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COMMUNICATION
DOI: 10.1039/C4CC09495F
activation by hydrogen bonding with the quinuclidine moiety of Notes and references
the catalyst. Simultaneously, the nucleophile will be directed to
a Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074
Aachen (Germany)
the Siꢀface of the nitroolefin, thus accounting for the observed
enantioselectivity. After the asymmetric Michael addition, the
silverꢀcatalyzed electrophilic activation of the internal alkyne
triggers the subsequent hydroalkoxylation. The 6ꢀendoꢀdig
cyclization proceeds via stereoselective antiꢀaddition of the
b Nara Institute of Science and Technology (NAIST), Ikoma (Japan)
Eꢀmail: enders@rwthꢀaachen.de
† Electronic Supplementary Information (ESI) available: See DOI: XXX.
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enol to the alkyne, accounting for the generally observed
Zꢀ
products. The generated vinylsilver intermediates are not stable
under the applied conditions, and undergo fast
protodeargentation yielding the pyranoꢀannulated pyrazoles and
releasing the catalyst for the next cycle.
In summary, we have developed a novel synthesis of chiral
pyranoꢀannulated pyrazoles by the combination of squaramide
and silver catalysis. The sequential catalytic system consisting
of an asymmetric Michael addition and
a subsequent
hydroalkoxylation gave the potentially bioactive pyranoꢀ
annulated pyrazoles under mild reaction conditions and with
low catalyst loading in excellent yields and enantioselectivities.
Further investigations towards the synthesis of hetereocycles
following similar orthogonal activation strategies are in
progress in our laboratories.
MeO
O
O
N
N
N
H
H
F3C
N
O
O
N
H
O
CF3
Ph
N
N
Ph
N
N
Me
O
Si-face
attack
2a
NO2
Ph
Me
H-Bo
1
Michael
addition
cat. D
R
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Ph
NO2
O
OH
Ph
N
Ph
O2N
N
N
Ph
Me
N
Me
Ph
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3a
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N
N
HO
Me
Ph
NO2
[Ag]
Ph
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N
N
Me
O
Ag
Ph
4a
Ph
NO2
prot
N
N
Me
o-
+HO
Ph
deargen
tation
[Ag]- NO2
Scheme 3 Proposed mechanism for the sequential catalytic domino
reaction.
11. CCDC1035443 (for 4i) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from the Cambridge
Support from the European Research Council (ERC
Advanced Grant 320493 “DOMINOCAT”) and the donation of
chemicals from the BASF SE is gratefully acknowledged.
4 | J. Name., 2014, 00, 1-3
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