Selective Transformations

The selective, and controllable, modification of complex molecules with disparate functional groups, for example, natural products, is a long-standing challenge that has been addressed using catalysts tuned to perform singular transformations, for example, C–H hydroxylation.

In research published in Nature Chemistry, and also highlighted in ChemistryWorld, researchers in the Gagné Group demonstrate silylium ions combined with reducing counterions to forge chemoselective transformations on complex bioactive compounds.

Fluoroarylborane catalysts can heterolytically split Si–H bonds to yield an oxophilic silylium, R3Si+, equivalent along with a reducing, H, equivalent. Together, these reactive intermediates enable the reduction of multiple functional groups.

Exogenous phosphine Lewis bases further modify the catalyst speciation and attenuate aggressive silylium ions for the selective modification of complex natural products. Manipulation of the catalyst, silane reagent and the reaction conditions provides experimental control over which site is modified, and how.

The ability to carry out varied and selective transformations under catalyst control across diverse natural product structures suggests that it will emerge as a powerful tool for the synthesis of new chemical entities that encircle the structure of natural products and drug candidates. Whether these structures have resulted from traditional medicinal chemistry, screening of natural product, fully synthetic libraries or diversity-oriented synthesis, the chemistry described in this publication will enable those hits to be diversified further, even if the substrates are already complex.