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A method is presented for the high-throughput monitoring of reaction kinetics in homogeneous catalysis, running up to 25 coupling reactions in a single reaction vessel. This method is demonstrated and validated on the Sonogashira reaction, analyzing the kinetics for almost 500 coupling reactions. First, one-pot reactions of phenylacetylene with a set of 20 different meta- and para-substituted aryl bromides were analyzed in the presence of 17 different Pd-phosphine complexes. In addition, the temperature-dependent Sonogashira reactions were examined for 21 different ArX (X=Cl, Br, I) substrates, and the corresponding activation enthalpies and entropies were determined by means of Eyring plots: ArI (DeltaH(not equal)=48-62 kJ mol(-1); DeltaS(not equal)=-71--39 J mol(-1) K; NO(2)-->OMe), ArBr (DeltaH(not equal)=54-82 kJ mol(-1), DeltaS(not equal)=-55-11 J mol(-1) K), and ArCl (DeltaH(not equal)=95-144 kJ mol(-1), DeltaS(not equal)=-6-100 J mol(-1) K). DFT calculations established a linear correlation of DeltaH( not equal) and the Kohn-Sham HOMO energies of ArX (X=Cl, Br, I) and confirmed their involvement in the rate-limiting step. However, despite different C--X bond energies, aryl iodides and electron-deficient aryl bromides showed similar activation parameters.

The electron-donating properties of eighteen N-heterocyclic carbenes (N,N'-bis(2,6-dimethylphenyl)imidazol)-2-ylidene and the respective dihydro ligands) with 4,4'-R substituted aryl rings (4,4'-R = NEt2, OMe, Me, H, SMe, F, Cl, Br, I) in the respective Grubbs II complexes were studied using electrochemical techniques. The nature of the 4-R substituent has a strong influence on the RuII/III redox potentials ranging between DeltaE1/2= +0.196 and +0.532 V. Three unsymmetrical Grubbs II complexes with 4-R not equal to 4-R' were also synthesized. Dynamic NMR spectroscopy revealed the restricted rotation around the (NHC)C-Ru bond (DeltaG = 89 kJ mol(-1) at 333 K) resulting in two atropisomers, respectively, with an isomer ratio close to unity. Each of the isomers, that is the two orientations of the 4-R/4-R' substituted mesityl ring with respect to the R=CHPh unit, gives rise to different redox potentials (4-R = NEt2, 4-R' = Br: DeltaE1/2= +0.232 and +0.451 V). In the oxidized Grubbs II complex (4-R = NEt2, H) and in the cathodic isomer the electron rich aryl ring is located above the Ru=CHPh unit. This orientational effect provides clear evidence for strong pi-pi through-space interactions in the RuIII complexes, assuming that the alternative through-bond transfer of electron density is equally efficient in both isomers.

A dicyclohexyl(2-sulfo-9-(3-(4-sulfophenyl)propyl)-9H-fluoren-9-yl)phosphonium salt was synthesized in 64% overall yield in three steps from simple commercially available starting materials. The highly water-soluble catalyst obtained from the corresponding phosphine and [Na(2)PdCl(4)] enabled the Suzuki coupling of a broad variety of N- and S-heterocyclic substrates. Chloropyridines (-quinolines) and aryl chlorides were coupled with aryl-, pyridine- or indoleboronic acids in quantitative yields in water/n-butanol solvent mixtures in the presence of 0.005-0.05 mol % of Pd catalyst at 100 degrees C, chloropurines were quantitatively Suzuki coupled in the presence of 0.5 mol % of catalyst, and S-heterocyclic aryl chlorides and aryl- or 3-pyridylboronic acids required 0.01-0.05 mol % Pd catalyst for full conversion. The key to the high activity of the Pd-phosphine catalyst is the rational design of the reaction parameters (i.e., the presence of water in the reaction mixture, good solubility of reactants and catalyst in n-butanol/water (3:1), and the electron-rich and sterically demanding nature of the phosphine ligand).

The electron-donating properties of N-heterocyclic carbenes ([N,N'-bis(2,6-dimethylphenyl)imidazol]-2-ylidene and the respective dihydro ligands) with 4,4'-R-substituted aryl rings (4,4'-R=NEt2, OC(12)H(25), Me, H, Br, S(4-tolyl), SO(4-tolyl), SO2(4-tolyl)) were studied. Twelve new N-heterocyclic carbene (NHC) ligands were synthesized as well as the respective iridium complexes [IrCl(cod)(NHC)] and [IrCl(CO)2(NHC)]. Cyclic voltammetry (DeltaE1/2) and IR (nu (CO)) can be used to measure the electron-donating properties of the carbene ligands. Modifying the 4-positions with electron-withdrawing substituents (4-R=-SO(2)Ar, DeltaE1/2=+0.92 V) results in NHC ligands with virtually the same electron-donating capacity as a trialkylphosphine in [IrCl(cod)(PCy3)] (DeltaE1/2 =+0.95 V), while [IrCl(cod)(NHC)] complexes with 4-R=NEt2 (DeltaE1/2= +0.59 V) show drastically more cathodic redox potentials and significantly enhanced donating properties.

The donor properties of aryl substituted N-heterocyclic carbenes are characterized by lone pair donation from the carbene carbon and, as is shown here, by donation of electron density of the aromatic pi-face of the NHC aryl groups towards the metal.

The Suzuki-Miyaura coupling of aryl chlorides and PhB(OH)(2) under biphasic conditions (DMSO/heptane) can be performed in almost quantitative yields over several cycles by means of polymeric Pd catalysts with soluble polyethylene glycol phase tags. Three sterically demanding and electron-rich phosphines 1-CH(2)Br,4-CH(2)P(1-Ad)(2)-C(6)H(4), and 2-PCy(2),2'-OH-biphenyl, and 2-PtBu(2),2'-OH-biphenyl were covalently bonded to 2000 Dalton MeOPEG-OH. The catalysts, which were formed in situ from Na(2)[PdCl(4)], the respective polymeric phosphine, KF/K(3)PO(4), and PhB(OH)(2), efficiently couple aryl chlorides at 80 degrees C at 0.5 mol % loading, resulting in a >90 % yield of the respective biphenyl derivatives. The use of polar phase tags allows the efficient recovery of palladium-phosphine catalysts by simple phase separation of the catalyst-containing DMSO solution and the product-containing n-heptane phase. The high activity (TOF) of the catalyst remains almost constant over more than five reaction cycles, which involve the catalytic reaction, separation of the product phase from the catalyst phase, and addition of new reactants to initiate the next cycle. The Buchwald type biphenyl phosphines form the most active Pd catalysts, which are 1.3-2.8 times more active than catalysts derived from diadamantyl-benzylphosphine, but appear to be less robust in the recycling experiments. There is no apparent leaching of the catalyst into the heptane solution (<0.05 %), as evidenced by spectrophotometric measurements, and contamination of the product with Pd is avoided.

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.

The availability of sodium ions can be regulated indirectly (through electron transfer reactions) and reversibly through the addition and removal of zinc ions. In this cyclic process (depicted on the right) a redox-responsive ferrocene substituted with two dipicolylamino ligands (Fcdpa) coordinates two Zn 2+ ions, while a redox-switchable ferrocene cryptand (Fccrypt) only forms stable complexes with Na + when the ligand is in its reduced form. L is a strong ligand such as 1,4,8,11-tetraazacyclotetradecane., (© 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)

The reactions of 1,3-bis(bromomethyl)-2-fluorobenzene with the bis(trifluoroacetamides) of 1,3-bis(aminomethyl)-2-fluorobenzene and 1,3-bis(aminomethyl)benzene yield the respective 1+1-condensed [3.3]-m-cyclophanes, respectively termed F(2)-phane (yield 39%) and HF-phane (yield 48%) without trifluoroacetamide groups. The reactions of F(2)-phane with 1,8-diiodo-3,6-dioxaoctane and 1,11-diiodo-3,6,9-trioxaundecane result in the respective 1+1-addition products 1,10-diaza-25,26-difluoro-4,7-dioxatetracyclo[8.7.7.1(12,16).1(19,23)]hexaeicosa-12,14,16(25),19,21,23(26)-hexene (= F(2)-[2.1.1]-cryptand) (yield 5%) and 1,13-diaza-28,29-difluoro-4,7,10-trioxatetracyclo[11.7.7.1(15,19).1(22,26)]nonaeicosa-15,17,19(28),22,24,26(29)-hexene (= F(2)-[3.1.1]-cryptand) (yield 39%). Analogous reactions of the HF-phane give the related macrocycles HF-[2.1.1]-cryptand (yield 68%) and HF-[3.1.1]-cryptand (yield 76%). The coordination of alkali and alkaline earth metal ions by these fluorophane cryptands results in significant shifts of the (19)F NMR resonances: F(2)-[2.1.1]-cryptand, delta -100.70 ppm; its Li(+) complex, delta -129.23 ppm. The (1)J(CF) coupling constant for such complexes is correlated with the degree of interaction between CF units and metal ions, and the most pronounced decrease (262 Hz to 232 Hz) is found for the lithium complex of the F(2)-[2.1.1]-cryptand. Competition experiments show the difluoro F(2)-[3.1.1]-cryptand to form significantly stronger complexes with Na(+) than the monofluoro HF-[3.1.1]-cryptand. In the crystal structure of F(2)-[2.1.1]-cryptand.NaCF(3)SO(3), the sodium ion displays an unusual F(2)O(4)N coordination sphere with extremely short sodium-fluorine distances: CF.Na(+) = 229.8(3), 235.7(4) pm; O-Na(+) = 228.5(4), 242.0(4), 243.8(4), 247.6(4) pm; N-Na(+) = 285.1(7) pm. In the closely related crystal structure of HF-[3.1.1]-cryptand.NaClO(4), the metal has an FO(5)N coordination sphere: CF.Na(+) = 236.0(4) pm; O-Na(+) = 234.8(6), 239.3(6), 240.3(12), 240.6(6), 285.7(17) pm; N-Na(+) = 272.3(6) pm. In the crystal structure of F(2)-[3.1.1]-cryptand.HCF(3)SO(3), the proton is in a pseudotetrahedral environment: N-H = 84 pm; O.HN = (216 pm; CF.HN = 224, 236 pm. This, however, is not considered indicative of significant CF.HN hydrogen bonding.