These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 14.06.2020 and posted on 16.06.2020by John Kavouris, Kathryn Kavouris, Victor M. Wambua, Roman Demerzhan, Philip Moquist, Mathew Vetticatt, Scott Schaus
Chiral amino alcohols are valuable building blocks in the synthesis of drugs, natural products, and
chiral ligands used in enantioselective catalysis. The Petasis borono-Mannich reaction is a
multicomponent condensation reaction of aldehydes, amines, and boronic acids to afford chiral
amines. This report describes a practical, easily scaled, enantioselective Petasis borono-Mannich
reaction of glycolaldehyde, with primary or secondary amines, and boronates catalyzed by BINOLderived catalysts to afford chiral 1,2-amino alcohols in high yields and enantioselectivities. The
reactions are executed at room temperature in ethanol or trifluorotoluene using commercially
available reagents and leverage an inherently attractive feature of the multicomponent reaction; the
ability to use amines and boronates that possess a wide range of structural and electronic properties.
Computational modeling of the diastereomeric transition states using DFT calculations identified a
non-conventional CH…O interaction as a key feature that selectively stabilizes the transition state
leading to the major enantiomer. The enantioselective catalytic reaction exemplifies a truly practical
multicomponent condensation to afford 1,2-amino alcohols in highly enantioenriched form.