Pd‐Catalyzed Carbonylative α‐Arylation of Aryl Bromides: Scope and Mechanistic Studies

Reaction conditions for the three‐component synthesis of aryl 1,3‐diketones are reported applying the palladium‐catalyzed carbonylative α‐arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)₂] (dba=dibenzylideneacetone) as the palladium source and 1,3‐bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two‐chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO‐releasing compound, 9‐methylfluorene‐9‐carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3‐diketones. A mechanistic investigation of this transformation relying on ³¹P and ¹³C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)₂] and DPPP was only reactive towards 4‐bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative‐addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3‐diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd⁰ precursor, [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)₂], its oxidative addition with 4‐bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α‐arylation of 4‐bromoanisole with either catalytic or stoichiometric [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)] over a short reaction time, led to the 1,3‐diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)₂] as the Pd source.     

Steric Effect of Carboxylate Ligands on Pd‐Catalyzed Intramolecular C(sp2)–H and C(sp3)–H Arylation Reactions

A bulky carboxylic acid bearing three cyclohexylmethyl substituents at the α‐position, namely, tri(cyclohexylmethyl)acetic acid, is demonstrated to act as an efficient ligand source in Pd‐catalyzed intramolecular C(sp²)?H and C(sp³)?H arylation reactions. The reactions proceed smoothly under mild reaction conditions, even at room temperature due to the steric bulk of the carboxylate ligands, which accelerates the rate‐determining C?H bond activation step in the catalytic cycle.     

Development of Chemo‐ and Enantioselective Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α‐Nitroesters

We describe the development of a Pd‐catalyzed decarboxylative asymmetric allylic alkylation of α‐nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo‐ and enantioselective C‐alkylation of electronically challenging benzylic nitronates and sterically encumbered 2‐allyl esters. Substrates were efficiently accessed in a combinatorial fashion by a cross‐Claisen/ α‐arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for α‐tertiary amine synthesis.     

Formal Gold‐to‐Gold Transmetalation of an Alkynyl Group Mediated by Palladium: A Bisalkynyl Gold Complex as a Ligand to Palladium

The reaction of [Au(C?C?n‐Bu)]_n with [Pd(η³‐allyl)Cl(PPh₃)] results in a ligand and alkynyl rearrangement, and leads to the heterometallic complex [Pd(η³‐allyl){Au(C?C?n‐Bu)₂}]₂ ( 3 ) with an unprecedented bridging bisalkynyl–gold ligand coordinated to palladium. This is a formal gold‐to‐gold transmetalation that occurs through reversible alkynyl transmetalations between gold and palladium.     

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide is described. In the reaction with allyl bromide, either a Pd(dba)₂? CuI combination (dba, dibenzylideneacetone) in DMF or copper(I) iodide in DMSO–THF readily catalyzes or mediates the coupling reaction of (Z)‐silyl(stannyl)ethenes at room temperature, producing novel vinylsilanes bearing an allyl group β to silicon with cis ‐disposition in good yields. Allyl chlorides as halides can be used in the CuI‐mediated reaction. CuI alone much more effectively mediates the cross‐coupling reaction with propargyl bromide in DMSO–THF at room temperature compared with a Pd(dba)₂? CuI combination catalysis in DMF, providing novel stereodefined vinylsilanes bearing an allenyl group β to silicon with cis ‐disposition in good yields. Copyright © 2008 John Wiley & Sons, Ltd.     

Redox‐Neutral α‐Allylation of Amines by Combining Palladium Catalysis and Visible‐Light Photoredox Catalysis

An unprecedented α‐allylation of amines was achieved by combining palladium catalysis and visible‐light photoredox catalysis. In this dual catalysis process, the catalytic generation of allyl radical from the corresponding π‐allylpalladium intermediate was achieved without additional metal reducing reagents (redox‐neutral). Various allylation products of amines were obtained in high yields through radical cross‐coupling under mild reaction conditions. Moreover, the transformation was applied to the formal synthesis of 8‐oxoprotoberberine derivatives which show potential anticancer properties.     

Palladium‐Catalyzed CH Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

A new mode of activation of an imine via a rare aza‐substituted π‐allyl complex is described. Palladium‐catalyzed C(sp³)? H activation of the N‐allyl imine and the subsequent nucleophilic attack by the α‐alkyl cyanoester produced the 1‐aza‐1,3‐diene as the sole regioisomer. In contrast, nucleophilic attack by the α‐aryl cyanoester exclusively delivered the 2‐aza‐1,3‐diene, which was employed in an inverse‐electron‐demand Diels–Alder reaction for heterobiaryl synthesis.     

Short communication: An alternative and effective catalyst in the stereo‐specific reaction of Z‐1‐aryl‐1‐stannyl‐2‐silylethenes with allyl bromide

The Pd(dba)₂‐catalyzed reaction of Z‐1‐aryl‐1‐(tributylstannyl)‐2‐(trimethylsilyl)ethenes with allyl bromide in the presence of copper(I) iodide is reported for the first time. The reaction in the presence of 0.5 mol% Pd(dba)₂ and 8 mol% CuI in dimethylformamide takes place at room temperature to give E‐2‐aryl‐1‐(trimethylsilyl)penta‐1,4‐dienes exclusively in isolated yields of 62–99%. A putative reaction mechanism is proposed. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis,Reactivity and Crystal Structures of the Palladium(II) Complexes with the Pyrimidine Containing Ligand: Crystal Structures of [Pd(PPh3)(η1‐C4H3N2)(η2‐S2CNC4H8)] and [Pd(PPh3)(η1‐C4H3N2)(η2‐Tp)]

Treatment of Pd(PPh₃)₄ with 5‐bromo‐pyrimidine [C₄H₃N₂Br] in dichloromethane at ambient temperature cause the oxidative addition reaction to produce the palladium complex [Pd(PPh₃)₂(η¹‐C₄H₃N₂)(Br)], 1 , by substituting two triphenylphosphine ligands. In acetonitrile solution of 1 in refluxing temperature for 1 day, it do not undergo displacement of the triphenylphosphine ligand to form the dipalladium complex [Pd(PPh₃)Br]₂{μ,η²‐(η¹‐C₄H₃N₂)}₂, or bromide ligand to form chelating pyrimidine complex [Pd(PPh₃)₂(η²‐C₄H₃N₂)]Br. Complex 1 reacted with bidentate ligand, NH₄S₂CNC₄H₈, and tridentate ligand, KTp {Tp = tris(pyrazoyl‐1‐yl)borate}, to obtain the η²‐dithiocarbamate η¹‐pyrimidine complex [Pd(PPh₃)(η¹‐C₄H₃N₂)(η²‐S₂CNC₄H₈)], 4 and η²‐Tp η¹‐pyrimidine complex [Pd(PPh₃)(η¹‐C₄H₃N₂)(η²‐Tp)], 5 , respectively. Complexes 4 and 5 are characterized by X‐ray diffraction analyses.     

Regioselective CF Bond Activation of Hexafluoropropylene on Palladium(0): Formation of a Cationic η2‐Perfluoroallylpalladium Complex

A chemoselective C(sp²)? F or C(sp³)? F bond activation of hexafluoropropylene (HFP) was achieved by adopting the proper combination of a Lewis acid co‐additive with a ligand which coordinates Pd⁰. The treatment of [(η²‐HFP)Pd(PCy₃)₂] with B(C₆F₅)₃ allowed a chemoselective C(sp³)? F bond cleavage of HFP to give a unique cationic perfluoroallypalladium complex. In this complex, the coordination mode of the perfluoroallyl ligand was considered to be of the unique η²‐fashion.     

Pd‐Catalyzed Reaction of Allyl Carbonate with Polyols: The Role of CO2 in Transesterification versus Etherification of Glycerol

An intermolecular Pd/PPh₃‐catalyzed transesterification of diallyl carbonate with glycerol to generate glycerol carbonate has been developed. Analysis of the reaction kinetics in THF indicates a first‐order dependence on Pd and diallyl carbonate, that the Pd bears two phosphines during the turnover limiting event, and that increasing the glycerol concentration inhibits reaction, possibly via change in the polarity of the medium. ¹³C isotopic labeling studies demonstrate that the Pd‐catalyzed transesterification requires at least one allyl carbonate moiety and that there is rapid equilibrium of the allyl carbonate with CO₂ in solution, even when present only at low concentrations. A mechanism that is consistent with these results involves oxidative addition of the allyl carbonate to Pd followed by reversible decarboxylation, with the intermediate η¹‐ and η³‐allyl Pd alkoxides mediating direct and indirect transesterification reactions with the glycerol. Using this model, successful simulations of the kinetics of reactions conducted under atmospheres of N₂ or CO₂ could be achieved, including switching in selectivity between etherification and transesterification in the early stages of reaction. Reactions with the higher polyols threitol and erythritol are also efficient, generating the terminal (1,2) monocarbonates with high selectivity.     

C‐Selective and Diastereoselective Alkyl Addition to β,γ‐Alkynyl‐α‐imino Esters with Zinc(II)ate Complexes

Since umpolung α‐imino esters contain three electrophilic centers, regioselective alkyl addition with traditional organometallic reagents has been a serious problem in the practical synthesis of versatile chiral α‐amino acid derivatives. An unusual C‐alkyl addition to α‐imino esters using a Grignard reagent (RMgX)‐derived zinc(II)ate was developed. Zinc(II)ate complexes consist of a Lewis acidic [MgX]⁺ moiety, a nucleophilic [R₃Zn]^? moiety, and 2 [MgX₂]. Therefore, the ionically separated [R₃Zn]^? selectively attacks the imino carbon atom ,which is most strongly activated by chelation of [MgX]⁺. In particular, chiral β,γ‐alkynyl‐α‐imino esters can strongly promote highly regio‐ and diastereoselective C‐alkylation because of structural considerations, and the corresponding optically active α‐quaternary amino acid derivatives are obtained within 5 minutes in high to excellent yields.     

Ligand‐Promoted C(sp3)−H Olefination en Route to Multi‐functionalized Pyrazoles

A Pd‐catalyzed/N‐heterocycle‐directed C(sp³)?H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd‐catalyzed C(sp³)?H olefination for the first time. Cu(OAc)₂ instead of Ag⁺ salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.     

Conversion of iminoacyl quinolinylpalladium (II) complexes into novel oxo‐pyrrolo[3,4‐b] quinolines via depalladation reactions

Oxidative addition reactions of quinolines 1a , b with Pd(dba)₂ in the presence of PPh₃ (1:2) in acetone gave dinuclear palladium complexes [Pd(C,N‐2‐C₉ H₄N‐CHO‐3‐R‐6)Cl(PPh₃)]₂ [(R = H ( 2a ), R = OMe ( 2b ), which were reacted with isocyanide XyNC (Xy = 2,6‐Me₂C₆H₃) to give novel iminoacyl quinolinylpalladium complexes 3a , b in good yields (81 and 77%). Cyclopalladated complexes 3a , b were also obtained in low yields (39 and 33.5%) via one‐pot reaction of 1a , b with isonitrile XyNC:Pd(dba)₂ (4:1). The reaction of 3a , b with Tl(TfO) (TfO = triflate, CF₃SO₃) in the presence of H₂O or EtOH causes depalladation reactions of complexes to provide the corresponding organic compounds 4a , b , 5a , b and 6a , b in yields of 41, 27 and 18 ? 19%, respectively. The products were characterized by satisfactory elemental analyses and spectral studies (IR, ¹H, ¹³C and ³¹P NMR). The crystal structures 2a , 3a and 3b were determined by X‐ray diffraction studies. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of (−)‐Erythrodiene and (+)‐7‐Epispirojatamol via Intramolecular Pd‐Catalyzed Allylzincation

Two spirobicyclic sesquiterpenoids, (−)‐erythrodiene ( 1 ) and (+)‐7‐epispirojatamol ( 30 ), were synthesized in enantiomerically pure form via an intramolecular allylzincation process. The allylzinc species were formed in the presence of Et₂Zn via transmetallation of a catalytically generated allylpalladium intermediate. Several Pd catalysts were tested for this transformation, and [Pd(OAc)₂]/Bu₃P (1 equiv.) was found to be, by far, the most effective. Whereas the preparation of 1 involved allylzincation of a tethered terminal olefin, 30 was formed via a novel intramolecular allyl zincation of a methyl ketone. Both reactions showed the same stereochemical preference, yielding the spirobicyclic products in 95 : 5 and 4 : 1 diastereoisomer ratios, respectively.     

The first stereospecific arylation of (Z)‐germyl(stannyl)ethenes with an aryl halide or heteroaryl halide under palladium‐catalysis

A combination catalyst of Pd(dba)₂‐PPh₃‐CuI‐LiCl or Pd(dba)₂‐P(2‐furyl)₃‐CuI‐LiCl effectively catalyzed the cross‐coupling of (Z)‐germyl(stannyl)ethenes with aryl halides, providing novel triethyl(2,2‐diarylethenyl)germanes in good to high yields. The reaction proceeds with retention of configuration. Cross‐coupling results in the formation of phenylene or phenyleneethynylene derivatives with terminal stereochemically defined vinylgermane unit(s). Copyright © 2008 John Wiley & Sons, Ltd.     

C(sp3)H Activation without a Directing Group: Regioselective Synthesis of N‐Ylide or N‐Heterocyclic Carbene Complexes Controlled by the Choice of Metal and Ligand

N‐Ylide complexes of Ir have been generated by C(sp³)?H activation of α‐pyridinium or α‐imidazolium esters in reactions with [Cp*IrCl₂]₂ and NaOAc. These reactions are rare examples of C(sp³)?H activation without a covalent directing group, which—even more unusually—occur α to a carbonyl group. For the reaction of the α‐imidazolium ester [ 3 H]Cl, the site selectivity of C?H activation could be controlled by the choice of metal and ligand: with [Cp*IrCl₂]₂ and NaOAc, C(sp³)?H activation gave the N‐ylide complex 4 ; in contrast, with Ag₂O followed by [Cp*IrCl₂]₂, C(sp²)?H activation gave the N‐heterocyclic carbene complex 5 . DFT calculations revealed that the N‐ylide complex 4 was the kinetic product of an ambiphilic C?H activation. Examination of the computed transition state for the reaction to give 4 indicated that unlike in related reactions, the acetate ligand appears to play the dominant role in C?H bond cleavage.     

Unusual selective allylation of norbornadiene in the presence of palladium nanoclusters

The reaction of norbornadiene (NBD) with allyl acetate in the presence of the nanocluster Pd₁₄₇phen₃₂O₆₀(OCOBu^t)₃₀ (Pd-147; phen is 1,10-phenanthroline) and PPh₃ in acetonitrile is nonselective and is accompanied by the decomposition of the cluster, affording the same allylation products of NBD as the reaction with Pd₃(OAc)₆ or Pd(dba)₂ (dba is dibenzylideneacetone) combined with PPh₃. In contrast, in the ionic liquid [bmim][BF₄] (bmim is 1-butyl-3-methylimidazolinium), the Pd-147 is not decomposed and the reaction occurs selectively to give methylidene(vinyl)norbornene as the sole product. The data obtained suggest that in an ionic liquid, the reaction under study is catalyzed by the nanocluster Pd-147 rather than by the products of its decomposition.     

The Nitrogen‐Assisted Triphenylphosphine Displacement of 3‐Hydroxypyridine and 3‐Aminopyridine Ligands in Palladium(II) Complexes: Crystal Structures of [Pd(PPh3)Br]2{μ,η2‐C5H3N(OH)}2 and [Pd(PPh3)Br]2{μ,η2‐C5H3N(NH2)}2

Treatment of Pd(PPh₃₎₄ with 2‐bromo‐3‐hydroxypyridine [C₅H₃N(OH)Br] and 3‐amino‐2‐bromopyridine [C₅H₃N(NH₂)Br] in dichloromethane at ambient temperature cause the oxidative addition reaction to produce the palladium complex [Pd(PPh₃₎₂{η¹‐C₅H₃N(OH)}(Br)], 2 and [Pd(PPh₃₎₂{η¹‐C₅H₃N(NH₂)}(Br)], 3 , by substituting two triphenylphosphine ligands, respectively. In dichloromethane solution of complexes 2 and 3 at ambient temperature for 3 days, it undergo displacement of the triphenylphosphine ligand to form the dipalladium complexes [Pd(PPh₃)Br]₂{μ,η²‐C₅H₃N(OH)}₂, 4 and [Pd(PPh₃)Br]₂{μ,η²‐C₅H₃N(NH₂)}₂, 5 , in which the two 3‐hydroxypyridine and 3‐aminopyridine ligands coordinated through carbon to one metal center and bridging the other metal through nitrogen atom, respectively. Complexes 4 and 5 are characterized by X‐ray diffraction analyses.     

Cationic palladium complex‐catalyzed carbonylation of 2,3‐dien‐1‐ols to 1,3‐diene‐2‐carboxylic acids and esters under mild conditions

A cationic palladium complex, [Pd(PPh₃)₂(MeCN)₂](BF₄)₂, catalyzed the carbonylation of 2,3‐dien‐1‐ols under mild conditions. The dienols bearing two or more alkyl substituents on the diene part afforded 1,3‐diene‐2‐carboxylic acids successfully in tetrahydrofuran (THF), while those possessing one or no alkyl substituent gave polymers of the products exclusively. The former afforded the corresponding methyl esters in good yields when the reactions were carried out in methanol, while the latter afforded mainly the Diels–Alder reaction products of the resulting esters. An alkylidene group‐substituted π‐allylpalladium species has been presumed to be an intermediate. Copyright © 2000 John Wiley & Sons, Ltd.