Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

Posted on 2023-01-25 - 13:46
The involvement of planar carbocation intermediates is generally considered undesirable in asymmetric catalysis due to the difficulty in gaining facial control and their intrinsic stability issues. Recently, suitably designed chiral catalyst(s) have enabled a guided approach of nucleophiles to one of the prochiral faces of carbocations affording high enantiocontrol. Herein, we present the vital mechanistic insights from our comprehensive density functional theory (B3LYP-D3) study on a chiral Ir-phosphoramidite-catalyzed asymmetric reductive deoxygenation of racemic tertiary α-substituted allenylic alcohols. The catalytic transformation relies on the synergistic action of a phosphoramidite-modified Ir catalyst and Bi(OTf)3, first leading to the formation of an Ir-π-allenyl carbocation intermediate through a turn-over-determining SN1 ionization, followed by a face-selective hydride transfer from a Hantzsch ester analogue to yield an enantioenriched product. Bi(OTf)3 was found to promote a significant number of ionic interactions as well as noncovalent interactions (NCIs) with the catalyst and the substrates (allenylic alcohol and Hantzsch ester), thus providing access to a lower energy route as compared to the pathways devoid of Bi(OTf)3. In the nucleophilic addition, the chiral induction was found to depend on the number and efficacy of such key NCIs. The curious case of reversal of enantioselectivity, when the α-substituent of the allenyl alcohol is changed from methyl to cyclopropyl, was identified to originate from a change in mechanism from an enantioconvergent pathway (α-methyl) to a dynamic kinetic asymmetric transformation (α-cyclopropyl). These molecular insights could lead to newer strategies to tame tertiary carbocations in enantioselective reactions using suitable combinations of catalysts and additives.

CITE THIS COLLECTION

Ghosh, Supratim; Changotra, Avtar; Petrone, David A.; Isomura, Mayuko; Carreira, Erick M.; Sunoj, Raghavan B. (2023): Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate. ACS Publications. Collection. https://doi.org/10.1021/jacs.2c10975
or
Select your citation style and then place your mouse over the citation text to select it.

SHARE

email
need help?