(228i) One-Pot Reactions Combining Rh Catalyzed Diazocoupling and Enzymatic Reduction to Efficiently Synthesize Enantioenriched Asymmetric 2-Substituted 1,4-Dicarbonyl Compounds

Authors: 
Denard, C. A., University of Illinois at Urbana-Champaign
Zhao, H., University of Illinois at Urbana-Champaign

The application of biocatalysis in the synthesis of fine chemicals and medicinal compounds has grown significantly in recent years. In addition, the development of either sequential or one-pot tandem system combining the reactivity of a chemical catalyst with the selectivity engendered by the active site of a protein has proved to be appealing since it can achieve levels of chemo-, regio-, and stereo- selectivity that are unattainable with a small molecule catalyst. In this study, we developed a one-pot process that utilizes a rhodium catalyzed diazocoupling and alkene reduction by enoate reductases to enable the enatioselective synthesis of 2-aryl 1,4-dicarbonyl compounds. This reaction coupled the two different diazo compounds with >9:1 selectivity over homocoupling and reduction occurred in up to 99% ee. The screening of several enoate reductases identified OPR1 from lycopersicum esculentum that enabled the efficient use of bulky tert-butyl esters in these reactions and provided the chiral non-symmetric diesters with great potential as synthetic intermediates. This study demonstrated a telescoped one-pot reaction as an alternative way to combine organometallic and enzymatic catalysis and accelerate the synthesis of fine chemicals by avoiding isolation and purification of intermediates.