piperidines and carbene

Synthesis of complex bioactive molecules is substantially facilitated by transformations that efficiently and stereoselectively generate polyfunctional compounds. Designing such processes is hardly straightforward, however, especially when the desired route runs counter to the inherently favored reactivity profiles. Furthermore, in addition to being efficient and stereoselective, it is crucial that the products generated can be easily and stereodivergently modified. Here, we introduce a catalytic process that delivers versatile and otherwise difficult-to-access organoboron entities by combining an allenylboronate, a hydride, and an allylic phosphate. Two unique selectivity problems had to be solved: avoiding rapid side reaction of a Cu-H complex with an allylic phosphate, while promoting its addition to an allenylboronate as opposed to the commonly utilized boron-copper exchange. The utility of the approach is demonstrated by applications to concise preparation of the linear fragment of pumiliotoxin B (myotonic, cardiotonic) and enantioselective synthesis and structure confirmation of netamine C, a member of a family of anti-tumor and anti-malarial natural products. Completion of the latter routes required the following noteworthy developments: (1) a two-step all-catalytic sequence for conversion of a terminal alkene to a monosubstituted alkyne; (2) a catalytic S

Topics: Alkadienes; Alkaloids; Boronic Acids; Catalysis; Copper; Cycloaddition Reaction; Heterocyclic Compounds; Indolizines; Methane; Molecular Structure; Piperidines; Stereoisomerism

Pd(II)-catalyzed C(sp(3))-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp(3))-H insertion step by the Pd(II)/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd(0)/Pd(II) catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems.

Topics: Catalysis; Ligands; Methane; Molecular Structure; Piperidines; Pyrans

A newly developed P,N-bidentate ligand enables enantioselective intramolecular cyclopropanation by a reactive α-oxo gold carbene intermediate generated in situ. The ligand design is based on our previously proposed structure (with a well-organized triscoordinated gold center) of the carbene intermediate in the presence of a P,N-bidentate ligand. A C2-symmetric piperidine ring was incorporated in the ligand as the nitrogen-containing moiety. A range of racemic transformations of α-oxo gold carbene intermediates have been developed recently, and this new class of chiral ligands could enable their modification for asymmetric synthesis, as demonstrated in this study.

Topics: Catalysis; Crystallography, X-Ray; Cyclopropanes; Gold; Ligands; Methane; Molecular Conformation; Nitrogen; Oxidation-Reduction; Phosphorus; Piperidines; Stereoisomerism

A facile synthesis of piperidine alkene-alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene-alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.

Topics: Alkaloids; Alkenes; Antineoplastic Agents; Catalysis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Heterocyclic Compounds; Humans; MCF-7 Cells; Methane; Molecular Conformation; Organometallic Compounds; Palladium; Piperidines; Structure-Activity Relationship

Structurally well-defined N-heterocyclic carbene silver chlorides and bromides supported by 1-cyclohexyl-3-benzylimidazolylidene (CyBn-NHC) or 1-cyclohexyl-3-naphthalen-2-ylmethylimidazolylidene (CyNaph-NHC) were synthesized by reaction of the corresponding imidazolium halides with silver(I) oxide while cationic bis(CyBn-NHC) silver nitrate was isolated under similar conditions using imidazolium iodide in the presence of sodium nitrate. Single-crystal X-ray diffraction revealed a dimeric structure through a nonpolar weak-hydrogen-bond supported Ag-Ag bond for 1-cyclohexyl-3-benzylimidazolylidene silver halides [(CyBn-NHC)AgX](2) (X = Cl, 1; Br, 2) but a monomeric structure for N-heterocyclic carbene silver halides with the more sterically demanding 1-cyclohexyl-3-naphthalen-2-ylmethylimidazolylidene ligand (CyNaph-NHC)AgX (X = Cl, 4; Br, 5). Cationic biscarbene silver nitrate [(CyBn-NHC)(2)Ag](+)NO(3)(-)3 assumed a cis orientation with respect to the two carbene ligands. The monomeric complexes (CyNaph-NHC)AgX 4 and 5 showed higher catalytic activity than the dimeric [(CyBn-NHC)AgX](2)1 and 2 as well as the cationic biscarbene silver nitrate 3 in the model three component reaction of 3-phenylpropionaldehyde, phenylacetylene and piperidine with chloride 4 performing best and giving product in almost quantitative yield within 2 h at 100 °C. An explanation for the structure-activity relationship in N-heterocyclic carbene silver halide catalyzed three component reaction is given based on a slightly modified mechanism from the one in literature.

Topics: Acetylene; Aldehydes; Alkynes; Amines; Bromides; Catalysis; Crystallography, X-Ray; Heterocyclic Compounds; Hydrogen Bonding; Ligands; Methane; Molecular Structure; Piperidines; Silver Compounds; Stereoisomerism; Structure-Activity Relationship; X-Ray Diffraction

Starting from [{Rh(cod)Cl}(2)] and 1,3-dimesitylimidazole-2-ylidenes the novel [RhCl(cod)(carbene)] complexes 1-5 have been synthesized, characterized, and tested in the hydroaminomethylation of aromatic olefins. The influence of different ligands and reaction parameters on the catalytic activity was investigated in detail applying 1,1-diphenylethylene and piperidine as a model system. The scope and limitations of the novel catalysts is shown in the preparation of 16 biologically active 1-amino-3,3-diarylpropenes. In general, high chemo- and regioselectivity as well as good yields of the desired products were achieved.

Topics: Alkenes; Amines; Catalysis; Hydrocarbons; Imidazoles; Ligands; Methane; Methylation; Models, Chemical; Molecular Structure; Organometallic Compounds; Pharmaceutical Preparations; Piperidines; Propane; Rhodium; Styrenes

Some 3,3'-(1-piperidino)substituted methylene-bis-isoxazoles were prepared via Mannich base and tested to verify their antiinflammatory-related activity. Human neutrophils stimulated with either PMA and f-MLP were used as the cellular model. The efficiency of eight differently substituted compounds (2-9) was established on their capacity to reduce the O(2)(-) production by activated human neutrophils. The rising hydrophobicity in the side-chain of methylene-bis-isoxazoles leads to a distinction in the neutrophil response against the two stimuli, favoring the inhibition of the PMA elicited cell activation and leaving inaffected the f-MLP induced cell responses. Compounds 8 and 9 are particularly active and abolish almost completely the neutrophil activation in the presence of PMA stimulus.

Topics: Humans; Hydrocarbons; Isoxazoles; Leukocytes; Methane; Piperidines

Topics: Animals; Anura; Humans; Methane; Piperidines