Applications of MTPA (Mosher) amides of secondary amines: Assignment of absolute configuration in chiral cyclic amines

Mosher's MTPA (methoxy(trifluoromethyl)phenylacetyl) technology is applied to the assignment of absolute configuration of several synthetic and natural chiral amines. The substrates are cyclic, secondary amines. The resulting amides usually contain significant populations of two rotamers, readily distinguished by ¹H NMR spectroscopy. Thus, two complementary sets of Δδ values are obtained from a single analysis, thereby enhancing the power of the method. A strategy for the MTPA derivatization of (the N-methyl tertiary amine in) the tropane alkaloid, cocaine, is also described. The exceptionally large Δδ values observed for these MTPA amides make this a valuable and reliable method for assignment of amine configuration (even in some cases where only one diastereomeric MTPA amide is readily available).