Enantioselective synthesis of a PKC inhibitor via catalytic C-H bond activation

[reaction: see text] The syntheses of two biologically active molecules possessing dihydropyrroloindole cores (1 and 2) were completed using rhodium-catalyzed imine-directed C-H bond functionalization, with the second of these molecules containing a stereocenter that can be set with 90% ee during cyclization using chiral nonracemic phosphoramidite ligands. Catalytic decarbonylation and direct indole/maleimide coupling provide efficient access to 2.     

A novel catalytic one-pot synthesis of carbazoles via consecutive amination and C-H activation

Sequential palladium catalysed amination and C-H activation reactions occur between 2-chloro-N-alkylated anilines and aryl bromides to give carbazoles in one pot.     

Catalytic performance of symmetrical and unsymmetrical sulfur-containing pincer complexes: synthesis and tandem catalytic activity of the first PCS-pincer palladium complex

The synthesis and catalytic applications of a new aryl-based unsymmetrical PCS-pincer complex are reported. Preparation of the robust air- and moisture-stable PCS-pincer palladium complex 5[X] started from the symmetrical alpha,alpha'-dibromo-meta-xylene and involved the selective substitution of one bromide by PPh(2)(BH(3)), followed by substitution of the second bromide by SPh and subsequent introduction of the palladium. The new PCS complexes (5[X]) were employed as catalysts in two important organic transformations. Firstly, complex 5[Cl] displays high catalytic activity in aldol reactions but enters the catalytic cycle as a precatalyst. Secondly, complex 5[BF(4)] displays tandem catalytic activity in the coupling of allyl chlorides with aldehydes and imines in the presence of hexamethylditin. In these tandem catalytic reactions the first process is the conversion of allyl chlorides into trimethylallyltin (and trimethyltin chloride) with Sn(2)Me(6), which is followed by catalytic allylation of aldehyde and sulfonimine substrates. In addition, we present a new catalytic process for the one-pot allylation of 4-nitrobenzaldehyde with vinyloxirane. The catalytic performance of the novel PCS-pincer palladium complex was compared to those of its symmetrical PCP- and SCS-pincer complex analogues. It was concluded that the unsymmetrical PCS complex advantageously unifies the attractive catalytic features of the corresponding symmetrical pincer complexes including both (pi-) electron-withdrawing (such as phosphorus) or (sigma-) electron-donating (such as sulfur and nitrogen) heteroatoms. Thus, in the aldol reaction the PCS-pincer palladium complex 5[X] provides a high turnover frequency, while in the tandem process both reactions are catalysed with sufficiently high activity.     

Theoretical studies on the intra- and intermolecular C-H activation by T-shaped pincer complexes

Three coordinated, T-shaped (PNP)M^I (M = Co, Ru, Rh, Os and Ir) and [(PCP)Pt⁰]⁻, as well as their reactivities for intra- and intermolecular C-H activation have been studied by DFT methods. The experimental observed reactivities were well reproduced. The calculation also generated structural and energetic information which the experimental values were not yet available. We found that the intramolecular C-H activation is in general possible for the low spin (PNP)M^I. Intermolecular C-H activation is not preferred either thermodynamically or kinetically, but could be in competition if the intramolecular activation is reversible. Using model compounds, we found that the intramolecular C-H activation reactivity is not sensitive to steric effects of the bulky ligands. However, the strain of the four-membered ring in the product significantly reduces the reactivity, and the driving force increases by 4.51-12.95 kcal/mol if the strain was largely removed by changing from a four-membered ring to a five-membered ring. The C-H activation step is quite difficult for metals with a d¹⁰ configuration. Part of the reason is that one phosphine ligand dissociates during the reaction because the product has a d⁸ configuration and prefers a square planar structure.     

Ruthenium [NNN] and [NCN]-type pincer complexes with phosphine coligands: synthesis,structures and catalytic applications

Transition Metal Chemistry - A series of ruthenium [NNN]- or [NCN]-type complexes (3–7) bearing PPh3 ancillary ligands have been synthesized from pyridine- or phenylene-bridged bis(triazoles)...     

Pd-catalyzed alkyl to aryl migration and cyclization: an efficient synthesis of fused polycycles via multiple C-H activation

A novel palladium migration methodology for the synthesis of complex fused polycycles has been developed. This process involves 1,4-palladium alkyl to aryl migrations via through-space C-H activation, followed by intramolecular arylation or an intermolecular Heck reaction providing a very efficient way to synthesize fused ring systems.     

'Hemilabile' silyl pincer ligation: platinum group PSiN complexes and triple C-H activation to form a (PSiC)Ru carbene complex

The first example of PSiN mixed-donor silyl pincer ligation is described. Studies involving platinum group metal complexes of [(2-(t)Bu(2)PC(6)H(4))(2-Me(2)NC(6)H(4))SiMe](-) ((t)Bu-PSiN-Me) confirmed that the ligand amino donor is labile. Within the coordination sphere of Ru, (t)Bu-PSiN-Me is transformed into a PSiC ligand via multiple C-H bond activation events.     

Organolutetium vinyl and tuck-over complexes via C-H bond activation

The vinyl C-H bond of tetramethylfulvene is activated in the presence of [(C5Me5)2LuH]x, 1, to form a vinyl organolutetium complex, (C5Me5)2Lu(CH=C5Me4), 2. Also formed in the reaction is the "tuck-over" complex, (C5Me5)2Lu(mu-H)(mu-eta1:eta5-CH2C5Me4)Lu(C5Me5), 3, containing a (CH2C5Me4)2- moiety long postulated to exist in organolutetium chemistry but never crystallographically characterized. Evidence for these C-H bond activations by a "(C5Me5)3Lu" intermediate, 4, is presented. Complex 3 can also be made in high yield by thermolysis of 1. Under H2, 1 catalytically hydrogenates TMF to C5Me5H.     

An unusual hydrogen migration/C-H activation reaction with group 3 metals

A novel hydrogen migration from the phenyl ring to the pyridine ring of an yttrium pyridyl complex supported by a 1,1'-ferrocene diamide ligand is reported. Density functional theory calculations were instrumental in probing the mechanism for this transformation.     

Total synthesis of (+)-lithospermic acid by asymmetric intramolecular alkylation via catalytic C-H bond activation

The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.     

Palladium-catalyzed cycloaddition of alkynyl aryl ethers with internal alkynes via selective ortho C-H activation

Alkynyl aryl ethers react with internal alkynes through selective ortho C-H activation by a palladium(0) catalyst to give substituted 2-methylidene-2H-chromenes. The alkynoxy group acts as a directing group to promote ortho C-H functionalization. Deuterium-labeling experiments indicated that the arylpalladium hydride complex is a key intermediate via oxidative addition. Various functional groups tolerate the present transformation to give the corresponding products.     

NCN pincer palladium complexes: their preparation via a ligand introduction route and their catalytic properties

A wide range of NCN pincer palladium complexes, [4-tert-butyl-2,6-bis(N-alkylimino)phenyl]chloropalladium (alkyl = n-butyl, benzyl, cyclohexyl, tert-butyl, adamantyl, phenyl, 4-methoxyphenyl), were readily prepared from trans-(4-tert-butyl-2,6-diformylphenyl)chlorobis(triphenylphosphine)palladium via dehydrative introduction of the corresponding alkylimino ligand groups (ligand introduction route) in excellent yields (71-98%). NMR studies on this route for forming pincer complexes revealed the intermediacy of [4-tert-butyl-2,6-bis(N-alkylimino)phenyl]chlorobis(triphenylphosphine)palladium which is in equilibrium with the corresponding NCN pincer complexes via coordination/dissociation of the intramolecular imino groups and triphenylphosphine ligands. A series of chiral NCN pincer complexes bearing pyrroloimidazolone units as the trans-chelating donor groups, [4-tert-butyl-2,6-bis{(3R,7aS)-2-phenylhexahydro-1H-pyrrolo[1,2-c]imidazol-1-on-3-yl}phenyl]chloropalladium, were also prepared from the same precursor via condensation with proline anilides in high yields. The catalytic properties of the NCN imino and the NCN pyrroloimidazolone pincer palladium complexes were examined in the Heck reaction and the asymmetric Michael reaction to demonstrate their high catalytic activity and high enantioselectivity.     

Novel access to carbodiphosphoranes in the coordination sphere of group 10 metals: template synthesis and protonation of PCP pincer carbodiphosphorane complexes of C(dppm)2

In a novel template synthesis of carbodiphosphoranes (CDPs), the phosphine functionalized CDP ligand C(dppm)(2) (dppm = Ph(2)PCH(2)PPh(2)) is formed in the coordination sphere of group 10 metals from CS(2) and 4 equivalents of dppm. The products are the PCP pincer complexes [M(Cl)(C(dppm)(2)-κ3P,C,P)]Cl (M = Ni, Pd, Pt) and 2 equivalents of dppmS. The compound C(dppm)(2), which is composed of a divalent carbon atom and two dppm subunits, represents a new PCP-type pincer ligand with the formally neutral carbon Lewis base of the CDP functionality as the central carbon. Treatment of [M(Cl)(C(dppm)(2)-κ3P,C,P)]Cl (M = Pd, Pt) with hydrochloric acid results in protonation at the CDP carbon atom and the formation of the PCP pincer complexes [M(Cl)(CH(dppm)(2)-κ3P,C,P)]Cl(2) (M = Pd, Pt). The PCP pincer ligand [CH(dppm)(2)](+) involves a formally cationic central carbon donor. The reaction of [Ni(Cl)(C(dppm)(2)-κ3P,C,P)]Cl with HCl leads to the extrusion of NiCl(2) and formation of the diprotonated CDP compound [CH(2)(dppm)(2)]Cl(2), from which the monoprotonated conjugate base [CH(dppm)(2)]Cl is obtained upon addition of bases, such as NH(3). The crystal structures of [M(Cl)(C(dppm)(2)-κ3P,C,P)]Cl (M = Ni, Pd, Pt), [Ni(Cl)(C(dppm)(2)-κ3P,C,P)](2)[NiCl(4)], [M(Cl)(CH(dppm)(2)-κ3P,C,P)]Cl(2) (M = Pd, Pt) as well as [CH(2)(dppm)(2)]Cl(2) and [CH(dppm)(2)]Cl are presented. A comparison of the solid state structures reveals interesting features, e.g. infinite supramolecular networks mediated by C-H···Cl hydrogen bond interactions and an unexpected loss of molecular symmetry upon protonation in the complexes [M(CH(dppm)(2)-κ3P,C,P)(Cl)]Cl(2) (M = Pd, Pt) as a result of the flexible ligand backbone. Additionally the new compounds were characterized comprehensively in solution by multinuclear (31)P, (13)C and (1)H NMR spectroscopy: Several spectroscopic parameters show a striking variability in particular regarding the carbodiphosphorane functionality. Furthermore the compound [Ni(Cl)(C(dppm)(2)-κ3P,C,P)]Cl was examined by cyclic voltammetry (CV) and could be shown to display quasi-reversible oxidative as well as reductive behaviour.     

Benzylic C-H activation and C-O bond formation via aryl to benzylic 1,4-palladium migrations

A procedure for benzylic C-H activation has been developed using a palladium 1,4-aryl to benzylic migration as a key step. Carboxylates and phenoxides readily trap the resulting benzylic palladium intermediates obtained from palladium ‘through space’ migration. Aryl bromides and iodides have been successfully employed in this reaction, furnishing moderate to good yields. The mechanism of this reaction has been studied by deuterium-labeling experiments, which suggest that the migration of palladium from an aryl to a benzylic position occurs reversibly. The reaction conditions developed for the migration process also oxidize the neighboring benzylic alcohols to the corresponding aldehydes and ketones.     

Chiral-at-metal complexes and their catalytic applications in organic synthesis

This tutorial review provides an introduction to the synthesis and characterization of chiral-at-metal complexes and their catalytic application in organic transformations. The synthetic access to these architectures either via chiral resolution or by employment of chiral ligands is described, characterization techniques for the complexes are referenced and the application of the R/S nomenclature is explained. Racemization and epimerization processes are often observed for the title compounds; the article gives mechanistic insights to these processes and describes how to recognize and document them. Finally, key catalytic applications in organic synthesis are presented and how the molecular architectures of the chiral-at-metal complexes lead to stereodifferentiation and, thus to enantiomeric excesses in the products.     

One-dimensional nanostructures of metals: large-scale synthesis and some potential applications

We review recent developments in our group regarding the solution-phase synthesis of one-dimensional nanostructures of metals. The synthetic approaches include solution-liquid-solid growth for nanowires of low-melting-point metals such as Pb; seed-directed growth for Ag nanowires, nanobeams, and nanobelts; kinetically controlled growth for Pt nanorods, nanowires, and multipods; and galvanic replacement for nanotubes of Au, Pt, and Pd. Both characterization and mechanistic studies are presented for each nanostructure. Finally, we highlight the electrical and plasmonic properties of these metal nanostructures and discuss their potential applications in nanoscale devices.     

C-C bond formation via C-H bond activation: catalytic arylation and alkenylation of alkane segments

A new system for catalytic arylation and alkenylation of alkane segments has been developed. The ortho-tert-butylaniline substrates and 2-pivaloylpyridine may be arylated and alkenylated at the tert-butyl group, while no functionalization occurred at more reactive C-H and other bonds. Arylation and alkenylation of these substrates are achieved in the presence of Ph2Si(OH)Me and Ph-CH=CH-Si(OH)Me2, respectively, and the catalytic amount of Pd(OAc)2 and stoichiometric oxidant (Cu(OAc)2, 2 equiv) in DMF. In contrast, the ortho-i-propylaniline substrate underwent cyclopalladation, but no arylation product was obtained. Complex compound 14 was synthesized via tandem arylation-alkenylation of tert-butylaniline 11. We hypothesize that the high selectivity of this system stems from the confluence of directing effect of the Schiff base or pyridine moiety and unique reactivity properties of a phenyl-palladium acetate species (Ph-Pd-OAc.Ln).     

C-H bond activation by unsymmetrical 2-(N-arylimino)pyrrolide Pt complexes: geometric effects on reactivity

Reactions of chloroplatinum methyl complexes with N-(arylimino)pyrrolide anions afford cis and trans neutral platinum methyl complexes. Isomers with methyl trans to the pyrrolide nitrogen activate benzene C-H bonds at 85 degrees C more than 80 times faster than the corresponding cis isomer. In addition, reactions of platinum dimethyl complexes with N-(arylimino)pyrroles (Ar = 4-substituted phenyl) in C6D6 at ambient temperature give unlabeled methane and cis methyl complex containing heavily deuterated Pt-Me. In contrast, bulky aryl substituents give methane isotopomers and trans-Pt-Ph product. The origins of these observations are discussed.