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A general synthetic route to inherently luminescent and optically active 6-fold substituted C3-symmetric and asymmetric biphenyl-based trianglimines has been developed. The synthesis of these hexa-substituted triangular macrocycles takes advantage of a convenient method for the synthesis of symmetrically and asymmetrically difunctionalized biphenyl dialdehydes through a convergent two-step aromatic nucleophilic substitution-one-pot Suzuki-coupling reaction protocol. A modular [3+3] diamine-dialdehyde cyclocondensation reaction between both the symmetrically and asymmetrically difunctionalized-4,4?-biphenyldialdehydes with enantiomerically pure (1R,2R)-1,2-diaminocyclohexane was employed to construct the hexa-substituted triangular macrocycles. B97-D/6-311G(2d,p) density functional theory determined structures and X-ray crystallographic analysis reveal that the six substituents appended to the biphenyl legs of the trianglimine macrocycles adopt an alternating conformation not unlike the 1,3,5-alternate conformation observed for calix[6]arenes. Reduction of the imine bonds using NaBH4 afforded the corresponding 6-fold substituted trianglamine without the need to alkylate the amine nitrogen atoms which could hinder their later use as metal coordination sites and without having to introduce asymmetric carbons.

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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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A novel bis-platinum(ii) terpyridine-based macrocycle has been quantitatively obtained by self-assembly; the Pt(ii) host binds neutral planar and electron-rich aromatic guests with good selectivity in DMSO. The Royal Society of Chemistry.

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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 can do it! A novel palladium-catalyzed reaction between the bulky alpha-carbon centers of two ketones has led to the construction of 2,3-diaryl-1,4-diketones by employing alpha-chloroketones as electrophiles and zinc ketone enolates as nucleophiles (see scheme). This reaction allows the synthesis of bulky 1,4-diketones and is complementary with classic nucleophilic substitution reactions. Copyright

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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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A convenient one-pot method for the synthesis of 4-arylquinolin-2(1H)-ones and 4-arylcoumarins has been described. The successive Heck reaction on substituted 2-iodoaniline and 2-iodophenol catalyzed by a Pd/nickel ferrite catalyst followed by in situ cyclization was the key step. The scope of this methodology was extended to the synthesis of bioactive 3-alkenyl derivatives of 4-arylquinolin-2(1H)-ones.

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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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DIHYDRO-PYRROLOPYRIDINONE INHIBITORS

The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, and R5 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

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

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Multimetallic complexes of group 10 and 11 metals based on polydentate dithiocarbamate ligands

The ligands KS2CN(Bz)CH2CH2N(Bz)CS 2K (K2L1), N(CH2CH 2N(Me)CS2Na)3 (Na3L2), and the new chelates {(CH2CH2)NCS2Na} 3 (Na3L3) and {CH2CH 2N(CS2Na)CH2CH2CH 2NCS2Na}2 (Na4L4), react with the gold(I) complexes [ClAu(PR3)] (R = Me, Ph, Cy) and [ClAu(IDip)] to yield di-, tri-and tetragold compounds. Larger metal units can also be coordinated by the longer, flexible linker, K2L1. Thus two equivalents of cis-[PtCl2(PEt3)2] react with K2L1 in the presence of NH4PF 6 to yield the bimetallic complex [L1{Pt(PEt 3)2}2](PF6)2. The compounds [NiCl2(dppp)] and [MCl2(dppf)] (M = Ni, Pd, Pt; dppp = 1,3-bis(diphenylphosphino)propane, dppf = 1,1′-bis(diphenylphosphino) ferrocene) also yield the dications, [L1{Ni(dppp)}2] 2+ and [L1{Ni(dppf)}2]2+ in an analogous fashion. In the same manner, reaction between [(L?2) (AuCl)2] (L?2 = dppm, dppf; dppm = bis(diphenylphosphino)methane) and KS2CN(Bz)CH2CH 2N(Bz)CS2K yield [L1{Au2(L? 2)}2]. The molecular structures of [L1{M(dppf)} 2](PF6)2 (M = Ni, Pd) and [L 1{Au(PR3)}2] (R = Me, Ph) are reported.

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

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Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.

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

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Molecular dials: Hindered rotations in mono- and diferrocenyl anthracenes and triptycenes

The syntheses, X-ray crystal structures, and molecular dynamics of 9-ferrocenylanthracene, 3, 9,10-diferrocenylanthracene, 4, 9- ferrocenyltriptycene, 7, and 9,10-diferrocenyltriptycene, 8, are reported. At 193 K, 3 exhibits Cs symmetry via oscillation of the ferrocenyl only about the anthracene plane; at higher temperatures, complete rotation about the C(9)-ferrocenyl linkage becomes evident with a barrier of 10.6 kcal mol -1. At 193 K, the ferrocenyls in 4 give rise to syn (C2v) and anti (C2h) rotamers that also interconvert at room temperature. In the corresponding triptycyl systems, 7 and 8, these rotational barriers increase to 17 kcal mol-1; 9,10-diferrocenyltriptycene exists as slowly interconverting meso and racemic rotamers, in which the ferrocenyl moieties are, respectively, eclipsed (C2v) or staggered (C 2). 2D-EXSY NMR data recorded with different mixing times indicate clearly that these interconversions proceed in a stepwise manner, for example, rac?meso?rac, thus behaving as a set of molecular dials.

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

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Catalytic asymmetric aldol equivalents in the enantioselective synthesis of the apoptolidinc aglycone

Aldol replacement: Catalytic asymmetric ketenealdehyde cycloadditions provide surrogates for traditional aldol additions in an enantioselective synthesis of apoptolidinoneC, the aglycone of the potent apoptosis regulator apoptolidinC. Eight of apoptolidinone C’s ten stereocenters derive directly from these catalytic acetate or propionate aldol equivalents.

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

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Design, Synthesis, Structure-Activity Relationship Studies, and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Modeling of a Series of O-Biphenyl Carbamates as Dual Modulators of Dopamine D3 Receptor and Fatty Acid Amide Hydrolase

We recently reported molecules designed according to the multitarget-directed ligand paradigm to exert combined activity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R). Both targets are relevant for tackling several types of addiction (most notably nicotine addiction) and other compulsive behaviors. Here, we report an SAR exploration of a series of biphenyl-N-[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates, a novel class of molecules that had shown promising activities at the FAAH-D3R target combination in preliminary studies. We have rationalized the structural features conducive to activities at the main targets and investigated activities at two off-targets: dopamine receptor subtype D2 and endocannabinoid receptor CB1. To understand the unexpected affinity for the CB1 receptor, we devised a 3D-QSAR model, which we then prospectively validated. Compound 33 was selected for PK studies because it displayed balanced affinities for the main targets and clear selectivity over the two off-targets. 33 has good stability and oral bioavailability and can cross the blood-brain barrier.

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