Journal of the American Chemical Society
Communication
Valium).24,25 Benzazepinones with the same N,N-dimethylami-
noethyl side chain are related to the FDA-approved drug
diltiazem,26 a potent calcium channel blocker (Cardizem), and
SQ 31,486, a candidate to reduce myocardial ischemia for
cardioprotective treatments.27
This report highlights the new integration of two distinct
Lewis base activation modes to achieve an enantioselective
organocatalytic formal [4 + 3] heterocycloaddition. This
challenging “dual activation” concept was successfully realized
through concomitant in situ generation of two reactive, transient
species: a nucleophilic NHC−homonenolate and a highly
electrophilic o-quinone methide. In a broader strategic sense,
the use of a second Lewis base compatible with NHCs to access
reactive electrophiles greatly expands the potential for new
reaction discovery with these powerful organocatalysts.
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ASSOCIATED CONTENT
* Supporting Information
Procedures, spectral data, and complete ref 25a. This material is
■
S
AUTHOR INFORMATION
Corresponding Author
■
Notes
(15) (a) Wan, P.; Barker, B.; Diao, L.; Fischer, M.; Shi, Y. J.; Yang, C.
Can. J. Chem. 1996, 74, 465. (b) Chiang, Y.; Kresge, A. J.; Zhu, Y. Pure
Appl. Chem. 2000, 72, 2299. (c) Van de Water, R. W.; Pettus, T. R. R.
Tetrahedron 2002, 58, 5367. (d) Luan, Y.; Schaus, S. E. J. Am. Chem. Soc.
2012, 134, 19965. (e) Willis, N. J.; Bray, C. D. Chem.Eur. J. 2012, 18,
9160. (f) Pathak, T. P.; Gligorich, K. M.; Welm, B. E.; Sigman, M. S. J.
Am. Chem. Soc. 2010, 132, 7870.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Prof. P. H.-Y. Cheong and R. Johnston (Oregon State
University) for performing DFT calculations and Dr. P. Sui
(Northwestern) for X-ray crystallographic assistance. Financial
support was provided by NIH NIGMS (R01 GM073072). A.O.
acknowledges the Basque Government for a predoctoral grant
and UPV/EHU (UFI QOSYC 11/22) for financial support.
(16) During review of this work, a related reaction involving the NHC-
catalyzed addition of homoenolate equivalents to stable o-QMs was
reported. See: Lv, H.; Jia, W.-Q.; Sun, L.-H.; Ye, S. Angew. Chem., Int. Ed.
2013, DOI: 10.1002/anie.201303903.
(17) Other sources of F− (Me4N·F, TBAF) gave only trace amounts of
product (see the SI).
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