As part of a program directed at developing synthetic methods of value to chemical biology and process chemistry alike, our research group has been engaged in developing minimally invasive, enzyme-based screening methods. In this presentation, we will describe a modification of our colorimetric enzymatic screening platform that has been utilized to optimize a new formal thiocyanopalladation/carbocyclization reaction in which a C-SCN bond is formed in unison with a C-C bond. This reaction was recently discovered as part of a much broader ‘combinatorial catalysis’ search for interesting (pseudo)halometalation/carbocyclization transformations. The optimization procedure described herein is accommodated in a 96-well format, and allows for the variation of key parameters for the transformation of interest, including pre-catalyst, metal loading, nucelophile loading, ligand and temperature. Optimized conditions are then applied to study of scope and mechanism of the title transformation, as well as its application to the construction of a diversified natural product core library, an approach that takes full advantage of the rich, but underutilized, chemistry of the thiocyanate functionality.

Discovery and optimization of a new formal thiocyanopalladation/carbocyclization transformation via enzymatic screening

254th National Meeting (2017)

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