Asymmetric Carbene‐Catalyzed Oxidation of Functionalized Aldimines as 1,4‐Dipoles

Abstract

The use of functionalized aldimines has been demonstrated as newly structural 1,4‐dipole precursors under carbene catalysis. More importantly, enantiodivergent organocatalysis has been successfully developed using carbene catalysts with the same absolute configuration, leading to both (R)‐ and (S)‐ enantiomers of six‐membered heterocycles with quaternary carbon centers. This strategy features a broad substrate scope, mild reaction conditions, and good enantiomeric ratio. DFT calculation results indicated that hydrogen bond C−H⋅⋅⋅F interactions between the catalyst and substrate are the key factors for controlling and even switching the enantioselectivity. These new 1,4‐dipoles can also react with isatin and its imines under carbene catalysis, allowing for access to the spiro oxindoles with excellent enantiomeric ratios.

Atroposelective Access to 1,3‐Oxazepine‐Containing Bridged Biaryls via Carbene‐Catalyzed Desymmetrization of Imines

“…Related carbene‐catalyzed formation of aza ‐Breslow intermediates for imine umpolung and asymmetric reactions have been reported by Lupton, [15a] Biju [15b] and our group [15c–d] . Besides, the carbene‐catalyzed oxidative imine umpolung for enantioselective [4+2] cycloaddition has been achieved by Fu [16a] and us [16b] in the mean time. This work represents the first success in developing oxidative imine umpolung to access the axially chiral compounds.…”

Prediction on chemoselectivity for selected organocatalytic reactions by the DFT version of the Hückel-defined free valence index

“…However, the HMO calculations are not accurate due to the nature of semi-empirical quantum chemical calculations. To solve this issue and promoted by our interest in organocatalysis 46,[60][61][62][63][64] and theoretical research experiences, [65][66][67][68][69] we believe that the DFT version of the HFV index should be more suitable to predict the actual active site of the organocatalytic reaction systems, in which the chemoselectivity is generally associated with the different active sites of the conjugated structures of the reactants or intermediates. As depicted in Scheme 1, the HFV index (denoted as F i ) represents the activity of the i atom obtained by the maximum π bond order of benchmark trimethylenemethane minus its related π bond orders, and the HFV index of the active carbon atom is obtained using F i = P max − P P ij .…”

Desymmetrization of N-Cbz glutarimides through N-heterocyclic carbene organocatalysis

“…Notably, NHC-catalyzed amide C-N bond activation remains to be established. As a part of our ongoing interest in organocatalysis [52][53][54][55][56] , we envisioned the imides, containing a more reactive amide bond and unknown in the area of NHC, might be activated by NHC and further realize asymmetric reactions [57][58][59] . If successful, this methodology will expand the scope of carbene chemistry.…”