C O M M U N I C A T I O N S
Table 2. Scope Study
(2 equiv) at -20 °C also led to an efficient Diels-Alder reaction
(eq 3). To our delight, a dienophile unit (i.e., fumarate) was allowed
in substrate 12 (eq 4), and a one-pot, sequential Au-catalyzed diene
formation and MeAlCl2-catalyzed intramolecular Diels-Alder
reaction was realized, offering rapid access to complex bicyclic
lactone 14 in 63% yield (eq 4). Of note, residual Au complexes
did not affect these Diels-Alder reactions.
In summary, propargylic pivalates with electronically unbiased
internal alkynes were selectively transformed into (1Z,3E)-2-
pivaloxy-1,3-dienes containing various functionalities. The unusual
selectivity of 1,2-acyloxy migration over the structurally preferred
3,3-rearrangement was realized. This reaction is highly stereo-
selective and can offer a rapid access to dienes for one-pot intra-/
intermolecular Diels-Alder reactions either under thermal condi-
tions or with Lewis acid catalysis.
Acknowledgment. The authors thank the generous financial
support from ACS PRF (43905-G1), ORAU and Merck and Sansan
Cao for some initial studies. The acquisition of an NMR spectrom-
eter and upgrade of an existing NMR spectrometer are funded by
NSF CHE-0521191.
b
a Only the (1Z,3E) isomer was observed except in entry 3. Isolated
Supporting Information Available: Experimental procedures,
compound characterization data. This material is available free of charge
c
d
yield. 30% of enone was isolated. 20% of enyne and 20% of enone
were formed.
substrate and only 10% conversion was observed after 10 h. A
cyclohexyl ring on the alkyne terminus was allowed, and terminally
disubstituted diene 7c was isolated in 80% yield although in this
case the enolic double bond exhibited eroded Z-selectivity (entry
3). This reaction also tolerated various protected hydroxyl groups
at different positions of the substrate (entries 4, 5, 8, and 9), allowing
facile access to pivaloxydienes with variously located oxygen
functionalities. Although the yield of 7i (entry 9) was low, its
alternative synthesis via enolate acylation is likely problematic due
to potentially facile elimination. To our delight, a phthalimide group
was allowed, thus offering protected amino groups in the diene
products (i.e., 7f and 7g). Of note is product 7f, where the
phthalimide group is directly attached to the diene. This reaction
did not work well with propargylic esters derived from ketones
(e.g., entry 10), and a major side reaction was the elimination to
form enynes. When a phenyl group is located in close proximity
to the propargylic moiety (e.g., entries 11 and 12), known
processes2e,9 compete effectively, thus limiting, to a certain extent,
the reaction scope.
The dienes formed via this method are excellent substrates for
the Diels-Alder reaction. For example, heating 7a with N-
phenylmaleimide in DCE at 80 °C for 12 h gave cycloadduct 10 in
quantitative yield (eq 1). Moreover, N-phenylmaleimide did not
affect the Au catalysis, and heating a mixture of pivalate 6a and
N-phenylmaleimide in the presence of IPrAuNTf2 for 17 h led to
78% isolated yield of 10 (eq 2). Treatment of the reaction mixture
of 2d after Au catalysis with methacrolein (2 equiv) and MeAlCl2
References
(1) For recent reviews on gold catalysis, see: (a) Zhang, L.; Sun, J.; Kozmin,
S. A. AdV. Synth. Catal. 2006, 348, 2271-2296. (b) Fu¨rstner, A.; Davis,
P. W. Angew. Chem., Int. Ed. 2007, 46, 3410-3449. (c) Hashmi, A. S.
K. Chem. ReV. 2007, 107, 3180-3211. For a review on Au-catalyzed
reactions of propargylic esters, see (d) Marion, N.; Nolan, S. P. Angew.
Chem., Int. Ed. 2007, 46, 2750-2752.
(2) (a) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804-16805. (b) Yu, M.;
Li, G.; Wang, S.; Zhang, L. AdV. Synth. Catal. 2007, 349, 871-875. (c)
Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414-8415. (d) Buzas,
A.; Gagosz, F. J. Am. Chem. Soc. 2006, 128, 12614-12615. (e) Marion,
N.; Diez-Gonzalez, S.; de Fremont, P.; Noble, A. R.; Nolan, S. P. Angew.
Chem., Int. Ed. 2006, 45, 3647-3650.
(3) For selected examples, see: (a) Miki, K.; Ohe, K.; Uemura, S. J. Org.
Chem. 2003, 68, 8505-8513. (b) Mamane, V.; Gress, T.; Krause, H.;
Fu¨stner, A. J. Am. Chem. Soc. 2004, 126, 8654-8655. (c) Shi, X.; Gorin,
D. J.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 5802-5803. (d)
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2005, 127, 18002-18003. (e) Amijs, C. H. M.; Lopez-Carrillo, V.;
Echavarren, A. M. Org. Lett. 2007, 9, 4021-4024.
(4) A recent calculation suggests that double 1,2-acyloxy migrations can also
account for the 3,3-rearrangement and all these transformations are
reversible. For reference, see: Correa, A.; Marion, N.; Fensterbank, L.;
Malacria, M.; Nolan, S. P.; Cavallo, L. Angew. Chem., Int. Ed. 2008, 47,
613.
(5) For a study with Pt(II) as catalyst, see: Hardin, A. R.; Sarpong, R. Org.
Lett. 2007, 9, 4547-4550.
(6) For related Cu and Pt catalysis, see: (a) Prasad, B. A. B.; Yoshimoto, F.
K.; Sarpong, R. J. Am. Chem. Soc. 2005, 127, 12468-12469. (b) Schwier,
T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.; Gevorgyan, V. J. Am.
Chem. Soc. 2007, 129, 9868-9878.
(7) For other Au-catalyzed diene formations, see: (a) Wang, S. Z.; Zhang,
L. M. Org. Lett. 2006, 8, 4585-4587. (b) Buzas, A. K.; Istrate, F. M.;
Gagosz, F. Org. Lett. 2007, 9, 985-988.
(8) (a) Li, G.; Zhang, L. Angew. Chem., Int. Ed. 2007, 46, 5156-5159. (b)
Ricard, L.; Gagosz, F. Organometallics 2007, 26, 4704-4707.
(9) Nevado, C.; Echavarren, A. M. Chem.sEur. J. 2005, 11, 3155-3164.
JA800001H
9
J. AM. CHEM. SOC. VOL. 130, NO. 12, 2008 3741