Gold(i)-catalyzed cycloisomerization of vinylidenecyclopropane-enes via carbene or non-carbene processes.
ABSTRACT: Gold catalyzed cycloisomerization of aromatic ring tethered vinylidenecyclopropane-enes provides a divergent synthetic protocol for the construction of O-containing fused heterocycles through controllable carbene or non-carbene related processes. The carbene induced process features a new amphiphilic strategy to generate a gold carbene via a rearrangement of vinylidenecyclopropane. Whereas, the electronic effect of the ortho-substituents switches the reaction mode onto the non-carbene related process, from which five- or six-membered rings are selectively produced through allyl-migration.
Project description:The combination of Ni(0) and an N-heterocyclic carbene act as a precatalyst for the cycloisomerization of enynes to afford 1,3-dienes. During the course of the reaction, a nickel hydride is formed from oxidative addition of the ortho C-H on the carbene ligand. Deuteriumn labeling studies are presented.
Project description:[reaction: see text] The tungsten-catalyzed cycloisomerization of alkynyl alcohols can be conducted without using photochemistry, using a stable tungsten Fischer carbene as the precatalyst for this transformation. A variety of alkynyl alcohols undergo cycloisomerization under these conditions to provide endocyclic enol ethers of five-, six-, and seven-membered ring sizes. The utility of this method is further demonstrated in the stereoselective synthesis of the disaccharide substructure of altromycin B.
Project description:A gold(i)-catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene, tricyclic cyclobutene, biscyclopropane and 1,3-cyclohexadiene derivatives in moderate to excellent yields. When the phenyl group was not ortho substituted, 1,4-cyclohexadienes could be produced. With an ortho substituent, three different products could be selectively synthesized by control of the temperature and the used gold(i) catalyst. The 1,5-enyne substrate first undergoes a classical enyne cycloisomerization to form a tricyclic cyclobutene key intermediate, which undergoes subsequent transformation to produce the desired products. A plausible reaction mechanism was proposed according to deuterium labeling experiments and intermediate trapping experiments, as well as DFT calculations. In our current reaction, the ortho substituent on the phenyl group controls the reaction outcome and the ortho substituent effect was found to originate from steric and electronic factors.
Project description:Two naphthalene-diimide (NDI) bis-imidazolium salts have been used as N-heterocyclic carbene (NHC) precursors for the preparation of NDI-functionalized complexes of rhodium and iridium of general formula [MCl(NDI-NHC)(COD)] (M=Rh, Ir; NDI-NHC=NDI-functionalized NHC ligand). Comparison of the IR spectra of the complexes [IrCl(NDI-NHC)(CO)<sub>2</sub> ] and their related one- and two-electron reduced forms, reveal that each one-electron reduction produces a decrease of the average ν(CO) of 9-10 cm<sup>-1</sup> , indicating a significant enhancement of the electron-richness of the metal. The [MCl(NDI-NHC)(COD)] complexes were tested in the catalytic cycloisomerization of alkynoic acids. The one-electron reduced forms showed greatly enhanced activities. For the cyclization of 5-hexynoic acid, the two-electron reduction of the ligand produced further enhancement of the catalytic activity, therefore showing that the catalyst can switch between three redox species with three distinct catalytic activities.
Project description:Herein we describe a multiple C-H functionalization reaction of carbazole heterocycles with diazoalkanes. We show that gold catalysts play a distinct role in enabling a multiple C-H functionalization reaction to introduce up to six carbene fragments onto molecules containing multiple carbazole units or to link multiple carbazole units into a single molecule. A one-pot stepwise approach enables the introduction of two different carbene fragments to allow orthogonal deprotection and straightforward derivatization.
Project description:Nine- and ten-membered N-heterocyclic carbene (NHC) ligands have been developed and for the first time their gold(I) complexes were synthesized. The protonated NHC pro-ligands 2?a-h were prepared by the reaction of readily available N,N'-diarylformamidines with bis-electrophilic building blocks, followed by anion exchange. In situ deprotonation of the tetrafluoroborates 2?a-h with tBuOK in the presence of AuCl(SMe<sub>2</sub> ) provided fast access to NHC-gold(I) complexes 3-10. These new NHC-gold(I) complexes show very good catalytic activity in a cycloisomerization reaction (0.1?mol?% catalyst loading, up to 100?% conversion) and their solid-state structures reveal high steric hindrance around the metal atom (%V<sub>bur</sub> up to 53.0) which is caused by their expanded-ring architecture.
Project description:Development of a synthetic route to the oxaphenalenone (OP) natural products neonectrolides B-E is described. The synthesis relies on gold-catalyzed 6-endo-dig hydroarylation of an unusual enynol substrate as well as a one-pot Rieche formylation/cyclization/deprotection sequence to efficiently construct the tricyclic oxaphenalenone framework in the form of a masked ortho-quinone methide (o-QM). A tandem cycloisomerization/[4 + 2] cycloaddition strategy was employed to quickly construct molecules resembling the neonectrolides. The tricyclic OP natural product SF226 could be converted to corymbiferan lactone E and a related masked o-QM. Our study culminates with the application of the tandem reaction sequence to syntheses of neonectrolides B-E as well as previously unreported exo-diastereomers.
Project description:A set of cycloisomerization methodologies of alkynyl ketones and imines with concurrent acyloxy, phosphatyloxy, or sulfonyloxy group migration, which allow for the efficient synthesis of multisubstituted furans and N-fused heterocycles, has been developed. Investigation of the reaction course by way of employing 17O-labeled substrates allowed for elucidation of the mechanisms behind these diverse transformations. It was found that, while the phosphatyloxy migration in conjugated alkynyl imines in their cycloisomerization to N-fused pyrroles proceeded via a [3,3]-sigmatropic rearrangement, the analogous cycloisomerization of skipped alkynyl ketones proceeds through two consecutive 1,2-migrations, resulting in an apparent 1,3-shift, followed by a subsequent 1,2-migration through competitive oxirenium and dioxolenylium pathways. Investigations of the 1,2-acyloxy migration of conjugated alkynyl ketones en route to furans demonstrated the involvement of a dioxolenylium intermediate. The mechanism of cycloisomerization of skipped alkynyl ketones containing an acyloxy group was found to be catalyst dependent; Lewis and Brønsted acid catalysts caused an ionization/SN1' isomerization to the allene, followed by cycloisomerization to the furan, whereas transition metal catalysts evoked a Rautenstrauch-type mechanistic pathway. Furthermore, control experiments in the cycloisomerization of skipped alkynyl ketones under transition metal catalysis revealed that, indeed, these reactions were catalyzed by transition metal complexes as opposed to Brønsted acids resulting from hydrolysis of these catalysts with eventual water. Further synthetic utility of the obtained phosphatyloxy-substituted heterocycles was demonstrated through their efficient employment in the Kumada cross-coupling reaction with various Grignard reagents.
Project description:Organocopper reagents smoothly react with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this novel cascade transformation, which proceeds via an SN2' substitution followed by a subsequent cycloisomerization step.
Project description:A mechanism of the Au-catalyzed cycloisomerization of propargylpyridines has been investigated. Both DFT computational and experimental results strongly support generation of a Au-carbene via a cyclization/proton transfer sequence over the previously proposed path involving a Au-vinylidene intermediate. For the ?-Si-substituted Au-carbene (G = SiR(3)), a 1,2-Si migration was shown to be kinetically favored over a 1,2-H shift. This study highlights the importance of alternative pathways that could explain reactivities commonly attributed to an alkyne-vinylidene isomerization in Au catalysis.