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

Sharath Chandra Mallojjala, Rahul Sarkar, Rachael W. Karugu, Madhu Sudan Manna, Sayan Ray, Santanu Mukherjee, Jennifer S. Hirschi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17399-17406
Number of pages8
JournalJournal of the American Chemical Society
Volume144
Issue number38
DOIs
StatePublished - Sep 28 2022

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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