PdII Catalyst Research Articles

Palladium-Catalyzed Ligand-Directed C−H Functionalization Reactions

1.1 Introduction to Pd-catalyzed directed C–H functionalization The development of methods for the direct conversion of carbon–hydrogen bonds into carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds remains a critical challenge in organic chemistry. Mild and selective transformations of this type will undoubtedly find widespread application across the chemical field, including in the synthesis of pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. Traditional approaches for the formation of such functional groups rely on pre-functionalized starting materials for both reactivity and selectivity. However, the requirement for installing a functional group prior to the desired C–O, C–X, C–N, C–S, or C–C bond adds costly chemical steps to the overall construction of a molecule. As such, circumventing this issue will not only improve atom economy but also increase the overall efficiency of multi-step synthetic sequences. Direct C–H bond functionalization reactions are limited by two fundamental challenges: (i) the inert nature of most carbon-hydrogen bonds and (ii) the requirement to control site selectivity in molecules that contain diverse C–H groups. A multitude of studies have addressed the first challenge by demonstrating that transition metals can react with C–H bonds to produce C–M bonds in a process known as “C–H activation”.1 The resulting C–M bonds are far more reactive than their C–H counterparts, and in many cases they can be converted to new functional groups under mild conditions. The second major challenge is achieving selective functionalization of a single C–H bond within a complex molecule. While several different strategies have been employed to address this issue, the most common (and the subject of the current review) involves the use of substrates that contain coordinating ligands. These ligands (often termed “directing groups”) bind to the metal center and selectively deliver the catalyst to a proximal C–H bond. Many different transition metals, including Ru, Rh, Pt, and Pd, undergo stoichiometric ligand-directed C–H activation reactions (also known as cyclometalation).2,3 Furthermore, over the past 15 years, a variety of catalytic carbon-carbon bond-forming processes have been developed that involve cyclometalation as a key step.1b–d,4 The current review will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium. Palladium complexes are particularly attractive catalysts for such transformations for several reasons. First, ligand-directed C–H functionalization at Pd centers can be used to install many different types of bonds, including carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon linkages. Few other catalysts allow such diverse bond constructions,5,6,7 and this versatility is predominantly the result of two key features: (i) the compatibility of many PdII catalysts with oxidants and (ii) the ability to selectively functionalize cyclopalladated intermediates. Second, palladium participates in cyclometalation with a wide variety of directing groups, and, unlike many other transition metals, promotes C–H activation at both sp2 and sp3 C–H sites. Finally, the vast majority of Pd-catalyzed directed C–H functionalization reactions can be performed in the presence of ambient air and moisture, making them exceptionally practical for applications in organic synthesis. While several accounts have described recent advances, this is the first comprehensive review encompassing the large body of work in this field over the past 5 years (2004–2009). Both synthetic applications and mechanistic aspects of these transformations are discussed where appropriate, and the review is organized on the basis of the type of bond being formed.

Hydrolytic Deallylation of N‐Allyl Amides Catalyzed by PdII Complexes

AbstractHydrolytic deallylation of N‐allyl amides to give amides and propanal can be achieved with PdII catalysts. The optimized catalyst consists of Pd(OCOCF3)2 and 1,3‐bis(diphenylphosphanyl)propane (DPPP). Several kinds of open‐chain N‐allyl amides and N‐allyl lactams undergo hydrolytic deallylation to give the corresponding amides and lactams in good to high yield. A mechanism which includes isomerization to enamides and subsequent hydrolysis is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Unraveling the o‐Methoxy Effect in the CO/Ethene Copolymerization Reaction by Diphosphanepalladium(II) Catalysis

AbstractRelevant steps in the CO/ethene copolymerization reaction, namely the migratory insertion of [Pd(Me)(CO)(P‐P)]BAr′4 and the carbonylation of the β‐keto chelates [Pd(CH2CH2C(O)Me)(P‐P)]BAr′4 have been studied by in situ high‐pressure NMR spectroscopy in CH2Cl2; P‐P = 1,2‐bis[bis(2‐methoxyphenyl)phosphanyl]ethane or 1,3‐bis[bis(2‐methoxyphenyl)phosphanyl]propane. This study, backed by batch catalytic reactions in the same solvent, has contributed to rationalizing the higher catalytic activity of PdII catalysts modified with o‐methoxy‐substituted diphosphane ligands as compared to analogous PdII catalysts with 1,2‐bis(diphenylphosphanyl)ethane (dppe) and 1,3‐bis(diphenylphosphanyl)propane (dppp) ligands. It was found that o‐MeO substituents on the phosphorus aryl rings ease the opening of the β‐chelate ring by CO and affect the kinetics of the overall CO/ethene copolymerization. Indeed, unlike the catalysts with the dppe and dppp ligands, the rate of carbonylation of the o‐MeO‐modified β‐keto chelates is limited by the Pd(alkyl)(CO) migratory insertion, which makes the overall copolymerization process independent of the CO pressure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Two-Faced Reactivity of Alkenes: cis- versus trans-Aminopalladation in Aerobic Pd-Catalyzed Intramolecular Aza-Wacker Reactions

A number of different PdII catalyst systems have been reported recently for the Wacker-type aerobic oxidative cyclization of alkenes bearing tethered nitrogen nucleophiles. This study examines the stereochemistry of the aminopalladation step with five different catalyst systems: Pd(OAc)2/DMSO (A), PdX2/pyridine [X = OAc (B), O2CCF3 (C)], Pd(IMes)(O2CCF3)2(OH2) (D), and Pd(O2CCF3)2/(-)-sparteine (E). Use of a stereospecifically deuterated cyclopentene substrate reveals that four of the five catalyst systems (A, B, C, and E) promote exclusive cis-aminopalladation of the alkene, whereas both cis- and trans-aminopalladation occur with the N-heterocyclic-carbene (NHC) catalyst system. If stoichiometric Brønsted base (NaOAc, Na2CO3) is added to the latter reaction conditions, however, only cis-aminopalladation is observed. The identity of the nitrogen nucleophile also affects the aminopalladation pathway, with results ranging from exclusively cis- to exclusively trans-aminopalladation. These results have important implications for ongoing efforts to develop enantioselective methods for Pd-catalyzed oxidative amination of alkenes.

Mechanistic Questions about the Reaction of Molecular Oxygen with Palladium in Oxidase Catalysis

Which pathway? Aerobic Pd-catalyzed oxidation reactions couple organic-substrate oxidation to the reduction of O2. Two pathways are prevalent for the regeneration of the active PdII catalyst (see scheme; SubH2= substrate; SubOx=oxidized substrate), and recent studies have provided a deeper fundamental understanding of the interactions of Pd with O2.

New Metal‐Catalyzed Synthesis of Quinoline and Chromene Skeletons

AbstractAlkoxy‐functionalized butadienylboronic esters have been synthesized starting from α,β‐unsaturated acetals and cross‐coupled with both N‐protected and N‐unprotected 2‐bromo‐ and 2‐iodoaniline, and with 2‐iodophenol. In particular, N‐tosyl‐protected dienylanilines can be transformed under mild conditions into quinolines and quinolinones, in the presence of a PdII catalyst. Moreover, the cross‐coupling reaction between butadienylboronic esters and iodophenol directly affords chromenes that can be successively transformed into chromenones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Gold(I)‐Catalyzed Cyclizations of 1,6‐Enynes: Alkoxycyclizations and exo/endo Skeletal Rearrangements.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Gold(I)‐Catalyzed Cyclizations of 1,6‐Enynes: Alkoxycyclizations and exo/endo Skeletal Rearrangements

Gold(I) complexes are the most active catalysts for alkoxy- or hydroxycyclization and for skeletal rearrangement reactions of 1,6-enynes. Intramolecular alkoxycyclizations also proceed efficiently in the presence of gold(I) catalysts. The first examples of the skeletal rearrangement of enynes by the endocyclic cyclization pathway are also documented. Iron(III) is also able to catalyze exo and endo skeletal rearrangements of 1,6-enynes, although the scope of this transformation is more limited. The gold(I)-catalyzed endocyclic cyclization proceeds by a mechanism different from those followed in the presence of PdII, HgII, or RhI catalysts.

A Bimetallic Catalyst and Dual Role Catalyst: Synthesis of N‐(Alkoxycarbonyl)indoles from 2‐(Alkynyl)phenylisocyanates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Palladium‐Catalyzed SN1 Reactions of Secondary Benzylic Alcohols: Etherification, Amination, and Thioetherification.

AbstractFor Abstract see ChemInform Abstract in Full Text.

"Walking" of the C-C pi bond over long distances in Pd-catalyzed reactions of 2,3-allenoic acids with omega-1-alkenyl halides.

Taking the bond for a walk: An ω-1-alkenyl group was introduced at the β position of butenolides by the PdII-catalyzed coupling/cyclization of 2,3-allenoic acids with ω-1-alkenyl halides (see scheme). The active PdII catalyst was regenerated through the combination of cyclic oxypalladation–carbopalladation with repeated dehydropalladation/hydropalladation–dehalopalladation.

Palladium‐Catalyzed SN1 Reactions of Secondary Benzylic Alcohols: Etherification, Amination, and Thioetherification

AbstractThe reaction of various secondary benzylic alcohols in the presence of PdII catalysts provides ethers in good to high yields. Unsymmetric ethers could also be obtained with good selectivity by coupling two different alcohols. Direct amination is observed with electron‐deficient anilines, and thioethers are prepared conveniently in high yields by the direct action of thiols on sec‐phenylethyl alcohol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Oxidative Cyclization-Dimerization Reaction of 2,3-Allenoic Acids and 1,2-Allenyl Ketones: An Efficient Synthesis of 4-(3′-Furanyl)butenolide Derivatives

The active PdII catalyst in the efficient oxidative cyclization/dimerization reaction between 2,3-allenoic acids 1 and 1,2-allenyl ketones 2 to give 4-(3′-furanyl)butenolide derivatives 3 may be regenerated from Pd0 after a cyclometalation/protonolysis step in the catalytic cycle.

Kinetics and mechanism of palladium(II) catalyzed chromium(VI) oxidation of mercury(I) in aqueous sulphuric acid

The CrVI oxidation of HgI in an aqueous acid medium occurs to a modest extent only in presence of PdII and in H2SO4 above ca. 0.20 mol dm−3. The reaction is first order in [CrVI] in the presence of PdII catalyst. The order in [HgI] is less than unity, whereas that in [PdII] is unity. Increase in [H2SO4] accelerates the reaction rate. The added products, CrIII and HgII, do not significantly effect the reaction rate. A mechanism involving HCrO4− and PdCl+ as the reactive species of oxidant and catalyst respectively, is proposed. The reaction constants involved in the mechanism have been evaluated.

Macromolecular-Multisite Catalysts Obtained by Grafting Diaminoaryl Palladium(ii) Complexes onto a Hyperbranched-Polytriallylsilane Support

Hyperbranched carbosilane compounds such as 1 are conveniently prepared, soluble supports for diaminoaryl PdII catalysts. The hyperbranched catalyst shows similar activity behavior to its parent mononuclear catalyst and provides a competitive alternative to the corresponding but more tediously produced dendrimer catalysts. Tf=F3CSO2.

Speculations on new mechanisms for Heck reactions

A mechanism for the olefination reaction is proposed, involving PdII/PdIV, in which a key step is reversible nucleophilic attack on the PdII-coordinated olefin to give an electron-rich σ-alkyl- or, with carbonate, a chelated σ-dialkyl-complex, which then oxidatively adds the organic halide e.g. ArX. Loss of nucleophile, migration of Ar from PdIV to coordinated olefin, β-hydrogen elimination and loss of HX then gives the product of olefination and regenerates the PdII catalyst.

BIPNOR: A New, Efficient Bisphosphine Having Two Chiral, Nonracemizable, Bridgehead Phosphorus Centers for Use in Asymmetric Catalysis

AbstractOptically active phosphorus ligands are widely used in homogeneous asymmetric catalysis. However, among the numerous available structures of this type, the subclass of optically active bisphosphines with at least one chiral phosphorus atom is rather underdeveloped. A bisphosphine with two chiral, nonracemizable bridgehead phosphorus centers, (meso,d/l)‐2,2′,3,3′‐tetraphenyl‐4,4′,5,5′‐tetramethyl‐6,6′‐bis‐1‐phosphanorborna‐2,5‐dienyl (BIPNOR), can be obtained by thermolysis of 1,1′‐bisphospholyl with diphenylacetylene. Here, we report the resolution of the d/l isomer by means of a chiral palladium complex to give the two optically active forms of BIPNOR. We then investigate the catalytic properties of BIPNOR, incorporated in RhI and RuII catalysts for the hydrogenation of olefins and ketones and in a PdII catalyst for asymmetric alkylation reactions. BIPNOR is shown to give good results in these catalytic reactions.

Neryl- and geranyltriethylammonium halides in the allylation of sodium diethyl malonate. The effect of the leaving group of the allylating reagent on the selectivity of the reaction

In the absence of catalysts,N-neryl-andN-geranyltriethylammonium halides can allylate sodium diethyl malonate to give terpene malonate derivatives. Using the above-mentioned ammonium salts, geranyl and neryl acetates, geranyl ethyl carbonate, and geranyl diethyl phosphate as examples, it has been shown that with Pd0 and PdII catalysts, the selectivity of the formation of neryl-, geranyl-, and linalylmalonates can be governed by varying the leaving group of the allylating agent.

Ready hydrogenation of nitrobenzene and benzonitrile with a polymer-bound palladium catalyst

A polymer-bound catalyst has been discovered which provides the first example of hydrogenation of nitro and nitrile functional groups with a PdII catalyst.