C O M M U N I C A T I O N S
Table 2. Azomethine Imine Scope
Supporting Information Available: Experimental procedures,
compound characterization data (PDF), and X-ray structure data (CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) (a) Barluenga, J.; Rodr´ıgues, F.; Fan˜ana´s, F. J.; Flo´rez, J. Top. Organomet.
Chem. 2004, 13, 59. (b) Barluenga, J.; Santamaría, J.; Toma´s, M. Chem.
ReV. 2004, 104, 2259. (c) Sierra, M. A.; Ferna´ndez, I.; Coss´ıo, F. P. Chem.
Commun. 2008, 4671.
(2) (a) Davies, H. M. L.; Clark, D. M.; Alligood, D. B.; Elband, G. R.
Tetrahedron 1987, 43, 4265. (b) Davies, H. M. L.; Hu, B. Tetrahedron
Lett. 1992, 33, 455.
(3) For descriptions of singlet vinylcarbene, see: (a) Hoffmann, R.; Zeiss, G. D.;
Van Dine, G. W. J. Am. Chem. Soc. 1968, 90, 1485. (b) Davis, J. H.;
Goddard, W. A., III; Bergman, R. G. J. Am. Chem. Soc. 1977, 99, 2427.
(c) Sevin, A.; Arnaud-Danon, L. J. Org. Chem. 1981, 46, 2346. (d)
Yoshimine, M.; Pacansky, J.; Honjou, N. J. Am. Chem. Soc. 1989, 111,
2785.
(4) (a) Bertrand, G. Ed.; Carbene Chemistry: From Fleeting Intermediates to
Powerful Reagents; FontisMedia: Lausanne, Dekker, New York, 2002. (b)
Moss, R. A., Platz, M. S., Jones, M., Jr., Eds.; ReactiVe Intermediate
Chemistry; Wiley-Interscience: Hoboken, NJ, 2004.
(5) Nucleophilic singlet vinylcarbenes react as 3-carbon units in cycloadditions
with olefins; see: Boger, D. L.; Wysocki, R. J., Jr. J. Org. Chem. 1988, 53,
3408.
(6) (a) Davies, H. M. L. Curr. Org. Chem. 1998, 2, 463. (b) Davies, H. M. L.;
Walji, A. M. In Modern Rhodium-Catalyzed Organic Reactions; Evans,
P. A., Ed.; Wiley-VCH: Weinheim, Germany, 2005; p 301.
(7) For the first use of the term carbenoid as a “description of intermediates
which exhibit reactions qualitatively similar to those of carbenes without
necessarily being free divalent carbon species,” see: Closs, G. L.; Moss,
R. A. J. Am. Chem. Soc. 1964, 86, 4042.
(8) For examples of formal [3+3] cycloaddition reactions of azomethine imines,
see: (a) Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 6330. (b)
Chan, A.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 5334. (c) Perreault,
C.; Goudreau, S. R.; Zimmer, L. E.; Charette, A. B. Org. Lett. 2008, 10,
689.
(9) For examples of gold-catalyzed intermolecular cycloaddition reactions using
propargyl esters, see: (a) Johansson, M. J.; Gorin, D. J.; Staben, S. T.;
Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002. (b) Gorin, D. J.; Dube´,
P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 14480. (c) Gorin, D. J.;
Watson, I. D. G.; Toste, F. D. J. Am. Chem. Soc. 2008, 130, 3736. (d)
Shapiro, N. D.; Toste, F. D. J. Am. Chem. Soc. 2008, 130, 9244.
(10) For additional examples of gold-catalyzed intermolecular cycloaddition
reactions, see: (a) Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc.
1986, 108, 6405. (b) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650. (c) Kusama, H.;
Miyashita, Y.; Takaya, J.; Iwasawa, N. Org. Lett. 2006, 8, 289. (d) Melhado,
A. D.; Luparia, M.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 12638. (e)
Zhang, G.; Huang, X.; Li, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130,
1814. (f) Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130, 12598.
(11) (a) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (b)
Hashmi, A. S. K. Chem. ReV. 2007, 107, 3180. (c) Gorin, D. J.; Toste,
F. D. Nature 2007, 446, 395. (d) Shen, H. C. Tetrahedron 2008, 64, 7847.
(e) Jime´nez-Nu´n˜ez, E.; Echavarren, A. M. Chem. ReV. 2008, 108, 3326.
(12) The major isomer was assigned to be cis by X-ray crystallography (see
Supporting Information).
a Reaction performed at room temperature. b 2 mmol scale.
cis-imine geometry and the preferred trans geometry of the
proposed gold-carbenoid intermediate.9d,18 To gain further insight
into the origin of the 1,2-cis stereoselectivity, secondary propargyl
ester 8c was reacted with tert-butyl substituted azomethine imine
4c (eq 5).19 In this case, a 2:1 mixture of diastereomers with respect
to the pyrazolidinone substituent, and favoring the 1,3-trans isomer
of 9c, was formed.20 Furthermore, the high diastereoselectivity in
the gold-catalyzed reactions of 3a can be rationalized by minimiza-
tion of unfavorable steric interactions between the propargyl ester
methyl groups and the ꢀ-substituent in the ring closing transition
state (eq 6). These results suggest that the diastereoselectivity is
determined during ring closing, rather than in the formation of
allylgold intermediate 10.13
(13) Similar cis-selectivity has been observed; see: ref 8. (a) Sua´rez, A.; Downey,
C. W.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 11244. (b) Bonin, M.;
Chauveau, A.; Micouin, L. Synlett 2006, 15, 2349.
(14) Employing a different propargyl ester (acetate or pivolate) provided no
change in selectivity.
(15) HCl, PtCl2, PdCl2(PPh3)2, [IrCl(cod)]2, and [RuCl2(CO)3]2 failed to promote
this reaction.
(16) Nevado, C.; Echavarren, A. M. Chem.sEur. J. 2005, 11, 3155.
(17) Additional evidence for a stepwise mechanism was obtained in the reaction
of azomethine imine 11, which furnished enamine 12 after ring fragmenta-
tion and tautomerization.
In conclusion, we have developed a gold(III)-catalyzed synthesis
of diazabicycles from readily available starting materials.21 This
report represents the first example of a formal cycloaddition between
alkenyl metal carbenoids and 1,3-dipoles. In contrast to the previ-
ously reported cycloadditions,9d,10f this reaction highlights the
difference in the reactivity of alkenyl Fischer carbenes and the
alkenyl Au-carbenoids generated from the rearrangement of pro-
pargyl esters. Further studies exploring and exploiting this difference
are ongoing and will be reported in due course.
(18) Witham, C. A.; Mauleo´n, P.; Shapiro, N. D.; Sherry, B. D.; Toste, F. D.
J. Am. Chem. Soc. 2007, 129, 5838.
(19) This substrate combination was chosen to aid in characterization of the
products. Nearly identical selectivites were observed in reactions employing
either 8a or 8c.
(20) The configuration of the minor isomer was confirmed by X-ray crystal-
lography (see Supporting Information).
(21) For further synthetic transformations of the diazabicycles, see the Supporting
Information.
Acknowledgment. We gratefully acknowledge NIHGMS (RO1
GM073932), Bristol-Myers Squibb, and Novartis for funding and
Johnson Matthey for the generous donation of AuCl3. Y.S. thanks
the China Scholarship Council (Grant No. [2008]3019) for a
predoctoral fellowship.
JA903863B
9
J. AM. CHEM. SOC. VOL. 131, NO. 33, 2009 11655