TY - JOUR
T1 - Mechanism and Origin of Remote Stereocontrol in the Organocatalytic Enantioselective Formal C(sp2)-H Alkylation Using Nitroalkanes as Alkylating Agents
AU - Chandra Mallojjala, Sharath
AU - Sarkar, Rahul
AU - Karugu, Rachael W.
AU - Manna, Madhu Sudan
AU - Ray, Sayan
AU - Mukherjee, Santanu
AU - Hirschi, Jennifer S.
N1 - Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/9/28
Y1 - 2022/9/28
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.2c02941
DO - 10.1021/jacs.2c02941
M3 - Article
C2 - 36108139
AN - SCOPUS:85138796746
SN - 0002-7863
VL - 144
SP - 17399
EP - 17406
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 38
ER -