I. Kim, J. Oh, O. Zee
Mar 19, 2007
Citations
0
Influential Citations
40
Citations
Journal
Tetrahedron
Abstract
Abstract A short and efficient stereoselective synthetic approach toward substituted piperidines, involving (2 S ,3 S )-3-hydroxypipecolic acid 1 , (2 R ,3 S )-3-hydroxypipecolic acid 3 , and their acid-reduced analogs 2 and 4 , has been developed. The requisite anti - and syn -1,2-amino alcohols 11 and 12 for the preparation of title four piperidine analogs 1 – 4 were synthesized via the regioselective and diastereoselective amination of anti - and syn -1,2-dibenzyl ethers 13 and 14 using chlorosulfonyl isocyanate (CSI). As a result, reaction of anti -1,2-dibenzyl ether 13 with CSI afforded exclusively the anti -1,2-amino alcohol 11 with the diastereoselectivity of 49:1 in toluene at −78 °C and syn -isomer 14 gave the syn -1,2-amino alcohol 12 as the major product with the diastereoselectivity of 12:1 in hexane at −78 °C. The result of these reactions could be explained by the neighboring group effect leading to retention of stereochemistry. In addition, conformational changes of trans -piperidine intermediate 9 in terms of the nature of N -protecting groups are described. The conformations of 9 and 24 – 28 were confirmed by 1 H NMR analysis and NOE correlation. Furthermore, the conformations of piperidines 18 and 23 with hydroxyl methyl substituent at C-2 were investigated by NMR spectroscopy.