Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, People's Republic of China.
J Org Chem. 2013 Sep 6;78(17):8305-11. doi: 10.1021/jo4007656. Epub 2013 Aug 19.
Full details of the direct and general method for the reductive alkylation of tertiary lactams and amides to give tertiary sec-alkylamines are presented. This one-pot method consists of in situ activation of a lactam or an amide with Tf2O/DTBMP, addition of a Grignard reagent, and reduction of the resulting iminium intermediates. Alkyl, benzyl, and aryl Grignard reagents and several reductants or reducing conditions (LiAlH4, NaBH4, Hantzsch ester, Bu3SnH, Pd(OH)2/C, H2) could be used effectively. Reductive alkylations of substituted lactams demonstrated good to excellent 1,3-asymmetric induction to provide the corresponding di- or trisubstituted pyrrolidine/piperidine in 6:1 (LiAlH4), 11:1 (Et3SiH), and 20:1 (catalytic hydrogenation) cis/trans diastereoselectivity, respectively. The versatility of this methodology was demonstrated by its application in the concise stereoselective synthesis of piperidine alkaloid (-)-morusimic acid.
本文详细介绍了一种将叔内酰胺和酰胺还原烷基化为叔仲烷基胺的直接和通用方法。该一锅法包括用 Tf2O/ DTBMP 原位活化内酰胺或酰胺，加入格氏试剂，然后还原生成的亚胺中间体。烷基、苄基和芳基格氏试剂以及几种还原剂或还原条件（LiAlH4、NaBH4、Hantzsch 酯、Bu3SnH、Pd(OH)2/C、H2）都可以有效地使用。取代的内酰胺的还原烷基化反应表现出良好到优秀的 1,3-不对称诱导，以提供相应的二取代或三取代吡咯烷/哌啶，顺式/反式非对映选择性分别为 6:1（LiAlH4）、11:1（Et3SiH）和 20:1（催化氢化）。该方法的多功能性通过其在简洁的立体选择性合成哌啶生物碱（-）-morusimic 酸中的应用得到了证明。
