Mechanism and Origin of Remote Stereocontrol in the Organocatalytic Enantioselective Formal C(sp2)–H Alkylation Using Nitroalkanes as Alkylating Agents

Experimental 13C kinetic isotope effects (KIEs) and density functional theory (DFT) calculations are used to evaluate the mechanism and origin of enantioselectivity in the formal C­(sp2)–H alkylative desymmetrization of cyclopentene-1,3-diones using nitroalkanes as the alkylating agent. An unusual combination of an inverse (∼0.980) and a normal (∼1.033) KIE is observed on the bond-forming carbon atoms of the cyclopentene-1,3-dione and nitroalkane, respectively. These data provide strong support for a mechanism involving reversible carbon–carbon bond formation followed by rate- and enantioselectivity-determining nitro group elimination. The theoretical free-energy profile and the predicted KIEs indicate that this elimination event occurs via an E1cB pathway. The origin of remote stereocontrol is evaluated by distortion–interaction and SAPT0 analyses of the E1cB transition states leading to both enantiomers.