کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5228565 | 1383637 | 2007 | 12 صفحه PDF | دانلود رایگان |
A short and efficient stereoselective synthetic approach toward substituted piperidines, involving (2S,3S)-3-hydroxypipecolic acid 1, (2R,3S)-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 â78 °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 â78 °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 1H 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.
Journal: Tetrahedron - Volume 63, Issue 12, 19 March 2007, Pages 2622-2633