Asymmetric Synthesis of Adjacent Tri- and Tetrasubstituted Carbon Stereocenters. Organocatalytic Aldol Reaction of an Hydantoin Surrogate with Azaarene 2-Carbaldehydes
- Authors:
- J. Izquierdo, N. Demurget, A. Landa, T. Brinck, J. M. Mercero, P. Dinér, M. Oiarbide, C. Palomo
- Year:
- 2019
- Journal:
- Chem. Eur. J.
- Volume:
- 25
- Initial page - Ending page:
- 12431 - 12438
- ISBN/ISSN:
- ISSN: 1521-3765 (web)
- DOI:
- 10.1002/chem.201902817
- Description:
-
Abstract: Abifunctional amine/squaramide catalyst promoted direct aldol addition of an hydantoin surrogate to pyridine 2-carbaldehyde N-oxides to affordadducts bearing two vicinal tertiary/quaternary carbonsinhigh diastereo- and enantioselectivity (d.r.upto>20:1; ee up to 98%) is reported. Acid hydrolysis of adducts followedby reduction of the N-oxidegroup yields enantiopure carbinol-tethered quaternary hydantoin-azaarene conjugates with denselyfunctionalized skeletons. DFT studies of the potential energy surface (B3LYP/6–31+ G(d)+ CPCM (dichloromethane)) of the reaction correlate the activity of differentcatalysts and support an intramole cular hydrogen-bond-assisted activationofthe squaramide moiety in the transition state of the catalytic reaction.