu(dpm)3 (1) is a superior shift reagent to its pyridine adduct, since substrates associate with the shift reagent through electron donation, e.g. (2), and competition to this weak association through availability of the pyridine lone pair is detrimental. r t-Bu /10 ( R—O :-Eu(dpm)3 Eul "? H 1. R = t-Bu la, R CF2CF2CF3 2 It was clear from many early experiments that the proton lanthanideinduced shifts are very largely pseudo-contacts in origin in the vast majority