(Digital Presentation) Diastereoselective Electrocatalytic Hydrogenation of Mono-Substituted Cyclohexanones in a Proton Exchange Membrane Reactor
Authors: Shimizu Yugo , Fukazawa Atsushi , Shida Naoki , Atobe Mahito 
Published: July 2022

Cyclic alcohols are important building blocks of pharmaceuticals, perfumes, and liquid crystals. For instance, 4-tert-butylcyclohexyl acetate, which is derived from 4-tert-butylcyclohexanol (1), is a commercialized synthetic fragrance that is used more than 106 kg per year. The fragrance of its cis-isomer is more potent odorant than that of its trans-isomer, and hence, cis-4-tert-butylcyclohexyl acetate is obtained by acetylation of the corresponding alcohol, i.e., cis-1.

On the other hand, cis-1 is generally obtained by the reduction of 4-tert-butylcyclohexanone (2). The use of sterically hindered L-selectride as a reductant gave 1 with 93% cis-isomer selectivity [1]. The stereoselective hydrogenation of ketone 2 to 1 with ruthenium-aminophosphine complexes using hydrogen gas and base also afford 96% cis-isomer [2]. Although high cis-selectivity is achieved by these methods, the use of hazardous reagents and their separation problems in the workup humper the large-scale application. Replacement of such homogeneous reductions (hydrogenations) by heterogeneous catalytic systems brings several economic and technical advantages. A major advantage of using heterogeneous catalysts is that the catalyst can be recovered from the reaction mixture by simple filtration. Therefore, the highly diastereoselective reduction (hydrogenation) of cyclic ketones using heterogeneous catalysts is a meaningful and challenging topic for sustainable chemistry.

Here, we demonstrate the electrocatalytic hydrogenation of mono-substituted cyclohexanones in a proton exchange membrane (PEM) reactor (Figure 1a). We have investigated the effect of catalyst materials and current density on the current efficiency and cis-selectivity of the desired products. As a result, it was found that the use of the PEM reactor with Rh catalyst gave 1 with high cis-selectivity (94%) and high current efficiency (93%), as shown in Figures 1b and c. In addition, it was also confirmed that the present system was capable of continuous operation for several tens of hours and gram-scale electrolysis without loss of diastereoselectivity. Unlike conventional hydrogenation methods that are carried out under high temperature and high pressure, the PEM reactor can carry out the desired hydrogenation reaction under ambient temperature and pressure, which also suggests a significant improvement in energy efficiency. Furthermore, the reaction products are easily separated and the catalyst is highly recyclable. Thus, the hydrogenation using PEM reactors can realize energy-saving and clean organic reaction processes.

The authors gratefully acknowledged support by JST CREST Grant No. JPMJCR18R1, Japan.

References

[1] Brown, H.C.; Krishnamurthy, S.J. Lithium Tri-sec-butylborohydride. New Reagent for the Reduction of Cyclic and Bicyclic Ketones with Super Stereoselectivity. Remarkably Simple and Practical Procedure for the Conversion of Ketones to Alcohols in Exceptionally High Stereochemical Purity. J. Am. Chem. Soc. 1972, 94, 7159–7161.

[2] Abdur-Rashid, K.; Chen, X.; Guo, R.; Jia, W. Method for the preparation of cis-4-tert-butylcyclohexanol. U.S. Patent 2010/0204524, A1, 2010.

Figure 1