MTPA (Mosher) amides of cyclic secondary amines: Conformational aspects and a useful method for assignment of amine configuration

被引:62
作者
Hoye, TR
Renner, MK
机构
[1] Department of Chemistry, University of Minnesota, Minneapolis
关键词
D O I
10.1021/jo952043h
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Mosher's MTPA (methoxy(trifluoromethyl)phenylacetyl) technology is a well-known tool used to determine the absolute configuration of chiral alcohols and primary amines. The technique now has been extended to include secondary amines. A number of MTPA amide derivatives have been prepared from cyclic amines. Both piperidines and pyrrolidines have been studied. A detailed discussion of the conformational issues associated with both amide bond rotation and ring flipping is presented. The observed H-1 NMR chemical shifts are correlated into a model that allows unambiguous determination of absolute configuration of cyclic secondary amines. While the presence of amide rotamers must be accounted for in the analysis, this is a relatively straightforward process that follows 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 assigning amine configuration.
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收藏
页码:2056 / 2064
页数:9
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