Mechanism and Origin of Remote Stereocontrol in the Organocatalytic C(sp2)-H Alkylation using Nitroalkanes as Alkylating Agents

Abstract

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.

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

“…We have used a combination of experimental 13 C KIEs and DFT calculations to study the mechanism and nature of the rate/enantioselectivity-determining step of the bifunctional tertiary aminourea-catalyzed formal C­(sp 2 )–H alkylation of cyclopentene-1,3-diones using nitroalkanes as the alkylating agent . Since the chiral center is formed remote from the reaction site, understanding the origin of enantioselectivity is not straightforward.…”