Structure–Activity Relationship of Formamides as Organocatalysts
noting that the yield of the allylated product by using 2-
piperidinone or 2-pyrrolidone as the catalyst was higher in
the polar solvent than in the nonpolar solvent, which again
suggests better solvation of the activated complex.
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Conclusions
In conclusion, our results show that formamides are bet-
ter activators than amides for the allylation of aromatic al-
dehydes with allyltrichlorosilane (1) in polar and nonpolar
solvents. The polar solvents (CH2Cl2 and CH3CN) ap-
peared to have an advantage over the nonpolar solvent (tol-
uene), which results from the enhanced solvation of the
Lewis acid–Lewis base complex. Our data further suggests
that the reactive conformation of the secondary amide acti-
vators is the cis conformation, and this also explains why
tertiary formamides are not effective activators. The ob-
served conformational preference is supported by an in-
crease in catalyst reactivity correlated with an increase in
the amount of cis conformation present in solution, and
this is positively associated with the size of the N-substitu-
ent on the secondary formamide. The results presented
herein are targeted at helping to understand the structure–
activity relationship of formamides as catalysts to aid in
future catalyst design efforts.
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Experimental Section
General Procedure for the Allylation of Benzaldehyde (2) with Allyl-
trichlorosilane by Employing Formamides: All reactions were car-
ried out in a 4 mL vial. All transfers of aldehyde and allylating
reagents were done by syringe. The appropriate formamide
(1 equiv.) was first added to the vial, followed by the internal refer-
ence standard amylbenzene, (ca. 10 μL, ca. 8 mg), the solvent (tolu-
ene, CH2Cl2, or CH3CN, 0.2 mL) and benzaldehyde (2,
0.19 mmol). The mixture was stirred at 20 °C followed by the ad-
dition of a solution of allylSiCl3 (1.4 equiv., 39 μL) in toluene,
CH2Cl2, or CH3CN (1:1 v/v with respect to allylSiCl3) by syringe.
The reaction was stirred at room temperature (20 °C) for 6 h and
quenched by adding saturated aqueous NaHCO3. Ether was then
added to extract the product. Analysis of the organic phase by
HPLC or GC and calculations based on the internal reference and
the product peak gave the yield of the product.
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Supporting Information (see footnote on the first page of this arti-
cle): Instrumentation, chemicals, procedures, and spectra.
Acknowledgments
[18] See the Supporting Information for additional activators em-
ployed.
Support from the University of South Carolina and Roche Caro-
lina, Inc. is gratefully acknowledged. The authors would like to
thank Mike Walla for the gas chromatography data collection.
Received: December 7, 2012
Published Online: March 7, 2013
Eur. J. Org. Chem. 2013, 2279–2283
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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