Efficient and general protocol for the copper-free sonogashira coupling of aryl bromides at room temperature

[reaction: see text]. A mild and general protocol for the copper-free Sonogashira coupling of aryl bromides with acetylenes has been developed. The use of (AllylPdCl)2 and P(t-Bu)3 provides the active Pd(0) catalyst that allows subsequent coupling of various alkynes at room temperature with good to excellent yields.     

Homogeneous catalysts supported on soluble polymers: biphasic Sonogashira coupling of aryl halides and acetylenes using MeOPEG-bound phosphine-palladium catalysts for efficient catalyst recycling

The Sonogashira coupling of various aryl bromides and iodides with different acetylenes was studied under biphasic conditions with soluble, polymer-modified catalysts to allow the efficient recycling of the homogeneous catalyst. For this purpose, several sterically demanding and electron-rich phosphines of the type R(P)PR(2) were synthesised. They are covalently linked to a monomethyl polyethylene glycol ether with a mass of 2000 Dalton (R(P)=MeOPEG(2000)) R(P)PR(2): -PR(2)= -CH(2)C(6)H(4)CH(2)P(1-Ad)(2), -C(6)H(4)-P(1-Ad)(2), -C(6)H(4)-PPh(2). To couple aryl iodides and acetylenes, the catalyst [(MeCN)(2)PdCl(2)]/2 R(P)-C(6)H(4)-PPh(2) was used in CH(3)CN/Et(3)N/n-heptane (5/2/5). The combined yields of coupling product over five reaction cycles are between 80-95 percent. There is no apparent leaching of the catalyst into n-heptane, as evidenced by (1)H NMR spectroscopy. The new catalyst [(MeCN)(2)PdCl(2)]/2 (1-Ad)(2)PBn can be used for room-temperature coupling of various aryl bromides and acetylenes in THF with HNiPr(2) as a base. A closely related catalyst Na(2)[PdCl(4)]/2 R(P)-CH(2)C(6)H(4)CH(2)P(1-Ad)(2) linked to the polymer was used to couple aryl bromides and acetylenes in DMSO or DMSO/n-heptane at 60 degrees C with 0.5 mol percent Na(2)[PdCl(4)], 1 mol percent R(P)PR(2) and 0.33 mol percent CuI. The combined yield of coupling products over five cycles is always greater than 90 percent, except for sterically hindered aryl bromides. The determination of the turnover frequency (TOF) of the catalyst indicates only a small decrease in activity over five cycles. Leaching of the catalyst into the product containing n-heptane solution could not be detected by means of (1)H NMR and TXRF; this is indicative of >99.995 percent catalyst retention in the DMSO solvent.     

A very efficient,copper-free palladium catalyst for the Sonogashira reaction with aryl halides

The new complex [Pd[t-Bu2PCH2N(CH2Ph)CH2P t-Bu2](OAc)2] is a very efficient catalyst for the Sonogashira cross-coupling reaction of aryl halides with acetylenes at room temperature, without co-catalyst.     

Dialkylterphenyl Phosphine-Based Palladium Precatalysts for Efficient Aryl Amination of N-Nucleophiles

A series of 2-aminobiphenyl palladacycles supported by dialkylterphenyl phosphines, PR₂Ar′ (R=Me, Et, iPr, Cyp (cyclopentyl), Ar′=Ar^Dipp2, Ar^Xyl2f, Dipp (2,6-C6H3-(2,6-C6H3-(CHMe2)2)2), Xyl=xylyl) have been prepared and structurally characterized. Neutral palladacycles were obtained with less bulky terphenyl phosphines (i.e., Me and Et substituents) whereas the largest phosphines provided cationic palladacycles in which the phosphines adopted a bidentate hemilabile k¹-P,η¹-C_arene coordination mode. The influence of the ligand structure on the catalytic performance of these Pd precatalysts was evaluated in aryl amination reactions. Cationic complexes bearing the phosphines PiPr₂Ar^Xyl2 and PCyp₂Ar^Xyl2 were the most active of the series. These precatalysts have demonstrated a high versatility and efficiency in the coupling of a variety of nitrogen nucleophiles, including secondary amines, alkyl amines, anilines, and indoles, with electronically deactivated and ortho-substituted aryl chlorides at low catalyst loadings (0.25–0.75 mol % Pd) and without excess ligand.     

A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under mild conditions.

In the presence of Cy2NMe, Pd/P(t-Bu)3 serves as an exceptionally mild and versatile catalyst for Heck reactions of aryl chlorides and bromides. A sterically and electronically diverse array of aryl bromides, as well as activated aryl chlorides, couple with a range of mono- and disubstituted olefins at room temperature, furnishing the arylated product with high E/Z stereoselection. The corresponding reactions of a broad spectrum of electron-neutral and electron-rich aryl chlorides proceed at elevated temperature, also with high selectivity. In terms of scope and mildness, Pd/P(t-Bu)3/Cy2NMe represents an advance over previously reported catalysts for these Heck coupling processes.     

Pd(PhCN)(2)Cl(2)/P(t-Bu)(3): a versatile catalyst for Sonogashira reactions of aryl bromides at room temperature

[reaction: see text] Pd(PhCN)(2)Cl(2)/P(t-Bu)(3) serves as an efficient and a versatile catalyst for room-temperature Sonogashira reactions of aryl bromides.     

Unprecedented long-range 1,7-bromination in gold complexes of N-(aryl)imino functionalized N-heterocyclic carbenes

An unique long-range 1,7-bromination reaction is observed in gold(iii) complexes of N-(aryl)imino functionalized N-heterocyclic carbene with the bromination occurring at two different carbon (sp(2) and sp(3)) centers spatially separated by ca. 6.4 A but existing in extended conjugation to each other. In particular, the unusual distant 1,7-brominated gold(iii) complexes [1-R-3-{N-(p-bromo-2,6-di-i-propylphenylimino)-2-phenyl-1-bromoethyl}imidazol-2-ylidene]AuBr(3) [R = Me (), i-Pr (), t-Bu (), -CH(2)Ph ()] were synthesized cleanly at room temperature under ambient conditions from the reactions of molecular bromine with the gold(i) complexes [1-R-3-{N-(2,6-di-i-propylphenylimino)-2-phenylethyl}imidazol-2-ylidene]AuCl [R = Me (), i-Pr (), t-Bu (), -CH(2)Ph ()]. All of the 1,7-bromination products (, , and ) have been structurally verified by X-ray diffraction studies.     

Substituent effects on chloro meso-tetra-ortho-alkylphenylporphinato iron catalyzed biomimetic oxidation of cyclohexane

Six sterically hindered chloro meso-tetra-ortho-alkylphenylporphinato irons (T(o-R)PPFe(HI)Cl, R = Me, Et, n-Pr, i-Pr, n-Bu, t-Bu) were synthesized and used to catalyze the monooxygenation of cyclohexane with PhIO. Both the yields of cyclohexanol and the relative rates of monooxygenation of cyclohexane catalyzed by T(o-R)PPFe(III)Cl were higher than those of TPPFe(III)Cl respectively. The order of the yields(%) of cyclohexanol and the rate of cyclohexanol formation in the monooxygenation of cyclohexane catalyzed by T(o-R)PPFe(III)Cl for the different substituents are: i-Pr(58) > Et(57) > n-Pr(52) > Me(51) > n-Bu(48) > t-Bu(46) > H(35) and i-Pr > Et > t-Bu > n-Pr > Me > n-Bu > H respectively. The special steric effect on the catalytic character of these different alkyl substituents in T(o-R )PPFe(III)Cl is proposed on the basis of the results.     

Photo-activation of Pd-catalyzed Sonogashira coupling using a Ru/bipyridine complex as energy transfer agent

The mixed catalyst system, Pd(CH3CN)2Cl2/P(t-Bu)3/[Ru(2,2'-bipyridine)3].2PF6, promotes the copper-free Sonogashira coupling reaction of aryl bromides at room temperature under irradiation of visible light.     

9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water

The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst at 100 degrees C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in>95% yield.     

Synthesis of zirconium, hafnium, and tantalum complexes with sterically demanding hydrazide ligands

The bulky hydrazine t-BuN(H)NMe2 was synthesized via hydrazone and t-BuN(H)N(H)Me intermediates as the major component in a 90:5:5 mixture consisting of t-BuN(H)NMe2, t-BuN(Me)N(H)Me, and t-BuN(Me)NMe2. Reacting the mixture with n-BuLi followed by distillation and fractional crystallization led to the isolation of the ligand precursor LiN(t-Bu)NMe2. Lithium hydrazides, LiN(R)NMe2, were reacted with metal chlorides to afford the hydrazide complexes M(N(Et)NMe2)4 (M = Zr or Hf), MCl(N(R)NMe2)3 (M = Zr, R = i-Pr or t-Bu; M = Hf, R = t-Bu), and TaCl3(N(i-Pr)NMe2)2. The X-ray crystal structures of [LiN(i-Pr)NMe2]4, [LiN(t-Bu)NMe2.THF]2, ZrCl(N(R)NMe2)3 (R = i-Pr or t-Bu), and TaCl3(N(i-Pr)NMe2)2 were determined. The structural analyses revealed that the hydrazide ligands in ZrCl(N(R)NMe2)3 (R = i-Pr or t-Bu) and TaCl3(N(i-Pr)NMe2)2 are eta2 coordinated.     

Cp2Fe(PR2)2PdCl2 (R = i-Pr, t-Bu) complexes as air-stable catalysts for challenging Suzuki coupling reactions

[reaction: see text] The use of Cp(2)Fe(PR(2))(2)PdCl(2) (R = i-Pr and t-Bu) in Suzuki coupling reactions were illustrated using a high throughput screening approach. The di-tbpfPdCl(2) catalyst was shown to be the more active catalyst for unactivated and sterically challenging aryl chlorides. Comparison studies using the commercial catalysts dppfPdCl(2), (Ph(3)P)(2)PdCl(2), (Cy(3)P)(2)PdCl(2), DPEPhosPdCl(2), dppbPdCl(2), dppePdCl(2), Pd(t-Bu(3)P)(2), and [Pd(mu-Br)(t-Bu(3)P)](2) were also done for selected cases to demonstrate the superior activities of di-tbpfPdCl(2) and di-isoppfPdCl(2).     

Variable trends in R-X bond dissociation energies (R = Me, Et, i-Pr, t-Bu)

[structure: see text] High level ab initio molecular orbital calculations confirm experimental indications that the effect of alkyl substituents (R = Me, Et, i-Pr, t-Bu) on R-X bond dissociation energies varies considerably according to the nature of X. A simple qualitative explanation in terms of valence-bond theory is presented, highlighting the increasing importance of the stabilization of R-X by the ionic R(+)X(-) configuration for electronegative X substituents (such as F, OH, and OCH(3)).     

Thermodynamics of vinyl ethers—XXI: Evaluation of some cis interaction energies

Thermodynamics of isomerization reactions on some substituted vinyl methyl ethers have been studied for evaluating the magnitudes of the interaction energies S[R¹... R²] between the substituents R¹ and R², juxtaposed in a cis position across the CC bond of vinyl ethers. The results obtained are (values given in kJ mol^-1): S[Me... t-Bu]=18.2±1.0, S[Ph...i-Pr]=11±2, S[i-Pr...Et] =6.1±0.6, S[i-Pr... i-Pr] = 6.0 ± 0.6, S[0...t-Bu]=2.9±0.5, S[O...i-Pr]= -0.7±0.5, S[O...Et] = ?1.5±0.5, S[O...Ph]= ?2.1+-0.6, and S[O... Me] =?2.9 ±0.2 (the symbol O stands for the ethereal oxygen atom of vinyl ethers). The negative interaction energy values reveal that the cis interaction between the ethereal oxygen and the alkyl (aryl) group concerned is stabilizing.     

Arylbiphenylene atropisomers: structure, conformation, stereodynamics, and absolute configuration

Anti and syn conformers, due to restricted sp(2)-sp(2) bond rotation, were detected in hindered 1,8-diarylbiphenylenes, the aryl moieties being phenyl groups bearing 0micron-alkyl substituents such as Me, Et, i-Pr, and t-Bu. By means of low-temperature NOE experiments, the corresponding structures were assigned and were found to be in agreement with the results of single-crystal X-ray diffraction. The interconversion barriers of these conformers were determined by line-shape simulation of the variable-temperature NMR spectra and the experimental values were reproduced satisfactorily by DFT calculations. In the case of the bulkiest aryl substituent investigated (i.e., 2-methylnaphthalene), the syn and anti atropisomers were stable enough as to be separated at ambient temperature. The two enantiomers (M,M and P,P) of the isomer anti were also isolated by enantioselective HPLC, and the theoretical interpretation of the corresponding CD spectrum allowed the absolute configuration to be assigned.     

13C NMR Investigation of Si-alkylsubstituted 1,3,5-Trisilacyclohexanes

¹³C NMR spectra of Si-alkylsubstituted derivatives of 1,3,5-trisilacyclohexanes have been recorded and analyzed. A systematic preparation of alkyl derivatives with mixed substituents made it possible to evaluate substituent-induced chemical shift (SCS) values for the ring carbon atoms in β and δ position. It is found that the β_e effect decreases in the order Me > Et > i-Pr > t-Bu. For the alkyl groups Me, Et, and i-Pr the β_a effect is smaller than the β_e effect. Axial SCS values for the t-Bu group are not accessible because chair conformations with an axial t-Bu group are unfavourable and tend to escape into a twisted boat form. The observed δ effects are small and do not show any obvious tendencies.     

Substituent effects on the gas-phase ring-chain tautomerism of 3,4,5,6-tetrahydro-2H-1,3-oxazines

The electron ionization mass spectra of five series of seven 2-aryl,4-R-substituted (R = Me, Et, i-Pr, t-Bu or Ph) 3,4,5,6-tetrahydro-2H-1,3-oxazines were recorded at 14 and 70 eV in order to study the ring-chain tautomeric equilibria in the gas phase. Certain fragment ions were associated with the ring or with the open-chain forms of the compounds. As in chloroform solution, the electron-withdrawing effect of the aryl substituent (p-NO(2), m-Br, p-Cl, H, p-Me, p-OMe and p-NMe(2)) shifts the equilibrium towards the ring form. The correlation of ring-chain equilibria (log K = [ring]/[chain]) with the Hammett sigma+ constants of the aryl substituents was in general good or satisfactory although in some cases the p-NMe(2) did not fit these correlations.     

Elimination reactions of N-alkyl-N-chlorothenylamines promoted by MeONa-MeOH and Et(2)NH-MeCN. Effect of the beta-aryl group on the imine-forming transition state

Elimination reactions of N-alkyl-N-chlorothenylamines 1-4 with MeONa-MeOH and Et(2)NH-MeCN have been studied kinetically. The elimination reactions are regiospecific, producing only the conjugated imines. The reactions are second order and exhibit substantial values of Hammett rho and k(H)/k(D), and an E2 mechanism is evident. The relative rates of elimination for Me/Et/i-Pr/t-Bu substituents are 1/0.5/0.2/0.02 with MeONa-MeOH and 1/0.4/0.2/0.06 with Et(2)NH-MeCN. The transition state structure changes toward more product-like as the base is changed from MeONa-MeOH to Et(2)NH-MeCN. Comparison with existing data reveals that the structure of the transition state is relatively insensitive to the beta-aryl group variation.     

Copolymerization of ethylene with polar monomers: chain propagation and side reactions. A DFT theoretical study using zwitterionic Ni(II) and Pd(II) catalysts

Calculations utilizing anionic substituted derivates of the cationic N(wedge)N--Ni(II) and Pd(II) diimine Brookhart complex have been carried out on the barriers of ethylene and acrylonitrile insertion into a M- methyl, propyl and CH(CN)Et bond for M = Ni, Pd. The possibility of side reactions such as chelate formation with the polar functionality and oligomerization of the active species after acrylonitrile insertion are explored. The diimine ring system N--N = -NR' 'CR(1)CR(2)NR' ' with R' ' = 2,6-C(6)H(3)(i-Pr)(2) and R(1),R(2) = Me was functionalized by adding one or two anionic groups (BF(3)(-), etc.) in place of i-Pr on the aryl rings or by replacing one Me diimine backbone group (R(1)) with BH(3)(-). The objective of this investigation is computationally to design catalysts for ethylene/acrylonitrile copolymerization that have activities that are comparable to that of the cationic Ni(II) diimine or at least the Pd(II) diimine Brookhart system for ethylene homopolymerization. Complexes that might meet this objective are discussed.     

Pd/P(t-Bu)(3): a mild and general catalyst for Stille reactions of aryl chlorides and aryl bromides

Pd/P(t-Bu)(3) serves as an unusually reactive catalyst for Stille reactions of aryl chlorides and bromides, providing solutions to a number of long-standing challenges. An unprecedented array of aryl chlorides can be cross-coupled with a range of organotin reagents, including SnBu(4). Very hindered biaryls (e.g., tetra-ortho-substituted) can be synthesized, and aryl chlorides can be coupled in the presence of aryl triflates. The method is user-friendly, since a commercially available complex, Pd(P(t-Bu)(3))(2), is effective. Pd/P(t-Bu)(3) also functions as an active catalyst for Stille reactions of aryl bromides, furnishing the first general method for room-temperature cross-couplings.