In summary, we have developed nickel-catalyzed cross-coupling reactions that enable a diastereodivergent and diastereoconvergent synthesis of tetrasubstituted alkenes from readily available enol tosylates. Notably, a data-rich high throughput optimization was guided by the kraken organophosphorus(III) descriptor library to identify a set of stereocomplementary monophosphine ligands. The methodology was successfully demonstrated on various tetrasubstituted alkene scaffolds and showed consistently high levels of yields and selectivities. Detailed experimental and computational studies provided insight into the complex catalytic system of this transformation and shed light on the key steps, isomerization and transmetalation, that influence the ligand dependent outcome of this reaction. Moreover, the applicability of this protocol was extended to Negishi and Kumada cross-coupling reactions. We plan to utilize the improved mechanistic understanding of this transformation to explore and develop similar isomerization processes. Finally, the application of the kraken organophosphorus(III) descriptor library in combination with high throughput experimentation is an emerging tool that we plan to continue to expand and exploit in the systematic and more streamlined optimization of other complex catalytic reactions.