Journal of the American Chemical Society
Communication
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(8) Selected examples of allylic phosphates in Pd-catalyzed allylic
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(Figure 3, path b). An SN2 displacement with palladium has
been proposed in studies on oxidative addition to benzyl
chloride.13 Based on our studies, we feel that substitution
followed by isomerization is occurring. Electron-rich benzyl
electrophiles are more reactive, requiring a less labile leaving
group. Increased electron density would stabilize the transition
state in an SN2 reaction, leading to charged intermediates.14 On
the other hand, low-valent palladium would better coordinate
to an electron-poor π system, which should have led to
increased reactivity. The lower reactivity of less electron-rich
electrophiles under identical conditions (Table 2) further
supports SN2 displacement as opposed to pre-coordination.
In conclusion, we have expanded the scope of asymmetric
benzylation to monocyclic benzylic electrophiles. Using
phosphate leaving groups to render benzyl groups more
reactive, we have developed a method for benzylating
azlactones. A tetrasubstituted stereocenter is generated in
high enantiomeric excess with a variety of electron-rich and
electron-neutral elecrophiles. The methodology provides access
to enantioenriched quaternary amino acids via hydrolysis of the
azlactone, which has been illustrated in the synthesis of α-
methyl-D-dopa. Further studies into asymmetric benzylation
scope are underway.
(9) Merck Index, 14th ed.; Merck: Whitehouse Station, NJ, 2007; p
6055.
(10) Tristram, E. W.; ten Broeke, J.; Reinhold, D. F.; Sletzinger, M.;
Williams, D. E. J. Org. Chem. 1964, 29, 2053.
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J. M.; Sletzinger, M. J. Org. Chem. 1968, 33, 1209. (b) Kawabata, T.;
Suzuki, H.; Nagae, Y.; Fuji, K. Angew. Chem., Int. Ed. 2000, 39, 2155.
(c) Leon-Romo, J. L.; Virues, C. I.; Avina, J.; Regla, I.; Juaristi, U.
Chirality 2002, 14, 144. (d) Seebach, D.; Aebi, J. D.; Naef, R.; Webber,
T. Helv. Chim. Acta 2004, 68, 144.
(12) Stierli, F.; Obrecht, D.; Heimgartner, H. Chimia 1984, 38, 432.
(13) Wong, P. K.; Lau, K. S. Y.; Stille, J. K. J. Am. Chem. Soc. 1974,
96, 5956.
(14) (a) Swain, C. G.; Langsdorf, W. P. Jr. J. Am. Chem. Soc. 1951,
73, 2813. (b) Kim, S. H.; Yoh, S.-D.; Lim, C.; Mishima, M.; Fujio, M.;
Tsuno, Y. J. Phys. Org. Chem. 1998, 11, 254.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and spectral data for unknown com-
pounds. This material is available free of charge via the Internet
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (CHE-0846427)
for their generous support of our programs. L.C. thanks the
Evelyn Laing McBain Fellowship Fund for financial support.
We also thank Johnson-Matthey for their generous gift of
palladium salts.
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