Rapid methylation on carbon frameworks useful for the synthesis of 11CH3-incorporated PET tracers: Pd(0)-mediated rapid coupling of methyl iodide with an alkenyltributylstannane leading to a 1-methylalkene

The Pd(0)-mediated rapid coupling of methyl iodide with an excess of alkenyltributylstannane was examined with the aim of incorporating a short-lived 11C-labeled methyl group into a biologically significant organic compound with a 1-methylalkene unit for the synthesis of a PET tracer. Four sets of reaction conditions (A-D) were used, all performed in DMF at 60 degrees C for 5 min. Condition B, using CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuCl/K2CO3 (1:40:0.5:4-6:2:5), works well in almost all cases. Condition D, using CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuX (X = Br, Cl, or I)/CsF (1:40:0.5-5:2-20:2-20:5-50), shows the best results with regard to general applicability to tin substrates, affording the corresponding methylated product in >90% yield based on consumption of methyl iodide. P(t-Bu)2Me was less effective than P(o-tolyl)3, particularly for alpha,beta-unsaturated carbonyl substrates. No regio- or stereoisomerization occurred under these reaction conditions. The efficiency of the protocol was demonstrated by synthesis of an 11C-methylated compound.     

Suzuki-Miyaura coupling reaction using pentafluorophenylboronic acid

[reaction: see text] We have found new conditions for the Suzuki-Miyaura coupling reaction applicable to pentafluorophenylboronic acid (C(6)F(5)B(OH)(2)) (1), which is an inactive substrate under normal conditions. The reactions of 1 with phenyl iodide or bromide under Pd(PPh(3))(4)/CsF/Ag(2)O or Pd(2)(dba)(3)/P(t-Bu)(3)/CsF/Ag(2)O catalytic system conditions gave 2,3,4,5,6-pentafluoro-1,1'-biphenyl (3a) in more than 90% yields. Combination of CsF and Ag(2)O was essential for promoting these reactions.     

Pd0‐Mediated Rapid Coupling between Methyl Iodide and Heteroarylstannanes: An Efficient and General Method for the Incorporation of a Positron‐Emitting 11C Radionuclide into Heteroaromatic Frameworks

The Pd⁰‐mediated rapid trapping of methyl iodide with an excess amount of a heteroaryl‐substituted tributylstannane has been investigated with the aim of incorporating a short‐lived ¹¹C‐labelled methyl group into the heteroaromatic carbon frameworks of important organic compounds, such as drugs with various heteroaromatic structures, in order to execute a positron emission tomography (PET) study of vital systems. The reaction was first performed by using our previously developed CH₃I/stannane/[Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuCl/K₂CO₃ (1:40:0.5:2:2:2) system in DMF at 60 °C for 5 min (conditions A), however, the reaction gave low yields for various heteroaromatic compounds. Increasing the amount of phosphine ligand (conditions B) led to a significant improvement in the yield, but the conditions were still not suitable for a range of basic heteroaromatic structures. Use of the CuBr/CsF system (conditions C) also provided a result similar to that obtained under conditions B with an increased amount of the phosphine. Thus, pyridine and related heteroaromatic compounds remained less reactive substrates. The problem was overcome by replacing the DMF solvent with N‐methyl‐2‐pyrolidinone (NMP). The reaction in NMP at 60–100 °C for 5 min using a CH₃I/stannane/[Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuBr/CsF (1:40:0.5:16:2:5) combination (conditions D) gave the methylated products in yields of more than 80 % (based on the reaction of CH₃I) for all of the heteroaromatic compounds listed in this study. Thus, the combined use of NMP and an increased amount of phosphine is important for promoting the reaction efficiently. The use of this general approach to rapid methylation has been well demonstrated by the synthesis of the PET tracers 2‐ and 3‐[¹¹C]methylpyridines by using [Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuBr/CsF (1:16:2:5) in NMP at 60 °C for 5 min, which gives the desired products in HPLC analytical yields of 88 and 91 %, respectively.     

Synthesis and properties of palladium diselenolenes: X-ray crystal structures of [Pd[SeC(R(1))=C(R(2))Se](PBu(3))(2)] [R(1), R(2) = (CH(2))(n), n = 4, 5, 6

The reaction between [Pd(2)(dba)(3)] (dba = dibenzylideneacetone), tributylphosphine, and a bis(cycloalkeno)-1,4-diselenin leads to either a mononuclear diselenolene [Pd[SeC(R(1))=C(R(2))Se](PBu(3))(2)] or a dinuclear diselenolene [Pd(2)[SeC(R(1))=C(R(2))Se](2)(PBu(3))(2)] [R(1), R(2) = (CH(2))(n), n = 4, 5, 6] depending on the stoichiometry employed. Treatment of the dinuclear diselenolenes with 1,2-bis(diphenylphosphino)ethane (dppe) provides a high-yielding route to the mononuclear species [Pd[SeC(R(1))=C(R(2))Se](dppe)]. All new compounds have been characterized by standard spectroscopic and analytical techniques, in particular by multinuclear NMR spectroscopy; the structure of each of the mononuclear tributylphosphine complexes has been determined by X-ray crystallography. Computational studies show that the observed asymmetry of the diselenolenes in the solid state is a result primarily of intramolecular repulsive interactions between the ligands.     

Synthesis of conformationally stable 1,8-diarylnaphthalenes: development of new photoluminescent sensors for ion-selective recognition

Highly constrained 1,8-diarylnaphthalenes exhibiting stability to isomerization have been prepared utilizing two consecutive CuO-promoted Stille cross-couplings of 1,8-dibromonaphthalene and 4-alkyl-9-trimethylstannylacridines. Screening of Pd catalysts Pd(PPh(3))(4), PdCl(2)dppf, or Pd(2)(dba)(3)/t-Bu(3)P and bases such as Cy(2)NMe, t-BuOK, K(3)PO(4), and Cs(2)CO(3) in DME or DMF revealed superior results of Stille over Suzuki coupling with acridylboronic acids or pinacolate derivatives. The meso syn- and C(2)-symmetric anti-isomers of 1,8-bis(4,4'-dimethyl-9,9'-diacridyl)naphthalene, 2, and 1,8-bis(4,4'-diisopropyl-9,9'-diacridyl)naphthalene, 3, did not show any sign of syn/anti-interconversion after heating to 180 degrees C for 24 h. Using the Eyring equation, we calculated the Gibbs standard activation energy for isomerization, DeltaG degrees (), to be higher than 180 kJ/mol. PM3 calculations of 2 and 3 suggest a highly congested structure exhibiting two parallel acridyl moieties perpendicular to the naphthalene ring. UV and fluorescence spectroscopy studies of 2 and 3 revealed remarkable quantum yields of these blue and green light emitters. Fluorescence titration experiments with the syn-isomer of 2 showed highly efficient quenching by Cu(II) ions, whereas almost no quenching effects were observed with Cu(I) and Zn(II) salts. The striking difference in fluorescence quenching was attributed to significant photoinduced electron transfer, resulting in nonradiative relaxation of excited Cu(II)-syn-2. Stern-V?lmer plots of syn-2 in the presence of CuCl(2) showed a sigmoidal quenching curve indicating cooperative recognition, whereas a linear response was observed with CuCl and ZnCl(2). Fluorescence experiments in the presence of various amounts of CuCl, CuBr, and Cu(ACN)(4)BF(4) proved that the quenching is cation selective and independent of the nature of counteranions.     

Palladium-Catalyzed Synthesis of 1,3-Dienes from Allenes and Organic Halides

A wide range of aryl and vinylic halides react with 1,1-dimethylallene (2a) and potassium carbonate in the presence of Pd(dba)(2) (dba = dibenzylideneacetone) in N,N-dimethylacetamide (DMA) at temperature 100-120 degrees C to give the corresponding dienes CH(2)C(CH(3))CRCH(2) (3a-o), where R is aryl or vinylic, in good to excellent yields. Higher yields of diene products were obtained for aryl bromides than for the corresponding aryl iodides and chlorides. Under similar reaction conditions, tetramethylallene (2b), 1-methyl-1-phenylallene (2c), 1-methyl-3-phenylallene (2d), and 1-cyclohexylallene (2e) also react with aryl and vinylic halides to give diene products (3p-w). For 2d, both E and Z isomers 3t and 3u of the diene product were observed. For 2e, two regioisomers 3vand 3w were isolated with 3w likely from alkene isomerization of 3v. Various palladium systems were tested for the catalytic activity of diene formation. In addition to Pd(dba)(2)/PPh(3), Pd(OAc)(2)/PPh(3), PdCl(2)(PPh(3))(2), and PdCl(2)(dppe) are also very effective as catalysts for the reaction of 2a with p-bromoacetophenone (1a) to give 3a. Studies on the effect of solvents and bases show that DMA and K(2)CO(3) are the solvent and base that give the highest yield of diene 3a. Possible mechanisms for this catalytic diene formation are proposed.     

Synthesis of triamidoamine ligands of the type (ArylNHCH(2)CH(2))(3)N and molybdenum and tungsten complexes that contain an [ArylNCH(2)CH(2))(3)N]3- ligand

Aryl bromides react with (H(2)NCH(2)CH(2))(3)N in a reaction catalyzed by Pd(2)(dba)(3) in the presence of BINAP and NaO-t-Bu to give the arylated derivatives (ArylNHCH(2)CH(2))(3)N [Aryl = C(6)H(5) (1a), 4-FC(6)H(4) (1b), 4-t-BuC(6)H(4) (1c), 3,5-Me(2)C(6)H(3) (1d), 3,5-Ph(2)C(6)H(3) (1e), 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3) (1f), 2-MeC(6)H(4) (1g), 2,4,6-Me(3)C(6)H(2) (1h)]. Reactions between (ArNHCH(2)CH(2))(3)N (Ar = C(6)H(5), 4-FC(6)H(4), 3,5-Me(2)C(6)H(3), and 3,5-Ph(2)C(6)H(3)) and Mo(NMe(2))(4) in toluene at 70 degrees C lead to [(ArNHCH(2)CH(2))(3)N]Mo(NMe(2)) complexes in yields ranging from 64 to 96%. Dimethylamido species (Ar = 4-FC(6)H(4), 3,5-Me(2)C(6)H(3)) could be converted into paramagnetic [(ArNHCH(2)CH(2))(3)N]MoCl species by treating them with 2,6-lutidinium chloride in tetrahydrofuran (THF). The "direct reaction" between 1a-f and MoCl(4)(THF)(2) in THF followed by 3 equiv of MeMgCl yielded [(ArNHCH(2)CH(2))(3)N]MoCl species (3a-f) in high yield. If 4 equiv of LiMe instead of MeMgCl are employed in the direct reaction, then [(ArNHCH(2)CH(2))(3)N]MoMe species are formed. Tungsten species, [(ArNHCH(2)CH(2))(3)N]WCl, could be prepared by analogous "direct" methods. Cyclic voltammetric studies reveal that MoCl complexes become more difficult to reduce as the electron donating ability of the [ArylNCH(2)CH(2))(3)N]3- ligand increases, and the reductions become less reversible, consistent with ready loss of chloride from ([(ArNHCH(2)CH(2))(3)N]MoCl)(-). Tungsten complexes are more difficult to reduce, and reductions are irreversible on the CV time scale.     

Insertion reactions into Pd[bond]O and Pd[bond]N bonds: preparation of alkoxycarbonyl,carbonato, carbamato,thiocarbamate, and thioureide complexes of palladium(II)

Mononuclear palladium hydroxo complexes of the type [Pd(N[bond]N)(C(6)F(5))(OH)] [(N[bond]N = 2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bipy), 1,10-phenanthroline (phen), or N,N,N',N'-tetramethylethylenediamine (tmeda)] have been prepared by reaction of [Pd(N[bond]N)(C(6)F(5))(acetone)]ClO(4) with KOH in methanol. These hydroxo complexes react, in methanol, with CO (1 atm, room temperature) to yield the corresponding methoxycarbonyl complexes [Pd(N[bond]N)(C(6)F(5))(CO(2)Me)]. Similar alkoxycarbonyl complexes [Pd(N[bond]N)(C(6)F(5))(CO(2)R)] (N[bond]N = bis(3,5-dimethylpyrazol-1-yl)methane); R = Me, Et, or (i)Pr) are obtained when [Pd(N[bond]N)(C(6)F(5))Cl] is treated with KOH in the corresponding alcohol ROH and CO is bubbled through the solution. The reactions of [Pd(N[bond]N)(C(6)F(5))(OH)] (N[bond]N = bipy or Me(2)bipy) with CO(2), in tetrahydrofuran, lead to the formation of the binuclear carbonate complexes [(N[bond]N)(C(6)F(5))Pd(mu-eta(2)-CO(3))Pd(C(6)F(5))(N[bond]N)]. Complexes [Pd(N[bond]N)(C(6)F(5))(OH)] react in alcohol with PhNCS to yield the corresponding N-phenyl-O-alkylthiocarbamate complexes [Pd(N[bond]N)(C(6)F(5))[SC(OR)NPh]]. Similarly, the reaction of [Pd(bipy)(C(6)F(5))(OH)] with PhNCO in methanol gives the N-phenyl-O-methylcarbamate complex [Pd(bipy)(C(6)F(5))[NPhC(O)OR]]. The reactions of [(N[bond]N)Pd(C(6)F(5))(OH)] with PhNCS in the presence of Et(2)NH yield the corresponding thioureidometal complexes [Pd(N[bond]N)(C(6)F(5))[NPhCSNR(2)]]. The crystal structures of [Pd(tmeda)(C(6)F(5))(CO(2)Me)], [Pd(2)(Me(2)bipy)(2)(C(6)F(5))(2)(mu-eta(2)-CO(3))].2CH(2)Cl(2), and [Pd(tmeda)(C(6)F(5))[SC(OMe)NPh]] have been determined.     

Syntheses and reactivities of disubstituted and trisubstituted fluorous pyridines with high fluorous phase affinities: solid state,liquid crystal,and ionic liquid-phase properties

Reactions of 2,6-dibromo-, 3,5-dibromo-, and 2,4,6-tribromopyridine with IZnCH(2)CH(2)R(f8) (R(f8) = (CF(2))(7)CF(3)) in THF at 65 degrees C in the presence of trans-Cl(2)Pd(PPh(3))(2) (5 mol %) gave the fluorous pyridines 2,6- and 3,5-NC(5)H(3)(CH(2)CH(2)R(f8))(2) (1 and 2; 85%, 31%) and 2,4,6-NC(5)H(2)(CH(2)CH(2)R(f8))(3) (3, 61%). Reaction of 2,6-pyridinedicarboxaldehyde with [Ph(3)PCH(2)CH(2)R(f8)](+)I(-)/K(2)CO(3) (p-dioxane/H(2)O, 95 degrees C) gave 2,6-NC(5)H(3)(CH[double bond]CHCH(2)R(f8))(2) (95%; 70:30 ZZ/ZE), which was treated with H(2) (1 atm, 12 h) and 10% Pd/C to yield 2,6-NC(5)H(3)(CH(2)CH(2)CH(2)R(f8))(2) (5, 95%), a higher homologue of 1. Longer reaction times afforded piperidine cis-2,6-HNC(5)H(8)(CH(2)CH(2)CH(2)R(f8))(2) (6, 98%). The stereochemistry was established by NMR analysis of the N-benzylpiperidine. Pyridines 1-3 and 5 are low-melting white solids with CF(3)C(6)F(11)/toluene partition coefficients (24 degrees C) of 93.8:6.2, 93.9:6.1, >99.7:<0.3, and 90.4:9.6, respectively (6, 93.6:6.4). Reaction of 1 and CF(3)SO(3)H gave a pyridinium salt, and Cl(2)Pd(NCCH(3))(2) (0.5 equiv) yielded trans-Cl(2)Pd(1)(2). The crystal structure of the former, which also exhibited liquid crystalline and ionic liquid phases, was determined.     

Coordination-driven self-assembly of 2D-metallamacrocycles using a new carbazole-based dipyridyl donor: synthesis, characterization, and C60 binding study

A new carbazole-based 90° dipyridyl donor 3,6-di(4-pyridylethynyl)carbazole (L) containing carbazole-ethynyl functionality is synthesized in reasonable yield using the Sonagashira coupling reaction. Multinuclear NMR, electrospray ionization-mass spectrometry (ESI-MS), including single crystal X-ray diffraction analysis characterized this 90° building unit. The stoichiometry combination of L with several Pd(II)/Pt(II)-based 90° acceptors (1a-1d) yielded [2 + 2] self-assembled metallacycles (2a-2d) under mild conditions in quantitative yields [1a = cis-(dppf)Pd(OTf)(2); 1b = cis-(dppf)Pt(OTf)(2); 1c = cis-(tmen)Pd(NO(3))(2); 1d = 3,6-bis{trans-Pt(C≡C)(PEt(3))(2)(NO(3))}carbazole]. All these macrocycles were characterized by various spectroscopic techniques, and the molecular structure of 2a was unambiguously determined by single crystal X-ray diffraction analysis. Incorporation of ethynyl functionality to the carbazole backbone causes the resulted macrocycles (2a-2d) to be π-electron rich and thereby exhibit strong emission characteristics. The macrocycle 2a has a large internal concave aromatic surface. The fluorescence quenching study suggests that 2a forms a ~1:1 complex with C(60) with a high association constant of K(sv) = 1.0 × 10(5) M(-1).     

Diphosphines possessing electronically different donor groups: synthesis and coordination chemistry of the unsymmetrical Di(N-pyrrolyl)phosphino-functionalized dppm analogue Ph2PCH2P(NC4H4)2

The unsymmetrical diphosphinomethane ligand Ph(2)PCH(2)P(NC(4)H(4))(2) L has been prepared from the reaction of Ph(2)PCH(2)Li with PCl(NC(4)H(4))(2). The diphenylphosphino group can be selectively oxidized with sulfur to give Ph(2)P(S)CH(2)P(NC(4)H(4))(2) 1. The reaction of L with [MCl(2)(cod)] (M = Pd, Pt) gives the chelate complexes [MCl(2)(L-kappa(2)P,P')] (2, M = Pd; 3, M = Pt) in which the M-P bond to the di(N-pyrrolyl)phosphino group is shorter than that to the corresponding diphenylphosphino group. However, the shorter Pd-P bond is cleaved on reaction of 2 with an additional 1 equiv of L to give [PdCl(2)(L-kappa(1)P)(2)] 4. Complex 4 reacts with [PdCl(2)(cod)] to regenerate 2, and with [Pd(2)(dba)(3)].CHCl(3) to give the palladium(I) dimer [Pd(2)Cl(2)(mu-L)(2)] 5, which exists in solution and the solid state as a 1:1 mixture of head-to-head (HH) and head-to-tail (HT) isomers. The palladium(II) dimer [Pd(2)Cl(2)(CH(3))(2)(mu-L)(2)] 6, formed by the reaction of [PdCl(CH(3))(cod)] with L, also exists in solution as a mixture of HH and HT isomers, although in this case the HT isomer prevails at low temperature and crystallizes preferentially. Complex 6 reacts with TlPF(6) to give the A-frame complex [Pd(2)(CH(3))(2)(mu-Cl)(mu-L)(2)]PF(6) 7. The reaction of L with [RuCp*(mu(3)-Cl)](4) leads to the dimer [Ru(2)Cp*(2)(mu-Cl)(2)(mu-L)] 8, for which the enthalpy of reaction has been measured. The reaction of L with [Rh(mu-Cl)(cod)](2) gives a mixture of compounds from which the dimer [Rh(2)(mu-Cl)(cod)(2)(mu-L)]PF(6) 9 can be isolated. The crystal structures of 2.CHCl(3), 3.CH(2)Cl(2), 4, 5.(1)/(4)CH(2)Cl(2), 6, 7.2CH(2)Cl(2), 8, and 9.CH(2)Cl(2) are reported.     

Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Stille cross-coupling of aryl chlorides

[reaction: see text] The Pd(2)(dba)(3)/P(i-BuNCH(2)CH(2))(3)N (1d) catalyst system is highly effective for the Stille cross-coupling of aryl chlorides with organotin compounds. This method represents only the second general method for the coupling of aryl chlorides. Other proazaphosphatranes possessing benzyl substituents also generate very active catalysts for Stille reactions. Noteworthy features of the method are: (a) commercial availability of ligand 1d, (b) the wide array of aryl chlorides that can be coupled, and (c) applicability to aryl, vinyl, and allyl tin reagents.     

Formation and coordination modes of the C4E4 moiety (E = COOMe) bound to two palladium(II) moieties

The transmetallation of the palladacyclopentadiene complex Pd{C(COOMe)C(COOMe)C(COOMe)C(COOMe)}(bipy) with the dicationic Pd(II) complex [Pd(bipy)(CH(3)CN)(2)][BF(4)](2) afforded a terminally σ-palladated diene complex [Pd(2){μ-η(1):η(1)-C(COOMe)C(COOMe)C(COOMe)C(COOMe)}(bipy)(2)(CH(3)CN)(2)][BF(4)](2). It was revealed by X-ray crystallographic analysis that replacement of the acetonitrile ligands in a terminally σ-palladated diene complex with PPh(3) ligands resulted in the conformation change of the σ-palladated diene moiety from skewed s-cis to planar s-trans. Treatment of a bis-triphenylphosphine dipalladium complex [Pd(2)(PPh(3))(2)(CH(3)CN)(4)][PF(6)](2) with dimethoxyacetylene dicarboxylate (DMAD) (1 equiv.) in acetonitrile resulted in the insertion of DMAD to the Pd-Pd bond to afford [Pd(2){μ-η(1):η(1)-C(COOMe)C(COOMe)}(PPh(3))(2)(CH(3)CN)(4)][PF(6)](2). Addition of the second DMAD gave the ylide-type complex [Pd(2){μ-η(2):η(3)-C(COOMe)C(COOMe)C(COOMe)C(COOMe)(PPh(3))}(PPh(3))(2)(CH(3)CN)(3)][PF(6)](2) of which the structure was determined by X-ray crystallographic analysis.     

Palladium(0)-catalyzed stereoselective cyclization of allenenes: divergent synthesis of pyrrolidines and 3-azabicyclo[3.1.0]hexanes from single allenenes

Two novel palladium(0)-catalyzed cyclizations of allenenes are described. Treatment of allenenes such as N-(1-alkyl-2,3-butadienyl)-N-allylsulfonamide with an aryl halide and K(2)CO(3) in the presence of a catalytic amount of Pd(PPh(3))(4) in dioxane affords 2,3-cis-pyrrolidines in a stereoselective manner. In sharp contrast, cyclization of the same allenenes using catalytic Pd(2)(dba)(3) x CHCl(3) in the presence of allyl methyl carbonate in CH(3)CN leads to stereoselective formation of a 3-azabicyclo[3.1.0]hexane framework in moderate yields.     

Synthesis and reactions of group 6 metal half-sandwich complexes of 2,2-dicyanoethylene-1,1-dichalcogenolates [(Cp*)M[E(2)C=C(CN)(2)](2)]-(M = Mo,W; E = S,Se)

A series of group 6 transition metal half-sandwich complexes with 1,1-dichalcogenide ligands have been prepared by the reactions of Cp*MCl(4)(Cp* = eta(5)-C(5)Me(5); M = Mo, W) with the potassium salt of 2,2-dicyanoethylene-1,1-dithiolate, (KS)(2)C=C(CN)(2) (K(2)-i-mnt), or the analogous seleno compound, (KSe)(2)C=C(CN)(2) (K(2)-i-mns). The reaction of Cp*MCl(4) with (KS)(2)C=C(CN)(2) in a 1:3 molar ratio in CH(3)CN gave rise to K[Cp*M(S(2)C=C(CN)(2))(2)] (M = Mo, 1a, 74%; M = W, 2a, 46%). Under the same conditions, the reaction of Cp*MoCl(4) with 3 equiv of (KSe)(2)C=C(CN)(2) afforded K[Cp*Mo(Se(2)C=C(CN)(2))(2)] (3a) and K[Cp*Mo(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))] (4) in respective yields of 45% and 25%. Cation exchange reactions of 1a, 2a, and 3a with Et(4)NBr resulted in isolation of (Et(4)N)[Cp*Mo(S(2)C=C(CN)(2))(2)] (1b), (Et(4)N)[Cp*W(S(2)C=C(CN)(2))(2)] (2b), and (Et(4)N)[Cp*Mo(Se(2)C=C(CN)(2))(2)] (3b), respectively. Complex 4 crystallized with one THF and one CH(3)CN molecule as a three-dimensional network structure. Inspection of the reaction of Cp*WCl(4) with (KSe)(2)C=C(CN)(2) by ESI-MS revealed the existence of three species in CH(3)CN, [Cp*W(Se(2)C=C(CN)(2))(2)]-, [Cp*W(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))]-, and [Cp*W(Se(Se(2))C=C(CN)(2))(2)]-, of which [Cp*W(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))]-(5) was isolated as the main product. Treatment of 2a with 1/4 equiv of S(8) in refluxing THF resulted in sulfur insertion and gave rise to K[Cp*W(S(2)C=C(CN)(2))(S(S(2))C=C(CN)(2))](6), which crystallized with two THF molecules forming a three-dimensional network structure. 6 can also be prepared by refluxing 2a with 1/4 equiv of S(8) in THF. 3a readily added one Se atom upon treatment with 1 mol of Se powder in THF to give 4 in high yield, while the treatment of 3a or 4 with 2 equiv of Na(2)Se in THF led to formation of a dinuclear complex [(Cp*Mo)(2)(mu-Se)(mu-Se(Se(3))C=C(CN)(2))] (7). The structure of 7 consists of two Cp*Mo units bridged by a Se(2-) and a [Se(Se(3))C=C(CN)(2)](2-) ligand in which the triselenido group is arranged in a nearly linear way (163 degrees). The reaction of 2a with 2 equiv of CuBr in CH(3)CN yielded a trinuclear complex [Cp*WCu(2)(mu-Br)(mu(3)-S(2)C=C(CN)(2))(2)] (8), which crystallized with one CH(3)CN and generated a one-dimensional chain polymer through bonding of Cu to the N of the cyano groups.     

Total synthesis of (-)-gambierol

The first total synthesis of (-)-gambierol (1), a marine polycyclic ether toxin, has been achieved. Key features of the successful synthesis include (1) a convergent union of the ABC and EFGH ring fragments (5 and 6, respectively) via our developed B-alkyl Suzuki-Miyaura cross-coupling strategy leading to the octacyclic polyether core 4 and (2) a late-stage introduction of the sensitive triene side chain by use of Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille coupling. The ABC ring fragment 5 was synthesized in a linear manner (B --> AB --> ABC), wherein the A ring was formed by intramolecular hetero-Michael reaction and the C ring was constructed via 6-endo cyclization of hydroxy epoxide 7. An improved synthetic entry to the EFGH ring fragment 6 is also described, in which SmI(2)-induced reductive cyclization methodology was applied to the stereoselective construction of the F and H rings, leading to 6 with remarkable overall efficiency. Stereoselective hydroboration of 5 and subsequent Suzuki-Miyaura coupling with 6 provided endocyclic enol ether 45 in high yield, which was then converted to octacyclic polyether core 4. Careful choice of the global deprotection stage was a key element for the successful total synthesis. Functionalization of the H ring and global desilylation gave (Z)-vinyl bromide 2. Finally, cross-coupling of 2 with (Z)-vinyl stannane 3 under Corey's Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille conditions completed the total synthesis of (-)-gambierol (1).     

Mechanism of the Stille reaction catalyzed by palladium ligated to arsine ligand: PhPdI(AsPh3)(DMF) is the species reacting with vinylstannane in DMF

The kinetics of the reaction of PhPdI(AsPh(3))(2) (formed via the fast oxidative addition of PhI with Pd(0)(AsPh(3))(2)) with a vinyl stannane CH(2)[double bond]CH[bond]Sn(n-Bu)(3) has been investigated in DMF. This reaction (usually called transmetalation step) is the prototype of the rate determining second step of the catalytic cycle of Stille reactions. It is established here that the transmetalation proceeds through PhPdI(AsPh(3))(DMF), generated by the dissociation of one ligand AsPh(3) from PhPdI(AsPh(3))(2). PhPdI(AsPh(3))(DMF) is the reactive species, which leads to styrene through its reaction with CH(2)[double bond]CH[bond]SnBu(3). Consequently, in DMF, the overall nucleophilic attack mainly proceeds via a mechanism involving PhPdI(AsPh(3))(DMF) as the central reactive complex and not PhPdI(AsPh(3))(2). The dimer [Ph(2)Pd(2)(mu(2)-I)(2)(AsPh(3))(2)] has been independently synthesized and characterized by its X-ray structure. In DMF, this dimer dissociates quantitatively into PhPdI(AsPh(3))(DMF), which reacts with CH(2)[double bond]CH[bond]SnBu(3). The rate constant for the reaction of PhPdI(AsPh(3))(DMF) with CH(2)[double bond]CH[bond]SnBu(3) has been determined in DMF for each situation and was found to be comparable.     

Condensation reactions of monomeric hydroxo palladium complexes with active methyl and methylene compounds

Heating a suspension of the monomeric hydroxo palladium complex of the type [Pd(N-N)(C(6)F(5))(OH)](N-N = bipy, Me(2)bipy, phen or tmeda) in methylketone (acetone or methylisobutylketone) under reflux affords the corresponding ketonyl palladium complex [Pd(N-N)(C(6)F(5))(CH(2)COR)]. On the other hand, the reaction of the hydroxo palladium complexes [Pd(N-N)(C(6)F(5))(OH)](N-N = bipy, phen or tmeda) with diethylmalonate or malononitrile yields the C-bound enolate palladium complexes [Pd(N-N)(CHX(2))(C(6)F(5))](X = CO(2)Et or CN), and the reaction of [Pd(N-N)(C(6)F(5))(OH)](N-N = bipy or phen) with nitromethane gives the nitromethyl palladium complexes [Pd(N-N)(CH(2)NO(2))(C(6)F(5))]. [Pd(tmeda)(C(6)F(5))(OH)] catalyses the cyclotrimerization of malononitrile. The crystal structures of [Pd(bipy)(C(6)F(5))(CH(2)COMe)].1/2Me(2)CO, [Pd(tmeda)(C(6)F(5))[CH(CO(2)Et)(2)]], [Pd(tmeda)(C(6)F(5))[CH(CN)(2)]] and [Pd(tmeda)(C(6)F(5))(CH(2)NO(2))].1/2CH(2)Cl(2) have been established by X-ray diffraction.     

Generation and coupling of [Mn(dmpe)2(C triple bond CR)(C triple bond C)]* radicals producing redox-active C4-bridged rigid-rod complexes

The symmetric d(5) trans-bis-alkynyl complexes [Mn(dmpe)(2)(C triple bond CSiR(3))(2)] (R = Me, 1 a; Et, 1 b; Ph, 1 c) (dmpe = 1,2-bis(dimethylphosphino)ethane) have been prepared by the reaction of [Mn(dmpe)(2)Br(2)] with two equivalents of the corresponding acetylide LiC triple bond CSiR(3). The reactions of species 1 with [Cp(2)Fe][PF(6)] yield the corresponding d(4) complexes [Mn(dmpe)(2)(C triple bond CSiR(3))(2)][PF(6)] (R = Me, 2 a; Et, 2 b; Ph, 2 c). These complexes react with NBu(4)F (TBAF) at -10 degrees C to give the desilylated parent acetylide compound [Mn(dmpe)(2)(C triple bond CH)(2)][PF(6)] (6), which is stable only in solution at below 0 degrees C. The asymmetrically substituted trans-bis-alkynyl complexes [Mn(dmpe)(2)(C triple bond CSiR(3))(C triple bond CH)][PF(6)] (R = Me, 7 a; Et, 7 b) related to 6 have been prepared by the reaction of the vinylidene compounds [Mn(dmpe)(2)(C triple bond CSiR(3))(C=CH(2))] (R = Me, 5 a; Et, 5 b) with two equivalents of [Cp(2)Fe][PF(6)] and one equivalent of quinuclidine. The conversion of [Mn(C(5)H(4)Me)(dmpe)I] with Me(3)SiC triple bond CSnMe(3) and dmpe afforded the trans-iodide-alkynyl d(5) complex [Mn(dmpe)(2)(C triple bond CSiMe(3))I] (9). Complex 9 proved to be unstable with regard to ligand disproportionation reactions and could therefore not be oxidized to a unique Mn(III) product, which prevented its further use in acetylide coupling reactions. Compounds 2 react at room temperature with one equivalent of TBAF to form the mixed-valent species [[Mn(dmpe)(2)(C triple bond CH)](2)(micro-C(4))][PF(6)] (11) by C-C coupling of [Mn(dmpe)(2)(C triple bond CH)(C triple bond C*)] radicals generated by deprotonation of 6. In a similar way, the mixed-valent complex [[Mn(dmpe)(2)(C triple bond CSiMe(3))](2)(micro-C(4))][PF(6)] [12](+) is obtained by the reaction of 7 a with one equivalent of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). The relatively long-lived radical intermediate [Mn(dmpe)(2)(C triple bond CH)(C triple bond C*)] could be trapped as the Mn(I) complex [Mn(dmpe)(2)(C triple bond CH)(triple bond C-CO(2))] (14) by addition of an excess of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) to the reaction mixtures of species 2 and TBAF. The neutral dinuclear Mn(II)/Mn(II) compounds [[Mn(dmpe)(2)(C triple bond CR(3))](2)(micro-C(4))] (R = H, 11; R = SiMe(3), 12) are produced by the reduction of [11](+) and [12](+), respectively, with [FeCp(C(6)Me(6))]. [11](+) and [12](+) can also be oxidized with [Cp(2)Fe][PF(6)] to produce the dicationic Mn(III)/Mn(III) species [[Mn(dmpe)(2)(C triple bond CR(3))](2)(micro-C(4))][PF(6)](2) (R = H, [11](2+); R = SiMe(3), [12](2+)). Both redox processes are fully reversible. The dinuclear compounds have been characterized by NMR, IR, UV/Vis, and Raman spectroscopies, CV, and magnetic susceptibilities, as well as elemental analyses. X-ray diffraction studies have been performed on complexes 4 b, 7 b, 9, [12](+), [12](2+), and 14.     

Reactivity of TCNE or TCNQ derivatives of quinonoid zwitterions: platinum-induced HCN elimination vs oxidative-addition

The reaction of the functional, zwitterionic quinonoid molecule (6E)-4-(butylamino)-6-(butyliminio)-3-oxo-2-(1,1,2,2-tetracyanoethyl)cyclohexa-1,4-dien-1-olate, [C(6)H-2-{C(CN)(2)C(CN)(2)H}]-4,6-(···NH n-Bu)(2)-1,3(···O)(2) (2), which has been previously prepared by regioselective insertion of TCNE into the C-H bond adjacent to the C···O bonds of the zwitterionic benzoquinone monoimine (6E)-4-(butylamino)-6-(butyliminio)-3-oxocyclohexa-1,4-dien-1-olate, C(6)H(2)-4,6-(···NHn-Bu)(2)-1,3-(···O)(2) (1), with 2 equiv of [Pt(C(2)H(4))(PPh(3))(2)], afforded the Pt(0) complex [Pt(PPh(3))(2)(4)] (6) (4 = 2-HCN; (6E)-4-(butylamino)-6-(butyliminio)-3-oxo-2-(1,2,2-tricyanoethenyl)cyclohexa-1,4-dien-1-olate), in which a tricyanoethenyl moiety is π-bonded to the metal. A metal-induced HCN elimination reaction has thus taken place. The same complex was obtained directly by the reaction of 1 equiv of the Pt(0) complex [Pt(C(2)H(4))(PPh(3))(2)] with the olefinic ligand [C(6)H-2-{C(CN)═C(CN)(2)}]-4,6-(···NHn-Bu)(2)-1,3-(···O)(2)) (4), previously obtained by the reaction of 2 with NEt(3) in THF. A similar reactivity pattern was observed between 2 and 2 equiv of the Pd(0) precursor [Pd(dba)(2)] in the presence of dppe, which led to [Pd(dppe)(4)] (7), which was also directly obtained from 4 and 1 equiv [Pd(dba)(2)]/dppe. In contrast to the behavior of the TCNE derivative 2, the reaction of the TCNQ derivative (6E)-4-(butylamino)-6-(butyliminio)-2-(dicyano(4-(dicyanomethyl)phenyl)methyl)-3-oxocyclohexa-1,4-dien-1-olate, [C(6)H-2-{C(CN)(2)p-C(6)H(4)C(CN)(2)H}]-4,6-(···NHn-Bu)(2)-1,3-(···O)(2)) (3), with 2 equiv of [Pt(C(2)H(4))(PPh(3))(2)] led to formal oxidative-addition of the C-H bond of the C(CN)(2)H moiety to give the Pt(II) hydride complex trans-[PtH(PPh(3))(2){N═C═C(CN)p-C(6)H(4)C(CN)(2)-2-[C(6)H-4,6-(···NHn-Bu)(2)-1,3-(···O)(2))}] (8). The molecular structures of 3, 4, 6·0.5(H(2)O), and 8·3(CH(2)Cl(2)) have been determined by single-crystal X-ray diffraction.