Anionic Olefin Metathesis Catalysts Enable Modification of Unprotected Biomolecules in Water.

Stability problems have limited the uptake of cationic olefin metathesis catalysts in chemical biology. Described herein are anionic catalysts that improve water-solubility, robustness, and compatibility with biomolecules such as DNA. A sulfonate tag is installed on the cyclic (alkyl)(amino) carbene (CAAC) ligand platform, chosen for resistance to degradation by nucleophiles, base, water, and β-elimination.

Probing Catalyst Degradation in Metathesis of Internal Olefins: Expanding Access to Amine-Tagged ROMP Polymers.

Ruthenium-promoted ring-opening metathesis polymerization (ROMP) offers potentially powerful routes to amine-functionalized polymers with antimicrobial, adhesive, and self-healing properties. However, amines readily degrade the methylidene and unsubstituted ruthenacyclobutane intermediates formed in metathesis of terminal olefins. Examined herein is the relevance of these decomposition pathways to ROMP (i.

Mesomeric Acceleration Counters Slow Initiation of Ruthenium-CAAC Catalysts for Olefin Metathesis (CAAC = Cyclic (Alkyl)(Amino) Carbene).

Ruthenium catalysts bearing cyclic (alkyl)(amino)carbene (CAAC) ligands can attain very high productivities in olefin metathesis, owing to their resistance to unimolecular decomposition. Because the propagating methylidene species RuCl(CAAC)(=CH) is extremely susceptible to bimolecular decomposition, however, turnover numbers in the metathesis of terminal olefins are highly sensitive to catalyst concentration, and hence loadings. Understanding how, why, and how rapidly the CAAC complexes partition between the precatalyst and the active species is thus critical.

Water-Accelerated Decomposition of Olefin Metathesis Catalysts.

Water is ubiquitous in olefin metathesis, at levels ranging from contaminant to cosolvent. It is also non-benign. Water-promoted catalyst decomposition competes with metathesis, even for "robust" ruthenium catalysts.

The Janus face of high trans-effect carbenes in olefin metathesis: gateway to both productivity and decomposition.

Ruthenium-cyclic(alkyl)(amino)carbene (CAAC) catalysts, used at ppm levels, can enable dramatically higher productivities in olefin metathesis than their N-heterocyclic carbene (NHC) predecessors. A key reason is the reduced susceptibility of the metallacyclobutane (MCB) intermediate to decomposition β-H elimination. The factors responsible for promoting or inhibiting β-H elimination are explored density functional theory (DFT) calculations, in metathesis of ethylene or styrene (a representative 1-olefin) by Ru-CAAC and Ru-NHC catalysts.

Routes to High-Performing Ruthenium-Iodide Catalysts for Olefin Metathesis: Ligand Lability Is Key to Efficient Halide Exchange.

Clean, high-yielding routes are described to ruthenium-diiodide catalysts that were recently shown to enable high productivity in olefin metathesis. For the second-generation Grubbs and Hoveyda catalysts (: RuCl(HIMes)(PCy)(=CHPh); : RuCl(HIMes)(=CHAr), Ar = CH-2-O Pr), slow salt metathesis is shown to arise from the low lability of the ancillary PCy or ether ligands, which retards access to the four-coordinate intermediate required for efficient halide exchange. To exploit the lability of the first-generation catalysts, the diiodide complex RuI(PCy)(=CHAr) was prepared by treating "Grubbs I" (RuCl(PCy)(=CHPh), ) with NaI, HC=CHAr (), and a phosphine-scavenging Merrifield iodide () resin.

Bimolecular Coupling in Olefin Metathesis: Correlating Structure and Decomposition for Leading and Emerging Ruthenium-Carbene Catalysts.

Bimolecular catalyst decomposition is a fundamental, long-standing challenge in olefin metathesis. Emerging ruthenium-cyclic(alkyl)(amino)carbene (CAAC) catalysts, which enable breakthrough advances in productivity and general robustness, are now known to be extraordinarily susceptible to this pathway. The details of the process, however, have hitherto been obscure.

The Impact of Water on Ru-Catalyzed Olefin Metathesis: Potent Deactivating Effects Even at Low Water Concentrations.

Ruthenium catalysts for olefin metathesis are widely viewed as water-tolerant. Evidence is presented, however, that even low concentrations of water cause catalyst decomposition, severely degrading yields. Of 11 catalysts studied, fast-initiating examples (e.

Challenging Metathesis Catalysts with Nucleophiles and Brønsted Base: Examining the Stability of State-of-the-Art Ruthenium Carbene Catalysts to Attack by Amines.

Critical to advancing the uptake of olefin metathesis in leading contexts, including pharmaceutical manufacturing, is identification of highly active catalysts that resist decomposition. Amines constitute an aggressive challenge to ruthenium metathesis catalysts. Examined here is the impact of 1,8-diazabicyclo[5.

Origin of the Breakthrough Productivity of Ruthenium-Cyclic Alkyl Amino Carbene Catalysts in Olefin Metathesis.

Examined herein is the basis for the outstanding metathesis productivity of leading cyclic alkyl amino carbene (CAAC) catalysts relative to their important N-heterocyclic carbene (NHC) predecessors, as recently demonstrated in the topical contexts of metathesis macrocyclization and the ethenolysis of renewable oils. The difference is traced to the stability to decomposition of the metallacyclobutane (MCB) intermediate. The CAAC catalysts are shown to undergo little to no β-H elimination of the MCB ring, a pathway to which the HIMes catalysts are highly susceptible.

Integrating Activity with Accessibility in Olefin Metathesis: An Unprecedentedly Reactive Ruthenium-Indenylidene Catalyst.

Access to leading olefin metathesis catalysts, including the Grubbs, Hoveyda, and Grela catalysts, ultimately rests on the nonscaleable transfer of a benzylidene ligand from an unstable, impure aryldiazomethane. The indenylidene ligand can be reliably installed, but to date yields much less reactive catalysts. A fast-initiating, dimeric indenylidene complex () is reported, which reconciles high activity with scaleable synthesis.

Bimolecular Coupling as a Vector for Decomposition of Fast-Initiating Olefin Metathesis Catalysts.

The correlation between rapid initiation and rapid decomposition in olefin metathesis is probed for a series of fast-initiating, phosphine-free Ru catalysts: the Hoveyda catalyst HII, RuCl(L)(═CHCH- o-O Pr); the Grela catalyst nG (a derivative of HII with a nitro group para to O Pr); the Piers catalyst PII, [RuCl(L)(═CHPCy)]OTf; the third-generation Grubbs catalyst GIII, RuCl(L)(py)(═CHPh); and dianiline catalyst DA, RuCl(L)( o-dianiline)(═CHPh), in all of which L = HIMes = N,N'-bis(mesityl)imidazolin-2-ylidene. Prior studies of ethylene metathesis have established that various Ru metathesis catalysts can decompose by β-elimination of propene from the metallacyclobutane intermediate RuCl(HIMes)(κ-CH), Ru-2. The present work demonstrates that in metathesis of terminal olefins, β-elimination yields only ca.

Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures.

Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles, with applications ranging from perfumery to production of antiviral drugs. Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be converted into the cyclic targets by catalysts that are sufficiently reactive to promote backbiting (e.

Decomposition of Olefin Metathesis Catalysts by Brønsted Base: Metallacyclobutane Deprotonation as a Primary Deactivating Event.

Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Major products, in addition to propenes, are base·HCl and olefin-bound, cyclometalated dimers [RuCl(κ-HIMes-H)(HC═CHR)] Ru-3. These are generated in ca.

A General Decomposition Pathway for Phosphine-Stabilized Metathesis Catalysts: Lewis Donors Accelerate Methylidene Abstraction.

Sterically accessible Lewis donors are shown to accelerate decomposition during catalysis, for a broad range of Grubbs-class metathesis catalysts. These include benzylidene derivatives RuCl(NHC)(PCy)(═CHPh) (Ru-2: NHC = HIMes, a; IMes, b; HIPr, c; IPr, d; HITol, e) and indenylidene complexes RuCl(NHC)(PCy)(═CH) (NHC = HIMes, Ru-2f; IMes, Ru-2g). All of these precatalysts form methylidene complex RuCl(NHC)(═CH) Ru-3 as the active species in metathesis of terminal olefins, and generate RuCl(NHC)(PCy)(═CH) Ru-4 as the catalyst resting state.

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty-Chemicals Manufacturing.

The recent uptake of molecular metathesis catalysts in specialty-chemicals and pharmaceutical manufacturing is reviewed.

The divergent effects of strong NHC donation in catalysis.

Strong σ-donation from NHC ligands (NHC = N-heterocyclic carbene) is shown to have profoundly conflicting consequences for the reactivity of transition-metal catalysts. Such donation is regarded as central to high catalyst activity in many contexts, of which the second-generation Grubbs metathesis catalysts (RuCl(NHC)(PCy)([double bond, length as m-dash]CHPh), ) offer an early, prominent example. Less widely recognized is the dramatically inhibiting impact of NHC ligation on initiation of , and on re-entry into the catalytic cycle from the resting-state methylidene species RuCl(NHC)(PCy)([double bond, length as m-dash]CH), .

Acrylate metathesis via the second-generation Grubbs catalyst: unexpected pathways enabled by a PCy3-generated enolate.

The diverse applications of acrylate metathesis range from synthesis of high-value α,β-unsaturated esters to depolymerization of unsaturated polymers. Examined here are unexpected side reactions promoted by the important Grubbs catalyst GII. Evidence is presented for attack of PCy3 on the acrylate olefin to generate a reactive carbanion, which participates in multiple pathways, including further Michael addition, proton abstraction, and catalyst deactivation.

A Ru-isocyanate initiator for fast, living, precisely controlled ring-opening metathesis polymerization at ambient temperatures.

The new complex Ru(NCO)(2)(IMes)(py)(2)(=CHPh) is the first ruthenium metathesis initiator capable of fast, controlled living polymerization of functionalized norbornenes at room temperature, irrespective of monomer bulk.

Chemical plants: high-value molecules from essential oils.

As society faces a future of dwindling petrochemical supplies at increasing cost, much attention has been focused on methods to degrade biomass into renewable commodity-chemical building blocks. Reported here is a powerful complementary approach that amplifies the complexity of molecular structures present in plant materials. Essential-oil phenylpropenoids are transformed via acrylate cross-metathesis into potent antioxidants that are widely used in perfumery and cosmetics, and in treating disorders associated with oxidative damage.

Ethylene-promoted versus ethylene-free enyne metathesis.

The role of ethylene in promoting metathesis of acetylenic enynes is probed within the context of ring-closing enyne metathesis, using first- and second-generation Grubbs catalysts. Under inert atmosphere, rapid catalyst deactivation is observed by calibrated GC-FID analysis for substrates with minimal propargylic bulk. MALDI-TOF mass spectra reveal a Ru(enyne)(2) derivative that exhibits very low reactivity toward both enyne and ethylene.

A reactive Ru-binaphtholate building block with self-tuning hapticity.

A versatile Ru-BINO building block is reported, which offers a straightforward entry point into the chemistry of atropisomeric binaphtholate complexes of ruthenium. Reaction of RuCl(2)(PPh(3))(3)6a with Tl(2)((S)-BINO) affords Ru((S)-BINO)(PPh(3))(2)7 as a mixture of isomers: in 7', the BINO ligand is bound via η(3)-CCO,η(1)-O' donors, and in symmetrical 7″, via η(3)-CCO,η(3)-O'C'C' interactions. The bis(enolate) BINO bonding mode in the latter, not previously observed for any metal, underscores the remarkable geometric and electronic flexibility of the binaphtholate moiety.

Getting ring-closing metathesis off the bench: reaction-reactor matching transforms metathesis efficiency in the assembly of large rings.

Reported is the first study of the influence of reactor configuration on the efficiency of a challenging ring-closing metathesis (RCM) reaction. With the intention of increasing the generality of RCM scaleup and reducing its dependence on substrate modification, macrocyclization of an unmodified, low effective-molarity diene was explored using different reactor types, in conjunction with a commercial, homogeneous Grubbs catalyst. Optimized performance is compared for a conventional batch reactor (BR), a continuous plug-flow reactor (PFR), and a continuous stirred-tank reactor (CSTR).