Full Paper

October 23, 2012

Investigating the Reactivity of Radical Cations: Experimental and Computational Insights into the Reactions of Radical Cations with Alcohol and p-Toluene Sulfonamide Nucleophiles

John M. Campbell, Hai-Chao Xu, and Kevin D. Moeller

J. Am. Chem. Soc., 2012, 134 (44), pp 18338–18344

The reactivity of electrochemically-generated radical cations towards alcohol and p-toluene sulfonamide nucleophiles was directly investigated through competition experiments. Alcohol-trapping of the radical cation is the kinetically favored pathway and is reversible. Trapping with the sulfonamide leads to the thermodynamic product. Both reaction pathways were investigated computationally with density functional theory (UB3LYP/6-31G(d)) calculations.

 

October 9, 2012

Site-Selective Chemistry and the Attachment of Peptides to the Surface of a Microelectrode Array

Melissae Stuart Fellet, Jennifer L. Bartels, Bo Bi, and Kevin D. Moeller

J. Am. Chem. Soc., 2012, 134 (40), pp 16891–16898

Peptides have been site-selectively placed on microelectrode arrays with the use of both thiol-based conjugate additions and Cu(I)-coupling reactions between thiols and aryl halides. The conjugate addition reactions used both acrylate and maleimide Michael acceptors. Of the two methods, the Cu(I)-coupling reactions proved far superior because of their irreversibility. Surfaces constructed with the conjugate addition chemistry were not stable at neutral pHs, especially the surface using the maleimide acceptor. Once a peptide was placed onto the array, it could be monitored in “real-time” for its interactions with a biological receptor.

 

January 20, 2012

Building Addressable Libraries: Amino Acid Derived Fluorescent Linkers

Takamasa Tanabe, Bo Bi, Libo Hu, Karl Maurer, and Kevin D. Moeller

Langmuir, 2012, 28 (3), 1689-1693

A new amino acid derived fluorescent linker for attaching molecules to the surface of a microelectrode array has been developed. Molecules to be monitored on an array are attached to the C-terminus of the linker, the N-terminus is then used to attach the linker to the array, and the side chain is used to synthesize a fluorescent tag. The fluorescent group is made with a one-step oxidative cycloaddition reaction starting from a hydroxyindole group. The linker is compatible with site-selective Cu(I)-chemistry on the array, it allows for quality control assessment of the array itself, and it is compatible with the electrochemical impedance experiments used to monitor binding events on the surface of the array.

 

January 20, 2011

Site-Selectively Functionalizing Microelectrode Arrays: The Use of Cu(I)-Catalysts

Jennifer Bartels, Peng Lu, Karl Maurer, Amy V. Walker, and Kevin D. Moeller

Langmuir, 2011, 27 (17), pp 11199–11205

Site-selective Cu(I)-catalyzed reactions have been developed on microelectrode arrays. The reactions are confined to preselected electrodes on the arrays using oxygen as the confining agent. Conditions initially developed for the Cu(I)-catalyzed click reaction have proven general for the coupling of amine, alcohol, and sulfur nucleophiles to both vinyl and aryl iodides. Differences between reactions run on 1-K arrays and reactions run on 12-K arrays can be attributed to the 1-K array reactions being divided cell electrolyses and the 12-K array reactions being undivided cell electrolyses. Reactions on the 12-K arrays benefit from the use of a non-sugar-derived porous reaction layer for the attachment of substrates to the surface of the electrodes. The reactions are sensitive to the nature of the ligand used for the Cu catalyst.

 

November 23, 2010

Building Addressable Libraries: Site-Selective Use of Pd(0) Catalysts on Microelectrode Arrays

Libo Hu, Melissae Stuart, Jun Tian, Karl Maurer, and Kevin D. Moeller

J. Am. Chem. Soc., 2010, 132 (46), pp 16610–16616

Site-selective Pd(0)-catalyzed reactions have been developed to functionalize a microelectrode array. Heck, Suzuki, and allylation reactions have all been accomplished. The reactions are compatible with both 1K and 12K arrays and work best when a nonsugar porous reaction layer is used. Suzuki reactions are faster than the Heck reactions and thus require more careful control of the reactions in order to maintain confinement. The allylation reaction requires a different confining agent than the Heck and Suzuki reactions but can be accomplished nicely with quinone as an oxidant for Pd(0).
 
February 16, 2010

Intramolecular Anodic Olefin Coupling Reactions and the Synthesis of Cyclic Amines

Hai-Chao Xu and Kevin D. Moeller

J. Am. Chem. Soc., 2010, 132 (8), 2839–2844

Anodic olefin coupling reactions using a tosylamine trapping group have been studied. The cyclizations are favored by the use of a less-polar radical cation and more basic reaction conditions. The most significant factor for obtaining good yields of cyclic product is the use of the more basic reaction conditions. However, a number of factors including the nature of both the solvent and the electrolyte used can influence the yield of the cyclizations. The cyclizations allow for the rapid synthesis of both substituted proline and pipecolic acid type derivatives.

 

September 11, 2009

Anodic Oxidations and Polarity: Exploring the Chemistry of Olefinic Radical Cations

Feili Tang and Kevin D. Moeller

Tetrahedron, 2009, 65(52), 10863-10875

The cyclization chemistry of radical cations derived from electron-rich olefins has been examined and the relationship between the polarization of the radical cation and the chemoselectivity of the reaction probed. It was found that more polarized radical cations favor carbon–carbon bond formation while less polarized radical cations favor carbon–heteroatom bond formation. A new approach to the synthesis of quaternary carbons was uncovered and the compatibility of ene diol ethers with anodic olefin coupling reactions examined.

 

September 3, 2007

Electrochemistry and Umpolung Reactions: New Tools for Solving Synthetic Challenges of Structure and Location

Feili Tang, Ceng Chen, Kevin D. Moeller
Synthesis 2007, 3411-3420

Electrochemistry is a powerful tool for initiating new umpolung reactions. In this paper, two examples are provided. One demonstrates the use of electrochemistry for reversing the polarity of known functional groups and triggering carbon-carbon bond formation. The second demonstrates the use of electrochemistry for reversing the polarity of a chemical reagent, a technique that allows for spatially locating synthetic transformations on addressable chips.

 

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