Kevin D. Moeller

Intramolecular Anodic Olefin Coupling Reactions: The Use of a Nitrogen Trapping Group

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. The cyclizations allow for the rapid synthesis of substituted proline derivatives.

Intramolecular Anodic Olefin Coupling Reactions and the Synthesis of Cyclic Amines

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.

Anodic Amide Oxidation/Olefin Metathesis Strategies: Developing a Unified Approach to the Synthesis of Bicyclic Lactam Peptidomimetics

Abstract In connection with efforts to build constrained peptidomimetics for the endocrine hormone TRH, a general strategy for the construction of bicyclic lactam peptide building blocks has been developed. This strategy used an anodic amide oxidation to selectively functionalize proline and then an olefin metathesis to build the desired lactam constraint. The route described provides a single approach for synthesizing both fully functionalized TRH analogs having seven- and eight-membered ring lactam constraints, as well as six- and seven-membered ring lactam analogs without the sidechain on the central amino acid.

Cyclization Reactions of Anode-Generated Amidyl Radicals

Amidyl radicals have been generated from amides under mild conditions electro-oxidatively. Their reactivity toward electron-rich double bonds to form five- and six-membered rings has been demonstrated experimentally and explored with density functional theory (DFT) calculations (UB3LYP/6-31G(d,p)).

Anodic electrochemistry and the use of a 6-volt lantern battery: A simple method for attempting electrochemically based synthetic transformations

Abstract A series of electrochemical transformations have been accomplished using a 6-volt lantern battery as a power supply. The reactions included both intramolecular anodic olefin coupling reactions and an anodic amide oxidation. In all cases, the reactions afforded preparatively useful amounts of product and demonstrated that electrochemical synthetic methods can be readily attempted without the need for specialized equipment.

Microelectrode Arrays and Ceric Ammonium Nitrate : A Simple Strategy for Developing New Site-Selective Synthetic Methods

Conditions for a site-selective ceric ammonium nitrate oxidation have been developed. The reactions proceed nicely on both 1K- and 12K-microelectrode arrays. The procedure for developing the reactions was very simple and demonstrated that the same reagents used for a solution-phase reaction can be used for a related site-selective reaction on a microelectrode array.

Oxidative Cyclization Reactions: Controlling the Course of a Radical Cation-Derived Reaction with the Use of a Second Nucleophile†

Construction of new ring systems: Oxidative cyclizations (see picture; RVC=reticulated vitreous carbon) have been conducted that use two separate intramolecular nucleophiles to trap an enol ether-derived radical cation intermediate. The reactions provide a means for rapidly trapping the radical cation intermediate in a manner that avoids competitive decomposition reactions.

Anodic amide oxidations: Conformationally restricted peptide building blocks from the direct oxidation of dipeptides

Abstract A pair of bicyclic lactam based conformationally restricted peptide mimetics have been synthesized in good yield by the direct anodic oxidation of dipeptides. This work highlights the simplicity of using electrochemistry to construct peptide mimetics and serves to further define the nature of the substituents that are compatible with an electrochemical procedure for annulating rings onto amino acid derivatives.

Insights into the Mechanism of Anodic N–N Bond Formation by Dehydrogenative Coupling

The electrochemical synthesis of pyrazolidine-3,5-diones and benzoxazoles by N-N bond formation and C,O linkage, respectively, represents an easy access to medicinally relevant structures. Electrochemistry as a key technology ensures a safe and sustainable approach. We gained insights in the mechanism of these reactions by combining cyclovoltammetric and synthetic studies. The electron-transfer behavior of anilides and dianilides was studied and led to the following conclusion: The N-N bond formation involves a diradical as intermediate, whereas the benzoxazole formation is based on a cationic mechanism. Besides these studies, we developed a synthetic route to mixed dianilides as starting materials for the N-N coupling. The compatibility with valuable functionalities like triflates and mesylates for follow-up reactions as well as the comparison of different electrochemical set-ups also enhanced the applicability of this method.

Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization

Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species.