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Scheme 6 Synthesis of (R)-arylpyrrolidines 5.
vicinal protons at C3 with different coupling constants
(8.1 and 3.7 Hz), resulting in a doublet x doublet at 5.13 ppm
{literature value for the enantiomeric (2S)-2-phenylpyrrolidine-
(R)-MTPA-amide: 5.14 ppm (d x d, J = 7.9, 3.7 Hz)}. The H2
methine proton of (2S)-2-phenylpyrrolidine-(S)-MTPA-amide
gave a triplet with a coupling of 7.3 Hz at 5.06 ppm {literature
value: 5.09 ppm (t, J = 7.6 Hz)}.
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´
The enantiomeric purity of (S)-2-(4-methylphenyl)pyrrolidine
5b was confirmed via NMR experiments using (R)-1-(9-anthryl)-
2,2,2-trifluoroethanol (Pirkle alcohol) as a chiral solvating
agent.21 When 1.7 equiv. of (R)-Pirkle alcohol was added to
(S)-2-(4-methylphenyl)pyrrolidine 5b, no chemical shift none-
quivalences could be observed in the 1H NMR spectrum.
However, upon addition of a small amount of (R)-2-(4-methyl-
phenyl)pyrrolidine 5b to the solution of (S)-5b, a well-resolved
spectral nonequivalence of the signal from the CH3-protons
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1
appeared in the H NMR spectrum (300 MHz, CDCl3).
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In conclusion, it is demonstrated that enantiopure 2-aryl-
pyrrolidines are prepared in high yield via stereoselective
reduction of g-chloro N-sulfinylketimines. Depending on the
chirality of the starting substrate, (RS,S)- and (SS,R)-2-aryl-1-
(tert-butanesulfinyl)pyrrolidines 3a–d became accessible in
high yield by reduction with lithium triethylborohydride.
Treatment of the stereochemically pure 2-aryl-1-(tert-butane-
sulfinyl)pyrrolidines 3a–d with a saturated solution of HCl in
dioxane afforded (S)- and (R)-2-arylpyrrolidine hydrochlorides
4a–d in high yield which were further neutralized to the
corresponding enantiomerically pure (S)- and (R)-2-arylpyrroli-
dines 5a–d in quantitative yield.
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The authors are indebted to Ghent University (GOA) and
the Research Foundation-Flanders (FWO-Vlaanderen) for
financial support of this research.
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ꢁc
This journal is The Royal Society of Chemistry 2010
3124 | Chem. Commun., 2010, 46, 3122–3124