C O M M U N I C A T I O N S
the nucleophile and the regio- and diastereoselectivity of the reaction
is highly unusual and provides the exciting prospect that, by careful
tuning of the nucleophile, great regio- and diastereocontrol of the
reaction can be exercised. The preference for bond formation at
the more substituted position of the π-allyl with even extremely
bulky nucleophiles is also noteworthy.
Acknowledgment. We thank the National Science Foundation
and National Institutes of Health (NIH-13598) for their generous
support of our programs. Y.Z. thanks Amgen for a graduate
fellowship. Mass spectra were provided by the Mass Spectrometry
Regional Center of the University of California, San Francisco,
supported by the NIH Division of Research Resources.
Figure 1. Mo enolate structures.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds. This material is available
References
(1) For recent reviews of catalytic asymmetric methods that generate
quaternary centers, see: (a) Douglas, C. J.; Overman, L. E. Proc. Natl.
Acad. Sci. U.S.A. 2004, 101, 5363. (b) Trost, B. M.; Jiang, C. Synthesis
2006, 369.
(2) For a few recent examples, see: (a) Brown, M. K.; May, T. L.; Baxter,
C. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 1097. (b) Martin,
D.; Kehrli, S.; d’Augustin, M.; Clavier, H.; Mauduit, M.; Alexakis, A. J.
Am. Chem. Soc. 2006, 128, 8416. (c) Fillion, E.; Wilsily, A. J. Am. Chem.
Soc. 2006, 128, 2774.
Figure 2.
Table 2. Variation of the Electrophiles
(3) For asymmetric allylic alkylations with Pd, see: (a) Trost, B. M. J. Org.
Chem. 2004, 69, 5813. For Ir, see: (b) Weix, D. J.; Hartwig, J. F. J. Am.
Chem. Soc. 2007, 129, 7720. For W, see: (c) Lloyd-Jones, G. C.; Pfaltz,
A. Angew. Chem., Int. Ed. Engl. 1995, 34, 462. For Cu, see: (d)
Kacprzynski, M. A.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 10676.
(4) (a) Trost, B. M.; Hachiya, I. J. Am. Chem. Soc. 1998, 120, 1104. (b)
Trost, B. M.; Dogra, K. J. Am. Chem. Soc. 2002, 124, 7256. (c) Trost, B.
M.; Dogra, K.; Franzini, M. J. Am. Chem. Soc. 2004, 126, 1944. (d) Trost,
B. M.; Zhang, Y. J. Am. Chem. Soc. 2006, 128, 4590.
(5) (a) Anthoni, U.; Christophersen, C.; Nielsen, P. H. In Alkaloids: Chemical
and Biological PerspectiVes; Pelletier, S. W., Ed.; Wiley: New York,
1999; Vol. 14, pp 163-236. For previous examples of catalytic asymmetric
methods that generate quaternary centers at the 3 position of oxindoles,
see: (b) Hills, I. D.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 3921. (c)
Lebsack, A. D.; Link, J. T.; Overman, L. E.; Stearns, B. A. J. Am. Chem.
Soc. 2002, 124, 9008. (d) Trost, B. M.; Frederiksen, M. U. Angew. Chem.,
Int. Ed. 2005, 44, 308.
entry
R
b/l
dr
ee
yield
1
2
3
4
5
6
3,4Cl2C6H3 (a)
4-OTBSC6H4 (b)
2-furyl (c)
2-thiophyl (d)
2-NHBocC6H4 (e)
2-(E)-butene (f)
6:1
19:1
12:1
13:1
19:1
6:1
5.5:1
8:1
6:1
8:1
19:1
6:1
89%
89%
91%
90%
93%
91%
87%
90%
92%
88%
89%
84%
case. Electronically, electron-withdrawing 3-aryl substituents should
stabilize both enolate complexes and slow down their interconver-
sion.13,14 Hence, we see a partial linear relationship between the
electronic property of the para-substituent and the regioselectivity
of the reaction.6 Furthermore, a more electron-rich molybdenum
should disfavor the reductive elimination and promote the equilibra-
tion between the two isomers. On the basis of this hypothesis, the
electron-rich bismethoxypyridine ligand should move toward a
Curtin-Hammett-type situation and favor reductive elimination via
the less hindered O-bound enolate to give the branched product as
observed (entry 22 vs 7, entry 21 vs 18).15
Several other aromatic, heteroaromatic, and polyenyl carbonates
also functioned well with oxindole 1d (Table 2). The reaction is
tolerant of a number of functional groups on the electrophile, and
good to excellent selectivity is observed for all substrates.
The relative and absolute stereochemistry was established by
X-ray crystallographic analysis of the product of entry 16 as shown
in Figure 2. Between the two depicted paths, path A is clearly
favored as the least sterically demanding in the transition state. This
stereochemical outcome is also consistent with our previous reports.4
In conclusion, we have reported a molybdenum-catalyzed allylic
alkylation reaction with oxindoles that proceeds with high regio-,
diastereo-, and enantioselectivity. The products of this reaction,
containing a quaternary center at the 3 position of the oxindole as
well as a vicinal tertiary center that are difficult to access via other
methods, are well suited for further elaborations toward indole
alkaloids. The correlation between the electronics and sterics of
(6) See Supporting Information for a Hammett plot of the regioselectivity
with electronically differentiated oxindoles.
(7) The enolate of 1t is not stable above rt. The reaction was performed at rt
with 20% catalyst loading.
(8) For mechanistic studies of the Mo reaction, see: (a) Lloyd-Jones, G. C.;
Krska, S. W.; Hughes, D. L.; Gouriou, L.; Bonnet, V. D.; Jack, K.; Sun,
Y.; Reamer, R. A. J. Am. Chem. Soc. 2004, 126, 702. (b) Hughes, D. L.;
Lloyd-Jones, G. C.; Krska, S. W.; Gouriou, L.; Bonnet, V. D.; Jack, K.;
Sun, Y.; Mathre, D. J.; Reamer, R. A. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5363.
(9) For recent X-ray characterizations of molybdenum enolate complexes,
see: (a) O-bound enolate: Morales, D.; Clemente, M. E. N.; Perez, J.;
Riera, L.; Riera, V. Organometallics 2003, 22, 4124. (b) C-bound
enolate: Cameron, P. A.; Britovsek, G. J. P.; Gibson, V. C.; Williams,
D. J.; White, A. J. P. Chem. Commun. 1998, 737, and references cited
therein.
(10) For examples of divergent reactivity of transition metal enolate complexes,
see: (a) Campora, J.; Maya, C. M.; Palma, P.; Carmona, E.; Gutierrez-
Puebla, E.; Ruiz, C. J. Am. Chem. Soc. 2003, 125, 1482. (b) Hartwig, J.
F.; Bergman, R. G.; Andersen, R. A. Organometallics 1991, 10, 3344.
(11) For a discussion of electronic and steric effects on reductive elimination
from Pd complexes, see: Culkin, D. A.; Hartwig, J. F. Organometallics
2004, 23, 3398.
(12) Such mechanism has been proposed in the π-allyl reactions with mercurial
acetate: Kitching, W.; Sakakiyama, T.; Rappoport, Z.; Sleezer, P. D.;
Winstein, S.; Young, W. G. J. Am. Chem. Soc. 1972, 94, 2239.
(13) The interconversion of C-enolate and O-enolate has been postulated to
occur through an η-3 oxoallyl complex: Hartwig, J. F.; Andersen, R. A.;
Bergman, R. G. J. Am. Chem. Soc. 1990, 112, 5670.
(14) Kinetic measurements of the equilibration between C-enolate and O-enolate
have been carried out for Ru-enolate complex13 and Ni-enolate complex10a
.
(15) For a study of the electronic effects of the pyridine ring in the ligand,
see: Belda, O.; Moberg, C. Synthesis 2002, 1601.
JA0755717
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