10.1002/chem.202004455
Chemistry - A European Journal
COMMUNICATION
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effective method to obtain tertiary alcohol (2S,3R)-12 in good
yield without any racemization. Note that THF was used for the
alcohol oxidation step in the one-pot synthesis, although MeCN
was used in the original report, and that the temperature control
was crucial in preventing the racemization. Dehydration of
(2S,3R)-12 and formation of the quaternary ammonium salt
completed the enantioselective synthesis of (+)-prifinium
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In summary, we have developed the La(OTf)3-catalyzed
regioselective intramolecular aminolysis of 3,4-epoxyamines
affording
the
expedient
synthesis
of
3-hydroxy-2-
alkylpyrrolidines. In this reaction, a catalytic Lewis acid activates
the epoxides in the presence of secondary amines to induce
anti-Baldwin 5-endo-tet cyclization. This reaction tolerates not
only simple alkyl/aryl groups, but also coordinative groups and
acid-labile functional groups. Cis-epoxy amine 4 exhibited the
opposite regioselectivity to trans-epoxy amines to afford
azetidine 5. The generality of the azetidine synthesis will be
reported in due course. Computational studies indicated that the
distortion energies of the epoxy amines may control the
regioselectivities. The use of the reaction we developed was
demonstrated by its application to the enantioselective synthesis
of a pyrrolidine-containing drug via a one-pot sequence of
chemoselective oxidation of an unprotected amino alcohol and
the subsequent alkylation of the resulting ketone as another key
step. We hope that this work will encourage research on the
development of other chemo- and regioselective reactions.
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Panger, S. E. Denmark, Org. Lett. 2020, 22, 2501-2505.
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[15] To obtain experimental supports for additional DFT calculations, the
intramolecular aminolysis of 1ae and 4 with TfOH was examined.
Unfortunately, the reaction of both the substrates afforded low (~10%)
yields of the corresponding azetidines. Therefore, we abandoned the
analysis of the intramolecular aminolysis of 1ae and 4 with proton by
DFT calculations.
Acknowledgements
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This work was partially supported by JSPS KAKENHI Grant Nos.
18H04232 (Precisely Designed Catalysts with Customized
Scaffolding), and 19H03347 and by Platform Project for
Supporting Drug Discovery and Life Science Research [Basis for
Supporting Innovative Drug Discovery and Life Science
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Research
(BINDS)]
from
AMED
under Grant No.
JP18am0101100. We thank Prof. Toshinobu Korenaga (Iwate
University) for useful discussion.
Keywords: Chemoselectivity • Regioselectivity • Cyclization •
Amines • Synthetic methods
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