57th Annual Report on Research 2012 Under Sponsorship of the ACS Petroleum Research Fund

We have recently communicated a portion of our work toward NHC-catalyzed anodic oxidation of aldehydes. Key observations include: 1) the anodic oxidation occurs at low oxidation potentials, 2) the redox reaction is self-sufficient, 3) thiazolylidines were the only class of NHC found to be effective, 3) equilibration between aldehyde and benzoin species competed with the desired reaction, but could be overcome, and 4) the reactions can be conducted with simple equipment setup.

Our recently developed method for EOC involved organocatalysis using thiazolylidines and bulk electrolysis with a three-electrode design (graphite anode, Pt basket cathode, Ag/AgNO3 reference electrode) and constant voltage of +0.1 V. Aldehyde substrates included a range of aromatic, heteroaromatic, and aliphatic compounds. Alcohol coupling partners included primary alcohols of varying functionality, with little or no reactivity observed from secondary and tertiary alcohols, respectively. During electrolysis we observed gas formation at the cathode consistent with the production of hydrogen gas, as expected considering the low hydrogen overvoltage of the Pt cathode. This mechanistic detail was further confirmed by trapping of the gas formed in the headspace of the electrochemical cell with Vaska’s complex to form the corresponding dihydride. The reaction displayed broad functional group tolerance and clean conversions to products, requiring minimal purification procedures. In general, good to high yields were obtained from both electron-rich and electron-poor benzaldehydes, excellent chemo-selectivity was observed in both the aldehyde and alcohol reactants, and heteroaromatic aldehydes were tolerated. Oxidation of nonaromatic aldehydes also proceeded smoothly, including aliphatic and α,β-unsaturated aldehydes. In general, in the presence of an N-(2,4,6-trimethylphenyl)-substituted catalyst, electron-deficient aldehydes displayed an increased extent of benzoin formation that severely inhibited efficient ester production. Taking advantage of the increased electrophilicity of the aldehydes, however, permitted the use of a bulkier NHC catalyst. Specifically, the N-(2,4-diisopropylphenyl) analogue shepherded reactivity away from benzoin condensation and furnished high yields of ester products in short reaction times.

To improve the overall practicality of the organocatalyzed anodic oxidations, we replaced the potentiostat with a simple battery. Our initial conditions involved using a two-electrode setup driven by commercial batteries. Use of a 6 V lantern battery failed to produce ester product, possibly due to destructive oxidation of the NHC catalyst. Reducing the voltage (1.5 V AA-cell) gave the desired product in 22% yield (reaction of p-tolualdehyde and benzyl alcohol to give benzyl toluate). Increasing the current while maintaining the voltage by assembling multiple batteries in parallel and using D-cell batteries led to improved reaction efficiencies, although ester production remained modest. Switching to a 1.2 V NiCd battery resulted in a more promising 67% yield after 26 h.

To achieve the necessary controlled potential, we assembled a simple voltage divider consisting of a 10 Ω resistor in parallel with the reaction cell, which together were in series with a 100 Ω resistor. Two 1.5 V D-cell batteries were arranged in parallel as the voltage source. This setup gave a measured voltage of +0.14 V across the cell during the experiment and furnished benzyl toluate in 78% isolated yield after 27 h at RT, and 85% isolated yield after 27 h at 45 °C. Similar success at 45 °C was achieved for 4-chlorobenzaldehyde (40 h, 90% yield), cinnamaldehyde (20 h, 94% yield), 4-methoxycinnamaldehyde (40 h, 93% yield), and nicotinaldehyde (6 h, 58% yield) each reacted with benzyl alcohol. We anticipate further development of our EOC approach toward aldehyde oxidations has the potential to achieve highly efficient syntheses of lactones, thioesters, amides, and ketones.