In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

The increasing demand to produce enantiomerically pure pharmaceuticals, agrochemicals, flavors, and other fine chemicals has advanced the field of asymmetric catalytic technologies.1,2 Among all asymmetric catalytic methods, asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral olefins, ketones, and imines, have become one of the most efficient methods for constructing chiral compounds.3 The development of homogeneous asymmetric hydrogenation was initiated by Knowles4a and Horner4b in the late 1960s, after the discovery of Wilkinson’s homogeneous hydrogenation catalyst [RhCl(PPh3)3]. By replacing triphenylphosphine of the Wilkinson’s catalystwithresolvedchiralmonophosphines,6Knowles and Horner reported the earliest examples of enantioselective hydrogenation, albeit with poor enantioselectivity. Further exploration by Knowles with an improved monophosphine CAMP provided 88% ee in hydrogenation of dehydroamino acids.7 Later, two breakthroughs were made in asymmetric hydrogenation by Kagan and Knowles, respectively. Kagan reported the first bisphosphine ligand, DIOP, for Rhcatalyzed asymmetric hydrogenation.8 The successful application of DIOP resulted in several significant directions for ligand design in asymmetric hydrogenation. Chelating bisphosphorus ligands could lead to superior enantioselectivity compared to monodentate phosphines. Additionally, P-chiral phosphorus ligands were not necessary for achieving high enantioselectivity, and ligands with backbone chirality could also provide excellent ee’s in asymmetric hydrogenation. Furthermore, C2 symmetry was an important structural feature for developing new efficient chiral ligands. Kagan’s seminal work immediately led to the rapid development of chiral bisphosphorus ligands. Knowles made his significant discovery of a C2-symmetric chelating bisphosphine ligand, DIPAMP.9 Due to its high catalytic efficiency in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids, DIPAMP was quickly employed in the industrial production of L-DOPA.10 The success of practical synthesis of L-DOPA via asymmetric hydrogenation constituted a milestone work and for this work Knowles was awarded the Nobel Prize in 2001.3k This work has enlightened chemists to realize * Corresponding author. 3029 Chem. Rev. 2003, 103, 3029−3069

New Chiral Phosphorus Ligands for Enantioselective Hydrogenation

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Hydrogenation is a core technology in chemical synthesis. High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The newly devised [RuCl(2)(phosphane)(2)(1,2-diamine)] complexes are excellent precatalysts for homogeneous hydrogenation of simple ketones which lack any functionality capable of interacting with the metal center. This catalyst system allows for the preferential reduction of a C=O function over a coexisting C=C linkage in a 2-propanol solution containing an alkaline base. The hydrogenation tolerates many substituents including F, Cl, Br, I, CF(3), OCH(3), OCH(2)C(6)H(5), COOCH(CH(3))(2), NO(2), NH(2), and NRCOR as well as various electron-rich and -deficient heterocycles. Furthermore, stereoselectivity is easily controlled by the electronic and steric properties (bulkiness and chirality) of the ligands as well as the reaction conditions. Diastereoselectivities observed in the catalytic hydrogenation of cyclic and acyclic ketones with the standard triphenylphosphane/ethylenediamine combination compare well with the best conventional hydride reductions. The use of appropriate chiral diphosphanes, particularly BINAP compounds, and chiral diamines results in rapid and productive asymmetric hydrogenation of a range of aromatic and heteroaromatic ketones and gives a consistently high enantioselectivity. Certain amino and alkoxy ketones can be used as substrates. Cyclic and acyclic alpha,beta-unsaturated ketones can be converted into chiral allyl alcohols of high enantiomeric purity. Hydrogenation of configurationally labile ketones allows for the dynamic kinetic discrimination of diastereomers, epimers, and enantiomers. This new method shows promise in the practical synthesis of a wide variety of chiral alcohols from achiral and chiral ketone substrates. Its versatility is manifested by the asymmetric synthesis of some biologically significant chiral compounds. The high rate and carbonyl selectivity are based on nonclassical metal-ligand bifunctional catalysis involving an 18-electron amino ruthenium hydride complex and a 16-electron amido ruthenium species.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010105%2940%3A1%3C40%3A%3AAID-ANIE40%3E3.0.CO%3B2-5

Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo‐ and Stereoselective Hydrogenation of Ketones

Synthetic applications of palladium catalysed carbonylation of organic halides

RECENT ADVANCES IN THE INVESTIGATION OF CARBONYLATION CATALYSTS Kinetics of Carbonylation Reactions Quantum-chemical Studies on the Mechanism of Transition Metal Catalysed Cabonylation Chelating Ligands with Various Bite-angles in Carbonylation Reactions (Electronic and Steric Effects of Ligands in Carbonylation Reactions) Reactivity of Pincer Complexes Towards Carbon Monoxide The Use of Heterobimetallic Systems in Carbonylations Homogenization of Heterogeneous Carbonylation Catalysts Novel Chiral Ligands Designed for Enantioselective Hydroformylation METHODOLOGICAL DEVELOPMENTS IN CARBONYLATION REACTIONS Enantioselective Carbonylation Reactions Asymmetric Cyclocarbonylations Microwave-promoted Cabonylations Recent Advances in Two-phase Carbonylation Ionic Liquids in Carbonylation Reactions Industrial Applications of Transition Metal Catalysed Carbonylation Reactions SYNTHETIC APPLICATION OF TRANSITION METAL CATALYSED CARBONYLATION REACTIONS Carbonylative Ring Expansion Reactions Carbonylation of Allenes Carbonylation of Oxiranes Homogeneous Carbonylation Reactions in the Synthesis of Compounds of Pharmaceutical Importance The Synthesis of O-, N- and S-containing Heterocycles in Homogeneous Carbonylation Reactions Pd-assisted Synthesis of Heterocycles via Carbonylation Reactions

Modern carbonylation methods

Ligands with phosphorus donor atoms have probably been the most studied ones in transition metal catalyzed reactions. Because of the recognition of the carbon-metal bonding properties and the mechanistic understanding of the basic catalytic reactions, the application of homogeneous catalytic reactions is steadily emerging. The definition of the scope and limitations has rendered many of the transition metalphosphorus ligand catalytic systems the most efficient solution to practical problems. Most of the “textbook” homogeneous catalytic reactions, among them enantioselective reactions, apply tertiary phosphines as most conventional ligands. Among the ligands with phosphorus of sp3 hybridization, the cyclic ligands have reached an impressive maturity. In spite of this fact, in general, the chemistry of phosphorus heterocycles is much less developed than the analogous nitrogen chemistry. It is especially true in the area of coordination chemistry, even though cyclic phosphines proved to be excellent ligands for catalysis.1-5 Thus, the main objective of this review is to shed some more light into the synthesis, coordination chemistry, and catalysis of some 3-, 4-, 5-, 6-, and 7-membered Pheterocycles of unprecedented structure not reviewed before. The objective of this paper is not to present a full coVerage of P(III) deriVatiVes, since several aspects of these types of P-heterocycles such as theoretical background, synthesis, * To whom correspondence should be addressed. E-mail: kollar@ttk.pte.hu. † This paper is dedicated to the memory of Professor Pascal Le Floch. György Keglevich was born in Budapest, Hungary, in 1957. He received his M.Sc. under the supervision of Professors L. Tõke and Imre Petneházy from the Technical University of Budapest in 1981. After getting the Ph.D., he was a postdoctoral fellow with Professor L. D. Quin (at Duke University, Durham, NC). In 1994, he received his D.Sc. from the Hungarian Academy of Sciences. After different teaching positions, he was appointed full professor at the Department of Organic Chemical Technology, Budapest University of Technology and Economics, in 1996, and he was the head of this Department in the period of 1999-2006. After a fusion in 2007, he has been the head of the Department of Organic Chemistry and Technology. His research interests include organophosphorus and environmentally friendly chemistry comprising P-heterocycles, low-coordinated P-fragments, P(III)-ligands, their boraneand transition metal complexes, catalytic reactions, selective syntheses, resolution of P(IV) compounds, microwave synthesis, ionic liquids, and optimization of reactions by on-line methods. Chem. Rev. 2010, 110, 4257–4302 4257

László Kollár

Papers

Synthetic applications of palladium catalysed carbonylation of organic halides

Modern carbonylation methods

P-heterocycles as ligands in homogeneous catalytic reactions.

NMR investigation of Pd(II)–Pd(0) reduction in the presence of mono- and ditertiary phosphines

Transition-Metal-Catalyzed Reactions in Steroid Synthesis