Direct and selective replacement of carbon-hydrogen bonds with new (such as C-C, C-O, C-N) represents an important long-standing goal in chemistry. These transformations have broad potential synthesis because C-H are ubiquitous organic substances. At the same time, achieving selectivity among many different remains a challenge. Here, we focus on functionalization complex substrates catalyzed by transition metal catalysts. We outline key concepts approaches aimed at settings discuss impact...

We have recently developed palladium-catalyzed methods for direct arylation of indoles (and other azoles) wherein high C-2 selectivity was observed both free (NH)-indole and (NR)-indole. To provide a rationale the ("nonelectrophilic" regioselectivity), mechanistic studies were conducted, using phenylation 1-methylindole as model system. The reaction order determined iodobenzene (zero order), indole (first catalyst order). These kinetic studies, together with Hammett plot, provided strong...

Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there a longstanding interest in development new opioid analgesics improved profiles. The alkaloids Southeast Asian plant Mitragyna speciosa, represented by prototypical member mitragynine, are an unusual class modulators distinct pharmacological properties. Here we describe...

Mitragyna speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally stimulant, analgesic, and treatment for opioid addiction. Recently, growing use in United States concerns that kratom represents an uncontrolled drug with potential abuse liability, highlighted need careful study its pharmacological activity. The major active alkaloid found mitragynine, has reported agonist analgesic activity vitro animal models, consistent...

Ar−Rh(III) pivalate complexes assembled in situ from the reaction of [RhCl(coe)2]2 (coe = cis-cyclooctene), [p-(CF3)C6H4]3P, and CsOPiv effectively catalyzed direct C-arylation free (NH)-indoles (NH)-pyrroles good yields with high regioselectivity. The displayed excellent functional group compatibility low moisture sensitivity. Kinetics studies support a mechanism involving phosphine displacement by indole complex 2 (resting state catalyst), followed rate-limiting C−H bond metalation.

A new ruthenium-catalyzed direct sp3 C-H to C-C bond transformation is disclosed. Specifically, a method for the alpha-arylation of cyclic amines, containing either permanent (pyridine, pyrimidine) or removable (amidine) directing groups, described. This cross-coupling reaction involves heating amine substrates with arylboronate ester at 150 degrees C in ketone solvent catalytic amount ruthenium carbonyl [Ru3(CO)12]. Arylboronate esters electron-withdrawing electron-donating substituents...

[reaction: see text] We herein report that PtCl(4) has proven to be a hydroarylation catalyst with an efficiency and substrate scope superior previously known methods. This demonstrated consistent performance arene-yne substrates of diverse structural features, including propargyl ethers, propargylamines, alkynoate esters, providing good excellent yields the 6-endo products (chromenes, dihydroquinolines, coumarins). In contrast, Pt(II), Pd(II), Ga(III) salts were shown sensitive substitution...

We present a new, practical method by which N-substituted indoles may be selectively arylated in the C2-position with good yields, low catalyst loadings, and high degree of functional group tolerance. Our investigation found that two competitive processes, namely, desired cross-coupling biphenyl formation, were operative this reaction. A simple kinetic model was formulated proved to instructive provided useful guidelines for reaction optimization; approach described within prove other...

The synthesis and catalytic evaluation of palladium complexes containing imidazolyl carbene ligand varying steric electronic properties is reported. These catalyze the efficient C−H arylation SEM-protected azole heteroarenes thus provide a good method for preparation wide range arylated free (NH)-azoles including pyrroles, indoles, imidazoles, imidazo[1,2-a]pyridines. reaction operationally simple; are insensitive to moisture.

A practical method for the intramolecular hydroalkylation of electron-deficient olefins has been developed. The direct transformation benzylic, tertiary, and sterically hindered secondary sp3 C−H bonds into C−C under action a catalytic amount variety Lewis acids is described. mechanism these transformations proposed to involve tandem hydride transfer/cyclization sequence.

This paper describes a phosphine-free palladium-catalyzed method for direct C-arylation of free (N−H)-indoles and pyrroles with iodo- bromoarene donors. Employing commercially available materials, this new operationally simple procedure provides rapid entry to wide range C-arylated including derivatives tryptamine. In the course study, profound halide effect was uncovered, affecting both efficiency regioselectivity indole arylation.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSelective Functionalization of Amino Acids in Water: A Synthetic Method via Catalytic C−H Bond ActivationBrian D. Dangel, James A. Johnson, and Dalibor SamesView Author Information Department Chemistry, Columbia University New York, York 10027 Cite this: J. Am. Chem. Soc. 2001, 123, 33, 8149–8150Publication Date (Web):July 31, 2001Publication History Received25 May 2001Revised2 July 2001Published online31 inissue 1 August...

C−H bond functionalization enables strategically new approaches to the synthesis of complex organic molecules including biologically active compounds, research probes and functional materials. To address shortcomings transition metal catalyzed processes, we have developed a approach direct coupling sp3 bonds alkenes based on Lewis acid-promoted hydride transfer. Activation α,β-unsaturated aldehydes ketones with acid triggers intramolecular transfer, leading zwitterionic intermediate, which...

The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. In order to observe uptake and from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the monoamine transporter. Using these probes image dopamine in striatum, made several observations pertinent plasticity. We found that fraction of vesicles releasing per stimulus was dependent on frequency. A kinetically distinct...

The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly cassette methodologies. These synthetic antigens were subsequently clustered (c) immunoconjugated to a carrier protein (KLH or BSA) lipopeptide (pam) for immunological study. Three conjugates used vaccinate groups mice, all preparations proved be immunogenic. Tn(c) covalently linked KLH (27−KLH) plus the adjuvant QS-21 was optimal vaccine, inducing high median IgM IgG titers...

Pyrazoles are important azole heteroarenes frequently found in pharmaceuticals and protein ligands, there has been a growing interest new synthetic methods for their preparation. We report the first catalytic intermolecular C-H arylation of pyrazoles, namely SEM-protected pyrazoles N-alkylpyrazoles, which lays foundation approach to synthesis complex arylated where arene rings directly attached predetermined positions heteroarene nucleus ("topologically obvious synthesis"). Through...

The core of teleocidin B4, a complex fragment natural product containing two quaternary stereocenters and penta-substituted benzene ring, was synthesized in four C−C bond-forming steps starting from tert-butyl derivative 1. first step involved alkenylation the group with vinyl boronic acid, followed by successful annulation cyclohexane ring to nucleus via an intramolecular Friedel−Crafts reaction. third required diastereoselective oxidative carbonylation geminal dimethyl group, at last...

The antitumor agent (−)-rhazinilam was synthesized in three major steps, namely the pyrrole synthesis, selective C−H bond activation, and direct macrolactam formation. key step involved asymmetric functionalization (dehydrogenation) of diethyl group segment intermediate 6. This achieved by attachment chiral platinum complexes to proximal nitrogen atom. A high degree selectivity (60−75% ee) via use oxazolinyl ketone auxiliaries.

We herein present a new oxidative cyclization of alkene−amide substrates under neutral and catalytic conditions. This overall transformation requires tandem sp3 C−H activation (at the position adjacent to amide nitrogen) C−C bond formation. Specifically, pyrrolidine 1 was converted pyrrolizidinone 3 indolizidinone 4 in 66% 17% yield, respectively, presence [Ir(coe)2Cl]2, carbene ligand IPr (1:1 metal/ligand ratio, 5−10 mol % Ir), hydrogen acceptor (NBE or TBE, 3−10 equiv). The results...

We report a catalytic intramolecular coupling between terminal unactivated alkynes and sp3 C−H bonds via through-space hydride transfer (HT-cyclization of alkynes). This method enables one-step preparation complex heterocyclic compounds by α-alkenylation readily available cyclic ethers amines. show that PtI4 is an effective Lewis acid catalyst for the activation attack subsequent C−C bond formation. In addition, we have shown activity neutral platinum salts (PtXn) can be modulated halide...

Fluorescent and luminescent reporters that signal molecular events of interest by modulating the ratio peaks in their emission profile have advantages over simply modulate intensity, since ratiometric measurement is concentration-independent allows them to be effective complex contexts, such as living cells or sensor microarrays. We herein describe a general platform for design probes based on heterometallic Tb3+/Eu3+ bis-lanthanide ensemble, consisting mixture, "cocktail", otherwise...

The hydride transfer initiated cyclization ("HT-cyclization") of aryl alkyl ethers, which leads to direct coupling sp(3) C-H bonds and activated alkenes, is reported. Readily available salicylaldehyde derived ethers are converted in one step dihydrobenzopyrans, an important class heteroarenes frequently found biologically active compounds. This process has not been previously reported, contrast known HT-cyclizations the corresponding tert-amines ("tert-amino effect" reactions).