C O M M U N I C A T I O N S
Table 1. Synthesis of N-Allyl Aziridines by Palladium-Catalyzed
Allylic Amination
Preliminary results indicate that this chemistry can be applied
to the preparation of enantiomerically enriched aziridines15 via
enantioselective allylation. The use of (R)-BINAP as a ligand
afforded the N-allyl aziridine 2j in 98% ee. Under similar reaction
conditions, cyclohexene imine afforded the corresponding N-allyl
aziridine (2h) in 97% ee.
In summary, we have uncovered the first example of palladium-
catalyzed allylic amination reaction using unprotected aziridines.
The observed regioselectivity favors valuable branched products
in the cases of aliphatic acetates, underscoring the decisive effect
of the amine on the course of allylic amination. The reasons for
these unusual regioselectivity patterns are the subject of ongoing
investigations. The process allows for the asymmetric allylic
amination of unprotected aziridines with high enantioselectivities
and creates a possibility to introduce aziridine moieties into
functionalized environments with high levels of regio- and enan-
tioselectivities, and high isolated yields.
Acknowledgment. We thank NSERC, CFI, ORDCF, ACS-PRF,
the University of Toronto, and Affinium Pharmaceuticals for
financial support. A.K.Y. is a Cottrell Scholar of Research
Corporation. I.D.G.W. would like to acknowledge an Ontario
Graduate Scholarship. S.A.S. is grateful to Pfizer for the 2003
Undergraduate Summer Fellowship. Mr. Greg Chen is acknowl-
edged for the preparation of 1c.
Supporting Information Available: Experimental procedures and
characterization data for all unknown compounds. This material is
References
(1) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921-2943.
(2) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1-14.
(3) (a) Burgess, K.; Liu, L. T.; Pal, B. J. Org. Chem. 1993, 58, 4758-4763.
(b) Ichikawa, Y.; Ito, T.; Nishiyama, T.; Isobe, M. Synlett 2003, 1034-
1036. (c) Ito, K.; Akashi, S.; Saito, B.; Katsuki, T. Synlett 2003, 1809-
1812. (d) Paquette, L. A.; Leit, S. M. J. Am. Chem. Soc. 1999, 121, 8126-
8127. (e) Magnus, P.; Lacour, J.; Coldham, I.; Mugrage, B.; Bauta, W.
B. Tetrahedron 1995, 51, 11087-11110. (f) Liu, H.; Liang, X.; Sohoel,
H.; Buelow, A.; Bols, M. J. Am. Chem. Soc. 2001, 123, 5116-5117. (g)
Trost, B. M.; Van Vranken, D. L. J. Am. Chem. Soc. 1993, 115, 444-
458.
(4) (a) Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim,
Germany, 2000. (b) Johannsen, M.; Jørgensen, K. A. Chem. ReV. 1998,
98, 1689-1708.
(5) Trost, B. M.; VanVranken, D. L. Chem. ReV. 1996, 96, 395-422.
(6) Watson, I. D. G.; Yudin, A. K. J. Org. Chem. 2003, 68, 5160-5167 and
references therein.
(7) (a) Sasaki, M.; Yudin, A. K. J. Am. Chem. Soc. 2003, 125, 14242-14243.
(b) Sasaki, M.; Dalili, S.; Yudin, A. K. J. Org. Chem. 2003, 68, 2045-
2047. (c) Siu, T.; Yudin, A. K. J. Am. Chem. Soc. 2002, 124, 530-531.
(8) Sweeney, J. B. Chem. Soc. ReV. 2002, 31, 247-258. Watson, I. D. G.;
Yudin, A. K. Curr. Opin. Drug DiscoVery DeV. 2002, 5, 906-917.
(9) (a) Alezra, V.; Bouchet, C.; Micouin, L.; Bonin, M.; Husson, H.-P.
Tetrahedron Lett. 2000, 41, 655-658. (b) Alezra, V.; Bonin, M.; Micouin,
L.; Policar, C.; Husson, H.-P. Eur. J. Org. Chem. 2001, 2589-2594.
(10) (a) You, S.-L.; Zhu, X.-Z.; Luo, Y.-M.; Hou, X.-L.; Dai, L.-X. J. Am.
Chem. Soc. 2001, 123, 7471-7472. (b) Hayashi, T.; Kishi, K.; Yamamoto,
A.; Ito, Y. Tetrahedron Lett. 1990, 31, 1743-1746.
a Reaction performed with 2 equiv of K2CO3. b Isolated after addition
of 1 equiv of PhSH to in situ prepared allyl aziridine in MeCN. c Volatile
products isolated after reaction with PhSH as per footnote b. d Reaction
performed with 2 equiv of allyl acetate. e Combined yield. f Linear to
branched ratio. g 0% de.
(11) (a) Trost, B. M.; Keinan, E. J. Org. Chem. 1979, 44, 3451-3457. (b)
Akermark, B.; Vitagliano, A. Organometallics 1985, 4, 1275-1283. (c)
Mizuno, M.; Shioiri, T. Chem. Commun. 1997, 2165-2166. (d) Murahashi,
S.-I.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y. J. Org. Chem. 1989, 54,
3292-3303. (e) Hutchins, R. O.; Wei, J.; Rao, S. J. J. Org. Chem. 1994,
59, 4007-4009.
acetate. The reaction between cinnamyl acetate and cyclohexene
imine favored the linear isomer (2c). The [Pd(η3-C3H5)Cl]2/BINAP
catalyst gave a 97% combined yield and produced the best product
distribution with a 92:8 ratio. This is the same regioselectivity that
is expected when alkylamines are used in the Pd-catalyzed allylic
amination.14
The N-allyl aziridines synthesized by this protocol can be
transformed into functionalized branched amines by established
ring-opening protocols. For instance, to access the N-allyl trans-
diamine (7), N-cinnamyl cyclohexene imine was opened with aniline
in 85% yield by our previously developed ring-opening chemistry
using a catalytic amount of B(C6F5)3.6
(12) Reaction of geranyl acetate with 5 mol % Pd(PPh3)4 in THF at 60 °C
gives full conversion to the background products in 6 h.
(13) Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J. J. Am. Chem. Soc. 1994,
116, 11151-11152.
(14) Recently, an exception for cinnamyl acetate was noted by Hartwig et al.
in the iridium system: (a) Kiener, C. A.; Shu, C.; Incarvito, C.; Hartwig,
J. F. J. Am. Chem. Soc. 2003, 125, 14272-14273. (b) Ohmura, T.;
Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 15164-15165.
(15) (a) Lee, W. K.; Ha, H.-J. Aldrichimica Acta 2003, 36, 57-63. (b) Cardillo,
G.; Gentilucci, L.; Tolomelli, A. Aldrichimica Acta 2003, 36, 39-50.
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