β-Amino esters are obtained with high levels of enantioselectivity via the conjugate addition of cyclic amines to unactivated α,β-unsaturated esters. A related strategy enables the kinetic resolution of racemic cyclic 2-arylamines, using benzyl acrylate as the resolving agent. Reactions are facilitated by an unprecedented selenourea-thiourea organocatalyst. As elucidated by DFT calculations and 13 C kinetic isotope effect studies, the ratelimiting and enantiodetermining step of the reaction is the protonation of a zwitterionic intermediate by the catalyst. This represents a rare case in which a thiourea compound functions as an asymmetric Brønsted acid catalyst.

A combination of experimental C kinetic isotope effects (KIEs) and high-level density functional theory (DFT) calculations is used to distinguish between "enamine" and "enol" mechanisms in the Michael addition of acetone to trans-β-nitrostyrene catalyzed by Jacobsen's primary amine thiourea catalyst. In light of the recent findings that the widely used O-incorporation probe for these mechanisms is flawed, the results described in this communication demonstrate an alternative probe to distinguish between these pathways. A key advantage of this probe is that quantitative mechanistic information is obtained without modifying experimental conditions. This approach is expected to find application in resolving mechanistic debates, while providing valuable information about the key transition state of organocatalyzed reactions involving the α-functionalization of carbonyls.

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.

Experimental 13C kinetic isotope effects (KIEs) and DFT calculations are used to evaluate the mecha-nism and the origin of enantioselectivity in the 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 (~1.030) 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 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 enantiomeric E1cB transition states.

Experimental 13C kinetic isotope effects (KIEs) and DFT calculations are used to evaluate the mecha-nism and the origin of enantioselectivity in the 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 (~1.030) 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 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 enantiomeric E1cB transition states.