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All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight O-glycoproteins that adopt extended linear structures. Glycosylation is integral to mucin function, but other characteristics that give rise to their advantageous biological activities are unknown. We postulated that the extended conformation of mucins is critical for their ability to block microbial virulence phenotypes. To test this hypothesis, we developed synthetic mucin mimics that recapitulate the dense display of glycans and morphology of mucin. We varied the catalyst in a ring-opening metathesis polymerization (ROMP) to generate substituted norbornene-derived glycopolymers containing either cis- or trans-alkenes. Conformational analysis of the polymers based on allylic strain suggested that cis- rather than trans-poly(norbornene) glycopolymers would adopt linear structures that mimic mucins. High-resolution atomic force micrographs of our polymers and natively purified Muc2, Muc5AC, and Muc5B mucins revealed that cis-polymers adopt extended, mucin-like structures. The cis-polymers retained this structure in solution and were more water-soluble than their trans-analogs. Consistent with mucin's linear morphology, cis-glycopolymers were more potent binders of a bacterial virulence factor, cholera toxin. Our findings highlight the importance of the polymer backbone in mucin surrogate design and underscore the significance of the extended mucin backbone for inhibiting virulence., NIBIB/NIH (Grant R01-EB017755), National Institute of Allergy and Infectious Diseases (Grant AI055258)

Addition of one equiv of water to Mo(CAr)[OCMe(CF 3 ) 2 ] 3 (1,2 - dimethoxyethane) ( 2, Ar = o-(OMe)C 6 H 4 ) in the presence of PPhMe 2 leads to formation of Mo(O)(CHAr)[OCMe(CF 3 ) 2 ] 2 (PPhMe 2 ) ( 3(PPhMe 2 ) ) in 3 4 % yield. Addition of one equiv of water alone to 2 produces the dimeric alkylidyne hydroxide complex, { Mo(CAr)[OCMe(CF 3 ) 2 ] 2 ( [mu]-OH)}2(dme) ( 4(dme)) in which each bridging hydroxide proton points toward an oxygen atom in an aryl methoxy group. Addition of PMe 3 to 4(dme) gives the alkylidene oxo complex, (3(PMe 3)), ananalog of 3(PPhMe 2)(95% conversion, 66% isolated). Treatment of 3(PMe 3) with two equiv of HCl gave Mo(O)(CHAr)Cl 2 (PMe 3)(5), which upon addition of LiO-2,6-(2,4,6-i-Pr 3 C 6 H 2) 2C 6 H 3 (LiOHIPT) gave Mo(O)(CHAr)(OHIPT)Cl(PMe 3)(6). Compound 6 in the presence of B(C6F5)3 will initiate the ring - opening metathesis polymeri- zation of cyclooctene, 5,6 - dicarbomethoxynorbornadiene (DCMNBD), and rac-5,6-dicarbomethoxynorbornene (DCMNBE), and the homocouplin g of 1-decene to 9-octa decene. The poly(DCMNBD) has a cis,syndiotactic structure, whereas poly(DCMNBE) has a cis,syndiotactic,alt structure. X - ray structures were obtained for 3(PPhMe 2 ), 4(dme), and 6., National Institutes of Health (U.S.) (GM-58426), National Science Foundation (U.S.) (CHE-0946721)

[Ar₂N₃]Mo(N)(O-t-Bu), which contains the conformationally rigid pyridine-based diamido ligand, [2,6-(ArNCH₂)₂NC₅H₃]²– (Ar = 2,6-diisopropylphenyl), can be prepared from H₂[Ar₂N₃], butyllithium, and (t-BuO)₃Mo(N). [Ar₂N₃]Mo(N)(O-t-Bu) serves as a catalyst or precursor for the catalytic reduction of molecular nitrogen to ammonia in diethyl ether between −78 and 22 °C in a batchwise manner with CoCp*₂ as the electron source and Ph₂NH₂OTf as the proton source. Up to ∼10 equiv of ammonia can be formed per Mo with a maximum efficiency in electrons of ∼43%., United States. Department of Energy (Award DE-SC0013307), National Science Foundation (U.S.) (Grant CHE- 0946721)

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity—namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products—and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D., National Institute of General Medical Sciences (U.S.) (Grant GM-59426), National Institute of General Medical Sciences (U.S.) (Grant CHE-1362763)

Molybdenum complexes with the general formula Mo(NR)(CHR′)(OR″)(Cl)(MeCN) (R = t-Bu or 1-adamantyl; OR″ = a 2,6-terphenoxide) recently have been found to be highly active catalysts for cross-metathesis reactions between Z-internal olefins and Z-1,2-dichloroethylene or Z-(CF₃)CH═CH(CF₃). In this paper we report methods of synthesizing new potential catalysts with the general formula M(NR)(CHR′)(OR″)(Cl)(L) in which M = Mo or W, NR = N-2,6-diisopropylphenyl or NC6F5, and L is a phosphine, a pyridine, or a nitrile. We also test and compare all catalysts in the cross-metathesis of Z-1,2-dichloroethylene and cyclooctene. Our investigations indicate that tungsten complexes are inactive in the test reaction either because the donor is bound too strongly or because acetonitrile inserts into a W═C bond. The acetonitrile or pivalonitrile Mo(NR)(CHR′)(OR″)(Cl)(L) complexes are found to be especially reactive because the 14e Mo(NR)(CHR′)(OR″)Cl core is accessible through dissociation of the nitrile to a significant extent. Pivalonitrile can be removed (>95%) from Mo(NAr)(CHCMe₂Ph)(OHMT)(Cl)(t-BuCN) (Ar = 2,6-diisopropylphenyl; OHMT = 2,6-dimesitylphenoxide) to give 14e Mo(NAr)(CHCMe₂Ph)(OHMT)Cl in solution as a mixture of syn and anti (60:40 at 0.015 M) nitrile-free isomers, but these 14e complexes have not yet been isolated in pure form. The syn isomer of Mo(NAr)(CHCMe₂Ph)(OHMT)Cl binds pivalonitrile most strongly. Other Mo(NR)(CHR′)(OR″)(Cl)(L) complexes can be activated through addition of B(C₆F₅)₃. High stereoselectivities (>98% Z,Z) of ClCH═CH(CH₂)₆CH═CHCl are not restricted to tert-butylimido or adamantylimido complexes; 96.2% Z selectivity is observed with boron-activated Mo(NC₆F₅)(CHR′)(OHIPT)(Cl)(PPhMe₂). So far no Mo═CHCl complexes, which are required intermediates in the test reaction, have been observed in NMR studies at room temperature., National Institutes of Health (U.S.) (Award GM-59426), National Science Foundation (U.S.) (Grant CHE-1463707), National Science Foundation (U.S.) (Grant CHE-0946721)

A new calix[6]azacryptand ligand has been prepared in six steps starting from 1,3,5-trismethoxycalix[6]arene. An X-ray study shows that this ligand has a sterically protected tren-based binding site at the bottom of a polyaromatic bowl and ether sites around its rim. It binds Zn²⁺ to give a complex in which zinc is in a trigonal bipyramidal geometry with a water bound in one apical position and two additional hydrogen-bonded waters that fill the calixarene cavity., United States. Department of Energy (Grant DE-SC0013307)

In the interest of preparing molybdenum and tungsten alkylidene complexes for olefin metathesis that are longer-lived at high temperatures (∼150 °C or above), we synthesized complexes that contain a phenoxide ligand with a 2-pyridyl in one ortho position and a mesityl (Mes) or 2,4,6-i-Pr₃C₆H₂ (Trip) in the other ortho position ([MesON]− or [TripON]−, respectively). The alkylidene (neophylidene) complexes that were prepared include W(O)(CHCMe2Ph)(Me2Pyr)(RON) (R = Mes or Trip), Mo(NC6F5)(CHCMe₂Ph)(RON)Cl, Mo(N-2,6-Me₂C₆H₃)(CHCMe₂Ph)(RON)Cl, Mo(N-t-Bu)(CHCMe₂Ph)(RON)Cl, and M(N-2,6-i-Pr₂C₆H₃)(CHCMe₂Ph)(TripON)(OTf) (M = Mo or W). The reaction between Mo(NAr)(CHCMe₂Ph)(TripON)(OTf) and ethylene yielded an ethylene complex, Mo(NAr)(C₂H₄)(TripON)(OTf)(ether). All neophylidene complexes were essentially unreactive toward terminal olefins at 22 °C and showed modest homocoupling activity (at 80 or 100 °C) and alkane metathesis activity (at 150 and 200 °C). W(O)(CHCMe₂Ph)(Me₂Pyr)(MesON) also stereoselectively polymerized several substituted norbornadienes at 100 °C., United States. Department of Energy (Grant DE-FG02-86ER13564), National Science Foundation (U.S.) (Grant CHE-0946721)

We synthesized Mo(NC[subscript 6]F[subscript 5])(CHCMe[subscript 2]Ph)(TPPO)(PPhMe[subscript 2])Cl (TPPO = 2,3,5,6‐tetraphenylphenoxide), Mo(NC[subscript 6]F[subscript 5])(CHCMe[subscript 2]Ph)(TTBTO)(PPhMe[subscript 2])Cl (TTBTO = 2,6‐di(3′,5′‐di‐tert‐butylphenyl)phenoxide), and Mo(NC[subscript 6]F[subscript 5])(CHCMe[subscript 2]Ph)(TPPO)(PPhMe[subscript 2])(CF[subscript 3]Pyr) (CF[subscript 3]Pyr = 3,4‐bistrifluoromethylpyrrolide), in order to evaluate them as catalysts for the homocoupling of 3‐methyl‐1‐butene. They were compared with Mo(NC[subscript 6]F[subscript 5])(CHCMe[subscript 2]Ph)(HMTO)(PPhMe[subscript 2])Cl (HMTO = 2,6‐dimesitylphenoxide), Mo(NC[subscript 6]F[subscript 5])(CHCMe[subscript 2]Ph)(HIPTO)(PPhMe[subscript 2])Cl (HIPTO = 2,6‐di(2′,4′,6′‐triisopropylphenyl)phenoxide), and several other Mo and Ru catalysts. In the best cases turnover numbers (TONs) of 400 – 700 were observed for the homocoupling of 3‐methyl‐1‐butene in a closed vessel (ethylene not removed). Keywords: Olefin metathesis, Homocoupling, Molybdenum, Ruthenium, 3‐Methyl‐1‐butene, National Science Foundation (U.S.), National Science Foundation (U.S.). Center for Chemical Innovation (CCI Center for Enabling New Technologies through Catalysis. Grant CHE‐1205189)

The largest industrial application of olefin metathesis today is the synthesis of propylene from ethylene and butenes(1) employing WO₃ on SiO₂, a relatively long-lived and regenerable catalyst that operates at 350–400 °C. It is widely proposed that high temperatures are required because the percentage of metal sites actually involved in the metathesis reaction is extremely low, or the reaction that generates alkylidenes is not a high yield reaction, or both. A recent paper by Copéret, Mashima, and co-workers(2) tackles head-on the question concerning how in WO₃/SiO₂ catalysts the alkylidene is formed from an olefin alone. Hundreds of papers have attempted to answer this question, although one has to admit that there may not be a single answer for all supported oxide catalysts or all olefins.

The positive effect of the addition of water to acetone hydrogenation by [RhH₂(PR₃)₂S₂]⁺ catalysts has been studied by DFT calculations. The studied energetic profiles reveal that the more favourable mechanistic path involves a hydride migration to the ketone followed by a reductive elimination that is assisted by two water molecules.

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: The potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization- A particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib- A potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis-was prepared by RCM carried out at a substrate c, National Institutes of Health (U.S.) (Grant GM-59426), National Science Foundation (U.S.) (Grant CHE-1362763)

This tutorial explores the major pathways of forming metal–carbon double bonds in high-oxidation-state alkylidene complexes that began with the alkylidene chemistry of tantalum complexes in the 1970s and continued with the organometallic chemistry of Mo, W, and Re and the development of homogeneous catalysts for the metathesis of olefins. It also explores recent findings in surface organometallic chemistry and discusses the link between molecularly defined and heterogeneous catalysts. Recent results suggest that heterogeneous olefin metathesis catalysts that are activated toward metathesis upon exposure to olefins produce a d[superscript 0] alkylidene through formation of a metallacyclopentane ring at d[superscript 2] metal sites followed by “a ring contraction” to a metallacyclobutane, a reaction that was first observed in tantalum chemistry., National Science Foundation (U.S.) (Grant CHE-1463707)

A “double benzyne” reaction between 1,3-dichloro-2-iodobenzene and 2,4,6-t-Bu₃C₆H₂MgBr followed by the addition of iodine led to 2,6-(2,4,6-t-Bu₃C₆H₂)₂C₆H₃I (HTBTI) in 65% yield. Lithiation of HTBTI with Li-t-Bu gave Li(Et₂O)₂HTBT from which HTBTSH, HTBTN₃, HTBTNH₂, and HTBTOH were prepared. An X-ray structure of W(OHTBT)₂Cl₄ shows that the two HTBTO ligands are trans to one another with the t-Bu₃C6H₂ groups on one HTBTO interdigitated with the t-Bu₃C6H₂ groups on the other HTBTO., National Institutes of Health (U.S.) (Award GM-59426)

The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations., National Institute of General Medical Sciences (U.S.) (Grant GM-59426)

Cis, syndiotactic A-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted- 5,6-norbornenes with "opposite" chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)- (CHR')(OR")(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. This approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers and catalysts., United States. Department of Energy (DE-FG02- 86ER13564)0

A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules., National Institutes of Health (U.S.) (grant GM-59426)

Four alternating AB copolymers have been prepared through ring-opening metathesis polymerization (ROMP) with Mo(NR)(CHCMe₂Ph)[OCMe(CF₃)₂]₂ initiators (R = 2,6-Me₂C₆H₃ (1) or 2,6-i-Pr₂C₆H₃ (2)). The A:B monomer pairs copolymerized by 1 are cyclooctene (A):2,3-dicarbomethoxy-7-isopropylidenenorbornadiene (B), cycloheptene (A′):dimethylspiro[bicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate-7,1′-cyclopropane] (B′), A:B′, and A′:B; A′:B′ and A:B′ are also copolymerized by 2. The >90% poly(A-alt-B) copolymers are formed with heterodyads (AB) that have the trans configuration. Evidence suggests that one trans hetero C═C bond is formed when A (A or A′) reacts with the syn form of the alkylidene made from B (syn-MB = syn-MB or syn-MB′) to give anti-MA, while the other trans C═C bond is formed when B reacts with anti-MA to give syn-MB. Cis and trans AA dyads are proposed to arise when A reacts with anti-MA in competition with B reacting with anti-MA., United States. Department of Energy (DE-FG02-86ER13564), United States. National Institutes of Health (GM-59426)

Molybdenum imido alkylidene and tungsten oxo alkylidene complexes that contain a tridentate “pincer” [ONO]²⁻ ligand have been prepared and treated with ethylene to give unsubstituted metallacyclobutane complexes that have a 16e count. Both Mo and W metallacyclobutane complexes exchange C₂D₄ into the metallacyclobutane ring at 22 °C at a rate that is first order in metal and zero order in C₂D₄. These metallacycles lose ethylene at least 10⁴–10⁵ times slower than reported 14e unsubstituted Mo and W metallacyclobutane complexes that have been explored in the literature that have a TBP geometry with the metallacyclobutane ring bound in the equatorial positions. Our studies suggest that breaking up the metallacyclobutane ring in these 16e d⁰ Mo or W complexes is slow because a 14e TBP metallacyclobutane complex cannot be accessed readily., National Science Foundation (U.S.) (CHE-1205189), National Science Foundation (U.S.) (CHE-0946721)

National Science Foundation (U.S.) (CHE-1111133), National Science Foundation (U.S.) (CHE-0946721)

Carbon–carbon double bonds are an integral part of the chemical industry and are widely found in natural products, from the small and simple (ethylene) to the large and complex. The ability to manipulate carbon–carbon double bonds to make other carbon–carbon double bonds in a catalytic and stereospecific fashion has revolutionized the way organic molecules and polymers are made today. This article outlines the development of modern molybdenum and tungsten alkylidene catalysts that can be designed at a molecular level to achieve a given result. Carbon–carbon triple bonds also can be manipulated in a similar manner with the appropriate alkylidyne catalyst. Although the 'alkene metathesis' and 'alkyne metathesis' reactions are now fifty to sixty years old, many problems remain that will require an even more detailed understanding of these most intricate, superficially simple reactions.

The first examples of catalyst-controlled stereoselective macrocyclic ring-closing metathesis reactions that generate Z-enoates as well as (E,Z)- or (Z,E)-dienoates are disclosed. Reactions promoted by 3.0–10 mol % of a Mo-based monoaryloxide pyrrolide complex proceed to completion within 2–6 h at room temperature. The desired macrocycles are formed in 79:21 to >98:2 Z/E selectivity; stereoisomerically pure products can be obtained in 43–75% yield after chromatography. Utility is demonstrated by application to a concise formal synthesis of the natural product (+)-aspicilin., United States. National Institutes of Health (GM-59426)

Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules., National Institute of General Medical Sciences (U.S.) (GM-59426 and GM-57212)

Ring-opening metathesis polymerization (ROMP) of methyl-N-(1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate (PhEtNNBE; (S) and racemic) was investigated employing six molybdenum and tungsten imido alkylidene initiators and two tungsten oxo alkylidene initiators. Of the six initiators that we proposed should yield cis,syndiotactic-poly[(S)-PhEtNNBE], two molybdenum OHMT alkylidene initiators, Mo(NR)(CHMe2Ph)(pyr)(OHMT) (R = 1-adamantyl (Ad) or 2,6-Me[subscript 2]C[subscript 6]H[subscript 3] (Ar′); OHMT = O-2,6-mesityl[subscript 2]C[subscript 6]H[subscript 3]; pyr = pyrrolide), and two tungsten oxo alkylidene initiators, W(O)(CHMe[subscript 2]Ph)(2,5-dimethylpyrrolide)(PMe2Ph)(OR) (OR = OHMT or (R)-OBr[subscript 2]Bitet where (R)-Br[subscript 2]BitetOH = (R)-3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-ol), produced essentially pure cis,syndiotactic-poly[(S)-PhEtNNBE]. Essentially pure cis,isotactic-poly[(S)-PhEtNNBE] was formed when (S)-PhEtNNBE was polymerized by Mo(NAr′)(CHCMe2Ph)(OBiphen[subscript CF3])(thf) or W(NAr′)(CHCMe[subscript 2]Ph)((S)-OBiphenMe) (OBiphenCF3 = 3,3′-di-tert-butyl-5,5′-bistrifluoromethyl-6,6′-dimethyl-1,1′-biphenyl-2,2′-diolate; (S)-OBiphen[subscript Me] = 3,3′-di-tert-butyl-5,5′,6,6′-tetramethyl-1,1′-biphenyl-2,2′-diolate). The best initiator for ROMP of rac-PhEtNNBE was Mo(NAd)(CHMe[subscript 2]Ph)(pyr)(OHMT) at 0 °C, which led to a polymer that is biased (∼80%) toward a cis,syndiotactic structure and that contains alternating enantiomers in the chain (cis,syndio,alt-poly[(rac)-PhEtNNBE])., United States. Department of Energy (grant DE-FG0286ER13564), Singapore. Agency for Science, Technology and Research (A*STAR International Fellowship), Alexander von Humboldt-Stiftung (Feodor Lynen Research Fellowship)

United States. Department of Energy (DE-FG02-86ER13564)

Partial bromination or epoxidation has been used to prove the tacticities of several stereoregular polymers made through ROMP methods with well-defined Mo or W initiators.Tacticities were proven for cis,isotactic and cis,syndiotactic poly(norbornene), poly(3-methyl-3-phenylcyclopropene), and poly(endo,anti-tetracyclododecene). Various limitations can prevent application of these proofs in general to stereoregular polymers prepared through ROMP., United States. Department of Energy (DE-FG02-86ER13564)

Molybdenum and tungsten alkylidene complexes that contain the sterically demanding hexaisopropylterphenylimido ligand, N-2,6-(2,4,6-i-Pr[subscript 3]C[subscript 6]H[subscript 2])[subscript 2]C[subscript 6]H[subscript 3] (NHIPT), have been prepared from Mo(N-t-Bu)[subscript 2]Cl[subscript 2](1,2-dimethoxyethane) or W(N-t-Bu)[subscript 2]Cl[subscript 2](pyridine)[subscript 2], employing tert-butylimido ligands as sacrificial proton acceptors. These complexes include M(NHIPT)(CH-t-Bu)Cl[subscrip 2] (M = Mo, W), Mo(NHIPT)(CH-t-Bu)(pyrrolide)[subscript 2], and Mo(NHIPT)(CH-t-Bu)(pyrrolide)(OC[subscript 6]F[subscript 5])(CH[subscript 3]CN). In all cases only anti alkylidene isomers are observed in solution, as a consequence of the steric demands of the NHIPT ligand. An X-ray structure of W(NHIPT)(CH-t-Bu)Cl[subscript 2] showed it to be a monomer with a disordered alkylidene that is 86% in the anti configuration and 14% in the syn configuration., National Science Foundation (U.S.) (Grant CHE-1111133), National Institutes of Health (U.S.) (Grant GM-59426), National Science Foundation (U.S.) (Grant CHE-0946721)

We report the synthesis of >98% cis,isotactic and cis,syndiotactic polynorbornene (poly(NBE)) and poly(endo,anti-tetracyclododecene) (poly(TCD)). Cis,isotactic poly(NBE) and poly(TCD) were prepared employing Mo-based biphenolate imido alkylidene initiators, Mo(NR)(CHCMe[subscript 2]Ph)(Biphen) (Biphen = e.g., 3,3′-(t-Bu)[subscript 2]-5,5′-6,6′-(CH[subscript 3])[subscript 4]-1,1′-biphenyl-2,2′-diolate), while cis,syndiotactic poly(NBE) and poly(TCD) were prepared employing W-based imido or oxo monoaryloxide pyrrolide (MAP) initiators, W(X)(CHR′)(Pyrrolide)(OTer) (X = NR or O; OTer = a 2,6-terphenoxide). Addition of 1-hexene or coordinating solvents such as THF do not decrease the stereospecificity of the polymerization. Cis,iso and cis,syndio dyads can be distinguished through examination of [superscript 1]H and [superscript 13]C NMR spectra of the two polymers in a mixture. The polymers were hydrogenated to give isotactic and syndiotactic H-poly(NBE) and H-poly(TCD)., United States. Department of Energy (grant DE-FG0286ER13564)

Ring-opening metathesis polymerization (ROMP) is used to prepare trans-poly(A-alt-B) polymers from a 1:1 mixture of A and B where A is a cyclic olefin such as cyclooctene (A[subscript 1]) or cycloheptene (A[subscript 2]) and B is a large norbornadiene or norbornene derivative such as 2,3-dicarbomethoxy-7-isopropylidenenorbornadiene (B[subscript 1]) or dimethylspirobicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate-7,1'cyclopropane (B[subscript 2]). The most successful initiators that were examined are of the type Mo(NR)(CHCMe[subscript 2]Ph)[OCMe(CF[subscript 3])[subscript 2]][subscript 2] (R = 2,6-Me[subscript 2]C[subscript 6]H[subscript 3] (1) or 2,6-iPr[subscript 2]C[subscript 6]H[subscript 3] (2)). The trans configuration of the AB linkages is proposed to result from the steric demand of B. Both anti-MB and syn-MB alkylidenes are observed during the copolymerization, where B was last inserted into a Mo=C bond, although anti-MB dominates as the reaction proceeds. Anti-MB is lower in energy than syn-MB, does not react readily with either A or B, and interconverts slowly with syn-MB through rotation about the Mo=C bond. Syn-MB does not readily react with B, but it does react slowly with A (rate constant ~1 M[superscript -1] s [superscript -1]) to give anti-MA and one trans-AB linkage. Anti-MA then reacts with B (rate constant ~300 M[superscript -1] s[superscript -1] or larger) to give syn-MB and the second trans-AB linkage. The reaction has been modeled using experimental data in order to obtain the estimated rate constants above. The reaction between anti-MA and A is proposed to give rise to AA linkages, but AA dyads can amount to <5%. Several other possible A and B monomers, initiators, and conditions were explored., United States. Dept. of Energy (Grant DE-FG02-86ER13564)

We report here the polymerization of several 7-isopropylidene-2,3-disubstituted norbornadienes, 7-oxa-2,3-dicarboalkoxynorbornadienes, and 11-oxa-benzonorbornadienes with a single tungsten oxo alkylidene catalyst, W(O)(CH-t-Bu)(OHMT)(Me2Pyr) (OHMT = 2,6-dimesitylphenoxide; Me2Pyr = 2,5-dimethylpyrrolide) to give cis, stereoregular polymers. The tacticities of the menthyl ester derivatives of two polymers were determined for two types. For poly(7-isopropylidene-2,3-dicarbomenthoxynorbornadiene) the structure was shown to be cis,isotactic, while for poly(7-oxa-2,3-dicarbomenthoxynorbornadiene) the structure was shown to be cis,syndiotactic. A bis-trifluoromethyl-7-isopropylidene norbornadiene was not polymerized stereoregularly with W(O)(CHCMe2Ph)(Me2Pyr)(OHMT) alone, but a cis, stereoregular polymer was formed in the presence of 1 equiv of B(C6F5)3., United States. Dept. of Energy (DE-FG02- 86ER13564), Defense Threat Reduction Agency (DTRA) (Chemical and Biological Technologies, grant BA12PHM123 in the “Dynamic Multifunctional Materials for a Second Skin D[MS]2” program)

A convergent diastereo- and enantioselective total synthesis of anticancer and antifungal macrocyclic natural product disorazole C1 is reported. The central feature of the successful route is the application of catalytic Z-selective cross-metathesis (CM). Specifically, we illustrate that catalyst-controlled stereoselective CM can be performed to afford structurally complex Z-alkenyl–B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high selectivity (pin = pinacolato). The resulting intermediates are then joined in a single-step operation through catalytic inter- and intramolecular cross-coupling to furnish the desired 30-membered ring macrocycle containing the critical (Z,Z,E)-triene moieties., National Institutes of Health (U.S.) (NIH (GM-59426)

Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring-opening/cross-metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule., National Institutes of Health (U.S.) (NIH grant GM-59426), National Institutes of Health (U.S.) (NIH grant GM-57212), AstraZeneca (Firm) (Graduate Fellowship), National Science Foundation (U.S.) (NSF award CHE-1362763)

We have employed 2,3-dicarbomethoxynorbornadiene (DCMNBD) as a monomer to explore new tungsten oxo alkylidene complexes as initiators for stereoregular ROMP (ring-opening metathesis polymerization). The initiators include MAP (monoaryloxide pyrrolide) oxo alkylidene complexes with the general formula W(O)(CHCMe[subscript 2]Ph)(Me[subscript 2]Pyr)(OAr) (Me[subscript 2]Pyr = 2,5-dimethylpyrrolide, OAr = an aryloxide) and W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2] (OR = an aryloxide or OC(CF[subscript 3])[subscript 3]), or PPh[subscript 2]Me or CH[subscript 3]CN adducts thereof. We have found that MAP initiators yield cis,syndiotactic-poly(DCMNBD) as a consequence of stereogenic metal control. In contrast, W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2](L) initiators (where L = PPh[subscript 2]Me or acetonitrile) are strongly biased toward formation of cis,isotactic structures, while W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2] initiators are strongly biased toward formation of cis,syndiotactic structures. Addition of B(C[subscript 6]F[subscript 5])[subscript 3] to W(O)(CHCMe[subscript 2]Ph)(Me[subscript 2]Pyr)(OR) species leads to a dramatic increase in the rate of polymerization and to an increase in the cis,syndiotacticity of the polymer (if not already high), while addition of B(C[subscript 6]F[subscript 5])[subscript 3] to W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2] initiators leads to a dramatic increase in the rate of polymerization and to the formation of highly cis,syndiotactic polymers. All evidence supports the proposal that 16e W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2](L) complexes can operate either through loss of L to yield 14e W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2] species (which yield largely cis,syndiotactic-poly(DCMNBD)) or by directly reacting with DCMNBD to yield an 18e intermediate and largely cis,isotactic-poly(DCMNBD). All polymerizations by W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2](L) and W(O)(CHCMe[subscript 2]Ph)(OR)[subscript 2] initiat, United States. Dept. of Energy (DE-FG02-86ER13564), National Science Foundation (U.S.) (CHE-1111133)

Steady-state and ultrafast transient absorption spectra were obtained for a series of conformationally constrained, isomerically pure polyenes with 5–23 conjugated double bonds (N). These data and fluorescence spectra of the shorter polyenes reveal the N dependence of the energies of six [superscript 1]B[subscript u] [superscript +] and two [superscript 1]A[subscript g] [superscript –] excited states. The [superscript 1]B[subscript u] [superscript +] states converge to a common infinite polyene limit of 15 900 ± 100 cm [superscript –1]. The two excited [superscript 1]A[subscript g] [superscript –] states, however, exhibit a large (∼9000 cm–1) energy difference in the infinite polyene limit, in contrast to the common value previously predicted by theory. EOM-CCSD ab initio and MNDO-PSDCI semiempirical MO theories account for the experimental transition energies and intensities. The complex, multistep dynamics of the 1[superscript 1]B[subscript u] [superscript +] → 2 [superscript 1]A[subscript g] [superscript –] → 1 [superscript 1]A[subscript g] [superscript –] excited state decay pathways as a function of N are compared with kinetic data from several natural and synthetic carotenoids. Distinctive transient absorption signals in the visible region, previously identified with S* states in carotenoids, also are observed for the longer polyenes. Analysis of the lifetimes of the 2 [superscript 1]A[subscript g] [superscript –] states, using the energy gap law for nonradiative decay, reveals remarkable similarities in the N dependence of the 2 [superscript 1]A[subscript g] [superscript –] decay kinetics of the carotenoid and polyene systems. These findings are important for understanding the mechanisms by which carotenoids carry out their roles as light-harvesting molecules and photoprotective agents in biological systems., United States. Dept. of Energy (DE-FG02-86ER13564), National Science Foundation (U.S.) (Grant EMT-0829916), National Institutes of Health (U.S.) (Grant GM-34548)

The first examples of catalytic cross-metathesis (CM) reactions that furnish Z-(pinacolato)allylboron and Z-(pinacolato)alkenylboron compounds are disclosed. Products are generated with high Z selectivity by the use of a W-based monoaryloxide pyrrolide (MAP) complex (up to 91% yield and >98:2 Z:E). The more sterically demanding Z-alkenylboron species are obtained in the presence of Mo-based MAP complexes in up to 93% yield and 97% Z selectivity. Z-selective CM with 1,3-dienes and aryl olefins are reported for the first time. The utility of the approach, in combination with catalytic cross coupling, is demonstrated by a concise and stereoselective synthesis of anticancer agent combretastatin A-4., National Institutes of Health (U.S.) (GM-59426), National Institutes of Health (U.S.) (GM-47480)

A tandem catalytic reaction has been developed as part of a process to discover tungsten-based olefin metathesis catalysts that have a strong preference for terminal olefins over cis or trans internal isomers in olefin metathesis. This tandem isomerization/terminal olefin metathesis reaction (ISOMET) converts C[subscript n] trans internal olefins into C[subscript 2n–2] cis olefins and ethylene. This reaction is made possible with Ru-based “alkene zipper” catalysts, which selectively isomerize trans olefins to an equilibrium mixture of trans and terminal olefins, plus tungsten-based metathesis catalysts that react relatively selectively with terminal olefins to give Z homocoupled products. The most effective catalysts are W(NAr)(C[subscript 3]H[subscript 6])(pyr)(OHIPT) (Ar = 2,6-diisopropylphenyl; pyr = pyrrolide; OHIPT = O-2,6-(2,4,6-i-Pr[subscript 3]C[subscript 6]H[subscript 2])[subscript 2]C[subscript 6]H[subscript 3]) and various [CpRu(P–N)(MeCN)]X (X[superscript –] = [B(3,5-(CF[subscript 3])[subscript 2]C[subscript 6]H[subscript 3])[subscript 4][superscript –]], PF[subscript 6][superscript –], B(C[subscript 6]F[subscript 5])[subscript 4][superscript –]) isomerization catalysts., National Science Foundation (U.S.). Center for Chemical Innovation. Center for Enabling New technologies through Catalysis (Phase II Renewal. CHE-120518), National Science Foundation (U.S.) (CHE-1059107)

n-Alkyl arenes were prepared in a one-pot tandem dehydrogenation/olefin metathesis/hydrogenation sequence directly from alkanes and ethylbenzene. Excellent selectivity was observed when (tBuPCP)IrH[subscript 2] was paired with tungsten monoaryloxide pyrrolide complexes such as W(NAr)(C[subscript 3]H[subscript 6])(pyr)(OHIPT) (1a) [Ar = 2,6-i-Pr[subscript 2]C[subscript 6]H[subscript 3]; pyr = pyrrolide; OHIPT = 2,6-(2,4,6-i-Pr[subscript 3]C[subscript 6]H[subscript 2])[subscript 2]C[subscript 6]H[subscript 3]O]. Complex 1a was also especially active in n-octane self-metathesis, providing the highest product concentrations reported to date. The thermal stability of selected olefin metathesis catalysts allowed elevated temperatures and extended reaction times to be employed., National Science Foundation (U.S.) (CCI Center for Enabling New Technologies through Catalysis (CENTC) Phase II Renewal (CHE-1205189))

Ring-opening metathesis polymerization of a series of 3-substituted cyclooctenes (3-MeCOE, 3-HexCOE, and 3-PhCOE) initiated by various Mo and W MAP complexes leads to cis,HT-poly(3-RCOE) polymers. The apparent rate of polymerization of 3-HexCOE by W(N-t-Bu)(CH-t-Bu)(Pyr)(OHMT) (1c; Pyr = pyrrolide; OHMT = O-2,6-Mesityl[subscript 2]C[subscript 6]H[subscript 3]) is greater than the rate of polymerization by Mo(N-t-Bu)(CH-t-Bu)(Pyr)(OHMT) (1b), but both gave the same cis,HT polymer structures. Formation of HT-poly(3-RCOE) employing 1c takes place via propagating species in which the R group (methyl, hexyl, or phenyl) is on C2 of the propagating alkylidene chain, a type of intermediate that has been modeled through the preparation of W(N-t-Bu)(CHCHMeEt)(Pyr)(OHMT). The rate of ROMP is exceedingly sensitive to steric factors: e.g., W(N-t-Bu)(CH-t-Bu)(Me[subscript 2]Pyr)(OHMT), the dimethylpyrrolide analogue of 1c, essentially did not polymerize 3-HexCOE at 22 °C. When a sample of W(N-t-Bu)(CHCHMeEt)(Pyr)(OHMT) and 3-methyl-1-pentene in CDCl[subscript 3] is cooled to −20 °C, the alkylidene resonances for W(N-t-Bu)(CHCHMeEt)(Pyr)(OHMT) disappear and resonances that can be ascribed to protons in a syn[subscript α]/syn[subscript α′] disubstituted trigonal bipyramidal metallacyclobutane complex appear. 3-Methyl-1-pentene is readily lost from this metallacycle on the NMR time scale at room temperature., United States. Dept. of Energy (DE-FG02-86ER13564)

The bisDFTO alkylidene complexes of molybdenum Mo(NR)(CHCMe2Ph)(DFTO)2 (R = 2,6-i-Pr2C6H3, 2,6-Me2C6H3, C6F5, 1-adamantyl; DFTO = 2,6-(C6F5)2C6H3O) and monoaryloxide monopyrrolide (MAP) complexes Mo(NR)(CHCMe2Ph)(Me2Pyr)(OAr) (Me2Pyr = 2,5-dimethylpyrrolide; R = C6F5, OAr = DFTO, 2,6-dimesitylphenoxide (HMTO); R = 2,6-Me2C6H3, OAr = DFTO) have been prepared in good yields. Addition of dicarbomethoxynorbornadiene (DCMNBD) to bisDFTO complexes yielded polymers that have a cis,isotactic structure. Polymerization of DCMNBD by Mo(NC6F5)(CHCMe2Ph)(Me2Pyr)(HMTO) gives a polymer that contains the expected cis,syndiotactic structure, but polymerization of DCMNBD by Mo(NR)(CHCMe2Ph)(Me2Pyr)(DFTO) (R = C6F5, 2,6-Me2C6H3) generates a polymer that has a cis,isotactic structure, the first observation of a cis,isotactic polymer prepared employing a MAP initiator. Norbornene is polymerized to give what is proposed to be highly tactic cis-polyNBE. Addition of ethylene to Mo(NC6F5)(CHCMe2Ph)(DFTO)2 leads to formation of Mo(NC6F5)(CH2CH2)(DFTO)2, which also behaves as an initiator for polymerization of DCMNBD to cis,isotactic-polyDCMNBD and norbornene to cis highly tactic polyNBE. Mo(NC6F5)(CH2CH2)(DFTO)2 reacts with 3-methyl-3-phenylcyclopropene (MPCP) to give Mo(NC6F5)(CHCHCMePh)(DFTO)2 in 50% yield., National Science Foundation (U.S.) (CHE- 1111133), United States. Dept. of Energy (DE-FG02-86ER13564), National Science Foundation (U.S.) (NSF (CHE-9808061))

Upon treatment with a molybdenum-carbene with bidentate substituted biaryl-o,o′-diphenoxide ligand 12, norbornene fused with N-aryl-endo-pyrrolidine 9a undergoes ROMP to give exclusively polynorbornene with cis, isotactic-selectivity. Bis(norbornenes) connected with ferrocene 18 or benzene 20 linkers yield the corresponding double-stranded ladderphanes 19 and 21, respectively with isotactic stereochemistry having all double bonds in Z-configuration. Like the corresponding ladderphanes with E-double bonds, ladderphane 19 also assembles on HOPG to give a highly ordered two-dimensional array as revealed by STM images.

Routes to new tungsten alkylidene complexes that contain tert-butylimido or adamantylimido ligands have been devised that begin with a reaction between WCl[subscript 6] and 4 equivalents of HNR(TMS) to give [W(NR)[subscript 2]Cl(μ-Cl)(RNH[subscript 2])][subscript 2] (R = t-Bu or 1-adamantyl). Alkylation leads to W(NR)[subscript 2](CH[subscript 2]R′)[subscript 2] (R′ = t-Bu or CMe[subscript 2]Ph), which upon treatment with pyridinium chloride yields W(NR)(CHR′)Cl[subscript 2](py)[subscript 2] complexes, from which W(NR)(CHR′)(pyrrolide)[subscript 2] and two W(N-t-Bu)(CHR′)(pyrrolide)(OAr) complexes (OAr = hexamethyl- or hexaisopropylterphenoxide) have been prepared., National Science Foundation (U.S.) (CHE-1111133), National Science Foundation (U.S.) (Grant CHE-0946721)

In this paper we describe the syntheses of several new stereogenic-at-metal imido alkylidene complexes of molybdenum, Mo(NR)(CHR′)(X)(Y), many of which had to be prepared through selective nucleophilic displacement reactions in imido alkylidene complexes. The reported compounds include Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)[subscript 2] (1a; MesPyr = 2-mesitylpyrrolide, Ad = 1-adamantyl), Mo(NAd)(CHCMe[subscript 2]Ph)(2-CNPyr)[subscript 2] (1b; 2-CNPyr = 2-cyanopyrrolide), Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)(OTPP) (2a; OTPP = 2,3,5,6-tetraphenylphenoxide), Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)(OBr[subscript 2]Bitet) (2b; OBr[subscript 2]Bitet = (R)-3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate), Mo(NAd)(CHCMe[subscript 2]Ph)(OHIPT)(2-Mespyr) (2c; HIPT = 2,6-(2,4,6-iPr[subscript 3]C[subscript 6]H[subscript 2])[subscript 2]C[subscript 6]H[subscript 3]), Mo(NAd)(CHCMe[subscript 2]Ph)(OTf)(OHIPT) (3), Mo(NAd)(CHCMe[subscript 2]Ph)(OTf)(OHIPT)(PMe[subscript 3]) (3(PMe[subscript 3])), Mo(NAd)(CHCMe[subscript 2]Ph)(2-CNPyr)(OHIPT) (4), Mo(NAd)(CHCMe[subscript 2]Ph)(OHIPT)(OCMe[subscript 3]) (5), Mo(NR)(CHCMe[subscript 2]Ph)(OR[subscript F6])(OHMT) (OR[subscript F6] = OCMe(CF[subscript 3])[subscript 2]; HMT = 2,6-Mes[subscript 2]C[subscript 6]H[subscript 3]; R = 2,6-iPr[subscript 2]C[subscript 6]H[subscript 3] (Ar, 6a), 2,6-Me[subscript 2]C[subscript 6]H[subscript 3] (Ar′, 6b), 2-iPrC[subscript 6]H[subscript 4] (Ar[sueprscript iPr], 6c), Ad (6d)), Mo(NR)(CHCMe[subscript 2]Ph)(OR[subscript F6])[N(H)HMT] (7a (R = Ar′) and 7b (R = Ar[superscript iPr])), and Mo(NAd)(CHCMe[subscript 2]Ph)(OR[subscript F6])(HMT) (8). X-ray structural studies were carried out on 1b, 2a–c, 3(PMe[subscript 3]), 4, 5, 6d, 7b, and 8. Compound 1b is an octamer in which two η[superscript 1]-pyrrolides are trans to one another at each metal center and cyano groups bind from neighboring Mo centers trans to the alkylidene and imido ligands., National Science Foundation (U.S.) (CHE-0841187), National Science Foundation (U.S.) (CHE-0946721), National Science Foundation (U.S.) (CHE-111133), National Science Foundation (U.S.) (CHE-9808061)

Efficient catalytic cross-metathesis reactions that afford Z-disubstituted allylic silyl or benzyl ethers are reported (see scheme, MAP=monoalkoxide pyrrolide). The approach, in combination with catalytic cross-coupling, provides a general entry to otherwise difficult-to-access alkyne-containing Z olefins., National Institutes of Health (U.S.) (GM-59426)

The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2–7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule., National Institutes of Health (U.S.) (GM-59426)

Reaction of W(O)[subscript 2](CH[subscript 2]-t-Bu)[subscript 2](bipy) with a mixture of ZnCl[subscript 2](dioxane), PMe[subscript 2]Ph, and trimethylsilyl chloride in toluene at 100 °C produced the known tungsten oxo alkylidene complex W(O)(CH-t-Bu)Cl[subscript 2](PMe[subscript 2]Ph)[subscript 2] (1a) in 45% isolated yield. The neophylidene analogue W(O)(CHCMe[subscript 2]Ph)Cl[subscript 2](PMe[subscript 2]Ph)[subscript 2] was prepared similarly in 39% yield. The reaction between 1a and LiOR (LiOR = LiOHIPT, LiOHMT) in benzene at 22 °C led to formation of the off-white W(O)(CH-t-Bu)Cl(OR)(PMe[subscript 2]Ph) complexes 4a (OR = OHMT = 2,6-dimesitylphenoxide) and 4b (OR = OHIPT = 2,6-(2,4,6-triisopropylphenyl)[subscript 2]phenoxide). Compound 4a serves as a starting material for the synthesis of W(O)(CH-t-Bu)(OHMT)(2,6-diphenylpyrrolide) (6), W(O)(CH-t-Bu)[N(C[subscript 6]F[subscript 5])[subscript 2]](OHMT)(PMe[subscript 2]Ph) (7), W(O)(CH-t-Bu)[OSi(t-Bu)[subscript 3]](OHMT) (8), and W(O)(CH-t-Bu)(OHMT)[subscript 2] (10). The reaction between 8 and ethylene was found to yield the square-pyramidal metallacyclobutane complex W(O)(C[subscript 3]H[subscript 6])[OSi(t-Bu)[subscript 3]](OHMT) (9), while the reaction between 10 and ethylene was found to yield the square-pyramidal metallacyclobutane complex W(O)(C[subscript 3]H[subscript 6])(OHMT)[subscript 2] (11). Compound 11 loses ethylene to yield isolable W(O)(CH[subscript 2])(OHMT)[subscript 2] (12). X-ray structures were determined for 6, 7, 9, and 12., National Science Foundation (U.S.) (CHE-1111133), National Science Foundation (U.S.) (CHE-9808061)

Alkyne metathesis by molybdenum and tungsten alkylidyne complexes is now ~45 years old. Progress in the practical aspects of alkyne metathesis reactions with well-defined complexes, as well as applications, in the last decade, guarantees that it is destined to become a useful method for the synthesis of organic molecules.

Addition of rac-DCENBE (2,3-dicarboethoxynorbornene) or rac-DCBNBE (2,3-dicarbo-tert-butoxynorbornene) to Mo(NAd)(CHCMe[subscript 2]Ph)(Pyr)(OHMT) (1a) (Ad = 1-adamantyl, OHMT = 2,6-dimesitylphenoxide, Pyr– = NC[subscript 4]H[subscript 4]–) led to the formation of polymers that have a cis,syndiotactic,alt structure analogous to the structure observed for the polymer obtained from rac-DCMNBE (2,3-dicarbomethoxynorbornene). The PDI of cis,syndio,alt-poly(DCBNBE) is low and decreases as the polymer length increases, and there is a linear relationship between the number of equivalents of monomer employed and the molecular weight of the polymers measured in THF versus polystyrene standards. In contrast, polymerization of (+)-DCMNBE by 1a at 25, 0, −25, and −40 °C yields a polymer that contains ~25% trans,isotactic dyads and 75% cis,syndiotactic dyads. A similar polymerization by Mo(NAd)(CHCMe[subscript 2]Ph)(Pyr)(OHIPT) (1b) (OHIPT = 2,6-(2,4,6-i-Pr[subscript 3])[subscript 2]C[subscript 6]H[subscript 3]) gives a polymer that contains cis,syndiotactic and trans,isotactic dyads in a ratio of ~8:92, respectively. This is the first report of synthesis of a norbornene polymer that has primarily a trans,isotactic structure. Addition of 100 equiv of (+)-DCMNBE, (−)-DCENBE, or (−)-DCBNBE to a toluene solution of W(O)(CH-t-Bu)(2,5-Me[subscript 2]NC[subscript 4]H[subscript 2])(OHMT)(PMe[subscript 2]Ph) (5) led to formation of ~99% cis,syndiotactic polymer. Cis,syndiotactic dyads arise through a mechanism that consists of a syn approach of the monomer to a syn alkylidene isomer followed by inversion of configuration at the metal center as a consequence of an exchange of aryloxide and pyrrolide ligands. The mechanism for formation of trans,isotactic dyads is one in which the monomer approaches in an anti fashion to the syn isomer followed by a “turnstile” rotation in the five-coordinate intermediate metallacyclobutane that allows the metallacylic ring to open productively with reten, United States. Dept. of Energy (DE-FG02-86ER13564)

Olefin metathesis catalysts for controlling the formation of trisubstituted macrocyclic Z alkenes have been developed. The most effective complexes are Mo alkylidenes with a pentafluorophenylimido group and two large aryloxide ligands. The macrocyclic lactone precursor to anticancer agents epothilones B and D is obtained in 73% yield and 91% Z selectivity in less than 6 hours at room temperature., National Institutes of Health (U.S.) (GM-59426)

Molybdenum and tungsten bispyrrolide alkylidene complexes that contain a 2,6-dimesitylphenylimido (NAr*) ligand have been prepared, in which the pyrrolide is the parent pyrrolide or 2,5-dimethylpyrrolide. Monoalkoxide pyrrolide (MAP) complexes were prepared through addition of 1 equiv of an alcohol to the bispyrrolide complexes. MAP compounds that contain the parent pyrrolide (NC[subscript 4]H[– over 4]) are pyridine adducts, while those that contain 2,5-dimethylpyrrolide are pyridine free. Molybdenum and tungsten MAP 2,5-dimethylpyrrolide complexes that contain O-t-Bu, OCMe(CF[subscript 3])[subscript 2], or O-2,6-Me[subscript 2]C[subscript 6]H[subscript 3] ligands were found to have approximately equal amounts of syn and anti alkylidene isomers, which allowed a study of the interconversion of the two employing [superscript 1]H–[superscript 1]H EXSY methods. The K[subscript eq] values ([syn]/[anti]) are all 2–3 orders of magnitude smaller than those observed for a large number of Mo bisalkoxide imido alkylidene complexes, as a consequence of the destabilization of the syn isomer by the sterically demanding NAr* ligand. The rates of interconversion of syn and anti isomers were found to be 1–2 orders of magnitude faster for W MAP complexes than for Mo MAP complexes., National Science Foundation (U.S.) (CHE-1111133), National Science Foundation (U.S.) (CHE-9808061), National Science Foundation (U.S.) (CHE-0946721)

We report the synthesis of Mo and W MAP complexes that contain O-2,6-(2,5-R[subscript 2]-pyrrolyl)[subscript 2]C[subscript 6]H[subscript 3] (2,6-dipyrrolylphenoxide or ODPP[superscript R]) ligands in which R = i-Pr, Ph. W(NAr)(CH-t-Bu)(Pyr)(ODPP[superscript Ph]) (4a; Ar = 2,6-disopropylphenyl, Pyr = pyrrolide) reacts readily with ethylene to yield a metallacyclobutane complex, W(NAr)(C[subscript 3]H[subscript 6])(Pyr)(ODPP[superscript Ph]) (5). The structure of 5 in the solid state shows that it is approximately a square pyramid with the WC[subscript 4] ring spanning apical and basal positions. This SP′ structure, which has never been observed as an actual intermediate, must now be regarded as an integral feature of the metathesis reaction., National Science Foundation (U.S.) (CHE-1111133), National Science Foundation (U.S.) (Center for Enabling New Technologies through Catalysis (CENTC) CHE-0650456), National Science Foundation (U.S.) (Grant CHE-0946721)