Scope and limitations of the Pd/BINAP-catalyzed amination of aryl bromides

Mixtures of Pd(2)(dba)(3) or Pd(OAc)(2) and BINAP catalyze the cross-coupling of amines with a variety of aryl bromides. Primary amines are arylated in high yield, and certain classes of secondary amines are also effectively transformed. The process tolerates the presence of several functional groups including methyl and ethyl esters, enolizable ketones, and nitro groups provided that cesium carbonate is employed as the base. Most reactions proceed to completion with 0.5-1.0 mol % of the palladium catalyst; in some cases, catalyst levels as low as 0.05 mol % Pd may be employed. Reactions are considerably faster if Pd(OAc)(2) is employed as the precatalyst, and the order in which reagents are added to the reaction has a substantial effect on reaction rate. It is likely that the catalytic process proceeds via bis(phosphine)palladium complexes as intermediates. These complexes are less prone to undergo undesirable side reactions which lead to diminished yields or catalyst deactivation than complexes of the corresponding monodentate triarylphosphines.     

Palladium-catalyzed aerobic intermolecular cyclization of acrylic acid with 1-octene to afford α-methylene-γ-butyrolactones: the remarkable effect of continuous water removal from the reaction mixture and analysis of the reaction by kinetic, ESI-MS, and XAFS measurements

Further study of our aerobic intermolecular cyclization of acrylic acid with 1-octene to afford α-methylene-γ-butyrolactones, catalyzed by the Pd(OCOCF(3))(2)/Cu(OAc)(2)?H(2)O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1)?equilibrium coordination of 1-octene to the Pd acrylate species, 2)?Markovnikov-type acryloxy palladation of 1-octene (1,2-addition), 3)?intramolecular carbopalladation, and 4)?β-hydride elimination. Byproduct 2-acryloxy-1-octene is formed by β-hydride elimination after step 2). These cyclization steps fit the Michaelis-Menten equation well and β-hydride elimination is considered to be a rate-limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd-O bond), η(3)-C(8)H(15) (Pd-C bond), or C(11)H(19)O(2) (Pd-C bond) moieties on the Pd center as the resting-state compounds. Furthermore, not only Cu(II), but also Cu(I), species are observed during the reaction time of 2-8?h when the reaction proceeds efficiently. This result suggests that the Cu(II) species is partially reduced to the Cu(I) species when the active Pd catalytic species are regenerated.     

Autoreduction of Pd-Co and Pt-Co cyanogels: exploration of cyanometalate coordination chemistry at elevated temperatures

Cyanogels are coordination polymers made from the reaction of a chlorometalate and a cyanometalate in aqueous solution, which undergo a sol-gel transition to form stable gels. At temperatures above 240 degrees C, the cyanide ligand acts as a reducing agent and reduces the metal centers to lower oxidation states. To understand the mechanism of the autoreduction, the thermal reduction of the Pd-Co cyanogel system formed by the reaction of PdCl4(2-) and Co(CN)6(3-) was studied in an inert atmosphere. It was found that the reduction proceeds through two polymeric cyanide-containing intermediates, CoPd(CN)4 and Pd(CN)2, that form upon reduction of Co(3+) to Co(2+) and involves a significant rearrangement of the coordination structure. The two intermediates upon further heating reduce to metallic products, which by solid-state diffusion form a single Pd/Co alloy product. CoPd(CN)4 was found to have a hydrated form Co(H2O)2Pd(CN)4 x 4 H2O with a layered structure crystallizing in an orthorhombic Pnma space group. The Pt-Co cyanogel was found to autoreduce via a similar route. CoPt(CN)4 was confirmed as an intermediate. Understanding of the mechanism of the cyanogel autoreduction is an important step toward better understanding of opportunities that cyanogels offer in materials chemistry, as well as an expansion of the knowledge of coordination chemistry at elevated temperatures in general.     

The Stereochemistry of the Reduction of Cyclic Enaminones

Summary.  The stereo- and regiochemistry of di-, tri-, and tetracyclic enaminones upon catalytic hydrogenation on Pd and Pt catalysts seems to be mainly a function of the catalyst and the medium. The highest stereoselectivity was observed for multiflorine on Pd/C in which 99% of equatorial alcohol were formed in this case, the formation of alcohols proceeds via a ketonic intermediate. On platinum, irrespective of the solvent used (EtOH, H₂O, AcOH, HCl), the hydrogenation reaction proceeds through ketonic (piperidone system) and dehydro (pyridone system) intermediates. In EtOH or H₂O solution, the dehydro product remains unchanged, whereas the ketonic intermediate is reduced to a mixture of epimeric alcohols. In HCl and acetic acid, both intermediates are hydrogenolyzed to a product with a methylene group, but the ketonic one is additionally reduced to a mixture of epimeric alcohols. Reductions with complex metal hydrides provide mixtures of epimeric alcohols with a predominance of equatorial orientation. The structures of products were determined by NMR spectroscopy and/or by GC-MS analysis. Received December 28, 2000. Accepted (revised) February 16, 2001     

Aryl transfer between Pd(II) centers or Pd(IV) intermediates in Pd-catalyzed domino reactions

A computational study has been performed to determine the mechanism of the key steps of Pd-catalyzed domino reactions in which C(sp2)-C(sp2) are formed from aryl and alkenyl halides. DFT calculations were done on model complexes of the proposed intermediates, with PH3 and H2O as ancillary ligands, to explore two possible mechanisms: the oxidative addition of aryl or alkenyl halides to palladacycles to give Pd(IV) intermediates, and the transmetalation-type reaction of aryl or alkenyl ligands between two Pd(II) centers, a palladacycle, and a Pd(II) complex formed by oxidative addition of aryl or alkenyl halides to Pd0. We have shown that oxidative addition of iodoethylene to Pd0 precursors is more favorable than oxidative addition to Pd(II) palladacycles, whereas transmetalation-type reactions between Pd(II) complexes are facile. Similar results were obtained with iodobenzene instead of iodoethylene and formamide as the ancillary ligand. These results suggest that Pd(IV) intermediates are not involved in these reactions.     

Palladium‐Catalyzed Aerobic Intermolecular Cyclization of Acrylic Acid with 1‐Octene to Afford α‐Methylene‐γ‐butyrolactones: The Remarkable Effect of Continuous Water Removal from the Reaction Mixture and Analysis of the Reaction by Kinetic,ESI‐MS,and XAFS Measurements

Further study of our aerobic intermolecular cyclization of acrylic acid with 1‐octene to afford α‐methylene‐γ‐butyrolactones, catalyzed by the Pd(OCOCF₃)₂/Cu(OAc)₂ ? H₂O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1) equilibrium coordination of 1‐octene to the Pd acrylate species, 2) Markovnikov‐type acryloxy palladation of 1‐octene (1,2‐addition), 3) intramolecular carbopalladation, and 4) β‐hydride elimination. Byproduct 2‐acryloxy‐1‐octene is formed by β‐hydride elimination after step 2). These cyclization steps fit the Michaelis–Menten equation well and β‐hydride elimination is considered to be a rate‐limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd? O bond), η³‐C₈H₁₅ (Pd? C bond), or C₁₁H₁₉O₂ (Pd? C bond) moieties on the Pd center as the resting‐state compounds. Furthermore, not only Cu^II, but also Cu^I, species are observed during the reaction time of 2–8 h when the reaction proceeds efficiently. This result suggests that the Cu^II species is partially reduced to the Cu^I species when the active Pd catalytic species are regenerated.     

Palladium‐Catalyzed Formal Hydroalkylation of Aryl‐Substituted Alkynes with Hydrazones

We have developed an unprecedented Pd‐catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio‐ and stereoselectivity to form (Z)‐alkenes, which are more difficult to generate compared to (E)‐alkenes. The reaction is compatible with a wide range of functional groups, including hydroxy, ester, ketone, nitrile, boronic ester, amine, and halide groups. Furthermore, late‐stage modifications of natural products and pharmaceutical derivatives exemplify its unique chemoselectivity, regioselectivity, and synthetic applicability. Mechanistic studies indicate the possible involvement of Pd‐hydride intermediates.     

Study of the Transient Reactive Pd(IV) Intermediate in the Pd(OAc)2‐Catalyzed Oxidative Coupling Reaction System by Electrospray Ionization Tandem Mass Spectrometry

Pd‐catalyzed oxidative coupling reaction was of great importance in the aromatic C? H activation and the formation of new C? O and C? C bonds. Sanford has pioneered practical, directed C? H activation reactions employing Pd(OAc)₂ as catalyst since 2004. However, until now, the speculated reactive Pd(IV) transient intermediates in these reactions have not been isolated or directly detected from reaction solution. Electrospray ionization tandem mass spectrometry (ESI‐MS/MS) was used to intercept and characterize the reactive Pd(IV) transient intermediates in the solutions of Pd(OAc)₂‐catalyzed oxidative coupling reactions. In this study, the Pd(IV) transient intermediates were detected from the solution of Pd(OAc)₂‐catalyzed oxidative coupling reactions by ESI‐MS and the MS/MS of the intercepted Pd(IV) transient intermediate in reaction system was the same with the synthesized authentic Pd(IV) complex. Our ESI‐MS(/MS) studies confirmed the presence of Pd(IV) reaction transient intermediates. Most interestingly, the MS/MS of Pd(IV) transient intermediates showed the reductive elimination reactivity to Pd(II) complexes with new C? O bond formation into product in gas phase, which was consistent with the proposed reactivity of the Pd(IV) transient intermediates in solution.     

Novel radical tandem 1,6-enynes thioacylation/cyclization: Au–Pd nanoparticles catalysis versus thermal activation as a function of the substrate specificity

We studied the reactivity of 1,6-enynes with thioacetic acid (AcSH) under either thermal conditions or in the presence of catalytic amounts of supported Au or Au–Pd nanoparticles (NPs) under mild conditions. The 1,6-enynes undergo a tandem thioacylation/cyclization to original cyclic products featuring either a homoallylic thioester function or an enol thioester function depending on the substrate topology. Interestingly, the former process was found more efficient when performed in the presence of Au–Pd NPs while the latter process can be efficiently carried out under thermal conditions (100 °C). The reaction proceeds by a radical mechanism and the presence of precious metal NPs seems to stabilize the formation of free radical intermediates, as supported by experimental and theoretical results.     

An improved synthesis of 3-aminoestrone

An efficient Pd(0)-catalyzed protocol for the rapid and efficient preparation of 3-aminoestrone via 3-benzylaminoestrone from estrone-triflate is described. The three step synthesis proceeds with an overall yield of about 55% using X-Phos as optimal ligand for the Pd(0)-catalyzed Buchwald-Hartwig amination.     

A novel palladium(0) catalysed tandem 1,3-allyl shift and Heck arylation

On treatment with Pd(PPh₃)₄ allyl vinyl ether (1) undergoes a Pd(0) catalysed 1,3 oxygen to carbon allyl shift to afford -allyl ketone (2). In the presence of both Pd(PPh₃)₄ and base the allyl vinyl ether undergoes a Pd(0) catalysed tandem 1,3 allyl shift and intramolecular Heck arylation to give the spiro indane (3). Mechanistic investigations suggest that the 1,3-allyl shift proceeds via a π-allyl palladium intermediate.     

A palladium-catalyzed multicomponent synthesis of imidazolinium salts and imidazolines from imines, acid chlorides, and carbon monoxide

A palladium-catalyzed multicomponent synthesis of imidazolinium carboxylates and imidazolines is described. The palladium catalyst [Pd(CH(R(1))N(R(2))COR(3))Cl](2), or [Pd(allyl)Cl](2), with P(t-Bu)(2)(2-biphenyl) can mediate the simultaneous coupling of two imines, acid chloride, and carbon monoxide into substituted imidazolinium carboxylates within hours under mild conditions (45 °C, 4 atm of CO). The reaction proceeds in good yield with aryl-, heteroaryl-, and alkyl-substituted acid chlorides, as well as variously functionalized imines. Imidazolines are formed via the initial generation of Mu?nchnone intermediates, followed by their cycloaddition with an in situ generated protonated imine. The addition of an amine base can intercept catalysis at Münchnone formation, which allows the subsequent cycloaddition of a second imine. The latter provides a route for the assembly of complex, polysubstituted imidazolinium carboxylates with independent control of all five substituents. The subsequent removal of the nitrogen substituent(s) provides an overall synthesis of imidazolines.     

Rationally designed pincer-type heck catalysts bearing aminophosphine substituents: Pd IV intermediates and palladium nanoparticles

The aminophosphine-based pincer complexes [C6H3-2,6-(XP(piperidinyl)2)2Pd(Cl)] (X=NH 1; X=O 2) are readily prepared from cheap starting materials by sequential addition of 1,1',1'-phosphinetriyltripiperidine and 1,3-diaminobenzene or resorcinol to solutions of [Pd(cod)(Cl)2] (cod=cyclooctadiene) in toluene under N2 in "one pot". Compounds 1 and 2 proved to be excellent Heck catalysts and allow the quantitative coupling of several electronically deactivated and sterically hindered aryl bromides with various olefins as coupling partners at 140 degrees C within very short reaction times and low catalyst loadings. Increased reaction temperatures also enable the efficient coupling of olefins with electronically deactivated and sterically hindered aryl chlorides in the presence of only 0.01 mol % of catalyst. The mechanistic studies performed rule out that homogeneous Pd 0 complexes are the catalytically active forms of 1 and 2. On the other hand, the involvement of palladium nanoparticles in the catalytic cycle received strong experimental support. Even though pincer-type Pd IV intermediates derived from 1 (and 2) are not involved in the catalytic cycle of the Heck reaction, their general existence as reactive intermediates (for example, in other reactions) cannot be excluded. On the contrary, they were shown to be thermally accessible. Compounds 1 and 2 show a smooth halide exchange with bromobenzene to yield their bromo derivatives in DMF at 100 degrees C. Experimental observations revealed that the halide exchange most probably proceeded via pincer-type Pd IV intermediates. DFT calculations support this hypothesis and indicated that aminophosphine-based pincer-type Pd IV intermediates are generally to be considered as reactive intermediates in reactions with aryl halides performed at elevated temperatures.     

Rate and mechanism of the reversible formation of cationic (eta3-allyl)-palladium complexes in the oxidative addition of allylic acetate to palladium(0) complexes ligated by diphosphanes

The oxidative addition of the allylic acetate, CH2=CH-CH2-OAc, to the palladium(o) complex [Pd0(P,P)], generated from the reaction of [Pd(dba)2, with one equivalent of P,P (P,P = dppb = 1,4-bis(diphenylphosphanyl)butane, and P,P = dppf = 1,1'-bis(diphenylphosphanyl)ferrocene), gives a cationic (eta3-allyl)palladium(II) complex, [(eta3-C3H5)Pd(P,P)+]. with AcO as the counter anion. This reaction is reversible and proceeds through two successive equilibria. The overall equilibrium constants have been determined in DMF. Compared with PPh3, the overall equilibrium lies more in favor of the cationic (eta3-allyl)palladium(II) complex when bidentate P,P ligands are considered in the order: dppb > dppf > PPh3. The reaction proceeds via a neutral intermediate complex [(eta2-CH=CH-CHCH2-OAc)Pd0(P,P)], which has been kinetically detected. The rate constants of the successive steps have been determined in DMF by UV spectroscopy and conductivity measurements. The overall complexation step of the Pd0 by the allylic acetate C=C bond is faster than the oxidative addition/ionization step which gives the cationic (eta3-allyl)palladium(II) complex.     

Allyl stannanes as electrophiles or nucleophiles in the palladium-catalyzed reactions with alkynes

The reactivity of the allyl stannanes can be inverted by changing the oxidation state of the catalyst from Pd(II) to Pd(0). Whereas with Pd(II) an anti nucleophilic attack of the allyl stannane on the alkyne takes place, the reaction with Pd(0) proceeds by oxidative addition to form (η³-allyl)palladium complexes leading to a formal syn addition to the alkyne. This mechanistic proposal is supported by DFT calculations.     

Catalytic asymmetric intramolecular aminopalladation: enantioselective synthesis of vinyl-substituted 2-oxazolidinones, 2-imidazolidinones, and 2-pyrrolidinones.

A new catalytic asymmetric synthesis of five-membered nitrogen heterocycles is reported. This synthesis employs ferrocenyloxazoline palladacycles (FOP trifluoroacetate catalysts) 2 and 4 and proceeds by a catalytic cycle involving Pd(II) intermediates. For example, prochiral (Z)-4-acetoxy-2-buten-1-ols are condensed with an arylsulfonyl isocyanate and the derived allylic N-arylsulfonylcarbamates cyclize in situ upon addition of 0.5-5 mol % of 2 or 4 to form 4-vinyloxazolidin-2-ones 6, 13, and 15 in high yield and 89-99% ee. The related 2-pyrrolidinone 19 and 2-imidazolidinone 18 are prepared in similar fashion. Pyrrolidinone 19 can be converted in two steps to the unnatural enantiomer of the GABA inhibitor vigabatrin 20.     

Factors controlling the energetics of the oxygen reduction reaction on the Pd-Co electro-catalysts: insight from first principles

We report here results of our density functional theory based computational studies of the electronic structure of the Pd-Co alloy electrocatalysts and energetics of the oxygen reduction reaction (ORR) on their surfaces. The calculations have been performed for the (111) surfaces of pure Pd, Pd(0.75)Co(0.25) and Pd(0.5)Co(0.5) alloys, as well as of the surface segregated Pd/Pd(0.75)Co(0.25) alloy. We find the hybridization of dPd and dCo electronic states to be the main factor controlling the electrocatalytic properties of Pd/Pd(0.75)Co(0.25). Namely the dPd-dCo hybridization causes low energy shift of the surface Pd d-band with respect to that for Pd(111). This shift weakens chemical bonds between the ORR intermediates and the Pd/Pd(0.75)Co(0.25) surface, which is favorable for the reaction. Non-segregated Pd(0.75)Co(0.25) and Pd(0.5)Co(0.5) surfaces are found to be too reactive for ORR due to bonding of the intermediates to the surface Co atoms. Analysis of the ORR free energy diagrams, built for the Pd and Pd/Pd(0.75)Co(0.25), shows that the co-adsorption of the ORR intermediates and water changes the ORR energetics significantly and makes ORR more favorable. We find the onset ORR potential estimated for the configurations with the O-OH and OH-OH co-adsorption to be in very good agreement with experiment. The relevance of this finding to the real reaction environment is discussed.     

Contemporaneous dual catalysis by coupling highly transient nucleophilic and electrophilic intermediates generated in situ

We report herein a new process, which we call contemporaneous dual catalysis, that selectively couples two highly reactive catalytic intermediates while overcoming competing trapping by stoichiometric reactive species also present in the reaction. The reaction proceeds via the convergence of a vanadium-catalyzed propargylic rearrangement and a palladium-catalyzed allylic alkylation. It generates a variety of α-allylated α,β-unsaturated ketones, which are not readily accessible by other means. Notably, this dual catalysis is achieved using low catalyst loadings (1.0 mol % [Pd], 1.5 mol % [V]) and gives good to excellent yields (up to 98%) of the desired products.     

Highly enantioselective Pd-catalyzed asymmetric hydrogenation of activated imines

Pd/bisphosphines complexes are highly effective catalysts for asymmetric hydrogenation of activated imines in trifluoroethanol. The asymmetric hydrogenation of N-diphenylphosphinyl ketimines 3 with Pd(CF3CO2)/(S)-SegPhos indicated 87-99% ee, and N-tosylimines 5 could gave 88-97% ee with Pd(CF3CO2)/(S)-SynPhos as a catalyst. Cyclic N-sulfonylimines 7 and 11 were hydrogenated to afford the useful chiral sultam derivatives in 79-93% ee, which are important organic synthetic intermediates and structural units of agricultural and pharmaceutical agents.     

Carbon(sp(3) )Fluorine Bond-Forming Reductive Elimination from Palladium(IV) Complexes

Pd(IV) -fluoride complexes, some of which are remarkably insensitive to water, have been synthesized and used in the title reaction, which proceeds with high selectivity to give the product of the C(sp(3) )?F coupling (see scheme, TfO=trifluoromethanesulfonate). Preliminary mechanistic studies implicate a pathway involving dissociation of pyridine followed by direct C?F coupling at the Pd center.