芝加哥大学董广彬教授：Catalysis-Enabled Non-Obvious Transformations for Structural Modification

报告题目：Catalysis-Enabled Non-Obvious Transformations for Structural Modification报 告 人：董广彬（芝加哥大学教授）报告时间：2024年8月12日上午10:30报告地点：五山科技园2号楼324报告厅（腾讯会议：775111221）主办单位：前沿软物质学院、华南软物质科学与技术高等研究院邀 请 人：吴钊教授 报告摘要：Structural modification or analogue synthesis, one of the cornerstones in drug discovery, is essential for lead optimization and development of analog drugs and follow-on drugs. Among various structural modification approaches, those that can directly manipulate or derivatize lead compounds are most attractive to medicinal chemists, as such “late-stage” modifications would allow divergent synthesis of a number of analogues from a common advanced intermediate. Currently, most late-stage modification methods are based on transforming existing more reactive functional groups or functionalizing C−H bonds. In contrast, transformations that are not intuitive or obvious have been rarely used for analog synthesis. This lecture focuses on three strategies that can realize non-obvious transformations for structural modification, which provide more direct access to valuable analogues that are either challenging or tedious to prepare. The first strategy is based on boron-insertion into ether C-O bonds via Ni/Zn tandem catalysis. The reaction goes through a cleavage-and-then-rebound mechanism. This method enables one-carbon ring expansion and swapping oxygen to nitrogen in cyclic ethers. The second strategy is based on the carbonyl 1,2-transposition enabled by the palladium/norbornene cooperative catalysis. This approach first converts the ketone to the corresponding alkenyl triflate that can then undergo the palladium/norbornene-catalyzed regioselective α-amination/ipso hydrogenation enabled by a bifunctional H/N donor. The resulting “transposed enamine” intermediate can subsequently be hydrolyzed to give the 1,2-carbonyl-migrated product. This method allows rapid access to unusual bioactive analogues through late-stage functionalization. The third approach is centered on a hook-and-slide strategy for homologation of tertiary amides and carboxylic acids with tunable lengths of the inserted carbon chain. Alkylation at the α-position of the amide (hook) is followed by highly selective branched-to-linear isomerization (slide) to effect amide migration to the end of the newly introduced alkyl chain; thus, the choice of alkylation reagent sets the homologation length. The key step involves a carbon–carbon bond activation process by a carbene-coordinated rhodium complex with assistance from a removable directing group. The approach is demonstrated for introduction of chains as long as 16 carbons and is applicable to homologation of complex bioactive molecules. 报告人简介:董广彬教授现为芝加哥大学化学系Weldon G. Brown讲席教授。其于2003年本科毕业于北京大学化学系，2009年在斯坦福大学Barry M. Trost教授课题组获得博士学位。2009—2011年在加州理工学院Robert H. Grubbs课题组从事博士后研究工作，2011-2016年在美国德州大学奥斯汀分校担任助理教授与CPRIT学者，2016起任职于芝加哥大学化学系，担任教授职务，且于2023年起担任Weldon G. Brown讲席教授。董广彬教授课题组的研究方向主要包括有机合成化学，金属有机化学，全合成与有机共轭材料，其在惰性碳碳与碳氢键活化、钯/降冰片烯协同催化、有机硼化学、有机共轭材料合成等领域都有很深的造诣。迄今为止以通讯作者身份发表超过170篇论文，其中包括Science (4篇)，Nature (3篇)，Nat. Chem. (7篇)， J. Am. Chem. Soc. (>50篇)等。其获得的主要奖项包括：ACS E. J. Corey Award (2023), Tetrahedron Young Investigator Award (2021), Arthur C. Cope Scholar (2017), Chan Memorial Award in Organic Synthesis (2018), Sloan Research Fellow (2014) 等。