"Inverted" Cyclic(Alkyl)(Amino)Carbene (CAAC) Ruthenium Complex Catalyzed Isomerization Metathesis (ISOMET) of Long Chain Olefins to Propylene at Low Ethylene Pressure.

Isomerization Metathesis (ISOMET) reaction is an emerging tool for "open loop" chemical recycling of polyethylene to propylene. Novel, latent N-Alkyl substituted Cyclic(Alkyl)(Amino)Carbene (CAAC)-ruthenium catalysts (5a-Ru, 3b-Ru - 6c-Ru) are developed rendering "inverted" chemical structure while showing enhanced ISOMET activity in combination with (RuHCl)(CO)(PPh3)3 (RuH) double bond isomerization co-catalyst. Systematic investigations reveal that the steric hindrance of the substituents on nitrogen and carbon atom adjacent to carbene moiety in the CAAC ligand have significantly improved the catalytic activity and robustness. In contrast to the NHC-Ru and CAAC-Ru catalyst systems known so far, these systems show higher isomerization metathesis (ISOMET) activity (TON: 7400) on the model compound 1-octadecene at as low as 3.0 bar optimized pressure, using technical grade (3.0) ethylene. The propylene content formed in the gas phase can reach up to 20% by volume.

Mechanochemical Scholl Reaction on Phenylated Cyclopentadiene Core: One-Step Synthesis of Fluoreno[5]helicenes.

In this study, we explore feasibility of the mechanochemical approach in the synthesis of tetrabenzofluorenes (fluoreno[5]helicenes). For this, commercially available phenylated cyclopentadiene precursors are subjected to the Scholl reaction in the solid state using FeCl3 as an oxidant and sodium chloride as the solid reaction medium. This ball milling process gave access to the 5-membered ring containing-helicenes in one synthetic step in high (95-96 %) isolated yields. The solution-phase reactions, however, were found to be moderate to low yielding in this regard (10-40 %).

Stereoselective Synthesis of Fluoroalkanes via FLP Mediated Monoselective C─F Activation of Geminal Difluoroalkanes.

A method of desymmetrization of geminal difluoroalkanes using frustrated Lewis pair (FLP) mediated monoselective C-F activation where a chiral sulfide is the Lewis base component is reported. The stereoselective reaction provides generally high yields of diastereomeric sulfonium salts with dr of up to 95:5. The distribution of diastereomers is found to be thermodynamically controlled via facile sulfide exchange. The use of enantiopure chiral sulfides allows for high stereospecificity in nucleophilic substitution reactions and the formation of stereoenriched products.

Insights into the Mechanism of Aluminum-Catalyzed Halodefluorination.

Aluminum has been reported to catalyze halodefluorination reactions, where aliphatic fluorine is substituted with a heavier halogen. Although it is known that stoichiometric aluminum halide can perform this reaction, the role of catalytic aluminum halide and organyl alane reagents is not well understood. We investigate the mechanism of the halodefluorination reaction using catalytic aluminum halide and stoichiometric trimethylsilyl halide. We explore the use of B(C6F5)3 as a catalyst to benchmark pathways where aluminum acts either as a Lewis acid catalyst in cooperation with trimethylsilyl halide or as an independent halodefluorination reagent which is subsequently regenerated by trimethylsilyl halide. Computational and experimental results indicate that aluminum acts as an independent halodefluorination reagent and that reactivity trends observed between different halide reagents can be attributed to relative barriers in halide delivery to the organic fragment, which is the rate-limiting step in both the aluminum halide- and B(C6F5)3-catalyzed pathways.

Experimental and computational insights into the mechanism of FLP mediated selective C-F bond activation.

Frustrated Lewis pairs (FLP) comprising of B(C6F5)3 (BCF) and 2,4,6-triphenylpyridine (TPPy), P(o-Tol)3 or tetrahydrothiophene (THT) have been shown to mediate selective C-F activation in both geminal and chemically equivalent distal C-F sites. In comparison to other reported attempts of C-F activation using BCF, these reactions appear surprisingly facile. We investigate this reaction through a combination of experimental and computational chemistry to understand the mechanism of the initial C-F activation event and the origin of the selectivity that prevents subsequent C-F activation in the monoactivated salts. We find that C-F activation likely occurs via a Lewis acid assisted SN1 type pathway as opposed to a concerted FLP pathway (although the use of an FLP is important to elevate the ground state energy), where BCF is sufficiently Lewis acidic to overcome the kinetic barrier for C-F activation in benzotrifluorides. The resultant intermediate salts of the form [ArCF2(LB)][BF(C6F5)3] (LB = Lewis base) are relatively thermodynamically unstable, and an equilibrium operates between the fluorocarbon/FLP and their activation products. As such, the use of a fluoride sequestering reagent such as Me3SiNTf2 is key to the realisation of the forward C-F activation reaction in benzotrifluorides. Selectivity in this reaction can be attributed to both the installation of bulky Lewis bases geminal to residual C-F sites and from electronic re-ordering of kinetic barriers (of C-F sites in products and starting materials) arising from the electron withdrawing nature of the pyridinium, phosphonium and sulfonium groups.

Late-Stage Formal Double C-H Oxidation of Prenylated Molecules to Alkylidene Oxetanes and Azetidines by Strain-Enabled Cross-Metathesis.

Prenylation is a ubiquitous late-stage modification in nature that often confers significantly improved bioactivity for secondary metabolites. While this lipophilic modification renders enhanced potency, the lipophilic tag(s) can diminish bioavailability and adversely alter drug transportation and metabolism. Thus, a functional-group-tolerant, mild, and selective late-stage C-H functionalization of prenyl tags would present a great potential in drug discovery programs but could also impact other fields, such as agrochemistry and chemical biology. Herein we report an exocyclic-strain-driven cross-metathesis reaction of prenyl tags, a formal double C-H oxidation protocol, that can be used for the selective late-stage derivatization of prenylated compounds and natural products. This methodology avoids the need for prefunctionalization of target molecules and affords ready access to an unprecedented library of oxo- and aza-prenylated complex molecules. Thus, in a broader context, this methodology extends late-stage functionalization beyond that available to nature.

Non-Fullerene Electron Acceptors Based on Hybridisation of Corannulene and Thiophene-S,S-Dioxide Motifs.

Herein we show that hybridisation of buckybowl corannulene and thiophene-S,S-dioxide motifs is a general approach for the preparation of high electron affinity molecular materials. The devised synthesis is modular and relies on thienannulation of corannnulene-based phenylacetylene scaffolds. The final compounds are highly soluble in common organic solvents. These compounds also exhibit interesting optical properties such as absorption and emission in the blue/green regions of the electromagnetic spectrum. Importantly, a bis-S,S-dioxide derivative exhibits three reversible reductions similar in their strength to the prevalent fullerene-based electron acceptor phenyl-C61 -butyric acid methyl ester (PC61 BM).

The Total Synthesis of Raistrickindole A.

The total synthesis of raistrickindole A has been achieved, thereby confirming the proposed structure as an N-hydroxylated DKP. In the first but less selective approach, the DKP was built up by cyclization of a diastereoisomerically mixed N-hydroxylated dipeptide. In the second approach, the same DKP was constructed stereoselectively by the intramolecular Mitsunobu reaction of a hydroxamic acid. The synthesis was completed by a stereoselective oxidative cyclization.

Alkali Metal Adducts of an Iron(0) Complex and Their Synergistic FLP-Type Activation of Aliphatic C-X Bonds.

We report the formation and full characterization of weak adducts between Li+ and Na+ cations and a neutral iron(0) complex, [Fe(CO)3(PMe3)2] (1), supported by weakly coordinating [BArF20] anions, [1·M][BArF20] (M = Li, Na). The adducts are found to synergistically activate aliphatic C-X bonds (X = F, Cl, Br, I, OMs, OTf), leading to the formation of iron(II) organyl compounds of the type [FeR(CO)3(PMe3)2][BArF20], of which several were isolated and fully characterized. Stoichiometric reactions with the resulting iron(II) organyl compounds show that this system can be utilized for homocoupling and cross-coupling reactions and the formation of new C-E bonds (E = C, H, O, N, S). Further, we utilize [1·M][BArF20] as a catalyst in a simple hydrodehalogenation reaction under mild conditions to showcase its potential use in catalytic reactions. Finally, the mechanism of activation is probed using DFT and kinetic experiments that reveal that the alkali metal and iron(0) center cooperate to cleave C-X via a mechanism closely related to intramolecular FLP activation.

Synthesis of azahelicenes through Mallory reaction of imine precursors: corannulene substrates provide an exception to the rule in oxidative photocyclizations of diarylethenes.

Typically, the synthesis of phenanthrene-based polycyclic aromatic hydrocarbons relies on the Mallory reaction. In this approach, stilbene (PhCH[double bond, length as m-dash]CHPh)-based precursors undergo an oxidative photocyclization reaction to join the two adjacent aromatic rings into an extended aromatic structure. However, if one C[double bond, length as m-dash]C carbon atom is replaced by a nitrogen atom (C[double bond, length as m-dash]N), the synthesis becomes practically infeasible. Here, we show the very first examples of a successful Mallory reaction on stilbene-like imine precursors involving the molecularly curved corannulene nucleus. The isolated yields exceed 90% and the resulting single and double aza[4]helicenes exhibit adjustable high affinity for electrons.

Establishing the Role of Triflate Anions in H2 Activation by a Cationic Triorganotin(IV) Lewis Acid.

Cationic Lewis acids (LAs) are gaining interest as targets for frustrated Lewis pair (FLP)-mediated catalysis. Unlike neutral boranes, which are the most prevalent LAs for FLP hydrogenations, the Lewis acidity of cations can be tuned through modulation of the counteranion; however, detailed studies on such anion effects are currently lacking in the literature. Herein, we present experimental and computational studies which probe the mechanism of H2 activation using iPr3SnOTf (1-OTf) in conjunction with a coordinating (quinuclidine; qui) and noncoordinating (2,4,6-collidine; col) base and compare its reactivity with {iPr3Sn·base}{Al[OC(CF3)3]4} (base = qui/col) systems which lack a coordinating anion to investigate the active species responsible for H2 activation and hence resolve any mechanistic roles for OTf- in the iPr3SnOTf-mediated pathway.

Mechanochemical Synthesis of Corannulene-Based Curved Nanographenes.

It is shown that corannulene-based strained π-surfaces can be obtained through the use of mechanochemical Suzuki and Scholl reactions. Besides being solvent-free, the mechanochemical synthesis is high-yielding, fast, and scalable. Therefore, gram-scale preparation can be carried out in a facile and sustainable manner. The synthesized nanographene structure carries positive (bowl-like) and negative (saddle-like) Gaussian curvatures and adopts an overall quasi-monkey saddle-type of geometry. In terms of properties, the non-planar surface exhibits a high electron affinity that was measured by cyclic voltammetry, with electrolysis and in situ UV/vis spectroscopy experiments indicating that the one-electron reduced state displays a long lifetime in solution. Overall, these results indicate the future potential of mechanochemistry in accessing synthetically challenging and functional curved π-systems.

Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones.

A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions.

Catalytic Activity of trans-Bis(pyridine)gold Complexes.

Gold catalysis has become one of the fastest growing fields in chemistry, providing new organic transformations and offering excellent chemoselectivities under mild reaction conditions. Methodological developments have been driven by wide applicability in the synthesis of complex structures, whereas the mechanistic understanding of Au(III)-mediated processes remains scanty and have become the Achilles' heel of methodology development. Herein, the systematic investigation of the reactivity of bis(pyridine)-ligated Au(III) complexes is presented, based on NMR spectroscopic, X-ray crystallographic, and DFT data. The electron density of pyridines modulates the catalytic activity of Au(III) complexes in propargyl ester cyclopropanation of styrene. To avoid strain induced by a ligand with a nonoptimal nitrogen-nitrogen distance, bidentate bis(pyridine)-Au(III) complexes convert into dimers. For the first time, bis(pyridine)Au(I) complexes are shown to be catalytically active, with their reactivity being modulated by strain.

Mechanism of Au(III)-Mediated Alkoxycyclization of a 1,6-Enyne.

Gold-mediated homogeneous catalysis is a powerful tool for construction of valuable molecules and has lately received growing attention. Whereas Au(I)-catalyzed processes have become well established, those mediated by Au(III) have so far barely been explored, and their mechanistic understanding remains basic. Herein, we disclose the combined NMR spectroscopic, single-crystal X-ray crystallographic, and computational (DFT) investigation of the Au(III)-mediated alkoxycyclization of a 1,6-enyne in the presence of a bidentate pyridine-oxazoline ligand. The roles of the counterion, the solvent, and the type of Au(III) complex have been assessed. Au(III) is demonstrated to be the active catalyst in alkoxycyclization. Alkyne coordination to Au(III) involves decoordination of the pyridine nitrogen and is the rate-limiting step.

Tandem double hydrophosphination of α,ß,γ,δ-unsaturated-1,3-indandiones: diphosphine synthesis, mechanistic investigations and coordination chemistry.

A metal-free tandem double hydrophosphination of extended conjugated indandiones has been established. Mechanistic investigations confirmed the consecutive manner of the nucleophilic addition reaction. Complexation of the generated keto-diphosphine resulted in the formation of an unexpected tridentate bridging ligand with an anionic P,O-bidentate and a neutral P-monodentate coordination mode on two palladium units. In the presence of an external chiral auxiliary, the coordinated diphosphines could be separated into their enantiomeric forms.

How an early or late transition state impacts the stereoselectivity of tetrahydropyran formation by intramolecular oxa-Michael addition.

The intramolecular oxa-Michael addition giving tetrahydropyrans has been examined experimentally using both acidic and basic catalysis. With acidic catalysis, the diequatorial product is exclusively obtained in a kinetically controlled reaction in all cases. Under basic conditions at low temperature, the reaction is again under kinetic control, but formation of the axial-equatorial isomer is generally favoured with an (E)-Michael acceptor, although isomerisation to the diequatorial isomer is observed at higher temperatures. Computationally, it is found that the acid catalysed reaction has a late transition state and the kinetic favouring of the diequatorial isomer has a steric explanation. In contrast, under strongly basic conditions, an early transition state is found. Electrostatic effects are likely to be the main contributor to the stereoselectivity for the (E)-isomer and steric interactions for the (Z)-isomer.

Synthesis of (-)-Cytisine Using a 6- endo aza-Michael Addition.

An asymmetric synthesis of (-)-cytisine has been achieved. The piperidine C-ring was formed using a stereodivergent intramolecular 6- endo aza-Michael addition. The B-ring was established by intramolecular pyridine N-alkylation. The absolute stereochemistry was established by an Evans acyl oxazolidinone enolate alkylation reaction that proceeded with an unexpected stereochemical outcome due to participation of the pyridine nitrogen lone pair.