MTPA (MOSHER) AMIDES OF CYCLIC SECONDARY-AMINES - CONFORMATIONAL ASPECTS AND A USEFUL METHOD FOR ASSIGNMENT OF AMINE CONFIGURATION

Mosher's MTPA (methoxy(trifluoromethyl)phenylacetyl) technology is a w ell-known tool used to determine the absolute configuration of chiral alcohols and primary amines. The technique now has been extended to in clude secondary amines. A number of MTPA amide derivatives have been p repared from cyclic amines. Both piperidines and pyrrolidines have bee n studied. A detailed discussion of the conformational issues associat ed with both amide bond rotation and ring flipping is presented. The o bserved H-1 NMR chemical shifts are correlated into a model that allow s unambiguous determination of absolute configuration of cyclic second ary amines. While the presence of amide rotamers must be accounted for in the analysis, this is a relatively straightforward process that fo llows from detailed evaluation of coupling constant data and is often aided by COSY. The exceptionally large Delta delta values observed for these MTPA amides make this a valuable and reliable method for assign ing amine configuration.