C O M M U N I C A T I O N S
Table 1. Palladium(II)-Catalyzed Aminoacetoxylation of Alkenesa
intermediate could then be oxidized by PhI(OAc)2 to an alkyl Pd-
(IV) intermediate.13 Finally, C-O bond forming reductive elimina-
tion from the Pd(IV) center would complete the aminoacetoxylation
process and regenerate the catalyst.7
In conclusion, we developed a mild, palladium(II)-catalyzed ring-
forming aminoacetoxylation of alkenes that is applicable to a range
of nitrogen nucleophiles and alkene substitution patterns. Our studies
indicate the possibility for high levels of reaction regio- and
stereocontrol, making this a potentially attractive method in organic
synthesis. Current work is aimed at exploring the scope of the
reaction with respect to both substrates and oxidants, the potential
for asymmetric induction in the aminoacetoxylation process, and
applications in complex molecule synthesis.
Acknowledgment. We thank Dr. Istvan Pelczer for NMR
spectroscopic assistance and Prof. Martin Semmelhack for helpful
discussions. This work was supported by a Bristol-Myers Squibb
Unrestricted Grant in Synthetic Organic Chemistry, Merck, Prin-
ceton University, and predoctoral fellowships from the ACS/
GlaxoSmithKline (E.J.A.) and Bristol Myers-Squibb (E.J.A.).
Supporting Information Available: Experimental procedures and
product characterization data. This material is available free of charge
a All reactions run with 1 equiv of substrate (0.2 M) and 2 equiv of
1
PhI(OAc)2 at 25 °C. All regio- and diastereoselectivities calculated by H
NMR. b Condition A: 10 mol % Pd(OAc)2, 1 equiv of Bu4NOAc, CH2Cl2.
Condition B: 5 mol % PdCl2(PhCN)2, CH2Cl2. Condition C: 10 mol %
Pd(OAc)2, 1:1 AcOH/Ac2O. c Isolated yields. d 1 equiv of PhI(OAc)2 used.
e Product 11 obtained as 2.3:1 (â: R) mixture of diastereomers.
References
(1) For a review of ionic processes, see: (a) Block, E.; Schwan, A. L. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 4, pp 329-362. For various transition
metal-mediated difunctionalizations, see: (b) Kolb, H. C.; VanNieuwen-
hze, M. S.; Sharpless, K. B. Chem. ReV. 1994, 94, 2483. (c) Muniz, K.;
Iesato, A.; Nieger, M. Chem. Eur. J. 2003, 9, 5581. (d) Li, G.; Wei, H.-
X.; Kim, S. H. Org. Lett. 2000, 2, 2249. (e) El-Qisairi, A. K.; Qaseer, H.
A.; Katsigras, G.; Lorenzi, P.; Trivedi, U.; Tracz, S.; Hartman, A.; Miller,
J. A.; Henry, P. M. Org. Lett. 2003, 5, 439. (f) Manzoni, M. R.; Zabawa,
T. P.; Kasi, D.; Chemler, S. R. Organometallics 2004, 23, 5618. (g) Lei,
A.; Lu, X.; Liu, G. Tetrahedron Lett. 2004, 45, 1785.
Scheme 1. Proposed Catalytic Cycle
(2) (a) Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 451. (b) Li, G.; Angert, H. H.; Sharpless, K. B. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2813. (c) Bodkin, J. A.; McLeod, M. D. J. Chem.
Soc., Perkin Trans. 1 2002, 2733. (d) Donohoe, T. J.; Johnson, P. D.;
Pye, R. J. Org. Biomol. Chem. 2003, 1, 2025. For seminal work involving
stoichiometric Pd(II), see: (e) Ba¨ckvall, J.-E. Tetrahedron Lett. 1975, 16,
2225. (f) Ba¨ckvall, J.-E., Bjo¨rkman, E. E. J. Org. Chem. 1980, 45, 2893.
(3) Bergmeier, S. C. Tetrahedron 2000, 56, 2561.
(4) (a) Hosokawa, T. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons: New York, 2002; Vol.
2, pp 2211-2225. (b) Tamaru, Y.; Kimura, M. Synlett 1997, 749. (c)
Hegedus, L. S.; Allen, G. F.; Bozell, J. J.; Waterman, E. L. J. Am. Chem.
Soc. 1978, 100, 5800.
(5) (a) Hegedus, L. S.; Allen, G. F.; Olsen, D. J. J. Am. Chem. Soc. 1980,
102, 3583. (b) Harayama, H.; Abe, A.; Sakado, T.; Kimura, M.; Fugami,
K.; Tanaka, S.; Tamaru, Y. J. Org. Chem. 1997, 62, 2113.
(6) (a) Brice, J. L.; Harang, J. E.; Timokhin, V. I.; Anastasi, N. R.; Stahl, S.
S. J. Am. Chem. Soc. 2005, 127, 2868. (b) Hegedus, L. S. Tetrahedron
1984, 40, 2415-2434.
(7) (a) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 9542. (b) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc.
2004, 126, 2300. (c) Yoneyama, T.; Crabtree, R. H. J. Mol. Catal. A 1996,
108, 35.
(8) See Supporting Information for details on control experiments.
(9) For a study on the effect of halide ligands on â-hydride elimination, see:
Wang, Z.; Zhang, Z.; Lu, X. Organometallics 2000, 19, 775.
(10) Zawada, P. U.; Banfield, S. C.; Kerr, M. A. Synlett 2003, 7, 971.
(11) Relative configuration of compound 15 was determined by chemical
correlation (see Supporting Information).
2-oxazolidinone in high yield (92%). We were pleased to find that
this reaction also proceeded with a high level of stereocontrol (9.5:1
dr from 10:1 Z:E mixture of 14).11 Although requiring thermal
instigation, the pure trans carbamate was a viable substrate as well,
yielding 17 in a highly diastereoselective fashion (>20:1 dr). From
these experiments, it appears that the aminoacetoxylation process
is a stereoselective trans alkene difunctionalization, and thus a
useful alternative to related cis-selective, metal-catalyzed alkene
aminohydroxylation processes.2
A possible catalytic cycle based on our findings is shown in
Scheme 1, although a number of details remain to be elucidated.
Pd(II)-mediated reversible trans-aminopalladation of the alkene12
generates a protonated intermediate that then undergoes an irrevers-
ible deprotonation step. The relative configurations of compounds
15 and 17, the increase in reaction rate upon the addition of
exogenous base, and the effect of the base on product regioselec-
tivity provide evidence for these steps. The neutral alkyl Pd(II)
(12) For example, see: (a) Ba¨ckvall, J.-E. Acc. Chem. Res. 1983, 16, 335. (b)
Hegedus, L. S.; A¨ kermark, B.; Zetterberg, K.; Olsson, L. F. J. Am. Chem.
Soc. 1984, 106, 7122. Currently, a mechanism involving cis-aminopal-
ladation followed by inversion cannot be discounted.
(13) Cu(OAc)2 (2.0 equiv), a standard oxidant for mediating Pd0/PdII cycle
catalysis, was ineffective.
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