Optimization Studies. At the outset of the investigation, preliminary experimental data indicated that monophosphine ligands effectively promoted a nickel(0) cross-coupling of enol tosylate 1a and pinacol boronate 2a to access representative tetrasubstituted alkene diastereomers 3aa (Figure , see SI for details). To further streamline efforts toward developing a ligand-controlled diastereoconvergent transformation, a datarich optimization approach was envisaged wherein chemical space analysis would guide high throughput experimentation (HTE). The kraken organophosphorus(III) descriptor library, which contains >190 conformationally relevant molecular descriptors for 1558 monodentate phosphorus ligands, was employed for this purpose (Figure ). The dimensionality of the descriptors for commercially available phosphine ligands within the library was reduced using principal component analysis. K-means clustering was applied to the resulting chemical space in order to facilitate the selection of 47 diverse ligands for HTE optimization. Ligands were selected from each of these clusters based on availability in our library as well as further curation for compatibility with the reaction conditions. Subsequently, a ~50:50 mixture of enol tosylate diastereomers (Z)-1a/(E)-1a was subjected to reaction with boronate 2a under the established baseline conditions (Ni(COD) 2 , K 3 PO 4 , THF/water (3:1)) with the 47 selected monophosphine ligands in a 96-well plate design (reactions were performed in duplicate, and both assay yield and E/Z ratio was determined for product 3aa in each case; see SI for details). Wide ranges of both reactivity and selectivity were observed, thereby validating the efficacy of the workflow for identification of a diverse ligand screening set. The selection of ligands from the kraken library was visualized using the non-linear dimensionality reduction technique Uniform Manifold Approximation and Projection (UMAP), which showed reasonably even coverage of the commercially available phosphine space in this projection (Figure ). The selectivity observed with each ligand is highlighted on the UMAP plot through the use of a color map, while the size of the point represents the observed yield. A clear region of higher (Z)-selectivity for alkene 3aa was observed in the eastern area of the ligand space, while the highest (E)-selectivity were observed in the central and western areas of the plot. In addition, (Z)-selective ligands were generally higher yielding than the (E)-selective ligands. In a few cases, multiple ligands from the same cluster were probed in order to test the hypothesis that monophosphines in the same regions of chemical space will react similarly and in general, similar reactivities and selectivities were observed (see SI for details). The same HTE screen was also repeated in t-AmOH in order to test the effect of solvent on the reaction. Representative HTE results are highlighted in Fig- . In general, the ligand had the most significant influence on selectivity and similar trends were observed in either solvent. Ultimately, P(4-FC 6 H 4 ) 3 (L1) in THF/H 2 O (3:1) and PCy 3 (L2) in t-AmOH provided the highest yield and selectivity for each product diastereomer (Z)-3aa and (E)-3aa, respectively (Figure ). PCy 3 (L2) has proven effective several Ni-catalyzed Suzuki-Miyaura cross-coupling reactions. Further optimization studies indicated a THF/H 2 O ratio of 4:1 to be slightly more effective for the (Z)-selective conditions (see SI for details). Similar trends in reactivity and selectivity were also observed upon performing the ligand HTE screen with two additional electronically differentiated enol tosylate substrates, thereby ensuring the optimized conditions were not limited to 1a (see SI for details).