Improved Catalysts for the Palladium-Catalyzed Synthesis of Oxindoles by Amide α-Arylation. Rate Acceleration, Use of Aryl Chloride Substrates, and a New Carbene Ligand for Asymmetric Transformations
TL;DR: Mechanistic studies showed that the reaction involves rate-limiting oxidative addition of aryl halide, and use of new, optically active heterocyclic carbene ligands gave substantial enantioselectivity in formation of an alpha,alpha-disubstituted oxindole.
Abstract: Catalysts comprised Pd(OAc)2 and either PCy3 or sterically hindered N-heterocyclic carbene ligands provide fast rates for a palladium-catalyzed synthesis of oxindoles by amide α-arylation. This catalyst system allowed for room-temperature reactions in some cases and reactions of aryl chlorides at 70 °C. Most important, reactions occurred in high yields under mild conditions to form the quaternary carbon in α,α-disubstituted oxindoles. The combined inter- and intramolecular reaction afforded an efficient synthetic method for formation of α-aryloxindole derivatives. Surprisingly, catalysts containing tert-butylphosphine ligands, which have been most reactive for ketone arylations, were less active than those containing PCy3. Use of new, optically active heterocyclic carbene ligands gave substantial enantioselectivity in formation of an α,α-disubstituted oxindole. In contrast, a variety of optically active phosphine ligands that were tested gave poor enantioselectivity. Mechanistic studies showed that the re...
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TL;DR: N-Heterocyclic carbenes have become universal ligands in organometallic and inorganic coordination chemistry as mentioned in this paper, and they not only bind to any transition metal, be it in low or high oxidation states, but also to main group elements such as beryllium, sulfur, and iodine.
Abstract: N-Heterocyclic carbenes have become universal ligands in organometallic and inorganic coordination chemistry. They not only bind to any transition metal, be it in low or high oxidation states, but also to main group elements such as beryllium, sulfur, and iodine. Because of their specific coordination chemistry, N-heterocyclic carbenes both stabilize and activate metal centers in quite different key catalytic steps of organic syntheses, for example, C-H activation, C-C, C-H, C-O, and C-N bond formation. There is now ample evidence that in the new generation of organometallic catalysts the established ligand class of organophosphanes will be supplemented and, in part, replaced by N-heterocyclic carbenes. Over the past few years, this chemistry has been the field of vivid scientific competition, and yielded previously unexpected successes in key areas of homogeneous catalysis. From the work in numerous academic laboratories and in industry, a revolutionary turning point in oraganometallic catalysis is emerging.
3,388 citations
TL;DR: New methods for the synthesis of complexes with N-heterocyclic carbene ligands such as the oxidative addition or the metal atom template controlled cyclized isocyanides have been developed recently.
Abstract: The chemistry of heterocyclic carbenes has experienced a rapid development over the last years. In addition to the imidazolin-2-ylidenes, a large number of cyclic diaminocarbenes with different ring sizes have been described. Aside from diaminocarbenes, P-heterocyclic carbenes, and derivatives with only one, or even no heteroatom within the carbene ring are known. New methods for the synthesis of complexes with N-heterocyclic carbene ligands such as the oxidative addition or the metal atom template controlled cyclization of β-functionalized isocyanides have been developed recently. This review summarizes the new developments regarding the synthesis of N-heterocyclic carbenes and their metal complexes.
2,454 citations
TL;DR: The basics of Pd-NHC chemistry are discussed to understand the peculiarities of these catalysts and a critical discussion on their application in C-C and C-N cross-coupling as well as carbopalladation reactions is given.
Abstract: Palladium-catalyzed C-C and C-N bond-forming reactions are among the most versatile and powerful synthetic methods. For the last 15 years, N-heterocyclic carbenes (NHCs) have enjoyed increasing popularity as ligands in Pd-mediated cross-coupling and related transformations because of their superior performance compared to the more traditional tertiary phosphanes. The strong sigma-electron-donating ability of NHCs renders oxidative insertion even in challenging substrates facile, while their steric bulk and particular topology is responsible for fast reductive elimination. The strong Pd-NHC bonds contribute to the high stability of the active species, even at low ligand/Pd ratios and high temperatures. With a number of commercially available, stable, user-friendly, and powerful NHC-Pd precatalysts, the goal of a universal cross-coupling catalyst is within reach. This Review discusses the basics of Pd-NHC chemistry to understand the peculiarities of these catalysts and then gives a critical discussion on their application in C-C and C-N cross-coupling as well as carbopalladation reactions.
1,471 citations
TL;DR: The catalytic asymmetric synthesis of the tetrasubstituted carbon stereocenter at the C-3 position of the oxindole framework integrates new synthetic methods and chiral catalysts.
Abstract: The 3,3′-disubstituted oxindole structural motif is a prominent feature in many alkaloid natural products, which include all kinds of tetrasubstituted carbon stereocenters, spirocyclic or not, all-carbon or heteroatom-containing. The catalytic asymmetric synthesis of the tetrasubstituted carbon stereocenter at the C-3 position of the oxindole framework integrates new synthetic methods and chiral catalysts, reflects the latest achievements in asymmetric catalysis, and facilitates the synthesis of sufficient quantities of related compounds as potential medicinal agents and biological probes. This review summarizes the recent progress in this area, and applications in the total synthesis of related bioactive compounds.
1,085 citations
TL;DR: The use of N-heterocyclic carbenes as ligands for transition metals has increased dramatically in the last few years, spurred on by their remarkable successes in the areas of metathesis chemistry and coupling reactions as discussed by the authors.
901 citations
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TL;DR: In this paper, the authors used Pd2(dba)3/P(t-Bu)3 as a catalyst for Suzuki cross-coupling of aryl and vinyl triflates.
Abstract: Through the use of Pd2(dba)3/P(t-Bu)3 as a catalyst, a wide range of aryl and vinyl halides, including chlorides, undergo Suzuki cross-coupling with arylboronic acids in very good yield, typically at room temperature; through use of Pd(OAc)2/PCy3, a diverse array of aryl and vinyl triflates react cleanly at room temperature. Together, these two catalyst systems cover a broad spectrum of commonly encountered substrates for Suzuki couplings. Furthermore, they display novel reactivity patterns, such as the selective cross-coupling by Pd2(dba)3/P(t-Bu)3 of an aryl chloride in preference to an aryl triflate, and they can be used at low loading, even for reactions of aryl chlorides. Preliminary mechanistic work indicates that a palladium monophosphine complex is the active catalyst in the cross-coupling of aryl halides.
1,413 citations
TL;DR: The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and P(t-Bu)(3) in a 1:1 ratio, and the reactions ofAryl chlorides occur atRoom temperature or 70 degrees C.
Abstract: The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and P(t-Bu)(3) in a 1:1 ratio, and the reactions of aryl chlorides occur at room temperature or 70 degrees C. The arylation of indoles and the new arylation of carbamates also occur when using P(t-Bu)(3) as ligand.
688 citations
TL;DR: This development provides a general solution to a long-standing limitation of this extremely powerful process-the poor reactivity of inexpensive and readily accessible aryl chlorides.
Abstract: From only commercially available reagents a wide array of Suzuki cross-couplings of aryl chlorides with arylboronic acids can be effected in excellent yield [Eq. (a)]. This development provides a general solution to a long-standing limitation of this extremely powerful process-the poor reactivity of inexpensive and readily accessible aryl chlorides. dba=dibenzylideneacetone.
642 citations
TL;DR: A unique combination of steric and electronic properties appears to determine the effectiveness of phosphanyl-substituted biphenyls as ligands in palladium-catalyzed aminations and Suzuki coupling of aryl chlorides at room temperature.
Abstract: A unique combination of steric and electronic properties appears to determine the effectiveness of phosphanyl-substituted biphenyls as ligands in palladium-catalyzed aminations and Suzuki coupling of aryl chlorides at room temperature [Eq. (1)]. The oxidative addition step is greatly accelerated, and transmetalation (or Pd-N bond formation) and reductive elimination processes are facilitated. Use of these ligands allows for Suzuki coupling at very low catalyst loadings (as little as 10(-6) mol % Pd). R"=cyclohexyl, tert-butyl.
626 citations
556 citations