Weiyin Gu    Huh June    Hong Sung Woo    Sveinbjörnsson Benjamin R.    Park Cheolmin    Robert H.Grubbs     Russell Thomas P.   

ACS Nano

2015

We demonstrated tandem ring-opening/ring-closing metathesis (RO/RCM) polymerization of monomers containing two cyclopentene moieties and postmodification via insertion polymerization. In this system, well-defined polymers were efficiently formed by tandem cascade RO/RCM reaction pathway. Furthermore, these polymers could be transformed to new A,B-alternating copolymers via a sequential cross metathesis reaction with a diacrylate. Additionally, we demonstrated the concept of multiple olefin metathesis polymerization in which the dicyclopentene and diacrylate monomers underwent all three olefin metathesis transformations (ring-opening, ring-closing, and cross metathesis) in one shot to produce A,B-alternating copolymer.

Lee Ho Keun    Bang Ki Taek    Hess Andreas    Robert H.Grubbs     Tae lim Choi   

Journal of the American Chemical Society

2015

The second edition of the ultimate reference in this field is completely updated and features more than 80% new content, with the focus on new developments in the field, especially in industrial applications. No other book covers the topic in such a comprehensive manner and in such high quality, and this new edition retains the three-volume format: Catalyst Development, Applications in Organic Synthesis and Polymer Synthesis. Edited by a Nobel laureate in the field, and with a list of contributors that reads like a "Who's-Who" of metathesis, this is an indispensable one-stop reference for organic, polymer and industrial chemists, as well as chemists working with organometallics.

Wenzel Anna G.    O'Leary Daniel J.    Khosravi Ezat    Robert H.Grubbs    

Handbook of Metathesis: Second Edition

2015

Olefin cross metathesis is a particularly powerful transformation that has been exploited extensively for the formation of complex products. Until recently, however, constructing Z-olefins using this methodology was not possible. With the discovery and development of three families of ruthenium-based Z-selective catalysts, the formation of Z-olefins using metathesis is now not only possible but becoming increasingly prevalent in the literature. In particular, ruthenium complexes containing cyclometalated NHC architectures developed in our group have been shown to catalyze various cross metathesis reactions with high activity and, in most cases, near perfect selectivity for the Z-isomer. The types of cross metathesis reactions investigated thus far are presented here and explored in depth.

Herbert Myles B.    Robert H.Grubbs    

Angewandte Chemie - International Edition

2015

The mechanism of C-H activation at metathesis-relevant ruthenium(II) benzylidene complexes was studied both experimentally and computationally. Synthesis of a ruthenium dicarboxylate at a low temperature allowed for direct observation of the C-H activation step, independent of the initial anionic ligand-exchange reactions. A first-order reaction supports an intramolecular concerted metalation-deprotonation mechanism with = 22.2 ± 0.1 kcal·mol for the parent N-adamantyl-N-mesityl complex. An experimentally determined =-5.2 ± 2.6 eu supports a highly ordered transition state for carboxylate-assisted C(sp)-H activation. Experimental results, including measurement of a large primary kinetic isotope effect (k /k = 8.1 ± 1.7), agree closely with a computed six-membered carboxylate-assisted C-H activation mechanism where the deprotonating carboxylate adopts a pseudo-apical geometry, displacing the aryl ether chelate. The rate of cyclometalation was found to be influenced by both the electronics of the assisting carboxylate and the ruthenium ligand environment. © 2014 American Chemical Society.

Cannon Jeffrey S.    Zou Lu-Feng    Peng Liu    Yu Lan    Oleary Daniel J.    Kendall Houk    Robert H.Grubbs    

Journal of the American Chemical Society

2014

We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole-TiO nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al-TiO) was prepared. The nanoparticle 1-Al-TiO was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO nanoparticles (bare, HO etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29 nm for 1-Al-TiO. Loading of 1-Al on the TiO surfaces was determined to be ca. 20-40 mg 1-Al/g TiO. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al-TiO as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al-TiO was found inside the cancer cells even at low doses (0.02-2 μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al-TiO showed minimal cytotoxic effects even at higher doses (2-2000 μg/mL) after 24 h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al-TiO at low doses (0.0003-3 μg/mL). Longer incubation times (after 48 and 72 h for U87-Luc) and higher doses (> 20 μg/mL 1-Al-TiO for U87-Luc and > 3 μg/mL 1-Al-TiO for PMH) showed decreased cell viability. © 2014 Elsevier Inc.

Blumenfeld Carl    Sadtler Bryce    Fernandez G. Esteban    Dara Lily    Nguyen Cathie    Alonso-Valenteen Felix    Medina-Kauwe Lali K.    Rex Moats    Nathan Lewis    Robert H.Grubbs     Harry Gray    Sorasaenee Karn   

Journal of Inorganic Biochemistry

2014

The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated alkenes were oxidized in up to 88% aldehyde yield and as high as 97% aldehyde selectivity. The aldehyde-selective oxidation enabled the rapid, enantioselective synthesis of an important pharmaceutical agent, atomoxetine. Finally, the influence of proximal functional groups on this anti-Markovnikov reaction was explored, providing important preliminary mechanistic insight. © 2014 American Chemical Society.

Wickens Zachary K.    Skakuj Kacper    Morandi Bill    Robert H.Grubbs    

Journal of the American Chemical Society

2014

Robert H.Grubbs    

Kobunshi

2014

We present a practical trifluoromethyl-directed Wacker-type oxidation of internal alkenes that enables rapid access to β-trifluoromethyl-substituted ketones. Allylic trifluoromethyl-substituted alkenes bearing a wide range of functional groups can be oxidized in high yield and regioselectivity. The distance dependence of the regioselectivity was established by systematic variation of the number of methylene units between the double bond and the trifluoromethyl group. The regioselectivity enforced by traditional directing groups could even be reversed by introduction of a competing trifluoromethyl group. Besides being a new powerful synthetic method to prepare fluorinated molecules, this work directly probes the role of inductive effects on nucleopalladation events. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lerch Michael M.    Morandi Bill    Wickens Zachary K.    Robert H.Grubbs    

Angewandte Chemie - International Edition

2014

Olefin metathesis has emerged as a promising strategy for modulating the stability and activity of biologically relevant compounds; however, the ability to control olefin geometry in the product remains a challenge. Recent advances in the design of cyclometalated ruthenium catalysts has led to new strategies for achieving such control with high fidelity and Z selectivity, but the scope and limitations of these catalysts on substrates bearing multiple functionalities, including peptides, remained unexplored. Herein, we report an assessment of various factors that contribute to both productive and nonproductive Z-selective metathesis on peptides. The influence of sterics, side-chain identity, and preorganization through peptide secondary structure are explored by homodimerization, cross metathesis, and ring-closing metathesis. Our results indicate that the amino acid side chain and identity of the olefin profoundly influence the activity of cyclometalated ruthenium catalysts in Z-selective metathesis. The criteria set forth for achieving high conversion and Z selectivity are highlighted by cross metathesis and ring-closing metathesis on diverse peptide substrates. The principles outlined in this report are important not only for expanding the scope of Z-selective olefin metathesis to peptides but also for applying stereoselective olefin metathesis in general synthetic endeavors. © 2014 American Chemical Society.

Mangold Shane L.    Oleary Daniel J.    Robert H.Grubbs    

Journal of the American Chemical Society

2014