Esteban P. Urriolabeitia

Primary amines as directing groups in the ru-catalyzed synthesis of isoquinolines, benzoisoquinolines, and thienopyridines

Isoquinolines, benzoisoquinolines, thieno[3,2-c]pyridines and fused heteroaryl[2,3-c] pyridines, with a wide variety of substituents at different positions of the aromatic or heteroaromatic rings, have been synthesized by Ru-catalyzed oxidative coupling of a broad range of benzylamines or heterocycles with internal alkynes. All benzylamines and heterocycles have unprotected primary amines as efficient directing groups.

Synthesis, characterization and catalytic activity in Heck-type reactions of orthometallated PdII and PtII complexes derived from (1R, 2R)-1,2-diaminocyclohexane

The chiral bis-imine (1R,2R)-C6H10-[ENCHC6H33,4-(OMe)2]21 (LH) reacts with [Pd(OAc)2] (1:1 molar ratio; OAc=acetate) giving the orthometallated [Pd(OAc)(C6H24,5-(OMe)22-CHN-(1R,2R)-C6H10NCHC6H3-3′,4′-(OMe)2-κ-C,N,N)] 2 (abbreviated as [Pd(OAc)(L-κ-C,N,N)]), through CH bond activation on only one of the aryl rings and N,N-coordination of the two iminic N atoms. 2 reacts with an excess of LiCl to give [Pd(Cl)(L-κ-C,N,N)] 3. The reaction of 3 with AgClO4 and neutral or anionic ligands L′ (1:1:1 molar ratio) affords [Pd(L-κ-C,N,N)(L′)](ClO4) (L′=PPh34a, NCMe 5, pyridine 6, p-nitroaniline 7) or [Pd(I)(L-κ-C,N,N)] 8. Complex 4a reacts with wet CDCl3 giving [Pd(C6H24,5-(OMe)22-CHN-(1R,2R)C6H10NH2-κ-C,N,N)(PPh3)](ClO4) 4b as a result of the hydrolysis of the CN bond not involved in the orthometallated ring. The molecular structure of 4b·CH2Cl2 has been determined by X-ray diffraction methods. Cleavage of the PdN bond trans to the Caryl atom can be accomplished by coordination of strongly chelating ligands, such as acetylacetonate (acac) or bis(diphenylphosphino)ethane (dppe), forming [Pd(acac-O,O′)(L-κ-C,N)] 9 and [Pd(L-κ-C,N)(dppe-P,P′)](ClO4) 12, while classical N,N′-chelating ligands such as 1,10-phenantroline (phen) or 2,2′-bipyridyl (bipy) behave as monodentate N-donor ligands yielding [Pd(L-κ-C,N,N)(κ1-N-phen)](ClO4) 10 and [Pd(L-κ-C,N,N)(κ1-N-bipy)](ClO4) 11. Treatment of 1 with PtCl2(DMSO)2 (1:1 molar ratio) in refluxing 2-methoxyethanol gives Cl2Pt[(NH2)2C6H10N,N′] 13a and [Pt(Cl)(C6H24,5-(OMe)22-CHN-(1R,2R)C6H10NH2-κ-C,N,N)] 13b, while [Pt(Cl)(L-κ-C,N,N)] 14 can be obtained by reaction of [Pt(μ-Cl)(η3-2-MeC3H4)]2 with 1 in refluxing CHCl3. Complexes 2 and 3 catalyzed the arylation of methyl acrylate giving good yields of the corresponding methyl cinnamates and TON up to 847 000. Complex 3 also catalyzes the hydroarylation of 2-norbornene, but with lower yields and without enantioselectivity.

Mechanistic Insights into the One-Pot Synthesis of Propargylamines from Terminal Alkynes and Amines in Chlorinated Solvents Catalyzed by Gold Compounds and Nanoparticles

Propargylamines can be obtained from secondary amines and terminal alkynes in chlorinated solvents by a three- and two-component synthesis catalyzed by gold compounds and nanoparticles (Au-NP) under mild conditions. The use of dichloromethane allows for the activation of two C-Cl bonds and a clean transfer of the methylene fragment to the final product. The scope of the reaction as well as the influence of different gold(III) cycloaurated complexes and salts has been investigated. The involvement of gold nanoparticles generated in situ in the process is discussed and a plausible reaction mechanism is proposed on the basis of the data obtained.

Bonding properties and bond activation of ylides: recent findings and outlook

The interaction of phosphorus and nitrogen ylides with metallic precursors has been examined from different points of view. The first one is related to the bonding properties of the ylides. Ylides with a unique stabilizing group bond through different atoms (the Calpha or the heteroatoms); while ylides with two stabilizing groups never coordinate through the Calpha atom. In the second section we examine the cause of the stereoselective coordination of bisylides of phosphorus, nitrogen and arsenic, and of mixed bisylides. We describe here the very interesting conformational preferences found in these systems, which have been determined and characterized. The DFT study of these bisylides has allowed for the characterization of strong intramolecular PO and AsO interactions, as well as moderate CHO[double bond, length as m-dash]C hydrogen bonds as the source of these conformational preferences. The third topic is related to the amazing reactivity of phosphorus ylides in bond activation processes. Depending on the nature of the metallic precursors, ylides can behave as sources of carbenes, of phosphine derivatives, of other ylides or of orthometallated complexes through P[double bond, length as m-dash]C, P-C or C-H bond activation reactions.

Metal complexes of biologically important ligands: Synthesis of amino acidato complexes of PdII containing a C,N-cyclometallated group as an ancillary ligand

Abstract New amino acidato complexes of Pd II of stoichiometry [Pd(CN)(Aa)] (CN C , N -cyclometallated ligand, Aa = N , O -amino acidato ligand) have been obtained by reaction of [Pd(CN)(acac)] (CN N , N -dimethylbenzylamine- C 2 , N (dmba) ( 1 ) or N , N -dimethyl( S - α -phenylethyl)amine- C 2 , N ( S -dmphea) ( 2 )) with glycine, chiral amino acids (alanine, phenylalanine and valine), and amino acid derivatives ( N -acetylglycine and N -acetyl- α , β -dehydroalanine) in MeOH. The compounds are characterized by IR, 1 H and 13 C NMR. The geometry of these complexes has been unambiguously determined by NOE difference experiments and NOESY measurements.

Functionalization of Methyl (R)-Phenylglycinate Through Orthopalladation: C−Hal, C−O, C−N, and C−C Bond Coupling

The ortho functionalization of methyl R-phenylglycinate has been easily achieved using the known orthopalladated complex [Pd(mu-Cl){R-C(6)H(4)(CH(CO(2)Me)NH(2))-2}](2) (1) as synthetic tool. Different functional groups have been introduced at the ortho position of the aryl ring. The reaction of (R)-1 with X(2) or PhI(OAc)(2) gives XC(6)H(4)(CH(CO(2)Me)NH(2))-2 (X = I, Br, OMe, OEt) through oxidative coupling, while the reaction with CO gives an isoindolone. (R)-1 also reacts with one, two, or three alkyne molecules to give different metal-containing or metal-free heterocycles. The resulting functionalized amino esters or heterocycles retain the chirality of (R)-1, according with the values of the optical rotation and the obtained ee values ranging from 22%-87%. The X-ray structures of six representative compounds have also been determined.

Synthesis and characterization of PdII complexes containing cyclic bis-ylides

The reaction of Ph2PCH2PPh2 (dppm) with ClCH2C(O)CH2Cl (1:1 molar ratio) in refluxing CHCl3 gives the new ylide-phosphonium salt 1, through quaternization of the two P atoms of the dppm and spontaneous loss of HCl. Compound 1 reacts with NEt3 in CHCl3 or CH2Cl2 solution (1:1 molar ratio) giving a mixture of the bis-ylide compound 2a and the ylide-methanide 2b (molar ratio 2a:2b=1:2). This mixture (prepared in situ) reacts with PdCl2(NCMe)2 to give the corresponding dichloride(bis-ylide) complex 3a (coordination through the two ylidic carbons) and the dichloride(ylide-methanide) complex 3b (coordination through the ylide carbon and the methanide carbon), in a molar ratio 3a:3b=1:2. The reaction of the mixture 3a:3b with AgClO4 (1:2 molar ratio, NCMe or Me2CO) in the presence of neutral ligands L gives the corresponding mixtures of the dicationic complexes [Pd(L)2(C,C-bis-ylide)](ClO4)2 (4a, L=NCMe; 5a, L=pyridine) and [Pd(L)2(C,C-ylide-methanide)](ClO4)2 (4b, L=NCMe; 5b, L=pyridine) (molar ratio 4a:4b=1:2; molar ratio 5a:5b=3:1). On the other hand, the reaction of Ph2PCH2PPh2 (dppm) with ClCH2C(CH2)CH2Cl (1:1 molar ratio) in refluxing ClCH2CH2Cl gives the bis-phosphonium salt 6. This salt reacts with LitBu and PdCl2(NCMe)2 (1:2.2:1 molar ratio) in THF affording the ylide-methanide complex 7. The crystal structures of complexes 3b·3dmso and 7·CHCl3 have been determined by X-ray diffraction.

Orthometallation as a Strategy in Pd-mediated Organic Synthesis

The orthopalladated complexes are among the most representative Pd(II) compounds. They display a wide prospect of applications, but they are mainly known by their use as intermediates in metal-mediated organic synthesis. In this review we describe how palladacycles are used to build up new molecules through regioselective formation of C-halogen, C-O, C-N, C-P, C-S and C-C bonds, either under catalytic or stoichiometric conditions. This methodology is based on the selective incorporation of the Pd into the organic skeleton to be modified and subsequent reactivity of the Pd-C bond toward different substrates. In many cases this strategy is alternative or even competitive, improving standard organic methods. The most recent achievements of the last five years will be covered here, presenting only the most impressive results.

Regioselective Orthopalladation of (Z)-2-Aryl-4-Arylidene-5(4H)-Oxazolones: Scope, Kinetico-Mechanistic, and Density Functional Theory Studies of the C–H Bond Activation

Orthopalladated complexes derived from (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared by reaction of the oxazolone with palladium acetate in acidic medium. The reaction is regioselective, only the ortho C-H bond of the arylidene ring being activated, producing a six-membered ring. The scope and reaction conditions of the orthopalladation are dependent on the acidity of the solvent. In CF(3)CO(2)H a large number of oxazolones can be metalated under mild conditions. As acidity decreases a lesser number of oxazolones can be efficiently palladated and harsher conditions must be used to achieve similar yields. The C-H bond activation in acidic medium agrees with an ambiphilic mechanism, as determined from kinetic measurements at variable temperature and pressure for different oxazolones substituted at the arylidene ring. The mechanism has been confirmed by density functional theory (DFT) calculations, where the formation of the six-membered ring is shown to be favored from both a kinetic and a thermodynamic perspective. In addition, the dependence of the reaction rate on the acidity of the medium has also been accounted for via a fine-tuning between the C-H agostic precoordination and the proton abstraction reaction in the overall process occurring on coordinatively saturated [Pd(κ(N)-oxazolone)(RCO(2)H)(3)](2+).

Synthesis and characterization of dinuclear complexes of PdII containing the (μ-NCS)2 skeleton

Abstract The reaction of [Pd(C ∧ N)acac)] [C ∧ N = dmba (2-(dimethylaminomethyl)phenyl- C 1 , N ), 8-mq (8-quinolylmethyl- C , N ); acac = acetylacetonate] with the 2-mercapto derivatives H[N ∧ S] {H[N ∧ S] = pySH (2-mercaptopyridine), bztzSH (2-mercaptobenzothiazole), pymSH (2-mercaptopyrimidine), bzmdSH (2-mercaptobenzimidazole), and tzSH (2-mercaptothiazoline)} in 1:1 molar ratio (CH 2 Cl 2 , room temperature) results in the protonation of the acetylacetonate ligand, which is eliminated as acetylacetone, and N , S -bridging coordination of the anionic groups [N ∧ S] − , giving the corresponding neutral dinuclear derivatives [Pd(C ∧ N)( μ -N ∧ S)] 2 (C ∧ N = dmba, N ∧ S = pyS 1 , bztzS 2 , pymS 3 , bzmdS 4 , tzS 5 ; C ∧ N = 8-mq, N ∧ S = pyS 6 , bztzS 7 , pymS 8 , bzmdS 9 , tzS 10 ). In these complexes, two [Pd(C ∧ N)] + fragments are bridged by two [N ∧ S] − ligands in a head-to-tail disposition and with a C- trans -to-N ligand arrangement around the palladium(II) centre. On the other hand, the reaction of [Pd(C ∧ N)(acac)] (C ∧ N = dmba, 8-mq) with the same 2-mercapto derivatives, but in 1:2.3 molar ratio (CH 2 Cl 2 , room temperature), allows the synthesis of the homoleptic dinuclear derivatives [Pd( μ -N ∧ S) 2 ] 2 (by protonation of both the acetylacetonate and the ortho -metallated ligands) only when N ∧ S = pyS 11 , bztzS 12 , pymS 13 , while for N ∧ S = bzmdS and tzS the corresponding [Pd(C ∧ N)( μ -N ∧ S)] 2 ( 4, 5, 9, 10 ) complexes were obtained. Complexes 1–13 have been characterized through IR and NMR spectroscopic methods.