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A number of ethyl 2-aryl-2-formylpent-4-enoates containing acyclic, all-carbon, aryl-substituted quaternary stereocenters have been synthesized via intermolecular palladium-catalyzed asymmetric allylic alkylation (Pd-AAA). Here, a 2-aryl-3-hydroxyacrylate was used as an unprecedented nucleophilic counterpart instead of the widely used ketonic substrate. This produced a very rare, all-carbon chiral center including an easily utilized aldehyde or ketone moiety. Chiral ligand (R,R)-DACH-naphthyl Trost ligand was found to be optimal in this Pd-AAA reaction and provided good to excellent yields (75-99%) and enantioselectivities (52-94%) with a range of analogues. To show the utility of this method, it was used to synthesize an all-carbon quaternary, alpha,alpha-disubstituted beta-lactone.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Some cationic eta3-propargylpalladium complexes were prepared upon treatment of the corresponding eta1-propargyl- or eta1- allenylbis(triphenylphosphine)palladium(II) chloride with Ag[BF4] or Na[BPh4]. The effectiveness of the latter reagent suggests that a eta1- propargyl- or eta1-allenyl(chloro)palladium complex equilibrates with a cationic eta3-propargylpalladium complex with the liberation of a Cl- ligand. A qualitative comparison of trends in a series of analogous equilibrium systems suggests that the eta3-coordination mode is favored to a greater extent when (i) propargyl ligands have an alkyl substituent at the propargylic position, (ii) phosphine ligands are bidentate, such as dppe, (iii) polar solvents are used, and (iv) the liberating ligand is a Cl- one. A possible implication of eta3-coordination of propargyl ligands in a catalytic cycle of Pd-catalyzed transformations of propargylic or allenylic substrates is presented.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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An enantioselective Pd-catalyzed DAAA of alpha-aryl-beta-oxo esters has been developed employing the (R,R)-ANDEN-phenyl Trost ligand to prepare a series of alpha-aryl-alpha-allyldihydrocoumarins and 3-isochromanones. A variety of aryl groups were successfully employed to afford the dihydrocoumarin and 3-isochromanone products in high yields up to 95% and ee’s up to 96%. Under these conditions, substrates containing di- and mono-ortho-substituted aryl groups gave the highest levels of enantioselectivities. This work represents the first example of the enantioselective preparation of all-carbon quaternary alpha-allyl-alpha-aryl dihydrocoumarins and 3-isochromanones.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The chromiumtricarbonyl complexed phenyl allene 4 can be readily synthesized by palladium catalyzed hydride reduction or dimethyl cuprate mediated reduction of suitable propargyl ester derivatives 3 and 5. This parent compound of chromiumcarbonyl complexed aryl allenes is fairly stable and is unambiguously characterized by an X-ray structure analysis. Thiolate adds to 4 to give a 3.5:1 distribution between the nonconjugated and the conjugated addition products 7 and 8 in good yield.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The ability to tune the reactivity of palladium carbenes derived from diphenylketene, which is dependent on the oxidation state of the metal center, is presented. Competition experiments illustrated that Pd(O) catalysts favor direct C-H functionalization of terminal alkynes and that Pd(II) catalysts lead to cyclopropanation of strained alkenes. In addition, a PdCl2- catalyzed cyclopropane isomerization of diphenylcyclo-propanes and an unprecedented Pd(II)-catalyzed domino cyclopropanation/isomerization reaction are described.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The rates of amine nucleophilic attack on the allyl ligand (k2) and the equilibrium constants (KE) for the displacement of bidentate ligands in Pd(II) allyl complexes of chelating pyridine-chalcogen ethers [Pd(eta3-allyl)(RN-XPh)]+ (R = H, Me; X = S, Se) are shown to depend strongly on the steric and electronic requirements of the reactants but are hardly affected by the nature of the chalcogen. Results about the reactivity and solution behaviour of these systems help build up a fairly complete mechanistic picture for this important class of reactions involving coordinated allyl species. In particular the reactivity of the complexes bearing pyridine-thioether ligands is close to that of their pyridine-selenoether analogues, probably owing to a balance of sigma and pi capabilities of the chalcogen atom. The associative nature of the ligand displacement is markedly affected by steric requirements which depend on the allyl bulkiness. The complexes bearing the ligands with methyl substituted pyridine are the more reactive, due to the destabilisation of the complex ground state induced by the distortion of the starting substrate. We also describe the fluxional behaviour of these species in terms of inversion of the chalcogen absolute configuration and apparent rotation of the allyl ligand.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A highly efficient palladium(0)-catalyzed asymmetric [3+2] cycloaddition using 3-diazooxindoles serving as dipolarophiles affords functionalized pyrazolidine derivatives in an atom-economical way. In addition, by trapping the pyrazolidine derivatives with maleimides, the corresponding spiropyrazolidine oxindoles containing multiple stereogenic centers have been obtained in high yields along with moderate to good levels of diastereoselectivity and enantioselectivity under mild conditions. Thus, a novel three-component one-pot tandem reaction has been developed.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) of enol carbonates derived from gamma-butyrolactones is reported, affording the corresponding enantioenriched alpha,alpha?-disubstituted gamma-butyrolactones in both high yields and high enantioselectivities (up to 94% ee). This method was eventually applied to the synthesis of chiral spirocyclic compounds.

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Palladium/carbon catalyst regeneration and mechanical application method

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Pd-catalyzed regio- and enantioselective allylic etherification of vinylethylene carbonates (VECs) with diols has been developed. By using cooperative catalysts of the chiral palladium complex and triethylborane in mild conditions, the process gave monoetherified and bisetherified polyglycol derivatives with tetrasubstituted stereocenters in high yields with complete regioselectivities and high levels of enantio- and diastereoselectivities.

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Palladium/carbon catalyst regeneration and mechanical application method

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Dihydroanthracene derivatives (1-6) containing imide (1-3) and amine (4-6) functions have been used for the stabilization of palladium nanoparticles, starting from Pd(0) and Pd(ii) organometallic precursors. Well-dispersed nanoparticles of mean size in the range ca. 1.9 to 3.6 nm could be obtained using Pd(0) precursors (PdLc and PdLd, where L = 1-6 and c and d mean the organometallic precursor involved, [Pd2(dba)3] and [Pd(ma)(nbd)] respectively). With the aim to evaluate the behaviour of homogeneous species and nanoparticles used as catalytic precursors, palladium complex coordinated to the diamine 6, [Pd(OAc)2(kappa2- N,N-6)], was prepared, reporting for the first time the X-ray diffraction structure of a metallic complex containing a ligand with a 9,10- dihydroanthracene backbone. Palladium systems were evaluated in Suzuki C-C coupling reactions and relevant differences were observed comparing the reactivity of the homogeneous systems in relation to that obtained using palladium nanoparticles as starting catalyst in relation to the activation of the C-Br bonds for deactivated substrates.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method