Industrial-Scale Palladium-Catalyzed Coupling of Aryl Halides and Amines -A Personal Account
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REVIEW DOI: 10.1002/adsc.200505158 Industrial-Scale Palladium-Catalyzed Couplingof Aryl Halides and Amines – A Personal Account Stephen L. Buchwald,a Christelle Mauger,b, e Gerard Mignani,b,* Ulrich Scholzc, d,* a Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Fax: (þ 1)-617-253-3297, e-mail: [email protected] b Rhodia, Centre de Recherche de Lyon, 85 rue des Fre`res Perret, BP62, 69192 Saint-Fons Cedex, France Fax: (þ 33)-4-72-89-68-55, e-mail: [email protected] c Lanxess Deutschland GmbH, Fine Chemicals Research & Development, 51368 Leverkusen, Germany d Current address: Boehringer Ingelheim Pharma GmbH & Co. KG, Dept. Process Development, 55216 Ingelheim am Rhein, Germany E-mail: [email protected] e Current address: Reckitt Benckiser, Dauson Lane, Hull HU8 7DS, United Kingdom E-mail: [email protected] Received: April 18, 2005; Accepted: July12, 2005 Abstract: The palladium-catalyzed coupling of amines 4 The Preparation of Arylpiperazines as a Model and aryl halides or aryl alcohol derivatives has ma- Process for the Scale-Up of Palladium-Catalyzed tured from an exotic small-scale transformation into Aromatic Amination a verygeneral, efficient and robust reaction during 5 Synthesis of Industrially Important Diarylamines the last ten years. This article reports several applica- byC ÀN coupling tions of this method from an industrial vantage point, 6 Synthesis of the Dialkylphosphinobiaryl Ligands including ligand synthesis, synthesis of arylpipera- 7 Synthesis of Chlorodicyclohexylphosphine zines, arylhydrazines and diarylamines. Much empha- 8 Synthesis of Ligands A and C sis in placed on issues of scale-up and safetyto under- 9 Synthesis of Ligand B line the potential of CÀN couplings as solutions for in- 10 Removal/Recycling of Palladium after the Reac- dustrial-scale synthetic problems. tion 11 Conclusions and Prospects for Future Work 1 Introduction 2 Motivation: Technologygives an Edge 3 The Synthesis of Arylhydrazones and their use as Keywords: amination; anilines; CÀN cross-coupling; Synthetic Intermediates homogeneous catalysis; palladium; phosphane ligands 1 Introduction rials, polymers, liquid crystals and xerographic materi- als.[2] The development of a new, general methodologyfor the Over the first ten years since its development, small- formation of aromatic carbon-nitrogen bonds is of great scale applications of the palladium-catalyzed aromatic significance in manyareas of organic synthesis. As the amination have appeared in publications from academ- Heck, Suzuki–Miyaura, Stille, Kumada and Negishi pro- ic, medicinal and process chemistrylaboratories. This cedures have revolutionized the waywe construct sp2C– method is able to connect highlyfunctionalized compo- sp2C bonds,[1] the palladium-catalyzed aromatic amina- nents and is compatible with a wide varietyof functional tion has the potential to modifyanalogouslyour ap- groups. This generalitymakes it well-suited for the con- proach to the synthesis of aniline derivatives. Aromatic struction of a bodyof amine analogues from a common carbon-nitrogen bonds are structural constituents for intermediate. The versatilityand applicabilityof the the preparation of compounds of interest to those method has been thoroughlydocumented in two recent in the pharmaceutical and agrochemical industries. reviews.[3] In addition, compounds with this motif are impor- tant for the preparation of new ligands, electronic mate- Adv. Synth. Catal. 2006, 348, 23 – 39 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 23 REVIEW Stephen L. Buchwald et al. Stephen L. Buchwald was Christelle C. Mauger was born (1955), raised and re- born in Saint-Loˆ in Nor- ceived his precollege edu- mandy(France) in 1974. cation in Bloomington, In- She completed her under- diana. He received his graduate degree at the Sc. B. degree, Magna Cum Universityof Caen and ob- Laude, in chemistry, from tained her Ph. D. degree in Brown Universityin 1977. organic chemistryin 2000 During his undergraduate under the guidance of Dr years he worked in the lab- Serge Masson (Labora- oratories of Professors toire de Chimie Mole´cu- Kathlyn A. Parker and laire et Thioorganique, David E. Cane at Brown Universityand Professor Caen, France). She then moved to Huddersfield Gilbert Stork at Columbia University. He entered (England) to join Avecia Pharmaceuticals for an in- Harvard Universityas a National Science Foundation dustrial postdoctoral position. She worked on the Predoctoral Fellow in 1977 and received his Ph. D. in rapid development of new routes to pharmaceutical 1982. His thesis work, under the supervision of Pro- intermediates and on the “CaTHy” catalytic transfer fessor JeremyR. Knowles, concerned the mechanism hydrogenation reaction. In 2001 she accepted a post- of phosphoryl transfer reactions in chemistry and bio- doctoral position granted byRhodia Organic at the chemistry. In early 1982 he took up a position as a Universityof Poitiers (Laboratoire de Catalyseen Myron A. Bantrell postdoctoral fellow at the Califor- Chimie Organique, France) where she worked in nia Institute of Technologywhere he worked in the the fields of fluorine chemistry. In 2002, she joined laboratoryof Professor Robert H. Grubbs. His Rhodia Recherches (Lyon Research Centre) as a re- work at Caltech concerned the studyof titanocene search engineer in the Process Research Group. Her methylenes as reagents in organic synthesis. During main area of activities was the development of pharma- this time he was also involved in work on the mech- ceutical intermediates using organometallic catalysis anism of the Ziegler–Natta polymerization. In 1984 and aromatic bond forming reactions (ABF). In Janu- he began as an assistant professor of chemistryat ary2006, she moved to the Reckitt Benckiser scientific the Massachusetts Institute of Technology. He was services department in Kingston-upon-Hull (UK). promoted to the rank of associate professor in 1989 and to Professor in 1993. He was named the Camille Ge´rard Mignani studied Dreyfus Professor of Chemistry in January of 1997. chemistryin Orsayand During his time at MIT he has received numerous Rennes Universities where honors including the Harold Edgerton FacultyAch- he received his Ph. D. ievement Award of MIT, an Arthur C. Cope Scholar (Docteur Inge´nieur) in Award, the 2000 Award in Organometallic Chemistry 1980 and his “The`se dE- from the American Chemical Society, a MERIT tat” in 1982 in the field of award from the National Institutes of Health, the organometallic chemistry Bristol-Myers Squibb Distinguished Achievement and homogeneous cataly- Award in Organic Synthesis (2005), the CAS Spot- sis especiallyin steroid light Award (2005) and the American Chemical Soci- chemistry(Rhoˆ ne-Poulenc etyAward for Creative Work in Synthetic Organic Grant) in Professor Da- Chemistry(2006). In 2000, he was elected as a mem- bards group. He joined the Rhoˆ ne-Poulenc Research ber in the American Academyof Arts and Sciences. group in Lyon in 1980 where he developed new proc- He has been a named lecturer at numerous universi- esses in organic and terpene chemistryand in homo- ties. He is the coauthor of 245 published or accepted geneous and heterogeneous catalysis. Thereafter he papers and 30 issued patents. He serves as a consul- performed postdoctoral research with Professor D. tant to Amgen, Merck, InfinityPharmaeuticals, Rho- Seyferth at the Massachusetts Institute of Technology dia Pharmaceutical Solutions, Lanxess, Englehard (Cambridge, U. S. A.) on ceramic precursors and or- and Collegium Pharmaceuticals. He and Eric Jacob- ganosilicon chemistry. He came back to Rhoˆ ne-Pou- sen have co-taught a short course on Organometallic lenc research where he developed new ceramic pre- Chemistryin Organic Synthesis at over 35 companies cursors, new non-linear optic derivatives, polymers, in the U. S. A. and in Europe. and homogeneous catalysis processes. He spent ten years as a Group Leader in Silicon Chemistry. His re- search interests were the poly-functionalization of 24 asc.wiley-vch.de 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2006, 348,23–39 Industrial-Scale Palladium-Catalyzed Coupling of Aryl Halides and Amines REVIEW polysiloxanes, new organometallic catalysis for orga- chemistryand received his diploma degree in Profes- nosilicon applications and the functionalization of sor E. Winterfeldts research group in 1996 on the mineral charges. Now, his research interests are the synthesis of unsymmetrical pyrazines. He stayed in new processes and scale-up in organic chemistry, or- Professor Winterfeldts group and spent the subse- ganometallic catalysis (homogeneous and heteroge- quent three years on the elaboration of bile acids as neous) and new methodologyin chemistrysynthesis. potential building blocks for the synthesis of cepha- He received the “Prix de la Recherche” in 1995, in lostatin analogues. After graduation he continued as 2001 “Prix RHODIA Group” and in 2004 “Prix Cen- a teaching assistant at Hannover Universityto finally tre de Recherches-RHODIA”. join the Central Research Department for homoge- neous catalysis of Bayer AG at the end of 1999. In Ulrich Scholz started his 2002, he moved to the process development depart- studies in chemistryin ment of the Bayer Chemicals Company, now Lanxess 1990 at the Universityof – Fine Chemicals as a project manager of the Special- Hannover, Germany. In ityChemicals Department. Since 2001, he also head- 1993, he joined