On Stereocontrol in Organocatalytic α-Chlorinations of Aldehydes

Abstract

A comprehensive analysis of the organocatalytic α‐chlorination of aldehydes with N‐chloroimides and differ‐ ent catalysts is presented. For this reaction, alternate mechanisms were proposed that differ in the role of resting state intermediates and the rationalization of the observed enantioselectivity. This manuscript aims at resolving these funda‐ mental questions on the basis of rigorous structural characterization of intermediates (configuration and conformation), NMR studies, ion mobility‐mass spectrometry, concentration profiles, isotope studies, and DFT calculations. <br>

Downstream Paradigm in Enamine Catalysis: Comment on “On Stereocontrol in Organocatalytic α-Chlorinations of Aldehydes”

“…"still no safe assignment of the minor species was possible." "NOE data was not entirely conclusive on the nature of the minor species and the process of the two interconverting aminal species…" "further analysis… may be needed to confirm the NMR shift assignments" 1 Only the calculated syn, and not the anti, assignments for species 11 and 14 (Y = succinimide and phthalimide, respectively) are given in the Ref. 1 manuscript itself.…”

“…A recent manuscript deposited on ChemRxiv entitled "On Stereocontrol in Organocatalytic α-Chlorinations of Aldehydes" (https://doi.org/10.26434/chemrxiv.14229875.v1) 1 by Ponath et al states that the work is a "comprehensive analysis of the organocatalytic α-chlorination of aldehydes with N-chloroimides and different catalysts" aimed at resolving different mechanistic interpretations in the literature. Because this manuscript directly challenges a body of work published by us between 2011-2016 (Burés et al), 2 we feel it is both appropriate and exigent for us to comment as well as contribute to this discourse with further results from our work.…”

“…These calculations run counter to the fact that aminals, and not chloroiminiums, are the experimentally observed intermediates in all the work under discussion. [1][2][3] In addition, neither Ref. 1 nor the earlier study of this system in Ref.…”