Cochran Brian M, Michael Forrest E
Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195-1700, USA.
Org Lett. 2008 Jan 17;10(2):329-32. doi: 10.1021/ol702891p. Epub 2007 Dec 22.
A highly diastereoselective intramolecular hydroamination is the key step in a modular synthesis of 2,6-disubstituted piperazines. The requisite hydroamination substrates were prepared in excellent yields by nucleophilic displacement of cyclic sulfamidates derived from amino acids. A variety of alkyl and aryl substituents at the 2-position were tolerated. The stereochemistry of the piperazines was determined to be trans by X-ray crystallography, which also showed the preferred conformation of the 2,6-disubstituted piperazine to be a twist-boat due to A(1,3) strain.
高度非对映选择性分子内氢胺化反应是2,6-二取代哌嗪模块化合成中的关键步骤。通过亲核取代由氨基酸衍生的环状氨基磺酸酯，以优异的产率制备了所需的氢胺化底物。2-位上可耐受多种烷基和芳基取代基。通过X射线晶体学确定哌嗪的立体化学为反式，这也表明由于A(1,3)应变，2,6-二取代哌嗪的优选构象为扭船型。
