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Pd-catalyzed selective tandem arylation-alkylation of 1,1-dihalo-1-alkenes with aryl- and alkylzinc derivatives to produce alpha-alkyl-substituted styrene derivatives

Trans -selective monoarylation of 1,1-dibromo- and 1,1-dichloro-1-alkenes (1) can be achieved in >80% yields and in ?98-99% stereoselectivity with arylzinc bromides in the presence of a catalytic amount of Cl2Pd(DPEphos) or Cl2Pd(dppb), the former permitting cleaner and higher yielding reactions. Although THF is a generally satisfactory solvent, ether and toluene are superior to THF in some cases. The second substitution of (Z)-alpha-bromostyrenes (3) with alkylzincs in the presence of 2 mol% of Pd(t Bu3P)2 proceeds to give the corresponding 2 in >90% yields and in ?98-99% stereoselectivity. Although somewhat less satisfactory, the use of Cl2Pd(DPEphos) permits a one-pot tandem arylation-alkylation.

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

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Dinuclear ruthenium and iron complexes containing palladium and platinum with tri-tert-butylphosphine ligands: Synthesis, structures, and bonding

The reaction of Pd(PBut3)2 with Ru(CO)5 yielded the dipalladium-diruthenium cluster complex Ru 2(CO)9[Pd(PBut3)]2, 10. The reaction of Pt(PBut3)2 with Ru(CO) 5 at room temperature afforded the diplatinum-diruthenium cluster complex Ru2(CO)9[Pt(PBut3)] 2, 12, and the monoplatinum-diruthenium cluster PtRu 2(CO)9(PBut3), 11. All three complexes contain a diruthenium group with bridging Pd(PBut 3) or Pt(PBut3) groups. Compound 11 can be converted to 12 by reaction with an additional quantity of Pt(PBu t3)2. The reaction of 12 with hydrogen at 68 C yielded the dihydrido complex Pt2Ru2(CO) 8(PBut3)2(mu-H)2, 13. This complex contains a Ru2Pt2 cluster with hydride ligands bridging two of the Ru-Pt bonds. The reaction of Fe2(CO) 9 with Pt(PBut3)2 yielded the platinum-diiron cluster complex PtFe2(CO)9(PBu t3), 14, which is analogous to 11. All new complexes were characterized crystallographically. Molecular orbital calculations of 10 reveal an unusual delocalized metal-metal bonding system involving the Pd(PBu t3) groups and the Ru2(CO)9 group.

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

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Unexpected intermolecular Pd-catalyzed cross-coupling reaction employing heteroaromatic carboxylic acids as coupling partners

Aryl-substituted five-membered heteroaromatics have attracted great interest over the past years due to their presence in a large number of pharmaceuticals and natural products. Recently, an advance in the preparation of these scaffolds was achieved by employing a C-H functionalization strategy. This method allows easy access to these biaryl motifs by precluding the necessity of preparing specific coupling partners, although poor regioselectivity is sometimes observed when more than one reactive C-H is present on the substrate. In an effort to circumvent this liability, we envisioned the use of a carboxylic acid moiety as a blocking group that could be later functionalized or removed. Remarkably, the coupling was found to occur exclusively at the position previously occupied by the acid, even in the presence of a reactive C-H group. This selective transformation was also found to proceed with other heteroaromatic carboxylic acids, allowing for the preparation of a variety of aryl-substituted heteroaromatics that would be difficult to obtain via other methods. Copyright

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

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Binuclear complexes of Ni(i) from 4-terphenyldithiophenol

Binuclear complexes of Ni(i) have been prepared from a 4-terphenyldithiophenol ligand. Steric effects were found to determine the formation of coordination isomeric structures that differ in the nature of metal-to-ligand bonding. Coordination of spatially demanding phosphine ligands PR3, R = C6H6, C6H11, at nickel sites results in a butterfly shaped thiolate-bridged Ni2(mu-S)2 motif. For smaller PMe3, the central pi-system of the 4-terphenyl backbone adopts a bis-allyl like mu-syn-eta3:eta3-C6H4 structure due to significant d-pi? Ni(i)-to-ligand charge transfer. Delocalisation indices delta(Ni-Ni) derived from DFT calculations provide a metric to assess the strength of electronic coupling of the Ni sites based on solid state structural data, and indicated less strong electronic coupling for the bis-allyl like structure with delta(Ni-Ni) = 0.225 as compared to 0.548 for the Ni2(mu-S)2 structural motif. A qualitative reactivity study toward CNCH3 as an auxiliary ligand has provided the first insight into the chemical properties of the bimetallic complexes presented.

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

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Palladium-catalyzed alpha-arylation of carboxylic acid derivatives with grignard reagent

The reaction of arylacetic acid with aryl halides in the presence of a palladium(0) catalyst proceeds with a Grignard reagent (2 equiv.) to afford diarylated acetic acids. Deprotonation was confirmed by treatment with allyl bromide, which revealed that the use of EtMgCl or tBuMgCl at room temperature to 60 C resulted in complete deprotonation. After deprotonation of (4-methoxyphenyl)acetic acid under such conditions, the resulting mixture was treated with 4-methoxybromobenzene in the presence of Pd(tBu3P) 2 (2 mol-%) as a catalyst to give bis(4-methoxyphenyl)acetic acid in 86% yield. The reaction with several aryl halides under similar conditions gave the corresponding diarylacetic acids. Copyright

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

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Phosphine-Scavenging Cationic Gold(I) Complexes: Alternative Applications of Gold Cocatalysis in Fundamental Palladium-Catalyzed Cross-Couplings

We have demonstrated that air-stable cationic gold(I) cocatalysts have the capacity to enhance the efficiency of palladium-catalyzed cross-couplings. Specifically, we determined that a 1:1 [Pd{P(t-Bu)3}2]/[Au{P(t-Bu)3}(NTf2)] system provides superior reactivity relative to [Pd{P(t-Bu)3}2], across Suzuki-Miyaura, Stille, and Mizoroki-Heck reactions performed under mild conditions. Our results are consistent with cationic gold(I) species serving primarily as phosphine scavengers in this chemistry, as recently predicted by density functional theory (DFT).

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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 Arylation of Arylboronic Acids with Yagupolskii-Umemoto Reagents

A Pd-catalyzed Suzuki cross-coupling of arylboronic acids with Yagupolskii-Umemoto reagents was explored. In contrary to trifluoromethylations, the Pd-catalyzed reaction of R-B(OH)2 and [Ar2SCF3]+[OTf]- provided the arylation products (R-Ar) in good to high yields. The reaction confirms that the S-Ar bonds of [Ar2SCF3]+[OTf]- can be readily cleaved in the presence of Pd complexes. The relatively electron-poor aryl groups of asymmetric [Ar1Ar2SCF3]+[OTf]- salts are more favorably transferred compared to the electron-rich ones. This reaction represents the first report of utilization of [Ar2SCF3]+[OTf]- as arylation reagents in organic synthesis.

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

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TRIAZOLOPYRIDAZINE

Disclosed are compounds of general formula (I) wherein the groups R1 to R3 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.

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

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Diastereoselective palladium-catalyzed arylcyanation/heteroarylcyanation of enantioenriched N -allylcarboxamides

A diastereoselective Pd-catalyzed arylcyanation/heteroarylcyanation of chiral N-allylcarboxamides using Zn(CN)2 as the cyanide source is reported. Nitrile-containing dihydroisoquinolinone products are obtained in good to excellent yields with up to >95:5 dr and with full preseveration of enantioenrichment. By circumventing a difficult nucleophilic cyanation of a hindered neopentyl iodide, this approach represents an improvement to the previously reported formal synthesis of (+)-corynoline.

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

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A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans

A mild and general protocol for the Pd(0)-catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/P(tBu)3 catalyst system enables the efficient coupling of o-bromoanilines at 60 C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (-)-aspergilazine A.

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