Communication

April 15, 2008

Anodic Cyclization Reactions and the Synthesis of (−)-Crobarbatic Acid

Hai-Chao Xua, John D. Brandta and Kevin D. Moeller
Tetrahedron Letters, 2008, 49(24), 3868-3871

A synthesis of (−)-crobarbatic acid is reported along with the first use of a vinyl-substituted ketene dithioacetal as a coupling partner for an anodic cyclization reaction. The use of the vinyl-substituted ketene dithioacetal enables the construction of a cyclic product having a tetrasubstituted carbon with a relative stereochemistry opposite to that originally obtained from the cyclization.

 

October 2, 2007

Anodic Coupling Reactions: A Sequential Cyclization Route to the Arteannuin Ring Skeleton

Honghui Wu and Kevin D. Moeller
Org. Lett., 2007, 9 (22), 4599–4602

A pair of intramolecular anodic olefin coupling reactions has been used to construct the arteannuin ring skeleton. Both coupling reactions took advantage of a furan ring as one of the coupling partners. In the first, it was found that an enol ether derived from an aldehyde was not an effective initiating group for the reaction. Instead, the cyclization benefited strongly from the use of a N,O-ketene acetal initiating group. In the second cyclization, an endocyclic enol ether was coupled to the furan ring. This second electrolysis reaction generated the key tetrasubstituted carbon at the center of the arteannuin ring skeleton.

 

September 26, 2007

Intramolecular Anodic Olefin Coupling Reactions: the Effect of Polarization on Carbon−Carbon Bond Formation

Feili Tang and Kevin D. Moeller
J. Am. Chem. Soc., 2007, 129 (41), pp 12414–12415

The ability of intramolecular anodic olefin coupling reactions to form new carbon−carbon bonds has been shown to depend on the polarization of the intermediate radical cation rather than how electron-rich it is. A series of substrates was studied that allowed for a direct comparison of these two parameters. The successful cyclizations led to the formation of highly functionalized bicyclic molecules containing four contiguous stereogenic atoms, one of which was tetrasubstituted. For the first time, an ene diol ether derivative was shown to be compatible with the cyclization reaction.

 

November 24, 2006

Building Addressable Libraries: The Use of a Mass Spectrometry Cleavable Linker for Monitoring Reactions on a Microelectrode Array

Ceng Chen, Gabriella Nagy, Amy V. Walker, Karl Maurer, Andy McShea, and Kevin D. Moeller
J. Am. Chem. Soc., 2006, 128 (50), 16020–16021

Time-of-flight secondary ion mass spectrometry (TOF SIMS) has been used in conjunction with a mass spectrometry cleavable linker to determine the percent conversion of reactions that were conducted site-selectively on an addressable microelectrode array. When combined with fluorescence techniques for analysis of the reactions, the TOF SIMS experiment provides a means for optimization of both reaction confinement and reaction efficiency on the microelectrode arrays.

 

October 3, 2006

Building Functionalized Peptidomimetics: Use of Electroauxiliaries for Introducing N-Acyliminium Ions into Peptides

Haizhou Sun, Connor Martin, David Kesselring, Rebecca Keller, and Kevin D. Moeller
J. Am. Chem. Soc., 2006, 128 (42), 13761–13771

A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.

 

July 3, 2006

Building Addressable Libraries: The Use of Electrochemistry for Spatially Isolating a Heck Reaction on a Chip

Jun Tian, Karl Maurer, Eden Tesfu, and Kevin D. Moeller
J. Am. Chem. Soc., 2005, 127 (5), 1392–1393

Pd(0) was generated at preselected sites on an electrochemically addressable chip and then utilized to effect a Heck reaction. The Pd(0) was confined to the preselected electrodes with the use of allylmethyl carbonate. Unlike most mediated electrochemical reactions, the electrolysis in this case was not used to convert a stoichiometric process into a catalytic one by recycling the metal. Instead, the unique environment of the chip was used to interfere with a catalytic process to make it stoichiometric. This was done to gain spatial control over the reaction. The development of a strategy for conducting Pd(0)-catalyzed reactions on the chips should greatly expand the synthetic chemistry available for building chip-based libraries.

 

January 28, 2006

Building Addressable Libraries: Site Selective Coumarin Synthesis and the “Real-Time” Signaling of Antibody−Coumarin Binding

Eden Tesfu, Kris Roth, Karl Maurer, and Kevin D. Moeller
Org. Lett., 2006, 8 (4), 709–712

The feasibility of using active semiconductor chips containing addressable arrays of microelectrodes for the “real-time” monitoring of biologically relevant binding events has been demonstrated by detecting the binding of a coumarin substrate by an anticoumarin antibody. The coumarin substrate was synthesized proximal to predetermined electrodes on the chip with the use of a Pd(II) reagent that was itself generated by using the selected electrodes. Once the coumarin was synthesized, its binding to the anticoumarin antibody was detected by monitoring the current associated with a ferrocene−ferrocinium ion redox cycle that was established between the electrodes on the chip and a remote auxiliary electrode.

 

December 13, 2005

Building Addressable Libraries: Spatially Isolated, Chip-Based Reductive Amination Reactions

Eden Tesfu, Karl Maurer, and Kevin D. Moeller

J. Am. Chem. Soc., 2006, 128 (1),  70–71

Pd(II) reagent has been generated at preselected sites on an electrochemically addressable chip and used to effect the oxidation of the neighboring alcohols on the polymer coating the chip’s surface. The resulting carbonyls were then used to accomplish site-selective reductive amination reactions on the chips. The work demonstrates that the confinement strategy developed for spatially isolated Wacker oxidations to specific sites on the chips is general and can be used for other Pd(II)-based reactions.
 
October 27, 2005

Electrochemically Assisted Heck Reactions

Jun Tian and Kevin D. Moeller
Org. Lett., 2005, 7 (24), pp 5381–5383

During efforts to develop chip-based Heck reaction chemistry, it was discovered that normal solution-phase Heck reactions can be dramatically accelerated using electrochemistry. The acceleration makes room temperature Heck reactions proceed at synthetically useful rates in the absence of added ligand. Presumably, the current passed through the reaction maintains a high level of active catalyst.

 

July 6, 2005

Oxidative Cyclization Reactions: Amide Trapping Groups and the Synthesis of Furanones

John D. Brandt and Kevin D. Moeller
Org. Lett., 2005, 7 (16), pp 3553–3556

Intramolecular anodic coupling reactions involving ketene dithioacetal radical cations and amide trapping groups have been examined. The reactions generate furanone products and benefit greatly from the addition of water to the reaction medium. The cyclization reactions lead to products having stereochemistry that is directly analogous to oxidative cyclization reactions utilizing ketene dithioiacetal radical cations and alcohol trapping groups.

 

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