Organic Letters
Letter
ASSOCIATED CONTENT
* Supporting Information
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S
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Experimental procedure, analyticaldata(1Hand 13CNMR,
Figure 1. Reaction model of enamine derived from proline andprolinate.
AUTHOR INFORMATION
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Corresponding Author
ORCID
alkynyliminecatalyzedbyprolinate, thesolvent isthehighlypolar
NMP. Under this condition, the enaminocarboxylate anion
intermediate would form a separated ion pair. Moreover,
according to the similar transition state of the Houk−List
model, the size of the counterion should affect the enantiose-
lectivity (see Figure 1A, where M = metal). However, almost-
perfect enantioselectivity is obtained, regardless of the prolinate
counterion. Thus, it would be difficult to explain these results
using the Houk−List model (Figure 1A).
Present Address
§Faculty of Science, Ibaraki University, 2-1-1 Bunkyo, Mito,
Ibaraki 310−8512, Japan.
Notes
We reported that potassium and tetrabutylammonium
prolinate salts are more reactive and enantioselective catalysts
in the α-aminoxylation reaction of aldehydes and nitro-
sobenzene.8 We have proposed a transition-state model, as
shown in Figure 1C. There are similarities between the α-
aminoxylation and the present Mannich reaction: In both
reactions, prolinate is more reactive and enantioselective than
proline, and proline and prolinate afford the same enantiomers.
The basicity of nitrogen of nitrosobenzene and alkynyl imine
would be similar. Thus, we would like to propose the following
reaction mechanism. Water, generated in the enamine formation,
would form a hydrogen bond with the carboxylate anion,16,17 and
this proton would protonate the nitrogen of imine (Figure 1B).
This model explains the effect of a countercation on the
enantioselectivity and the same absolute configurations of the
products using prolinate salt and proline as a catalyst.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank Professor Dieter Seebach at ETH for valuable
discussions. This work was supported by JSPS KAKENHI
(Grant No. JP16H01128) in Middle Molecular Strategy.
REFERENCES
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(1) the enaminocarboxylate is more nucleophilic than
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Figure 2. Oxazolidinone intermediate 3.
In summary, we have found the asymmetric three-component
Mannich reaction for metal or ammonium prolinate to act as an
effective and reactive catalyst to provide excellent enantioselec-
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this is the rare syn-selective, asymmetric Mannich reaction of
alkynyl imine and aldehyde, which supplements the known anti-
selective Mannich reaction. Since metal and ammonium prolinate
are easily prepared and inexpensive, the present method would be
useful for the preparation of chiral propargyl amine derivatives.
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