Piou, Tiffany Romanov-Michailidis, Fedor Ashley, Melissa A. Romanova-Michaelides, Maria Rovis, Tomislav Stereodivergent Rhodium(III)-Catalyzed cis-Cyclopropanation Enabled by Multivariate Optimization The design of stereodivergent transformations is of great interest to the synthetic community as it allows funneling of a given reaction pathway toward one stereochemical outcome or another by only minor adjustments of the reaction setup. Herein, we present a physical organic approach to invert the sense of induction in diastereoselective cyclopropanation of alkenes with <i>N</i>-enoxy­phthalimides through rhodium­(III) catalysis. Careful parametrization of catalyst–substrate molecular determinants allowed us to interrogate linear-free energy relationships and establish an intuitive and robust statistical model that correlates an extensive number of data points in high accuracy. Our multivariate correlations-steered mechanistic investigation culminated with a robust and general diastereo­divergent cyclopropanation tool where the switch from <i>trans</i>- to <i>cis</i>-diastereo­induction is attributed to a mechanistic dichotomy. Selectivity might be determined by the flexibility of rhodacyclic intermediates derived from ring-opened versus -unopened phthalimides, induced by both their respective ring size and the Sterimol <b>B</b><sub><b>1</b></sub> parameter of the Cp<sup>X</sup> ligand on rhodium. Stereodivergent;enoxy;stereochemical outcome;alkene;induction;diastereoselective cyclopropanation;ring size;reaction setup;Careful parametrization;dichotomy;multivariate correlations-steered;Cp X ligand;Rhodium;linear-free energy relationships;investigation;approach;rhodium;Multivariate Optimization;ci;Sterimol B 1 parameter;flexibility;determinant;data points;catalysi;tool;ring-opened;Enabled;catalyst;Selectivity;rhodacyclic intermediates;cis-Cyclopropanation;stereodivergent transformations;accuracy;correlate;Herein;phthalimide;model;reaction pathway 2018-07-23
    https://acs.figshare.com/articles/dataset/Stereodivergent_Rhodium_III_-Catalyzed_cis-Cyclopropanation_Enabled_by_Multivariate_Optimization/6849545
10.1021/jacs.8b04243.s003