Nickamine: a General Catalyst for Cross Coupling of Alkyl Halides and Direct Alkylation

154 CHIMIA 2012, 66, No. 4 Laureates: awards and Honors, sCs FaLL Meeting 2011 doi:10.2533/chimia.2012.154 Chimia 66 (2012) 154–158 © Schweizerische Chemische Gesellschaft Nickamine: A General Catalyst for Cross Coupling of Alkyl Halides and Direct Alkylation Xile Hu* Werner Prize winner 2011 Abstract: A nickel pincer complex, Nickamine, is shown to be an active catalyst for a large number of reactions including cross coupling of non-activated alkyl halides and direct C–H alkylation of alkynes and aromatic heterocycles. This work was rewarded by the 2011 Werner Prize from the Swiss Chemical Society. Keywords: C–H functionalization · Cross coupling · Homogeneous catalysis · Organometallic chemistry · Nickel 1. Introduction 2. Motivation I am thrilled to receive, together with Werner was the first to correctly pro- Prof. Reto Dorta, the 2011 Werner Prize. pose the structure of coordination com- This is not only because it is a distin- plexes. He did most of his work using amine guished honor for young investigators in and aqua complexes of first-row transition Switzerland, but also because I teach co- metals. For this reason, these compounds ordination chemistry at EPFL, and Prof. are often called ‘Werner complexes’. One Alfred Werner was the founding father of of Werner’s greatest achievements was this discipline. Coordination chemistry is the preparation of hexol in 1914, the first Xile Hu was born in 1978 in Putian, an integral component of my research pro- non-carbon-containing chiral compound China. He received a B.S. degree from gram. Together with a group of motivated (Fig. 1).[11] Peking University (2000) and a Ph.D. de- andtalentedco-workers,wehave embarked Another major breakthrough in coor- gree from the University of California, San on several research projects in homogene- dination chemistry was the synthesis and Diego(2004;advisor:Prof.KarstenMeyer). ous catalysis,[1,2] bio-mimetic chemis- structural elucidation of ferrocene in early He then carried out a postdoctoral study at try,[3–8] and energy-related electrocataly- 1950s (Fig. 1). It marked the birth of mod- the California Institute of Technology (ad- sis.[9,10] The starting point of these projects ern organometallic chemistry. E.O. Fischer visor: Prof. Jonas Peters) before joining the is often the synthesis of new coordination and G. Wilkinson received the Nobel Prize faculty of École Polytechnique Fédérale de compounds. The Werner Prize recognizes in 1973 for their work on sandwich com- Lausanne (EPFL) as a tenure-track assis- our contributions to the development of pounds of this type.[12,13] And another im- tant professor in 2007. His research inter- synthetic methodologies. Herein I describe portant contribution of Wilkinson is the de- ests span from organometallic chemistry, some representative examples of our work velopment of Wilkinson’s catalyst, a four- synthetic methodology, asymmetric ca- in this area; these examples all feature the coordinate complex [Rh(PPh ) Cl] (Fig. 3 3 talysis to bio-mimetic and bio-speculated catalytic applications of Nickamine, a new 1).[14] This compound is a good catalyst for coordination chemistry to electrocatalysis Ni catalyst developed in the group. many homogeneous reactions especially and artificial photosynthesis. Fig. 1. Legendary coordination com- NH3 (SO4)3 pounds. H3N NH3 Fe Co NH3 HO NH3 H H N O OH 3 Ferrocene Co Co OH H3N O H NH *Correspondence: Prof. Dr. X. L. Hu 3 Ph P PPh NH3 HO 3 3 Ecole Polytechnique Fédérale de Lausanne Co Rh NH3 Institute of Chemical Sciences and Engineering H3N Ph3P EPFL-ISIC-LSCI NH3 Cl CH-1015 Lausanne Tel.: +41 21 693 9781 Hexol Wilkinson's Fax: +41 21 693 9305 Catalyst E-mail: [email protected] Laureates: awards and Honors, sCs FaLL Meeting 2011 CHIMIA 2012, 66, No. 4 155 hydrogenation. In retrospect, Wilkinson’s applications of Nickamine in cross cou- ganometallic reagents such as zinc, boron, work revealed a winning recipe for catalyst pling reactions (Scheme 1).[21] It was found or silicon nucleophiles. Grignard reagents design: precious metals plus soft ligands. that [(MeN N)Ni-alkyl)] reacted cleanly are normally not compatible with func- 2 In the last 10 years, three Nobel prizes have with alkyl halides to form [(MeN N)Ni-X)] tional groups because they are too reactive. 2 been awarded for the advances in homoge- (X = halide) and alkyl-alkyl coupled prod- Grignard reagents can however be more at- neous catalysis, and catalysts based on pre- ucts. Because [(MeN N)Ni-X)] could react tractive coupling partners because they are 2 cious metals and soft ligands show again with alkyl Grignard reagents to form back inexpensive, easy to synthesize, and often their superiority: Rh and Ru phosphine [(MeN N)Ni-alkyl)] (Scheme 1), a catalytic commercially available. 2 complexes for hydrogenation,[15,16] Ru car- alkyl–alkyl coupling reaction was conceiv- Indeed, we were able to develop a bene/phosphine complexes for olefin me- able using 1 as catalyst. Such a coupling method to couple functionalized alkyl ha- tathesis,[17] and Pd phosphine complexes reaction is challenging because metal alkyl lides with alkyl Grignard reagents using for cross coupling.[18,19] intermediates have the tendency to under- 1 as catalyst (Scheme 2). The best yields Despite tremendous progress, homoge- go unproductive β-H elimination.[25–27] As were obtained at –35 °C, just above the neous catalysis is far from being problem- a result, new alkyl–alkyl coupling methods melting point of the reaction mixture. solved. One major challenge has arisen are of contemporary interest. Primary alkyl iodides and bromides and exactly because many useful catalysts are We were delighted to find that complex secondary alkyl iodides could be coupled. based on precious and rare metals such as 1 catalyzed the cross coupling of non-ac- The reactions tolerated a large number of Ru, Pd, Pt, Rh, Au, and Ir. The sustainabil- tivated alkyl halides with alkyl Grignard sensitive functional groups such as ester, ity of chemical processes based on these regents in high efficiency.[22] The reactions amide, keto, ether, thioether, acetal, nitrile, catalysts is called in question. Meanwhile, took place at a low temperature (–20 °C). and heterocycles. catalysts made of base metals such as Mn, Since Grignard reagents might tolerate Encouraged by this first success in Fe, Co, Ni, and Cu, are not developed to various functional groups at this temper- methodology development, we decided to the same degree. This state-of-the-art has ature, we thought it might be possible to further explore the Ni-catalysis. An obvi- largely motivated our work in base metal couple functionalized alkyl halides with ous next step was to expand the substrate catalysis. Our starting point happened to alkyl Grignard reagents under similar con- scope. Thus, we wondered whether we be a Werner-type complex – Nickamine (1; ditions. In general, this type of alkyl–alkyl could couple functionalized alkyl halides Fig. 2). coupling necessitates the use of mild or- with aryl and heteroaryl nucleophiles. The name ‘Nickamine’ reflects the composition of this compound – nickel as Me II 2 1 Me II 1 2 metal and amine as ligand. The pincer-type [( N2N)Ni -alkyl ] + alkyl -X [( N2N)Ni -X] + alkyl -alkyl bis(amino)amide ligand MeN Nwas chosen 2 because we thought nitrogen donors would match better first-row transition metal ions X=halide according to the hard-soft-acid-base prin- ciple.[20] The synthesis of the ligand and its Alkyl2-MgX coordination chemistry were straightfor- [21–23] ward. Scheme 1. Reactivity and regeneration of [(MeN N)Ni-alkyl)] complexes. 2 NMe 2 3mol% 1 N Ni Cl FG-Alkyl1-X + Alkyl2-MgCl FG-Alkyl1_Alkyl2 -35oC, DMA NMe2 FG =functional groups <1hour X=Br, Ifor primary substrates 29 examples, 56 –99% yields Nickamine (1) X=Ifor secondary substrates Selected products: Fig. 2. Structural formula of Nickamine. O n O C4H9 3. Cross Coupling of Alkyl Halides n C4H9 N O n Et N Catalyzed by Nickamine C4H9 2 78 % 72 % Nickamine was a useful starting mate- n O O O C4H9 n O rial for the synthesis of other Ni complexes C5H11 bearing the same pincer MeN N ligand. For O 2 examples, salt metathesis and transmetal- 60 % 99 % 91 % lation reactions of 1 yielded [(MeN N) 2 Ni-R)], where R is an alkyl, aryl, methox- N Ph O O O n ide, or triflate group.[21,22] It was interest- n C4H9 O C4H9 ing that [(MeN N)Ni-alkyl)] complexes 2 Ph were stable in solution, even when heated 60 % to 80 °C. It turns out that β-H elimination 75 % 99 % for these complexes is kinetically feasible, n n tBuO S C4H9 HO C8H17 but thermodynamically uphill,[24] and that N is why these complexes did not decompose O via β-H elimination. 56 % 79 %(2equiv.RMgCl) 86 % The reactivity of [(MeN N)Ni-alkyl)] 2 with alkyl halides provides the basis for the Scheme 2. Alkyl-alkyl Kumada coupling using Nickamine as catalyst. 156 CHIMIA 2012, 66, No. 4 Laureates: awards and Honors, sCs FaLL Meeting 2011 3mol% 1 solvent at a low temperature (e.g. –78 °C). FG-Alkyl1-X + FG-(hetero)Aryl2-MgX FG-Alkyl1-FG-(hetero)Aryl2 The reaction conditions are complicated 25 mol% and inconvenient, and the carcinogenic ef- TMEDA or O-TMEDA FG =functional groups THF,RT, 1hr fect of HMPA is a source of concern. At Primary R-Br,R-I; room temperature, alkali metal acetylides Secondary R-I are quite reactive and may lead to a low >70examples, 51 –99% yields functional group tolerance. We found that Selected products: using 1 as catalyst and O-TMEDA as ad- ditive, general and efficient cross coupling of non-activated alkyl halides with alkynyl Grignard reagents could be achieved MeO NN (Scheme 4).[29] The catalysis again had a O C8H17 O N wide scope and high group tolerance.

Load more