Rationalization of an Unusual Solvent‐Induced Inversion of Enantiomeric Excess in Organocatalytic Selenylation of Aldehydes

Abstract

An unusual solvent-induced inversion of the sense of enantioselectivity observed in the α-selenylation of aldehydes catalyzed by a diphenylprolinol silyl ether catalyst is correlated to the presence of intermediates formed subsequent to the highly selective C-Se bond-forming step in the catalytic cycle. This work provides support for a mechanistic concept for enamine catalysis and includes a general role for "downstream intermediates" in selectivity outcomes in organocatalysis.

An Air‐ and Water‐Stable Hydrogen‐Bond‐Donor Catalyst for the Enantioselective Generation of Quaternary Carbon Stereocenters by Additions of Substituted Cyanoacetate Esters to Acetylenic Esters

“…In terms of reactions that can be effected with organocatalysts, zero order behavior with respect to one or both substrates is not unusual . Initial regimes with positive order, as observed in Figures and S18, have been attributed to the interval required for accumulating both substrates on the catalyst to form the intermediate . Also, reactions of metal containing catalysts that are zero order in catalyst have ample precedent …”

On Stereocontrol in Organocatalytic α-Chlorinations of Aldehydes

“…A stereospecific protonation/hydrolysis which, was not further detailed, would lead to the chloroaldehydes in an enantiomeric ratio identical to the ratio of the observed aminals. 24 The apparent correlation between the ratio of two rapidly equilibrating species (cause) and the ratio of two product enantiomers (effect) led the authors to formalize a new concept for stereochemical control in organocatalysis entitled the "Curtin-Hammett paradigm".…”

“…The 1 H-NMR spectra of the isolated and crystallographically characterized aminals were compared to the NMR spectra recorded during the reactions and our stereochemical assignments were compared to those reported in the literature. 23,24 Aminals Derived from Isovaleraldehyde, NCS and the 1 st Generation MacMillan Catalyst ent-3a (NMR…”

“…The 1 H-NMR spectrum (CDCl3) is in accordance with that the literature. 24,25 Figure SI-3. 1 H-NMR spectra of the α-chlorination reaction (isovaleraldehyde, NCS, catalyst ent-3b•TFA) in different solvents after 60 min.…”

“…The spectroscopic data ( 1 H-and 13 C-NMR) are in accordance with the major aminal from the literature. 24,25 6, 179.2, 173.9, 138.6, 129.3, 128.8, 126.8, 88.5, 76.7, 65.4, 61.8, 41.1, 37.0, 31.7, 29.1, 28.2, 27.9, 26.9, 21.2, 15.8 ppm. 2924, 2871, 1774, 1702, 1456, 1328, 1172, 1136, 820,…”