Enantioselective [1,2]-Stevens rearrangement of quaternary ammonium salts. A mechanistic evaluation

Abstract

Using a supramolecular asymmetric ion pairing strategy, an enantioselective [1,2]-Stevens is feasible on substrates devoid of stereogenic quaternary nitrogen atoms.

Cascade and RCM syntheses of chiral tricyclic alkaloids from (S)-1,2,3,4-tetrahydro isoquinoline carboxylic acid

“…The enantioselectivity of the latter step involves intramolecular transfer of chirality from the quaternary asymmetric nitrogen to the adjacent C-position, namely from the ylide spirocycle axis to the newly formed sp 3 13 The enantiomeric excesses for compounds 4 and 5 (52% and 40%, respectively) were measured by using the chiral reagent Eu(hfc) 3 , and by comparing the shift separations observed in the 1 H NMR spectra to those of the benzazepinones obtained submitting the racemic diazocompound 2 to the same treatment. Current efforts are directed to optimizing the synthetic approach to larger cyclic aminoacids that could prove useful in peptide mimic design.…”

“…General 1 H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were recorded on a Varian VXR-300 spectrometer with TMS as internal standard. Infrared (IR) spectra were performed on a FT/IR-480plus JASKO spectrophotometer.…”

NMR enantiodifferentiation of quaternary ammonium salts of Tröger base

“…This is quite surprising for us as an effective NMR enantiodifferentiation of configurationally labile cations in low polarity solvents usually entails the occurrence of a stereocontrol from the anion onto the cation. 21,23,25,26,[32][33][34]89,90 So far, there is essentially no exception to this ''rule''. At this stage, several hypotheses can be considered to explain the lack of stereocontrol: (i) a surprising lack of a chiral recognition even in the presence of a strong NMR enantiodifferentiation or (ii) an actual lack of equilibration between the enantiomers of cations 8 in the NMR conditions that we have used.…”

“…More recently, this NMR split efficiency of BINPHAT was confirmed in several reports dealing with chiral spiro biaryl ammonium ions of type 7; the solvents of choice being either CDCl 3 or CD 2 Cl 2 (e r 8.93; l 5.2 3 10 230 C m). [32][33][34] Although efficient NMR enantiodifferentiation is regularly achieved among ions in ''low polarity'' halogenated solvents, it is not the case in high polarity solvents as a result of weaker electrostatic interactions. 35,36 Cations and anions, and small organic ones in particular, tend to behave as dissociated ion pairs in such solvents and hence a sharp decrease in NMR enantiodifferentiation.…”

Beyond Wishful Thinking and Sweet Dreams

“…[19] Other striking examples of the role of chiral ions include the binol-derived Binphat ligand in the Stevens rearrangement. [20] Timm Graening (TU Berlin) discussed in his talk the design of heteroleptic dirhodium catalysts for selective carbene insertion reactions. The idea of having reduced symmetry could favorably alter the electronic properties around the two rhodium centers.…”