Determination of dibenzo[b,f]-1,4-oxazepine by diazotization cleavage of azomethine bond

A spectrophotometric determination of dibenzo[b,f]-1,4-oxazepine (CR) has been elaborated, which is based on a diazotation cleavage of azomethine bond followed by a coupling reaction. Twelve coupling agents have been used in the experiments and the following three agents have been recommended for the determination: N-(1-naphthyl)ethylenediamine dihydrochloride (L(Q) = 85 mg/ml), 7-hydroxy-4-methyl coumarin (L(Q) = 105 mg/ml) and 1-naphthol (L(Q) = 110 mg/ml). 2-[2-(hydroxy-l-naphthylazo) phenoxy]benzaldehyde has been identified by (1)H and (13)C NMR and elementary analysis as the product which results from the diazotization reaction followed by coupling of the CR substance with 2-naphthol. The azo-dye prepared by the described reactions shows azo-hydrazo tautomerism.     

A stable Schrock-type hafnium-silylene complex

The first stable hafnium-silylene complex, (eta-C5H4Et)2(PMe3)Hf=Si(SiMetBu2)2 (6) was obtained in the form of the phosphine adduct as red crystals by the coupling reaction of 1,1-dilithiosilane (1) with 0.9 equiv of (eta-C5H4Et)2HfCl2 in dry toluene at -50 degrees C, followed by treatment with an excess of PMe3 at -50 degrees C. In the 29Si NMR spectrum of 6, the signal from the silylene ligand is shifted greatly downfield at 295.4 ppm, with a JSiP coupling constant of 15.0 Hz. X-ray crystallographic analysis of 6 revealed that the Si-Hf bond length (2.6515(9) A) is about 5% shorter than typical Si-Hf single bonds, obviously indicating the double-bond character between the silicon and hafnium atoms. The compound 6 was found to be a Schrock-type silylene complex, a conclusion that was supported by the natural population analysis (NPA) charge distribution for the model complex, (eta-C5H4Et)2(PMe3)Hf=Si(SiMe3)2 (8), showing a negative charge on the silicon atom (-0.34).     

Kinetic and spectroscopic studies of the [palladium(Ar-bian)]-catalyzed semi-hydrogenation of 4-octyne

The kinetics of the stereoselective semi-hydrogenation of 4-octyne in THF by the highly active catalyst [Pd{(m,m'-(CF(3))(2)C(6)H(3))-bian}(ma)] (2) (bian = bis(imino)acenaphthene; ma = maleic anhydride) has been investigated. The rate law under hydrogen-rich conditions is described by r = k[4-octyne](0.65)[Pd][H(2)], showing first order in palladium and dihydrogen and a broken order in substrate. Parahydrogen studies have shown that a pairwise transfer of hydrogen atoms occurs in the rate-limiting step. In agreement with recent theoretical results, the proposed mechanism consists of the consecutive steps: alkyne coordination, heterolytic dihydrogen activation (hydrogenolysis of one Pd-N bond), subsequent hydro-palladation of the alkyne, followed by addition of N-H to palladium, reductive coupling of vinyl and hydride and, finally, substitution of the product alkene by the alkyne substrate. Under hydrogen-limiting conditions, side reactions occur, that is, formation of catalytically inactive palladacycles by oxidative alkyne coupling. Furthermore, it has been shown that (Z)-oct-4-ene is the primary reaction product, from which the minor product (E)-oct-4-ene is formed by an H(2)-assisted, palladium-catalyzed isomerization reaction.     

Mechanisms of C-C and C-H alkane reductive eliminations from octahedral Pt(IV): reaction via five-coordinate intermediates or direct elimination?

The Pt(IV) complexes P(2)PtMe(3)R [P(2) = dppe (PPh(2)(CH(2))(2)PPh(2)), dppbz (o-PPh(2)(C(6)H(4))PPh(2)); R = Me, H] undergo reductive elimination reactions to form carbon-carbon or carbon-hydrogen bonds. Mechanistic studies have been carried out for both C-C and C-H coupling reactions and the reductive elimination reactions to form ethane and methane are directly compared. For C-C reductive elimination, the evidence supports a mechanism of initial phosphine chelate opening followed by C-C coupling from the resulting five-coordinate intermediate. In contrast, mechanistic studies on C-H reductive elimination support an unusual pathway at Pt(IV) of direct coupling without preliminary ligand loss. The complexes fac- P(2)PtMe(3)R (P(2) = dppe, R = Me, H; P(2) = dppbz, R = Me) have been characterized crystallographically. The Pt(IV) hydrides, fac-P(2)PtMe(3)H (P(2) = dppe, dppbz), are rare examples of stable phosphine ligated Pt(IV) alkyl hydride complexes.     

A new route to 7-substituted derivatives of n-[4-(2-[2-amino-3,4-dihydro-4-oxo-7H-pyrrolo(2,3-d)pyrimidin-5-yl]ethyl)benzoyl]-L-glutamic acid [ALIMTA (LY231514, MTA)

Alkylation of various primary amines with crotyl bromide, followed by DMAP-promoted acylation with methyl malonyl chloride to 4 and then manganic triacetate dihydrate/cupric acetate induced radical cyclization, gave 1-substituted-4-vinyl-3-carbomethoxy-2-pyrrolidinones (5). Thiation to the thiolactams 6 and guanidine cyclization then gave a series of 2-amino-3,4-dihydro-4-oxo-5-vinyl-7-substituted pyrrolo[2,3-d]pyrimidines (7). Palladium-catalyzed C-C coupling with diethyl 4-iodobenzoylglutamate led in one step via an unexpected redox reaction to the diethyl esters 9 of a series of 7-substituted derivatives of ALIMTA (LY231514, MTA), from which the target analogues 10 were readily prepared by saponification. Attempted deprotection at position 7 was successful in only one case (9d, R = CH(2)C(6)H(3)(OMe)(2)(-3',4'), which resulted in a known pentultimate precursor (9, R = H) of ALIMTA. The 7-substituted derivatives 10 proved to be inactive in vitro as inhibitors of cell division.     

The first total synthesis of concanamycin f (concanolide a)

A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.     

Electronic coupling in 1,4-(COS)2C6H4 linked MM quadruple bonds (M = Mo, W): the influence of S for O substitution

Electronic structure calculations employing density functional theory on the compounds [(HCO2)3M2]2(mu-X-C6H4-X) where M = Mo and W and -X = -CO2, -COS and -CS2 reveal that the successive substitution of oxygen by sulfur leads to enhanced electronic coupling as evidenced by the increased energy separation of the metal delta orbital combinations which comprise the HOMO and HOMO-1. This enhanced coupling arises principally from a lowering of the LUMO of the X-C6H4-X bridge which, in turn, increases mixing with the in-phase combination of the M2 delta orbitals. The compounds [(Bu(t)CO2)3M2]2(mu-SOC-C6H4-COS), where M = Mo and W, have been prepared from the reactions between M2(O2CBu(t))4 and the thiocarboxylic acid 1,4-(COSH)2C6H4 in toluene and the observed spectroscopic and electrochemical data indicate stronger electronic coupling of the M2 centers in comparison to the closely related terephthalate compounds.     

B(C6F5)3‐Catalyzed Tandem Friedel‐Crafts and C−H/C−O Coupling Reactions of Dialkylanilines

Tandem Friedel‐Crafts (FC) and C?H/C?O coupling reactions catalyzed by tris(pentafluorophenyl) borane (B(C₆F₅)₃) were achieved without using any other additive in the absence of solvent. This process can be used for the reactions between a series of dialkylanilines and vinyl ethers with good isolated yields of bis(4‐dialkylaminophenyl) compounds. Based on combined theoretical and experimental studies, the possible reaction mechanism was proposed. B(C₆F₅)₃ can activate the C=C and C?O bond for FC and C?H/C?O coupling reactions respectively. The FC reaction is slow, which is followed by a fast C?H/C?O coupling.     

Temperature- and solvent-dependent binding of dihydrogen in iridium pincer complexes

Mixtures of deuterium labeled complexes (p-XPOCOP)IrH2-xDx (1-6-d0-2) {POCOP = [C6H2-1,3-[OP(tBu)2]2] X = MeO (1), Me (2), H (3), F (4), C6F5 (5), and ArF = 3,5-(CF3)2-C6H3 (6)} have been generated by reaction of (p-XPOCOP)IrH2 complexes with HD gas in benzene followed by removal of the solvent under high vacuum. Spectroscopic analysis employing 1H and 2D NMR reveals significant temperature and solvent dependent isotopic shifts and HD coupling constants. Complexes 1-6-d1 in toluene and pentane between 296 and 213 K exhibit coupling constants JHD of 3.8-9.0 Hz, suggesting the presence of an elongated H2 ligand, which is confirmed by T1(min) measurements of complexes 1, 3, and 6 in toluene-d8. In contrast, complex 6-d1 exhibits JHD = 0 Hz in CH2Cl2 or CDCl2F whereas isotopic shifts up to -4.05 ppm have been observed by lowering the temperature from 233 to 133 K in CDCl2F. The large and temperature-dependent isotope effects are attributed to nonstatistical occupation of two different hydride environments. The experimental observations are interpreted in terms of a two component model involving rapid equilibration of solvated Ir(III) dihydride and Ir(I) dihydrogen structures.     

(Star PS)-block-(Linear PI)-block-(Star PS) Triblock Copolymers – Thermoplastic Elastomers with Complex Branched Architectures

Polystyrene-block-polyisoprene-block-polystyrene triblock copolymers were synthesized with star-shaped branching in the polystyrene phase. The block copolymers were formed through sequential anionic polymerization by first synthesizing linear polystyrene, followed by star coupling using 4-(chlorodimethylsilyl)styrene, then the polymerization of isoprene, followed by difunctional coupling with dichlorodimethylsilane. The polymerization was followed by gel permeation chromatography and the resulting copolymers were characterized by ¹H NMR spectroscopy to examine the polyisoprene microstructure.     

Photo-induced coupling of tertiary amines with Ugi-derived dehydroalanines as a practical device in the synthesis to 2,4-diaminobutyric acid derivatives

An Ir-mediated photocatalytic coupling of tertiary amines with Ugi-dehydroalanines was developed as an entry to medicinally important 2,4-diaminobutyric acid derivatives. In the process the 2,4-diaminobutyric acid framework is assembled directly embedded into a peptoide structure, via the construction of the C₃(sp³)–C₄(sp³) bond, through a CH functionalization. The photocatalyzed oxidation of the tertiary amine produce a free radical intermediate which reacts with the double bond present in the dehydroalanines. The complete protocol comprises an Ugi 4-CR followed by an elimination reaction and the photo-induced coupling. Using this strategy, 15 new diversely substituted unnatural α,γ-diamino acids peptide derivatives were prepared in low to good yields.     

Synthetic,structural, and mechanistic studies on the oxidative addition of aromatic chlorides to a palladium (N-heterocyclic carbene) complex: relevance to catalytic amination

The oxidative addition products trans-[Pd(NHC)(2)(Ar)Cl] (NHC = cyclo-C[N(t)BuCH](2); Ar = Me-4-C(6)H(4), MeO-4-C(6)H(4), CO(2)Me-4-C(6)H(4)) have been isolated in good yields from the reactions of ArCl with the amination precatalyst [Pd(NHC)(2)] and structurally characterized. The former undergo reversible dissociation of one NHC ligand at elevated temperatures, and a value of 25.57 kcal mol(-1) has been determined for the Pd-NHC dissociation enthalpy in the case where Ar = Me-4-C(6)H(4). Detailed kinetic studies have established that the oxidative addition reactions proceed by a dissociative mechanism. Rate data for the oxidation addition of Me-4-C(6)H(4)Cl to [Pd(NHC)(2)] compared to that obtained for the [Pd(NHC)(2)]-catalyzed coupling of morpholine with 4-chlorotoluene are consistent with a rate-determining oxidative addition in the catalytic amination reaction. The relative rates of oxidative addition of the three aryl chlorides to [Pd(NHC)(2)] (CO(2)Me-4-C(6)H(4)Cl > Me-4-C(6)H(4)Cl > MeO-4-C(6)H(4)Cl) reflect the electronic nature of the substituents and also parallel observed trends in coupling efficiency for these aryl halides in aminations.     

Synthesis of a ligand based upon a new entry into the 3-hydroxy-N-alkyl-2(1H)-pyridinone ring system and thermodynamic evaluation of its gadolinium complex

The synthesis of a new, more water soluble derivative of TREN-Me-3,2-HOPO (tris[(3-hydroxy-1-methyl-2-oxo-1,2- didehydropyridine-4-carboxamido)ethyl]amine) is presented. The synthesis starts with the condensation reaction of (N-methoxyethylamino)acetonitrile hydrochloride and oxalyl chloride to give 3,5-dichloro-N-(methoxyethyl)-2(1H)-pyrazinone. The 3-position is readily substituted with a benzyloxy group, and the pyrazinone is converted to ethyl 3-(benzyloxy)-N-(methoxyethyl)-2(1H)-pyridinone-4-carboxylate by a Diels-Alder cycloaddition with ethyl propiolate. Basic deprotection of the ester followed by activation, coupling to tren, and acidic deprotection of the benzyl groups gives the ligand TREN-MOE-3,2-HOPO (tris[(3-hydroxy-1-(methoxyethyl)- 2-oxo-1,2-didehydropyridine-4-carboxamido)ethyl]amine). The gadolinium complex of TREN-MOE-3,2-HOPO was prepared by metathesis, starting from gadolinium chloride. The solubility of the new metal complex is significantly enhanced. The four protonation constants (determined by potentiometry) for TREN-MOE-3,2-HOPO (log Ka1 = 8.08, log Ka2 = 6.85, log Ka3 = 5.81, log Ka4 = 4.98) are virtually identical to those reported for the parent ligand. The stability constants for the gadolinium complex of TREN-MOE-3,2-HOPO determined by potentiometry (log beta 110 = 19.69(2), log beta 111 = 22.80(2)) and by spectrophotometry (log beta 110 = 19.80(1), log beta 111 = 22.88(1), log beta 112 = 25.88(1)) differ slightly from those for the parent ligand; this follows from a change in the complexation model in which a new diprotonated species, [Gd(TREN-MOE-3,2-HOPO)(H)2]2+, was included. The presence of this extra species was demonstrated by factor analysis, comparison of spectral data, and nonlinear least-squares refinement. Significant formation of this species is observed between pH 3 and pH 1.5.     

Reduction of carbodiimides by samarium(II) bis(trimethylsilyl)amides-formation of oxalamidinates and amidinates through C-C coupling or C-H activation

The reaction of [Sm{N(SiMe3)2}2(THF)2] (THF=tetrahydrofuran) with carbodiimides RN=C=NR (R=Cy, C6H3-2,6-iPr2) led to the formation of dinuclear SmIII complexes via differing C-C coupling processes. For R=Cy, the product [{(Me3Si)2N}2Sm(micro-C2N4Cy4)Sm{N(SiMe3)2}2] (1) has an oxalamidinate [C2N4Cy4]2- ligand resulting from coupling at the central C atoms of two CyNCNCy moieties. In contrast, for R=C6H3-2,6-iPr2, H transfer and an unusual coupling of two iPr methine C atoms resulted in a linked formamidinate complex, [{(Me3Si)2N}2Sm{micro-(RNC(H)N(Ar-Ar)NC(H)NR)}Sm{N(SiMe3)2}2] (2) (Ar-Ar=C6H3-2-iPr-6-C(CH3)2C(CH3)2-6'-C6H3-2'-iPr). Analogous reactions of RN=C=NR (R=Cy, C6H3-2,6-iPr2) with the SmII "ate" complex [Sm{N(SiMe2)3Na] gave 1 for R=Cy, but a novel C-substituted amidinate complex, [(THF)Na{N(R)C(NR)CH2Si(Me2)N(SiMe3)}Sm{N(SiMe3)2}2] (3), for R=C6H3-2,6-iPr2, via gamma C-H activation of a N(SiMe3)2 ligand.     

C-H Activation and C-C coupling of arenes by cationic Pt(II) complexes

The synthesis and characterization of cationic platinum complexes of the type [(R(2)PC(2)H(4)PR(2))PtMe(OEt(2))]BAr(F) (R = Cy, Et) are reported. These electrophilic platinum cations are found to react quantitatively with arenes (benzene, toluene) at room temperature by undergoing intermolecular C-H activation with concomitant C-C coupling to generate complexes of the type [[Pt(R(2)PC(2)H(4)PR(2))](2)(mu-eta(3):eta(3)-biaryl)][BAr(F)](2). The dianionic biaryl ligands in these compounds exhibit a rare mu-eta(3):eta(3)-bis-allyl bonding mode and can be removed from the complex with stoichiometric oxidants to generate the free biaryl and [(R(2)PC(2)H(4)PR(2))Pt(mu-X)](2)[BAr(F)](2) (R = Cy, Et; X = Cl, I). The cationic platinum complexes [(R(2)PC(2)H(4)PR(2))PtMe(OEt(2))]BAr(F) (R = Cy, Et) are also quite reactive with water, forming the bridging hydroxide complexes [(R(2)PC(2)H(4)PR(2))Pt(mu-OH)](2)[BAr(F)](2) (R = Cy, Et). A possible mechanism is proposed for the C-C coupling reaction based upon the structures of these bridging biphenyl complexes, which provides a new perspective for the related palladium-catalyzed oxidative coupling of arenes to form biaryls.     

Synthesis of bromo-, boryl-, and stannyl-functionalized 1,2-bis(trimethylsilyl)benzenes via Diels-Alder or C-H activation reactions

1,2-Bis(trimethylsilyl)benzenes are key starting materials for the synthesis of benzyne precursors, Lewis acid catalysts, and certain luminophores. We have developed efficient, high-yield routes to functionalized 4-R-1,2-bis(trimethylsilyl)benzenes, starting from either 1,2-bis(trimethylsilyl)acetylene/5-bromopyran-2-one (2) or 1,2-bis(trimethylsilyl)benzene (1)/bis(pinacolato)diborane. In the first reaction, 5 (R = Br) is obtained through a cobalt-catalyzed Diels-Alder cycloaddition. The second reaction proceeds via iridium-mediated C-H activation and provides 8 (R = Bpin). Besides its use as a Suzuki reagent, compound 8 can be converted into 5 with CuBr(2) in i-PrOH/MeOH/H(2)O. Lithium-bromine exchange on 5, followed by the addition of Me(3)SnCl, gives 10 (R = SnMe(3)), which we have applied for Stille coupling reactions. A Pd-catalyzed C-C coupling reaction between 5 and 8 leads to the corresponding tetrasilylbiphenyl derivative. The bromo derivative 5 cleanly undergoes Suzuki reactions with electron-rich as well as electron-poor phenylboronic acids.     

C4−H alkoxylation of 6-bromoindole and its application to the synthesis of breitfussin B

Subjecting 6-bromoindole to an iridium-catalysed triborylation-diprotodeborylation sequence followed by Chan-Evans-Lam coupling gives 6-bromo-4-methoxyindole in good overall yield. This indole C4?H alkoxylation process was used in a formal synthesis of the natural product breitfussin B.     

New titanium complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands formed through sequential intramolecular C-C bond-forming reactions

A series of new titanium(IV) complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands, cis-9,10-PhenH(2)(NR)(2)Ti(O(i)Pr)(2) [PhenH(2) = 9,10-dihydrophenanthrene, R = 2,6-(i)Pr(2)C(6)H(3) (2a), 2,6-Et(2)C(6)H(3) (2b), 2,6-Me(2)C(6)H(3) (2c)], cis-9,10-PhenH(2)(NR(1))(NR(2))Ti(O(i)Pr)(2) [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (2d); R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Me(2)C(6)H(3) (2e)], and [cis-9,10-PhenH(2)(NR(1))(2)][o-C(6)H(4)(CH=NR(2))]TiO(i)Pr [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (3a); R(1) = 2,6-(i)Pr(2)C(6)H(3), 2,6-Me(2)C(6)H(3) (3b)], have been synthesized from the reactions of TiCl(2)(O(i)Pr)(2) with o-C(6)H(4)(CH=NR)Li [R = 2,6-(i)Pr(2)C(6)H(3), 2,6-Et(2)C(6)H(3), 2,6-Me(2)C(6)H(3)]. The symmetric complexes 2a-2c were obtained from the reactions of TiCl(2)(O(i)Pr)(2) with 2 equiv of the corresponding o-C(6)H(4)(CH=NR)Li followed by intramolecular C-C bond-forming reductive elimination and oxidative coupling processes, while the asymmetric complexes 2d-2e were formed from the reaction of TiCl(2)(O(i)Pr)(2) with two different types of o-C(6)H(4)(CH=NR)Li sequentially. The complexes 3a and 3b were also isolated from the reactions for complexes 2d and 2e. All complexes were characterized by (1)H and (13)C NMR spectroscopy, and the molecular structures of 2a, 2b, 2e, and 3a were determined by X-ray crystallography.     

Mechanistic insight into fragmentation reactions of titanapinacolate complexes

Reactions between terminal alkynes or aromatic ketones and titanapinacolate complexes (DMSC)Ti(OCAr(2)CAr(2)O) (2, Ar = Ph, and 3, Ar = p-MeC(6)H(4); DMSC = 1,2-alternate dimethylsilyl-bridged p-tert-butylcalix[4]arene dianion) occur via rupture of the C-C bond of the titanacycle. Thus, reactions of 2 and 3 with terminal alkynes produce 2-oxatitanacyclopent-4-ene or 2-oxatitanacycloheptadiene complexes along with free Ar(2)CO. These compounds have been characterized spectroscopically and by X-ray crystallography. Because metallapinacolate intermediates have been implicated in important C-C bond-forming reactions, such as pinacol coupling and McMurry chemistry, the mechanism of the fragmentation reactions was studied. Analysis of the kinetics of the reaction of (DMSC)Ti[OC(p-MeC(6)H(4))(2)C(p-MeC(6)H(4))(2)O] (3) with Bu(t)Ctbd1;CH revealed that the fragmentation reactions proceed via a preequilibrium mechanism, involving reversible dissociation of titanapinacolate complexes into (DMSC)Ti(eta(2)-OCAr(2)) species with release of a ketone molecule, followed by rate-limiting reaction of (DMSC)Ti(eta(2)-OCAr(2)) species with an alkyne or ketone molecule.     

二萜(±)-表-马氏醇的合成

本文报道(±)-表-马氏醇的合成(epi-mayol)(1)的全合成,将8-羟基香叶醛(4)与溴代苯硫醚(5)在Cr(Ⅱ)作用下立体选择地缩合生成苏式-(2E,8E,12E)-3,9,13-三甲基-6-异丙烯基-2,8,12-十四碳三烯-7,14-二羟基苯硫醚(6).6转变为对甲苯磺酸酯后,在LDA作用下闭华得华化产物(2E,6E,10E)-1-羟基-3,7,11-三甲基-9- 苯硫基-14-异丙基-2,6,10-十四碳环三烯(9),9脱去苯硫基得目标化合物1.