Viso Alma, Fernández de la Pradilla Roberto, Flores Aida, García Ana, Tortosa Mariola, López-Rodríguez María L
Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain.
J Org Chem. 2006 Feb 17;71(4):1442-8. doi: 10.1021/jo052077h.
Enantiopure 1-benzyl-2,3-disubstituted piperazines (4) have been synthesized by treatment of N-sulfinyl-N-benzyldiamino alcohols (1) with diethyl oxalate and sodium methoxide followed by reduction with borane. Alternatively, the sulfinamido group was preserved by an N-acylation/cyclization protocol using alpha-chloroacetyl chloride that led to the synthesis of N-sulfinyl ketopiperazines (11). Ensuing elimination of the sulfinyl group with NaH produced imino ketopiperazines (9) that are suitably functionalized for nucleophilic addition to the imino moiety. Stereoselective and high yielding allylation of imino ketopiperazines (9c) was achieved under Barbier conditions using CeCl3.7H2O as the additive.
对映体纯的1-苄基-2,3-二取代哌嗪（4）的合成方法如下：先用草酸二乙酯和甲醇钠处理N-亚磺酰基-N-苄基二氨基醇（1），然后用硼烷还原。另外，通过使用α-氯乙酰氯的N-酰化/环化方案保留亚磺酰胺基，从而合成了N-亚磺酰基酮哌嗪（11）。随后用NaH消除亚磺酰基，得到亚氨基酮哌嗪（9），其经过适当官能化，可用于对亚氨基部分进行亲核加成。在Barbier条件下，以CeCl3·7H2O作为添加剂，实现了亚氨基酮哌嗪（9c）的立体选择性和高产率烯丙基化反应。
