Co-Catalyzed Sequetial Hydrogenation and Selective Markovnikov Hydrohydrazidation of Terminal Aliphatic Alkynes
Zhan Lu (浙江大學(xué))
陸展 博士 2003年畢業(yè)于浙江大學(xué)化學(xué)系并獲得浙江省優(yōu)秀畢業(yè)生。同年被保送為浙江大學(xué)化學(xué)系直博生，師從于麻生明院士，主要從事炔丙醇及官能團(tuán)化聯(lián)烯的可調(diào)控高選擇性金屬碳化加成反應(yīng)研究。2008年，加入美國威斯康星大學(xué)麥迪遜分?；瘜W(xué)系，師從Shannon S. Stahl教授作博士后研究，主要課題為氧氣參與的鈀催化氧化反應(yīng)研究及應(yīng)用。2009-2012年在同一學(xué)校的Tehshik P. Yoon教授研究小組從事博士后研究，主要方向?yàn)榭梢姽獯呋瘎┰谟袡C(jī)環(huán)化反應(yīng)中的應(yīng)用研究。2013年1月起歷任浙江大學(xué)化學(xué)系博士生導(dǎo)師，特聘研究員，教授。兼任浙江大學(xué)化學(xué)前瞻技術(shù)中心獨(dú)立PI。主要從事于基于手性配體設(shè)計(jì)的地球豐產(chǎn)過渡金屬不對稱催化和可見光催化反應(yīng)研究。 個(gè)人主頁： https://person.zju.edu.cn/en/lu 內(nèi)容簡介 反應(yīng)條件篩選和應(yīng)用實(shí)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. 前景展望和機(jī)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.
