Co-Catalyzed Sequetial Hydrogenation and Selective Markovnikov Hydrohydrazidation of Terminal Aliphatic Alkynes
Zhan Lu (浙江大学)
陆展 博士 2003年毕业于浙江大学化学系并获得浙江省优秀毕业生。同年被保送为浙江大学化学系直博生，师从于麻生明院士，主要从事炔丙醇及官能团化联烯的可调控高选择性金属碳化加成反应研究。2008年，加入美国威斯康星大学麦迪逊分校化学系，师从Shannon S. Stahl教授作博士后研究，主要课题为氧气参与的钯催化氧化反应研究及应用。2009-2012年在同一学校的Tehshik P. Yoon教授研究小组从事博士后研究，主要方向为可见光催化剂在有机环化反应中的应用研究。2013年1月起历任浙江大学化学系博士生导师，特聘研究员，教授。兼任浙江大学化学前瞻技术中心独立PI。主要从事于基于手性配体设计的地球丰产过渡金属不对称催化和可见光催化反应研究。 个人主页： https://person.zju.edu.cn/en/lu 内容简介 反应条件筛选和应用实例 Under nitrogen atmosphere, treatment of 4-phenyl-1-butyne 1a with benzyl 2-diaxo-2-phenylacetate 2a in the presence of Co(OAc)2 and N-oxazolinylphenyl 8-aminoquinoline (OPAQ) L1 as cocatalysts and phenyl silane and H2O as hydrogen donor, delivered the desired product 3a in 83% yield. Control experiments showed that all of the reagents were necessary for the reaction to occur. 前景展望和机理研究 The practicality of this new alkyne functionalization methodology was examined with gram scale synthesis of 3a. Further transformations of the semi-hydrogenation/hydrohydrazidation products into hydrazine hydrochloride 5, pyrazole 6, 1,3-disubstituted indazole 7 and even the protected primary amines 8a-8b, and an antihistamine drug promethazine 9a was also synthesized by the simple three-step operation. Scheme 4. Further transformations of the obtained semi-hydrogenation/hydrohydrazidation products. To gain insights into the reaction mechanism, several control experiments were conducted, as well as deuterium labelling and radical clock experiments. The preliminary data suggested a cobal-hydride species being the catalytic reactive species, which is responsible both for the semi-hydrogenation of alkynes and for the hydrohydrazidation of the in situ generated alkenes. Scheme 5. Mechanstic studies and a plausible reaction mechanism. END
With the optimal reaction conditions in hand, the authors evaluated various terminal alkyl alkynes. The reaction expressed good tolerance towards functional groups: ethers, esters, oxalates, amides, acetals, halides, free alcohols and free amines all remained intact after reaction.
