The legacy of Ei-ichi Negishi: Eternal optimism and excellence

Ei-ichi Negishi will remain known for pioneering and promoting the development of transition-metal catalyzed reactions in organic synthesis as well fostering excellence critical thinking among his collaborators. During lifetime, with wife Sumire by side, he conquered many continents: chemical world, name is associated cross-coupling, cascade reactions, carbopalladation, zirconocene chemistry, asymmetric synthesis; life, we remember him a kind, generous, approachable individual that mastered golfing, singing, skiing, other things. His scientific career was devoted to exploring chemistry transition metals mean synthetize efficiently selectively complex building blocks synthesis, while training next generation passing on passion research world.…observing out loud witnessing thought process taught us lot about how raise questions early project always seek simplification.Prof. often reminded (chemistry) like exploration new (chemical) one has be prepared, eyes wide open, ready continue or change course action, keeping our ultimate goal mind fresh spirit—eternal optimism. Born July 14, 1935 Manchuria Japanese citizen, grew up region child before moving Korea and, ultimately, Tokyo area Japan, where spent high school university years. this period discovered skating, choir met to-be lifelong beloved partner wife, Sumire. graduated from University Bachelor’s degree engineering 1958 joined Teijin polymer chemist.1Negishi E. Magical power metals: past, present, future (Nobel Lecture).Angew. Chem. Int. Ed. Engl. 2011; 50: 6738-6764Crossref PubMed Scopus (574) Google Scholar Thanks Fulbright scholarship, moved United States 1960 undertake PhD at Pennsylvania, physical exposed frontier sciences following seminars featuring Nobel laureates including Prof. Herbert C. Brown, others. After graduation 1963, returned Japan reintegrated Teijin, but decided move back 1966 carry post-doctoral stay aforementioned H.C. Brown Prize 1979) Purdue became assistant until 1972. There, worked organoboron Akira Suzuki (future co-listed laureate), developed, instance, thexylborane. In 1972, Syracuse (New York) an professor promoted associate 1976. There began journey through cross-coupling reaction, focusing first organozinc compounds palladium organometallics (B, Al, Zr, etc.) metal catalysts, particular, Ni. This also time when sport practiced good quality level entire life (he especially enjoyed double diamond slopes Vail Squaw Valley, instances group members). He then 1979 full continued rest academic there retirement 2019. means synthesize world. awarded Chemistry 2010 contribution field cross-coupling. prize shared Profs. Richard F. Heck recognition impact their chemistries efficient drugs, agrochemicals, polymers. career, made several additional landmark contributions focused assembling molecules via Zr- Pd-catalyzed highlighting organometallic synthesis. work reported ca. 400 publications recognized numerous awards accolades: J. S. Guggenheim Memorial Foundation Fellowship (1987), Chemical Society Award (1996), ACS Awards Organometallic (1998) Creative Work Synthetic Organic (2010), Alexander von Humboldt (1998–2001) few. elected member American Academy Arts Sciences (2011) National (2014). The knowledge Ziegler Natta Negishi’s background combined exposure Laureates (including, time, Laureate collaborator Brown) studying Pennsylvania certainly influenced desire explore catalysis. Early someone deeply respected admired, being professor, showed nickel complexes could catalyze formation carbon-carbon bonds stable organohalide (R–X) (R′–M) compounds. simple concept enables molecular structures “LEGO” game-like approach, it referred himself. A far broader range electrophiles nucleophiles used beyond what typically done time; SN2-reactions are large limited sp3-sp3 coupling, opened possibility spi-spj (i, j = 1, 2, 3) coupling stereoselective manner applicable, hence its potential synthesis.1Negishi Scholar,2Negishi Palladium- nickel-catalyzed cross coupling. selective method bond formation.Acc. Res. 1982; 15: 340-348Crossref (1132) probably best illustrated vitamin intermediates, E,Z-stereochemistry olefins needs fully controlled. These works aroused interest (1) build multiple series using carbopalladation carbonylation generate complexity—polycyclic structures—from linear acyclic chains step, (2) organozirconium ultimately led converting Ziegler-Natta-like polymerization catalyst into enantioselectively natural products motifs, which discussed further detail within two sections. related (in all likelihood) can exploit insertion alkyne palladium-carbon carrying insertions sequence create avoiding termination (β-hydrogen elimination) yielding polycyclic precursors. most emblematic example one-step conversion molecule so-called “zipper” reaction provide ABCD rings cholesterol-like moieties relay functions, complementing Johnson annulation process.3Zhang Y. Metal-promoted cyclization. 25. Palladium-catalyzed carbometalation alkynes alkenes route cyclic structures.J. Am. Soc. 1989; 111: 3454-3455Crossref (191) Scholar,4Negishi Copéret Ma Liou S.-Y. Liu Cyclic Carbopalladation. Versatile Methodology Construction Compounds.Chem. Rev. 1996; 96: 365-394Crossref (721) Moving 1,1-disubstituted alkenes, functions provided access [3.1.0] [4.1.0] bicyclic (containing cyclopropane unit) involved them intermediates apparent “endo-mode” cyclization, leads inversion stereochemistry olefin function—illustrating fine balance between β-hydrogen/alkyl transfer/insertion chemistry.5Owczarczyk Z. Lamaty Vawter E.J. Apparent endo-mode alkene configuration exo-mode cyclization-cyclopropanation rearrangement.J. 1992; 114: 10091-10092Crossref (110) Combining carbonylative conditions creation very structures, 7 thus installing stereocenters, carbonyl groups, ester functionalities.6Sugihara T. Owczarczyk Harring L.S. Deferred Carbonylative Esterification Pd-Catalyzed Carbometalation-Carbonylation Cascade.J. 1994; 116: 7923-7924Crossref (93) Scholar,7Copéret Palladium-Catalyzed Cyclization Cascades Iododienes and-trienes.Angew. 38: 2125-2126Crossref (28) need stereocontrol alkenyl derivatives complement approaches fueling organozirconocene organoaluminium chemistries, carboalumination alkynes.8Negishi Takahashi Patterns stoichiometric catalytic synthetic interest.Acc. 27: 124-130Crossref (434) Here, synergy “super-electrophiles”; would fact state “two better than one”.9Negishi quarter century explorations chemistry.Dalton Trans. 2005; 5: 827-848Crossref (88) topic discover “Negishi” reagent10Negishi Cederbaum F.E. Reaction dichloride alkyllithiums alkyl Grignard reagents convenient generating “zirconocene” equivalant use zirconium-promoted cyclization alkynes, dienes, enynes, diynes.Tetrahedron Lett. 1986; 2829-2832Crossref (609) Scholar,11Negishi Montchamp J.-L. Anastasia L. Elizarov A. Choueiry D. Zirconium-catalyzed enynes aluminacycles compounds.Tetrahedron 1998; 39: 2503-2506Crossref (62) detailed mechanistic studies instance Dzemilev importance β-H abstraction key elementary step catalysis derivatives. reagent, putative 14-electron species formally empty orbitals lone pair, applied ways Pauson-Khand-like such pentalenic acid phorbol illustrative examples.12Agnel G. Highly stereo-and regiocontrolled cyclopentannulation allylphosphonate conjugate addition hydroboration-oxidation-elimination. Synthesis virtually complete regiocontrol.J. 1991; 113: 7424-7426Crossref (85) Scholar,13Wender P.A. McDonald Studies tumor promoters. 9. second-generation phorbol.J. 1990; 112: 4956-4958Crossref (180) Applied enabled unusual [3.3.0]-bicyclooctanones trans-stereochemistry metallacyclopentanes viewed mere resonance di-olefin complexes.8Negishi Scholar,14Rousset C.J. Swanson D.R. Zirconocene-promoted bicyclization 6-and 7-dienes produce trans-zirconabicyclo [3.3. 0] octanes cis-zirconabicyclo [4.3. nonanes.Tetrahedron 30: 5105-5108Crossref (173) Ultimately coming closely Ziegler-Natta polymerization, developed β-substituted alkyl-alkanols required stereocontrolled single metal-carbon bond; effort took years because fast, competitive β-hydrogen elimination processes observed metallocenes. Exploiting bulky Erker-ligand success15Kondakov D.Y. enantioselective methylalumination monosubstituted alkenes.J. 1995; 117: 10771-10772Crossref (152) Scholar,16Negishi Kondakov An odyssey carbotitanation zirconium-catalysed alkenes.Chem. 25: 417-426Crossref (98) introduction groups broad skeletons iterative approach.1Negishi kept strong personal professional connections native country. Over years, scientists, academia industry, laboratory, longer stays some researchers. Among them, cite case Dr. Tamotsu Takahashi, who zirconium started own (where currently Sapporo), ties Negishi. fact, had chance part exchanges. proud culture sharing us—we were fortunate food, go lunch times Heisei, restaurant (yes, Lafayette); Polaroid pictures still posted wall last check—it 2011 celebrate Another country relationship laboratory France. Indeed, may wonder stage why these “French” co-authors write text legacy co-authors—F.C., D.C., C.C., F.L., J.L.M., C.R.—come same undergraduate master’s study program (CPE Lyon [Ecole Supérieure de Chimie Physique Electronique Lyon], called ESCIL Industrielle Lyon] fusion another Lyon) post-doc 20 30 ago. CPE France sent more 50% students and/or do one-year internship abroad validate degree, already late seventies. intricacies French education system difficult integrate graduate programs time—a director (Y. Bonnet) able convince universities value students, opening join department Lyon, Victor former Yves Chauvin 2005 metathesis) alumnus, focus industrial combining engineering, fundamental chemistry. foreign languages management, number disciplines. We have outstanding instructors catalysis, Goré Malacria, only few, presented explained latest development, even curriculum. They us, present contemporary literature large-scale (which quite educational time). gastronomy capital France, Lafayette, IN mid-eighties nineties lifestyle us. However, peaceful beautiful campus (and above) proximity Chicago (with Cubs baseball team, blues bars, museums) asset ideal place PhDs! Our PhD. Working blessing: observing simplification. point never experiments “to fill-in tables” rather carefully design answer well-posed demonstrate generality (the shortcoming elegance) approach. While critical, honest, frank, accessible offered genuine feedback, confidence oneself inspiring introspection. “See me, please—EN” Post-it notes stuck notebook desk (close wooden bench row hoods), indicating important discussion results take directions emerge. Each memorable conferences—whether challenged golf, ping pong, skiing singing karaoke. advocate work/life balance; art sport, encouraging excel whatever do. Years later, see way managing. true mentor, transmitting ethic collaborators research. Some went industry later understood real work. thrill discover, invent, bring innovative solutions forever; hope happiness, eternal optimism, excellence.Scheme 1. (A) days, orbital symmetry concept. (B) Exploration (e.g., zipper-mode cyclisation) sequential carbonylation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Left: extract minutes co-authors, F.L. (every meeting documented correspondents). Right: giving class just after informed recipient Chemistry—2010. Credit: University.View (PPT)Scheme 2. Carboalumination. reagent zirconocene. (C) (ZACA) applications.View golfing. Family. Top right: crew (left; D.C.) during visit Huet (right; charge international relation together (center)—1992. Lamaty. Bottom Negishi, friends, picture includes F.C., J.L.M.) symposium organized University—2000. University).View (PPT) thankful Mrs. Donna L Bertram (Purdue University) helping materials, particular manuscript.