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Enantioselective Difunctionalization of Alkenes by a Palladium-Catalyzed Heck/Sonogashira Sequence

Sonogashira-type cross-couplings are one of the most significant alkynylations in organic chemistry. One of the first palladium-catalyzed intramolecular Heck/Sonogashira reactions of alkenes with terminal alkynes is now reported. With this method, a variety of uniquely substituted chiral benzene-fused heterocycles bearing a propargyl-substituted all-carbon quaternary stereocenter were obtained in a straightforward, high-yielding, and highly stereoselective manner under mild conditions. Salient features of this process include the use of readily available substrates, high selectivities, a broad substrate scope as well as versatile product functionalizations.

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

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Pd-Catalyzed diastereoselective [3 + 2] cycloaddition of vinylcyclopropanes with sulfamate-derived cyclic imines

The palladium-catalyzed diastereoselective [3 + 2] cycloaddition reaction of vinylcyclopropanes with sulfamate-derived cyclic imines worked efficiently under mild reaction conditions, providing 2,3-dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]oxathiazine 5,5-dioxide derivatives in good to excellent yields.

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

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Chiral amino alcohol derived bis-phosphoramidite pincer palladium complexes and their applications in asymmetric allylation of aldimines

Novel P-stereogenic bis-phosphoramidite pincer palladium complexes 1 and 2 derived from (S)-(-)-alpha,alpha-diphenyl-2-pyrrolidinemethanol and (S)-(+)-indolinemethanol, respectively, were synthesized in reasonable yields (i.e., 55-62%) by using a flexible, modular synthetic approach and were characterized by X-ray crystal structure determination. Reacting (S)-(+)-indolinemethanol with PCl3 leads to the formation of a novel P-chiral building block, which exhibits good thermal stability of its stereochemical features. This enabled the design and development of new P-chiral bisphosphoramidite pincer arene ligands and their corresponding metal complexes. The molecular structure of the new indolinemethanol-derived phosphoramidite pincer metal complex screens quadrants I and III, which is in contrast to the previously reported L-proline-derived P-chiral ligands that screen quadrants II and IV. The bis-phosphoramidite pincer palladium, complexes 1 and 2 are active catalysts for asymmetric homoallylation of sulfonimines, where low (ee 33%) or no enantioselectivity was observed for reactions catalyzed by 2 and 1, respectively. Preliminary catalytic results revealed that enantiomeric excess values varied by using differently functionalized sulfonimines, suggesting that, both electronic properties and steric congestion of sulfonimines affect, the transition state of the electrophilic attack of the 1nallyl Pd intermediate in the allylation.

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

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Novel Di- and Trinuclear Palladium Complexes Supported by N,N?-Diphosphanyl NHC Ligands and N,N?-Diphosphanylimidazolium Palladium, Gold, and Mixed-Metal Copper-Gold Complexes

The reaction of the trinuclear complex [Ag3(mu3-PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)3 (Ag3; PCNHCP = N,N?-bis(di-tert-butylphosphanyl)imidazol-2-ylidene) with [Pd(dba)2] afforded the trinuclear palladium complex [Pd3(mu3-PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)2 (Pd3) and the dinuclear palladium(I) complex [Pd2(mu2-PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)2 (Pd2). The assignment of the oxidation state of the metals in the mixed-valence Pd3 chain as Pd0-PdII-Pd0 was based on the reactivity of the complex with 2,6-dimethylphenyl isocyanide and density functional theory calculations. Reaction of PCNHCP with [PdMe2(tmeda)] afforded the palladium(II) complex [PdMe2(PCNHCP,kappaP,kappaCNHC)] (Pd-Me2), with PCNHCP acting as a bidentate ligand. The reaction of PCNHCP with [Pd(dba)2] led to a dinuclear palladium(0) complex [Pd2(mu2-PCNHCP,kappaP,kappaCNHC,kappaP)](dba) (Pd2-dba); attempted replacement of the remaining dba by PCNHCP failed. The imidazolium triflate PCHP, precursor to PCNHCP, was reacted with [Pd2(dba)3]¡¤CHCl3 to give the (2 + 2) metalla-mesocyclic cationic palladium(0) complex [Pd2(mu2-PCHP,kappaP,kappaP)2] (PCHP-Pd2), which resisted further deprotonation of the imidazolium cation. In contrast, PCHP reacted with [AuCl(tht)] to give [Au2Cl2(mu2-PCHP,kappaP,kappaP)] (PCHP-Au2), in which one Au-Cl moiety is bound to each P donor. Further reaction of PCHP-Au2 with [Au{N(SiMe3)2}(PPh3)] afforded a mixture of the trinuclear [Au3(mu3-PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)3 (Au3) and [AuCl(PPh3)], while reaction with [CuMes]5, where Mes = 2,4,6-trimethylphenyl, resulted in a novel, centrosymmetric, heterometallic complex [Au2Mes2(Cu4Cl4)(PCHP,kappaP,kappaP)2] (PCHP-AuCu) featuring a new PCHP-AuMes metalloligand bridging a Cu¡¤¡¤¡¤Cu diagonal of a Cu4Cl4 cubane via the P and AuMes functionalities.

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

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Low valent palladium benzoquinone complexes bearing different spectator ligands. the versatile coordinative capability of benzoquinone

The synthesis of some benzoquinone palladium complexes bearing different spectator ligands was carried out and the hapticity of the coordinated olefin was inferred from the features of their 1H and 13C NMR spectra. It was shown that benzoquinone coordinates either eta2 and eta4 and that its coordinative choice is not easily predictable, although the eta2 coordination seems to be predominant in the presence of rigid ancillary ligands. The coordinative capability of benzoquinone was tested by means of thermodynamic and kinetic reference reactions and its slightly enhanced inertness with respect to the isofunctional naphthoquinone was assessed. Finally, the re-crystallization by slow diffusion at low temperature of diethylether in a dichloromethane solution of the complex [Pd(eta2-bq)(TTbQ-Me)] (bq = benzoquinone, TTbQMe = 8-t-Butylsulfanyl-2-methyl-quinoline) allows the separation of the dimer [Pd2(eta2-bq)(TTbQ-Me)2] whose solid state structure was resolved.

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

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Heterobimetallic Fe-Pd and Fe-Pt NCN pincer complexes (NCN = [C6H2(CH2NMe2)2-2 ,6]-)

The meta-diaminoaryl ferrocenes Fc-NCN-H (3) and Fc-C{triple bond, long}C-NCN-H (5) (Fc = (eta5-C5H5)(eta5-C5 H4)Fe, NCN-H = C6H3(CH2NMe2)2-3, 5) can be used as precursors in the preparation of heterobimetallic transition metal complexes of structural type Fc-NCN-MX (NCN = [C6H2(CH2NMe2)2-2 ,6]-; MX = PdCl (7), PtCl (8), PtI (9)) and Fc-C{triple bond, long}C-NCN-MX (MX = PdCl (11), PdI (12), PtCl (13)), respectively. They are accessible by applying different synthesis procedures, including oxidative addition and metallation-transmetallation processes. Cyclovoltammetric studies show that the ferrocene moieties in 3, 5, 7-9 and 11-13 can reversibly be oxidised. The potential of the Fe(II)/Fe(III) redox couple decreases with increasing electron density at the NCN pincer unit. The use of 8 as a possible (electro)chemical sensor in the detection of SO2 is discussed as well. The solid-state structures of 8 and 13 are reported. The crystals of 8 contain two molecules of 8 in the asymmetric unit. The plane of the C6H2 moiety is with 27.2(3) and 38.2(3) tilted towards the C5H4 entity, while in 13 an angle of 45.9(3) can be found. The d8-electron configured platinum atoms possess a somewhat distorted square-planar surrounding, setup by two Me2NCH2 ortho-substituents, the NCN Cipso carbon atom and the chloride ligand.

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

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Catalytic Asymmetric Total Synthesis of (-)-Galanthamine and (-)-Lycoramine

The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)-lycoramine (2) have been achieved by using a conceptually new strategy featuring two metal-catalyzed reactions as the key steps. A new method for the construction of 3,4-fused benzofurans has been developed through a palladium-catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric synthesis of 1 and 2, a ScIII/N,N?-dioxide complex was used to catalyze the enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center.

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

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Gorlos-phos: Addressing the stereoselectivity in palladium-catalyzed exo-mode cyclization of allenes with a nucleophilic functionality

A novel catalyst system has been indentified for addressing the long-standing issue of Z/E stereoselectivity in palladium-catalyzed exo-mode cyclization reactions of allenes bearing a nucleophilic functionality with organic halides or their equivalents. The readily accessible, sterically hindered monophosphine ligand Gorlos-Phos¡¤HBF4 imparts a remarkable stereocontrolling ability with broad generality under Pd catalysis.

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

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Mechanistic insight into the palladium-catalyzed 1,4-oxidation of 1,3-dienes to 1,4-dicarboxy-alk-2-enes

Side products get involved: The 1,4-oxidation of a diene transforms a simple hydrocarbon into an extremely useful intermediate. A complex formed in situ between palladium and a bicyclic Diels-Alder adduct, which is produced as a side product during the reaction, was responsible for the high rate and high diastereoselectivity observed in the oxidation of cyclohexadiene (see scheme).

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

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Palladium-Catalyzed Carbonylation of sec- and tert-Alcohols

A general palladium-catalyzed synthesis of linear esters directly from sec- and tert-alcohols is described. Compared to the classic Koch?Haaf reaction, which leads to branched products, this new transformation gives the corresponding linear esters in high yields and selectivity. Key for this protocol is the use of an advanced palladium catalyst system with L2 (pytbpx) as the ligand. A variety of aliphatic and benzylic alcohols can be directly used and the catalyst efficiency for the benchmark reaction is outstanding (turnover number up to 89 000).

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