Oxidative addition of the imidazolium cation to zerovalent Ni, Pd, and Pt: a combined density functional and experimental study

Oxidative addition of different imidazolium cations to zerovalent group 10 metals, to afford heterocyclic carbene complexes, has been investigated by both density functional theory (DFT) and experimental studies. The theoretical analysis shows that addition of imidazoliums to Pt(0) and Ni(0) is more exothermic than to Pd(0), and Ni(0) is predicted to react with a much lower barrier than either Pt(0) or Pd(0). Strongly basic supporting ligands on the metal, as well as cis-chelating ligands, increase the exothermicity of the reaction and also lower the activation barrier. The addition of 2-H imidazoliums is easier and more exothermic than addition of 2-alkylimidazoliums, and a halo-imidazolium is expected to further lower the barrier to oxidative addition and increase the exothermicity. The DFT results show that all three of the metals should be able to oxidatively add imidazolium cations under appropriate conditions. Experimental studies confirmed that oxidative addition is possible, and a number of Pt- and Pd-carbene complexes were prepared via oxidative addition of imidazolium salts to M(0) precursors. Most significantly, oxidative addition of 2-H azolium salts was found to readily occur, and the reaction of 1,3-dimethylimidazolium tetrafluoroborate with Pt(PPh(3))(2) and Pt(PCy(3))(2) affords [PtH(dmiy)(PPh(3))(2)]BF(4) (10) and [PtH(dmiy)(PCy(3))(2)]BF(4) (11), while reaction between 3,4-dimethylthiazolium tetrafluoroborate and Pt(PCy(3))(2) yields [PtH(dmty)(PCy(3))(2)]BF(4) (12) (dmiy = 1,3-dimethylimidazolin-2-ylidene, dmty = 3,4-dimethylthiazolin-2-ylidene). Addition of 2-iodo-1,3,4,5-tetramethylimidazolium tetrafluoroborate to Pt(PPh(3))(4) or Pd(dcype)(dba) yields [PtI(tmiy)(PPh(3))(2)]BF(4) (9) and [PdI(tmiy)(dcype)]BF(4) (14), respectively (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, dcype = 1,3-bis(dicyclohexylphosphino)ethane)). X-ray crystal structures are reported for complexes 9 and 11 (cis and trans). These studies clearly show for the first time that oxidative addition of imidazolium and thiazolium cations is possible, and the results are discussed in terms of the ramifications for catalysis in imidazolium-based ionic liquids with both carbene-based and non-carbene-based complexes.     

Neutral and Anionic Square Planar Palladium(0) Complexes Stabilized by a Silicon Z-Type Ligand

Anionic [Pd(0)−X]⁻ ate complex were proposed as key intermediates in Pd-catalyzed cross-coupling for decades, but their isolation remained elusive. Herein, a chelating Lewis acidic bis(amidophenolato)silane is introduced as a strong Z-type ligand which enables the characterization of the first anionic [Pd(0)−X]⁻ ate complex. Intriguingly, these compounds and the neutral L−Pd(0) analogs exhibit a square planar coordination that is highly unusual for a d¹⁰ metal. Theoretical methods scrutinize the interaction between the Lewis acidic Si(IV) center and the late transition metal, while reactivity studies shed light on the potential role of anionic additives in oxidative addition reactions.     

Alpha-retinals as rhodopsin chromophores--preference for the 9-Z configuration and partial agonist activity

The visual pigment rhodopsin, the photosensory element of the rod photoreceptor cell in the vertebrate retina, shows in combination with an endogenous ligand, 11-Z retinal, an astonishing photochemical performance. It exhibits an unprecedented quantum yield (0.67) in a highly defined and ultrafast photoisomerization process. This triggers the conformational changes leading to the active state Meta(rhodopsin) II. Retinal is covalently bound to Lys-296 of the protein opsin in a protonated Schiff base. The resulting positive charge delocalization over the terminal part of the polyene chain of retinal creates a conjugation defect that upon photoexcitation moves to the opposite end of the polyene. Shortening the polyene as in 4,5-dehydro,5,6-dihydro (alpha), 5,6-dihydro or 7,8-dihydro-analogs might facilitate photoisomerization of a 9-Z and a 11-Z bond. Here we describe pigment analogs generated with bovine opsin and 11-Z or 9-Z 4,5-dehydro,5,6-dihydro-retinal that were further characterized by UV-Vis and FTIR spectroscopy. The preference of opsin for native 11-Z retinal over the 9-Z isomer is reversed in 4,5-dehydro,5,6-dihydro-retinal. 9-Z 4,5-dehydro,5,6-dihydro-retinal readily generated a photosensitive pigment. This modification has no effect on the quantum yield, but affects the Batho<-->blueshifted intermediate (BSI) equilibrium and leads to a strong decrease in the G-protein activation rate because of a downshift of the pK(a) of the Meta I<-->Meta II equilibrium.     

7,8-dihydro retinals outperform the native retinals in conferring photosensitivity to visual opsin

The visual pigment rhodopsin presents an astonishing photochemical performance. It exhibits an unprecedented quantum yield (0.67) in a highly defined and ultrafast photoisomerization process. This triggers the conformational changes leading to the active state Meta II of this G protein-coupled receptor. The responsible ligand, retinal, is covalently bound to Lys-296 of the protein in a protonated Schiff base. The resulting positive charge delocalization over the terminal part of the polyene chain of retinal creates a conjugation defect that upon photoexcitation moves to the opposite end of the polyene. Shortening the polyene as in 5,6-dihydro- or 7,8-dihydro analogues might facilitate photoisomerization of a 9-Z and an 11-Z bond. Here we describe pigment analogues generated with bovine opsin and 11-Z 7,8-dihydro retinal or 9-Z 7,8-dihydro retinal. Both isomers readily generate photosensitive pigments that differ remarkably in spectral properties from the native pigments. In addition, in spite of the more flexible 7,8 single bond, both analogue pigments exhibit strikingly efficient photoisomerization while largely maintaining the activity toward the G-protein. These results bear upon the activation of ligand-gated signal transducers such as G protein-coupled receptors.     

Kinetics and mechanistic aspects of the Heck reaction promoted by a CN-palladacycle

In the Heck reaction between aryl halides and n-butyl acrylate, the palladacycle {Pd[kappa(1)-C, kappa(1)-N-C=(C(6)H(5))C(Cl)CH(2)NMe(2)](mu-Cl)}(2), 1, is merely a reservoir of the catalytically active Pd(0) species [1](Pd colloids or highly active forms of low ligated Pd(0) species) that undergoes oxidative addition of the aryl halide on the surface with subsequent detachment, generating homogeneous Pd(II) species. The main catalytic cycle is initiated by oxidative addition of iodobenzene to [1], followed by the reversible coordination of the olefin to the oxidative addition product. All the unimolecular subsequent steps are indistinguishable kinetically and can be combined in a single step. This kinetic model predicts that a slight excess of alkene relative to iodobenzene leads to a rapid rise in the Pd(0) concentration while when using a slight excess of iodobenzene, relative to alkene, the oxidative addition product is the resting state of the catalytic cycle. Competitive experiments of various bromoarenes and iodoarenes with n-butyl acrylate catalyzed by 1 and CS, CP, and NCN palladacycles gave the same rho value (2.4-2.5 for Ar-Br and 1.7-1.8 for Ar-I) for all palladacycles employed, indicating that they generate the same species in the oxidative addition step. The excellent fit of the slope with the sigma(0) Hammett parameter and the entropy of activation of -43 +/- 8 J mol(-1) K(-1) are consistent with an associative process involving the development of only a partial charge in the transition state for the oxidative step of iodobenzene.     

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.     

Pd(II)/Lewis Acid Catalyzed Intramolecular Oxidative C−H Amination to Construct Carbazoles with Dioxygen

Transition-metal-catalyzed oxidative C−H amination reactions are among the most attractive topics in organic synthesis to construct nitrogen-containing motifs. The challenge is that most of these reactions employed stoichiometric oxidants to achieve satisfied catalytic efficiencies. Herein, we report a Pd(II)/LA-catalyzed (LA: Lewis acid) oxidative C−H amination reaction of 2-acetaminobiphenyls to construct carbazoles by using dioxygen balloon as the sole oxidant source, and the presence of LA sharply improved the catalytic efficiency of Pd(OAc)₂. Remarkably, in certain cases, the deacetylation of the annulation product happened under standard conditions to afford free carbazoles as the final product. The H/D exchange studies confirmed the reversibility of C−H activation and also disclosed multiple C−H activation sites by using −NAc and −NTs as the directing groups. In addition, the palladacycle compound was identified through ¹H NMR characterizations and proved to be the intermediate prior to the carbazole formation.     

A Carbohydrate Approach to the Enantioselective Synthesis of 1,3-Polyols

Treatment of per-O-benzoyl-D-glycero-D-gulo-heptono-1,4-lactone (2) with tertiary amines afforded selectively and with good yields the (5H)-furan-2-one derivatives 3, 4, and 5, formed by controlled elimination of one, two, or three molecules of benzoic acid, respectively. The stereochemistry for the exocyclic double bonds of 4 and 5 was determined by means of NMR techniques. Particularly, the furanone 4 was obtained from 2 ( approximately 90% yield) as a mixture of the E and Z diastereoisomers, which were separated by column chromatography or, more efficiently, by HPLC. The catalytic hydrogenation of compounds 4-E and 4-Z took place diastereoselectively, due to the chiral induction of the stereocenter located in the lateral chain. Thus, hydrogenation of 4-E led to a mixture of the 4,5-dihydro-(3H)-furan-2-ones having 3R,5S,2'S (D-xylo, 6) and 3S,5R,2'S (D-arabino, 7) configurations, with 6 as the major product; whereas the 4-Z isomer gave the same mixture, but being 7 preponderant. On hydrogenation of the original 4-E/Z mixture, compound 6 was obtained pure after recrystallization. O-Debenzoylation of 6gave 9, which was reduced with NaBH(4) to the 3,5-dideoxy-meso-xylo-heptitol (11). The peracetate (12) and perbenzoate (13) of the latter were prepared, and the 1-(tert-butyldiphenylsilyl)oxy derivative (16) was also synthesized via the 3'-(silyloxy)-4,5-dihydro-(3H)-furan-2-one 14. Chemoselective reduction of the lactone function of 6 with diisoamylborane gave the 2,5,6-tri-O-benzoyl-3,6-dideoxy-D-xylo-heptofuranose (17). The 3,5-dideoxy-D-arabino-heptitol (18), a diastereoisomer of 11, was also isolated and characterized.     

Synthesis of 9-alkylidene-9H-fluorenes by a novel, palladium-catalyzed cascade reaction of aryl halides and 1-aryl-1-alkynes.

In the presence of a palladium catalyst and NaOAc, aryl iodides react with 1-aryl-1-alkynes to afford 9-alkylidene-9H-fluorenes in good yields. The products from this reaction are highly dependent on the base employed. This process appears to involve (1) oxidative addition of the aryl iodide to Pd(0), (2) alkyne insertion, (3) rearrangement of the resulting vinylic palladium intermediate to an arylpalladium species, and (4) aryl-aryl coupling with simultaneous regeneration of the Pd(0) catalyst. Consistent with this mechanism is the fact that 9-alkylidene-9H-fluorenes can also be prepared by the Pd-catalyzed rearrangement of 1,1-diaryl-2-iodo-1-alkenes.     

Synthesis of 9-alkylidene-9H-fluorenes by a novel palladium-catalyzed rearrangement

In the presence of a palladium catalyst and NaOAc, aryl iodides react with 1-aryl-1-alkynes to afford 9-alkylidene-9H-fluorenes in good yields. This process appears to involve (1) oxidative addition of the aryl iodide to Pd(0), (2) alkyne insertion, (3) rearrangement of the resulting vinylic palladium intermediate to an arylpalladium species, and (4) aryl-aryl coupling with simultaneous regeneration of the Pd(0) catalyst.     

DFT Investigation on the Mechanism of Pd（0） Catalyzed Sonogashira Coupling Reaction

Based on DFT calculations, the catalytic mechanism of palladium(0) atom, commonly considered as the catalytic center for Sonogashira cross-coupling reactions, has been analyzed in this study. In the cross-coupling reaction of iodobenzene with phenylacetylene without co-catalysts and bases involved, mechanistically plausible catalytic cycles have been computationally identified. These catalytic cycles typically occur in three stages: 1) oxidative addition of an iodobenzene to the Pd(0) atom, 2) reaction of the product of oxidative addition with phenylacetylene to generate an intermediate with the Csp bound to palladium, and 3) reductive elimination to couple the phenyl group with the phenylethynyl group and to regenerate the Pd(0) atom. The calculations show that the first stage gives rise to a two-coordinate palladium (Ⅱ) intermediate (ArPdI). Starting from this intermediate, the second oxidative stage, in which the C–H bond of acetylene adds to Pd(Ⅱ) without co-catalyst involved, is called alkynylation instead of transmetalation and proceeds in two steps. Stage 3 of reductive elimination of diphenylacetylene is energetically favorable. The results demonstrate that stage 2 requires the highest activation energy in the whole catalysis cycle and is the most difficult to happen, where co-catalysts help to carry out Sonogashira coupling reaction smoothly.     

Distinct mechanisms for the oxidative addition of chloro-, bromo-, and iodoarenes to a bisphosphine palladium(0) complex with hindered ligands

We report an example of a bisphosphine palladium(0) complex with hindered ligands that undergoes oxidative addition of chloro-, bromo-, and iodoarenes in high yield. Addition of PhX (X = I, Br, Cl) to [Pd(Q-phos-tol)2] produced [Pd(Q-phos-tol)(Ph)(I)], [Pd(Q-phos-tol)(Ph)(Br)], and [Pd(Q-phos-tol)(Ph)(Cl)]2. To study the mechanisms of the oxidative addition of the three haloarenes to [Pd(Q-phos-tol)2], we determined the order of the reaction on the concentration of ligand and haloarene. The different haloarenes reacted through different mechanistic pathways. Addition of iodobenzene occurred by irreversible associative displacement of a phosphine. Addition of bromobenzene occurred by rate-limiting dissociation of phosphine. Addition of chlorobenzene occurred by reversible dissociation of phosphine, followed by rate-limiting oxidative addition. The mechanism of exchange of ligands from the Pd(0)L2 was also studied. The rate constant value for dissociation of ligand calculated from ligand exchange experiments is in agreement with the value calculated through experiments on oxidative addition.     

Allylic ionization versus oxidative addition into vinyl C-X bonds by Pd with polyfunctional olefin templates

The chemoselectivity of activation by a (PPh3)4Pd catalyst on a series of small, olefin-based compounds that were substituted with a variety of allylic and vinylic functional groups was studied. Of particular note, the allylic acetate of 1-acetoxy-2-bromo-2-propene (7) was selectively ionized by Pd in the presence of a malonate nucleophile, while oxidative addition of the C-Br bond to Pd occurred exclusively in the presence of a boronic acid nucleophile. When the acetate nucleophile was used, no ionization of the acetate leaving group occurred at all, which was proven by the use of deuterium-labeled substrates (e.g., 11). This report demonstrates that the nucleophile interacts in some way with Pd prior to catalyst activation of the substrate. Certainly in the case of the malonate nucleophile, this is without precedent and contradicts the central dogma of how these proposed catalytic cycles operate.     

A bimetallic catalyst and dual role catalyst: synthesis of N-(alkoxycarbonyl)indoles from 2-(alkynyl)phenylisocyanates

3-allyl-N-(alkoxycarbonyl)indoles are synthesized via the reaction of 2-(alkynyl)phenylisocyanates and allyl carbonates in the presence of Pd(PPh(3))(4) (1 mol %) and CuCl (4 mol %) bimetallic catalyst. It is most probable that Pd(0) acts as a catalyst for the formation of a pi-allylpalladium alkoxide intermediate and Cu(I) behaves as a Lewis acid to activate the isocyanate, and the cyclization step proceeds with a cooperative catalytic activity of Pd and Cu. On the other hand, N-(alkoxycarbonyl)indoles are produced via the reaction of 2-(alkynyl)phenylisocyanates and alcohols under a catalytic amount of Na(2)PdCl(4) (5 mol %) or PtCl(2) (5 mol %). Pd(II) or Pt(II) catalyst exhibits dual roles; it acts as a Lewis acid to accelerate the addition of alcohols to isocyanates and as a typical transition-metal catalyst to activate the alkyne for the subsequent cyclization.     

Ni(II), Pd(II) and Pt(II) complexes of PNP and PSP tridentate amino-phosphine ligands

The ligands D((CH(2))(2)NHPiPr(2))(2) (D = NH 1, S 2) react with (dme)NiCl(2) or (PhCN)(2)MCl(2) (M = Pd, Pt) to give complexes of the form [D((CH(2))(2)NHPiPr(2))(2)MX]X (X = Cl, I; M = Ni, Pd, Pt) which were converted to corresponding iodide derivatives by reaction with Me(3)SiI. Reaction of 1 or 2 with (COD)PdMeCl affords facile routes to [κ(3)P,N,P-NH((CH(2))(2)NHPiPr(2))(2)PdMe]Cl (8a) and [κ(3)P,S,P-S((CH(2))(2)NHPiPr(2))(2)PdMe]Cl (9a) in high yields. An alternative synthetic approach involves oxidative addition of MeI to a M(0) precursor yielding [κ(3)P,N,P-HN(CH(2)CH(2)NHPiPr(2))(2)NiMe]I (10), [κ(3)P,N,P-HN(CH(2)CH(2)NHPiPr(2))(2)MMe]I (M = Pd 8b Pt 11) and [κ(3)P,S,P-S(CH(2)CH(2)NHPiPr(2))(2)MMe]I (M = Pd 9b, Pt 12). Alternatively, use of NEt(3)HCl in place of MeI produces the species [κ(3)P,N,P-HN(CH(2)CH(2)NHPiPr(2))(2)MH]X (X = Cl, M = Ni 13a, Pd 14a, Pt 16a). The analogs containing 2; [κ(3)P,S,P-S((CH(2))(2)NHPiPr(2))(2)MH]X (M = Pd, X = PF(6)15: M = Pt, X = Br, 17a, PF(6)17b) were also prepared in yields ranging from 74-93%. In addition, aryl halide oxidative addition was also employed to prepare [κ(3)P,N,P-HN(CH(2)CH(2)NHPiPr(2))(2)MC(6)H(4)F]Cl (M = Ni 18, Pd 19) and [κ(3)P,S,P-S((CH(2))(2)NHPiPr(2))(2)Pd(C(6)H(4)F)]Cl (20). Crystal structures of 3a, 4a, 5a, 6a, 8a, 9a, 14b and 16b are reported.     

Synthesis, structure, theoretical studies, and Ligand exchange reactions of monomeric, T-shaped arylpalladium(II) halide complexes with an additional, weak agostic interaction

A series of monomeric arylpalladium(II) complexes LPd(Ph)X (L = 1-AdPtBu2, PtBu3, or Ph5FcPtBu2 (Q-phos); X = Br, I, OTf) containing a single phosphine ligand have been prepared. Oxidative addition of aryl bromide or aryl iodide to bis-ligated palladium(0) complexes of bulky, trialkylphosphines or to Pd(dba)2 (dba = dibenzylidene acetone) in the presence of 1 equiv of phosphine produced the corresponding arylpalladium(II) complexes in good yields. In contrast, oxidative addition of phenyl chloride to the bis-ligated palladium(0) complexes did not produce arylpalladium(II) complexes. The oxidative addition of phenyl triflate to PdL2 (L = 1-AdPtBu2, PtBu3, or Q-phos) also did not form arylpalladium(II) complexes. The reaction of silver triflate with (1-AdPtBu2)Pd(Ph)Br furnished the corresponding arylpalladium(II) triflate in good yield. The oxidative addition of phenyl bromide and iodide to Pd(Q-phos)2 was faster than oxidative addition to Pd(1-AdPtBu2)2 or Pd(PtBu3)2. Several of the arylpalladium complexes were characterized by X-ray diffraction. All of the arylpalladium(II) complexes are T-shaped monomers. The phenyl ligand, which has the largest trans influence, is located trans to the open coordination site. The complexes appear to be stabilized by a weak agostic interaction of the metal with a ligand C-H bond positioned at the fourth-coordination site of the palladium center. The strength of the Pd.H bond, as assessed by tools of density functional theory, depended upon the donating properties of the ancillary ligands on palladium.     

Oxidative addition of aryl tosylates to palladium(0) and coupling of unactivated aryl tosylates at room temperature

Aryl tosylates are attractive substrates for Pd-catalyzed cross-coupling reactions, but they are much less reactive than the more commonly used aryl triflates. We report the oxidative addition of aryl tosylates to Pd(PPF-t-Bu)[P(o-tolyl)3] and to Pd(CyPF-t-Bu)[P(o-tolyl)3] at room temperature to produce the corresponding palladium(II) aryl tosylate complexes. In the presence of added bromide ions, arylpalladium(II) bromide complexes were formed. The rate of oxidative addition was accelerated by addition of either coordinating or weakly coordinating anions, and the reactions were faster in more polar solvents. The mild conditions for oxidative addition allowed for the development of Pd-catalyzed Kumada couplings and amination reactions of unactivated aryl tosylates at room temperature. The catalysts for these mild couplings of aryl tosylates were generated from palladium precursors and the sterically hindered Josiphos-type ligands that induced oxidative addition of aryl tosylates to Pd(0) at room temperature.     

Autocatalytic oxidative addition of PhBr to Pd(PtBu3)2 via Pd(PtBu3)2(H)(Br)

We report that oxidative addition of bromobenzene to Pd(PtBu3)2 occurs by an unusual autocatalytic mechanism. Studies on the effect of various additives showed that the degree of rate acceleration followed the trend: (PtBu3)Pd(Ph)(Br) approximately (HPtBu3)Br < [(PtBu3)Pd(mu-Br)]2 < (PtBu3)2Pd(H)(Br). Studies on the reactions of Pd(PtBu3)2 in the presence of (PtBu3)2Pd(H)(Br) showed that the concentration of (PtBu3)2Pd(H)(Br) decreased only after the Pd(0) complex had been consumed. These data indicated that the catalyst in this process is (PtBu3)2Pd(H)(Br). Thermal decomposition of the three-coordinate oxidative addition product (PtBu3)Pd(Ar)(Br) during the reaction of Pd(PtBu3)2 and bromoarenes ultimately leads to formation of (PtBu3)2Pd(H)(Br). Parallel reactions of bromobenzene with (PtBu3)2Pd(H)(Br) and Pd(PtBu3)2 showed that the bromoarenes reacted considerably faster with the Pd(II) species than with the Pd(0) species. We therefore propose a catalytic cycle for oxidative addition in which PBut3.HBr reacts with the Pd(0) species to form (PtBu3)2Pd(H)(Br), and (PtBu3)2Pd(H)(Br) reacts with the bromoarene, possibly though the anionic species [HPtBu3+][(PtBu3)Pd(Br)-], to form [Pd(PtBu3)(Ar)(Br)].     

Oxidative addition of palladium(0) complexes generated from

The major complex formed in solution from [[Pd0(dba)2]+1P-N] mixtures is [Pd0(dba)(P-N)] (dba=trans,trans-dibenzylideneacetone; P-N=PhPN, 1-dimethylamino-2-diphenylphosphinobenzene; FcPN, N,N-dimethyl-1-[2-(diphenylphosphino)ferrocenyl]methylamine; OxaPN, 4,4'-dimethyl-2-(2-diphenylphosphinophenyl)-1,3-oxazoline). Each complex consists of a mixture of isomers involved in equilibria: two 16-electron rotamer complexes [Pd0(eta2-dba)(eta2-P-N)] and one 14-electron complex [Pd0(eta2-dba)(eta1-P-N)] observed for FcPN and OxaPN. [Pd0(dba)(PhPN)] and [SPd0(PhPN)] (S solvent) react with PhI in an oxidative addition: [SPd0(PhPN)] is intrinsically more reactive than [Pd0(dba)(PhPN)]. This behavior is similar to that of the bidentate bis-phosphane ligands. When the PhPN ligand is present in excess, it behaves as a monodentate phosphane ligand, since [Pd0(eta2-dba)(eta1-PhPN)2] is formed first by preferential cleavage of the Pd-N bond instead of the Pd olefin bond. [Pd0(eta1-PhPN)3] is also eventually formed. [Pd0(dba)(FcPN)] and [Pd0(dba)(OxaPN)] are formed whatever the excess of ligand used. [SPd0(FcPN)] and [SPd0)(OxaPN)] are not involved in the oxidative addition. The 16-electron complexes [Pd0(eta2-dba)(eta2-FcPN)] and [Pd0(eta2-dba)(eta2-OxaPN)] are found to react with PhI via a 14-electron complex as has been established for [Pd0(eta2-dba)(eta1-OxaPN)]. Once again, the cleavage of the Pd-N bond is favored over that of Pd-olefin bond. This work demonstrates the higher affinity for [Pd0(P-N)] of dba compared with the P-N ligand, and emphasizes once more the important role of dba, which either controls the concentration of the most reactive complex, [SPd0(PhPN)], or is present in the reactive complexes, [Pd0(dba)(FcPN)] or [Pd0(dba)(OxaPN)], and thus contributes to their intrinsic reactivity.     

On the mechanism of an asymmetric alpha,beta-unsaturated carboxylic acid hydrogenation: application to the synthesis of a PGD2 receptor antagonist

Ruthenium complexes employing axially chiral ligands were found to be effective asymmetric hydrogenation catalysts for the reduction of alpha,beta-unsaturated ene acid 1-E to give 2, a prostaglandin D2 (PGD2) receptor antagonist. With [(S-BINAP)Ru(p-cymene)Cl2]2 (3, S-BINAP = (S)-(+)-2,2'-bis(diphenylphospino)-1,1'-binapthyl), it was discovered that low hydrogen pressures (<30 psi) were essential to achieve high enantioselectivities (92% ee). A detailed mechanistic study was undertaken to elucidate this pressure dependence. It was determined that compound 1-E is in a ruthenium-catalyzed equilibrium with endocylic isomer 1-Endo and in photochemical equilibrium with Z isomer 1-Z. Each isomer could be hydrogenated to give 2, albeit with different rates and enantioselectivities. Hydrogenation of 1-Endo with 3 was found to give 2 in high enantiomeric excess, regardless of pressure and at a rate substantially faster than that of hydrogenation of 1-E and 1-Z. In contrast, isomers 1-E and 1-Z exhibited pressure-dependent enantioselectivities, with higher enantiomeric excesses obtained at lower pressures. A rationale for this pressure dependence is described. Deuterium labeling studies with 1-Endo and tiglic acid were used to elucidate the mechanism of hydride insertion and product release from ruthenium. Under neutral conditions, protonolysis was the major pathway for metal-carbon cleavage, while under basic conditions, hydrogenolysis of the metal-carbon bond was predominant.