Zhang Chengxi, Wu Xianqing, Qu Jingping, Chen Yifeng
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
J Am Chem Soc. 2024 Sep 25;146(38):25918-25926. doi: 10.1021/jacs.4c09556. Epub 2024 Sep 12.
Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications in biochemistry, medicinal chemistry, and materials science. Herein, we report a cobalt-catalyzed aza-Barbier reaction of dehydroglycines with unactivated alkyl halides to afford unnatural α-amino esters with high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use of moisture-, air-sensitive organometallic reagents, and stoichiometric chiral auxiliaries, enabling the conversion of a variety of primary, secondary, and even tertiary unactivated alkyl halides to α-alkyl-amino esters under mild conditions, thus leading to broad functional group tolerance. The expedient access to biologically active motifs demonstrates the practicality of this protocol by reducing the number of synthetic steps and enhancing the reaction efficiency.
对映体富集的非天然氨基酸是有机化学中一种常见的结构单元，在生物化学、药物化学和材料科学领域有着广泛的应用。在此，我们报道了一种钴催化的脱氢甘氨酸与未活化卤代烃的氮杂巴比耶反应，可高对映选择性地得到非天然α-氨基酯。这种催化还原烷基化加成方法避免了使用对水分和空气敏感的有机金属试剂以及化学计量的手性助剂，能够在温和条件下将各种伯、仲甚至叔未活化卤代烃转化为α-烷基-氨基酯，从而具有广泛的官能团耐受性。通过减少合成步骤数量和提高反应效率，便捷地获得生物活性结构单元证明了该方法的实用性。
