Chem. Rev. 2000, 100, 3009−3066 3009 The Heck Reaction as a Sharpening Stone of Palladium Catalysis Irina P. Beletskaya* and Andrei V. Cheprakov Department of Chemistry, Moscow State University, 119899 Moscow, Russia Received January 10, 2000 Contents art organic synthesis. Among basic types of pal- ladium-catalyzed transformations, the Heck reaction I. Introduction 3009 and related chemistry occupy a special place. Though II. The Heck Catalytic Engine 3010 in specific areas other palladium-catalyzed transfor- A. Preactivation Step 3011 mations such as, e.g., allylic substitution of cross- B. Oxidative Addition 3012 coupling may seem to be more advanced, none can C. Migratory Insertion 3012 match Heck chemistry in resourceful versatility, the D. Termination 3017 overwhelming ability to spawn new, hitherto unex- E. Palladium Hydride Elimination 3017 pected applications, and resolving challenges. The III. The Chase for the Highest Activity 3019 task to comprehensively review Heck chemistry is A. Phosphine-Assisted Catalysis 3019 now a hopeless adventure and would require a B. Palladacycles 3024 multivolume set. To find all instances of its applica- tions, the literature must be manually browsed, C. Carbene Complexes 3029 article by article, page by page. More and more often D. Underligated and Phosphine-Free Systems 3030 researchers do not bother to mention in the titles, E. Phase-Transfer Agents in Heck Chemistry 3030 abstracts, or keywords if they used Heck-type chem- F. Palladium Nanoparticles and the Problem of 3035 istry in their syntheses, because it became one of Catalyst Deactivation basic tools of organic preparations, a natural way to IV. Extensions of Common Heck Chemistry 3037 assemble molecules. A. Less Usual Means of Activation 3037 There are a number of masterful reviews covering 1. Effects of Pressure and Microwave 3037 different aspects of Heck chemistry.1-15 The goal of Heating this review is to try to cover Heck chemistry from a B. Less Usual Media 3038 different angle. We shall consistently try to elucidate 1. Aqueous Heck Chemistry 3038 and discuss everything what makes Heck chemistry 2. Molten Salts 3041 so intriguingly flexible, expandable, adaptable, and 3. Supercritical and Subcritical Fluids 3042 unpredictable. Indeed, most organic reactions, par- 4. Fluorous Systems 3043 ticularly catalytic ones, are well defined and specific Downloaded by Bert Maes on August 13, 2009 C. Recyclable (Phase-Separation) Catalysis 3043 to require some particular reagents and catalysts, to 1. Liquid−Liquid Systems 3044 operate within a confined domain, the definition of 2. Solid−Liquid Systems 3046 which includes a more or less limited scope and D. Less Usual Leaving Groups 3050 optimal conditions, solvents, ligands, etc. Several Published on July 21, 2000 http://pubs.acs.org | doi: 10.1021/cr9903048 1. Diazonium Salts 3050 general procedures cover almost all conceivable ap- plications. Yields for similar substrates can be ex- 2. Iodonium Salts 3052 trapolated. 3. Thallium(III) and Lead(IV) Derivatives 3053 4. Acid Chlorides and Anhydrides 3053 Nothing like that is true for Heck chemistry. The limits of scope are blurred, the substrates which E. Other Metals as Catalysts 3054 yesterday had been considered as unheckable are F. Less Usual Substrates and Heck-Like 3055 being cracked on need with yet another improvement. Reactions The catalyst is often anything containing palladium, 1. Involvement of Palladium Enolates 3056 even in homeopathic doses, and other metals can 2. Heck-Like Reactions with Aromatic 3058 perform the task in the absence of palladium. As far Substrates as the solvent type, almost any media seems to have 3. Other Types of Unsaturated Substrates 3059 been already tried and none has been altogether 4. Conjugation of Pd(IV)/Pd(II) Processes 3060 discarded. On the other hand, often a small variation with Pd(II)/Pd(0) Catalysis of substrate structure, nature of base, ligands, tem- V. References 3061 perature, pressure, etc., leads to unpredictable re- sults. Trends in reactivity and selectivity are uneven I. Introduction and often break when nobody would expect. Brand- name precious ligands which worked miracles for Palladium catalysis has achieved the status of an some sophisticated transformations often fail in the indispensable tool for both common and state-of-the- simplest cases. An obvious question of what is the 10.1021/cr9903048 CCC: $35.00 © 2000 American Chemical Society Published on Web 07/21/2000 3010 Chemical Reviews, 2000, Vol. 100, No. 8 Beletskaya and Cheprakov first place with the catalytic arylation and alken- ylation of olefins, that is the original Heck or Mizo- roki-Heck reaction, discovered independently by Mizoroki16 and Heck17 and developed by Heck in a number of fundamental papers into a general method of organic chemistry. The reaction presents one of the simplest ways to obtain variously substituted olefins, dienes, and other unsaturated compounds, many of which are useful as dyes, UV screens, pharmaceuticals, etc. The reac- tion is also useful in polymerization chemistry, giving access to conjugated polymers applicable, e.g., as new materials for optoelectronic devices. The reaction can be catalyzed by palladium com- plexes with or without phosphine ligands (phosphine- Irina Beletskaya received her Diploma degree in 1955, her Ph.D. degree assisted vs phosphine-free catalysis). A primary role in 1958, and her Doctor of Chemistry degree in 1963 from Moscow State University. The subject for the latter was Electrophilic Substitution at of phosphine ligands is to support palladium in its Saturated Carbon. She became a Full Professor in 1970 and in 1974 a zero oxidation state in the form of stable PdL4 or PdL3 Corresponding Member of the Academy of Sciences (USSR) of which species. The phosphine-assisted method may be she became a full member (Academician) in 1992. She is currently Head regarded as conservative, as it relies not on a priori of the Laboratory of Organoelement Compounds, Department of Chemistry, unknown reactivity of palladium catalyst in a given Moscow State University. Irina Beletskaya is Chief Editor of the Russian catalytic cycle, but rather on ligands which can Journal of Organic Chemistry. She was President of the Organic Chemistry sustain the catalytically active species even outside Division of IUPAC from 1989 to 1991. She was the recipient of the Lomonosov Prize (1979), the Mendeleev Prize (1982), and the Nes- of the catalytic cycle. The phosphine-assisted ap- meyanov Prize (1991). She is the author of over 500 articles and 4 proach is the classical and well-established method monographs. Her current scientific interests are focussed on (i) transition- which gives excellent results in a majority of cases. metal catalysis in organic synthesis; (ii) organic derivatives of lanthanides; Then why seek anything else? and (iii) carbanions and nucleophilic aromatic substitution. The reasons are both economical and chemical. Phosphine ligands are expensive, toxic, and unrecov- erable. In large-scale applications on industrial and semi-industrial scale, the phosphines might be a more serious economical burden than even palladium itself, which can be recovered at any stage of produc- tion or from wastes. The chemical reason is lower reactivity of fully ligated complexes of palladium, the main result of which is the need for higher loads of catalyst to achieve appropriate rates of reaction and therefore further aggravation of procedure cost. Downloaded by Bert Maes on August 13, 2009 Both underligated and phosphine-free catalysis are opposite to the phosphine-assisted conservative meth- odology. It relies not on the intrinsic stability of properly ligated isolable complexes, but rather on Published on July 21, 2000 http://pubs.acs.org | doi: 10.1021/cr9903048 making zerovalent palladium species run for life Andrei V. Cheprakov graduated from the Department of Chemistry of within the Heck catalytic cycle or die as inactive Moscow State University in 1983 and joined Professor I. Beletskaya’s black sediments. Underligated Pd(0) species (the Laboratory of Organoelement compounds. His Ph.D. theses were devoted term underligated means that a given palladium to the oxidative halogenation of aromatic compounds and were defended complex bears less strongly bonded ligands than is in 1989. Currently he is a docent at the Chair of Organic Chemistry of required to form a stable complex) are intrinsically Moscow University. His research interests include the palladium-catalyzed reactions in aqueous and microheterogeneous media, catalytic activity of unstable to survive outside of the cycle but are likely nanoparticles, and the chemistry and synthesis of extended porphyrins. to have higher reactivity; therefore, their stationary concentration in a catalytic system is much lower. best catalyst and procedure remains unanswered Unlike phosphine-assisted systems which are based even for the simplest cases, though studied in hun- on thoughtful design and knowledge of intimate dreds of works. Heck chemistry continues to be a details of coordination chemistry, phosphine-free fascinating puzzle. It is multidimensional and along systems are illegitimate children of circumstance. each of its dimensions intersects with the domains Nevertheless, there is a hope that on gathering more of other palladium-catalyzed processes with common data on such reactions, some helpful trends could be steps, ideas, techniques. Tuning Heck chemistry evaluated and used to refine the procedures. The reciprocates