Tetraethylammonium Salts as Solid, Easy to Handle Ethylene Precursors and Their Application in Mizoroki-Heck Coupling.

In this study, we introduce a convenient Heck vinylation protocol that eliminates the requirement for ethylene gas as a coupling partner. In contrast to traditional methodologies, quaternary ammonium salts can serve as solid olefin precursors under ambient atmosphere conditions. The practicality of this method, distinguished by its convenience and safety in a one-pot reaction, renders it appealing for applications in research and discovery context.

Hydrogenative Cycloisomerization and Sigmatropic Rearrangement Reactions of Cationic Ruthenium Carbenes Formed by Catalytic Alkyne gem-Hydrogenation.

gem-Hydrogenation of propargyl alcohol derivatives with [CpX Ru(MeCN)3 ]PF6 (CpX =substituted cyclopentadienyl) as catalysts affords cationic pianostool ruthenium carbene complexes which are so electrophilic that they attack a tethered olefin to furnish cyclopentene products; cyclopropanation or metathesis do not compete with this novel transformation. If the transient carbenes carry appropriate propargylic substituents, however, they engage in ([2,3]-sigmatropic) rearrangements to give enol esters (carbonates, carbamates, sulfonates) or alkenyl halides. Both pathways are unprecedented in the vast hydrogenation literature. The proposed mechanistic scenarios are in line with labeling experiments and spectroscopic data; most notably, PHIP NMR spectroscopy (PHIP=parahydrogen induced polarization) provides compelling evidence that the reactions are indeed triggered by highly unorthodox gem-hydrogenation events.

An Anionic Dinuclear Ruthenium Dihydrogen Complex of Relevance for Alkyne gem-Hydrogenation.

During an investigation into the fate of ruthenium precatalysts used for light-driven alkyne gem-hydrogenation reactions with formation of Grubbs-type ruthenium catalysts, it was found that the reaction of [(IPr)(η6 -cymene)RuCl2 ] with H2 under UV-irradiation affords an anionic dinuclear σ-dihydrogen complex, which is thermally surprisingly robust. Not only are anionic σ-complexes in general exceedingly rare, but the newly formed species seems to be the first example lacking any structural attributes able to counterbalance the negative charge and, in so doing, prevent oxidative insertion of the metal centers into the ligated H2 from occurring.

Difunctionalization of C-C σ-Bonds Enabled by the Reaction of Bicyclo[1.1.0]butyl Boronate Complexes with Electrophiles: Reaction Development, Scope, and Stereochemical Origins.

Difunctionalization reactions of C-C σ-bonds have the potential to streamline access to molecules that would otherwise be difficult to prepare. However, the development of such reactions is challenging because C-C σ-bonds are typically unreactive. Exploiting the high ring-strain energy of polycyclic carbocycles is a common strategy to weaken and facilitate the reaction of C-C σ-bonds, but there are limited examples of highly strained C-C σ-bonds being used in difunctionalization reactions. We demonstrate that highly strained bicyclo[1.1.0]butyl boronate complexes (strain energy ca. 65 kcal/mol), which were prepared by reacting boronic esters with bicyclo[1.1.0]butyl lithium, react with electrophiles to achieve the diastereoselective difunctionalization of the strained central C-C σ-bond of the bicyclo[1.1.0]butyl unit. The reaction shows broad substrate scope, with a range of different electrophiles and boronic esters being successfully employed to form a diverse set of 1,1,3-trisubstituted cyclobutanes (>50 examples) with high diastereoselectivity. The high diastereoselectivity observed has been rationalized based on a combination of experimental data and DFT calculations, which suggests that separate concerted and stepwise reaction mechanisms are operating, depending upon the migrating substituent and electrophile used.

Grubbs Metathesis Enabled by a Light-Driven gem-Hydrogenation of Internal Alkynes.

[(NHC)(cymene)RuCl2 ] (NHC=N-heterocyclic carbene) complexes instigate a light-driven gem-hydrogenation of internal alkynes with concomitant formation of discrete Grubbs-type ruthenium carbene species. This unorthodox reactivity mode is harnessed in the form of a "hydrogenative metathesis" reaction, which converts an enyne substrate into a cyclic alkene. The intervention of ruthenium carbenes formed in the actual gem-hydrogenation step was proven by the isolation and crystallographic characterization of a rather unusual representative of this series carrying an unconfined alkyl group on a disubstituted carbene center.

Hydrogenative Cyclopropanation and Hydrogenative Metathesis.

The unusual geminal hydrogenation of a propargyl alcohol derivative with [CpX RuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap.

Alkyne gem-Hydrogenation: Formation of Pianostool Ruthenium Carbene Complexes and Analysis of Their Chemical Character.

Parahydrogen (p-H2 ) induced polarization (PHIP) NMR spectroscopy showed that [CpX Ru] complexes with greatly different electronic properties invariably engage propargyl alcohol derivatives into gem-hydrogenation with formation of pianostool ruthenium carbenes; in so doing, less electron rich CpX rings lower the barriers, stabilize the resulting complexes and hence provide opportunities for harnessing genuine carbene reactivity. The chemical character of the resulting ruthenium complexes was studied by DFT-assisted analysis of the chemical shift tensors determined by solid-state 13 C NMR spectroscopy. The combined experimental and computational data draw the portrait of a family of ruthenium carbenes that amalgamate purely electrophilic behavior with characteristics more befitting metathesis-active Grubbs-type catalysts.

Iron-Catalyzed Ring-Closing C-O/C-O Metathesis of Aliphatic Ethers.

Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring-closing reactions. Herein, we report an iron-catalyzed ring-closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.

The Delicate Balance of Preorganisation and Adaptability in Multiply Bonded Host-Guest Complexes.

Rigidity and preorganisation are believed to be required for high affinity in multiply bonded supramolecular complexes as they help reduce the entropic penalty of the binding event. This comes at the price that such rigid complexes are sensitive to small geometric mismatches. In marked contrast, nature uses more flexible building blocks. Thus, one might consider putting the rigidity/high-affinity notion to the test. Multivalent crown/ammonium complexes are ideal for this purpose as the monovalent interaction is well understood. A series of divalent complexes with different spacer lengths and rigidities has thus been analysed to correlate chelate cooperativities and spacer properties. Too long spacers reduce chelate cooperativity compared to exactly matching ones. However, in contrast to expectation, flexible guests bind with chelate cooperativities clearly exceeding those of rigid structures. Flexible spacers adapt to small geometric host-guest mismatches. Spacer-spacer interactions help overcome the entropic penalty of conformational fixation during binding and a delicate balance of preorganisation and adaptability is at play in multivalent complexes.

Carbopalladation of C-C σ-bonds enabled by strained boronate complexes.

Transition-metal-catalysed cross-coupling reactions, particularly those mediated by palladium, are some of the most broadly used chemical transformations. The fundamental reaction steps of such cross-couplings typically include oxidative addition, transmetallation, carbopalladation of a π-bond and/or reductive elimination. Herein, we describe an unprecedented fundamental reaction step: a C-C σ-bond carbopalladation. Specifically, an aryl palladium(II) complex interacts with a σ-bond of a strained bicyclo[1.1.0]butyl boronate complex to enable addition of the aryl palladium(II) species and an organoboronic ester substituent across a C-C σ-bond. The overall process couples readily available aryl triflates and organoboronic esters across a cyclobutane unit with total diastereocontrol. The pharmaceutically relevant 1,1,3-trisubstituted cyclobutane products are decorated with an array of modular building blocks, including a boronic ester that can be readily derivatized.

Manganese-Catalyzed Multicomponent Synthesis of Pyrroles through Acceptorless Dehydrogenation Hydrogen Autotransfer Catalysis: Experiment and Computation.

A new base metal catalyzed sustainable multicomponent synthesis of pyrroles from readily available substrates is reported. The developed protocol utilizes an air- and moisture-stable catalyst system and enables the replacement of themutagenic α-haloketones with readily abundant 1,2-diols. Moreover, the presented method is catalytic in base and the sole byproducts of this transformation are water and hydrogen gas. Experimental and computational mechanistic studies indicate that the reaction takes place through a combined acceptorless dehydrogenation hydrogen autotransfer methodology.