Complex molecule synthesis by electrocatalytic decarboxylative cross-coupling.

Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges. Although this approach forms the basis of undergraduate curriculum in organic chemistry and strategic applications of most synthetic methods, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.