ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Facile Synthesis of Isochromanones and
Isoquinolones by AuCl3 Catalyzed
Cascade Triggered by an Internal
Nucleophile
Kavirayani R. Prasad* and Chinta Nagaraju
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received April 22, 2013
ABSTRACT
Synthesis of isochromanones and isoquinolones comprising a quaternary center with high diastereoselectivity was realized via a AuCl3 catalyzed
tandem intramolecular exo-dig heterocyclization/enol isomerization/Claisen rearrangement sequence in excellent yields. The reaction is general
and amenable for the synthesis of structurally diverse analogues.
The advent of gold catalysis in organic synthesis has
seen a virtual rush in recent years in developing synthetic
strategies based on gold complexes. A variety of gold
catalysts with a number of substrates that include a
combination of alkene, alkyne, and heteroatoms leading
to the evolution of diverse reactions for the construction of
carbo- and heterocyclic compounds were developed.1
Claisen rearrangement [in general 3,3-sigmatropic rear-
rangements], a reaction that has a profound impact in
organic synthesis,2 was also a subject of investigation with
gold catalysts. Dean Toste’s group disclosed the first
successful gold catalyzed Claisen rearrangement of
vinyl propargyl ethers for the synthesis of homoallenic
alcohols.3 Similarly, 3,3-sigmatropic rearrangement of
allenyl vinyl ethers was also reported by the Kraft and
Xu groups.4 Herein we report a novel strategy, hitherto
unexplored, involving a combination of tandem exo-dig
heterocylizationÀenol isomerizationÀClaisen rearrange-
ment triggered by an internal nucleophile to yield isochro-
manones and isoquinolones (Figure 1), which were
important scaffolds present in a number of natural
products.
(1) For selected reviews on gold-catalyzed cyclizations, see: (a)
Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180. (b) Gorin, D. J.; Sherry,
B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351. (c) Li, Z.; Brouwer, C.;
He, C. Chem. Rev. 2008, 108, 3239. (d) Corma, A.; Leyva-Perez, A.;
Sabater, M. J. Chem. Rev. 2011, 111, 1657. (e) Huang, H.; Zhou, Y.; Liu,
~~
H. Beilstein J. Org. Chem. 2011, 7, 897. (f) Nunez, E. J.; Echavarren,
A. M. Chem. Rev. 2008, 108, 3326.
(2) (a) Claisen, L. Ber. 1912, 45, 3157. (b) For a review on Claisen
rearrangement see: Castro, A. M. M. Chem. Rev. 2004, 104, 2939.
(3) (a) Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978.
Figure 1. Isochromanone and isoquinolone.
~
(b) Mauleon, P.; Krinsky, J. L.; Toste, F. D. J. Am. Chem. Soc. 2009, 131,
4513. (c) Horino, Y.; Luzung, M. R.; Toste, F. D. J. Am. Chem. Soc. 2006,
128, 11364. (d) For theoretical treatment of gold mediated Claisen re-
arrangement, see: Vidhani, D. V.; Cran, J. W.; Krafft, M. E.; Manoharan,
M.; Alabugin, I. V. J. Org. Chem. 2013, 78, 2059.
(4) (a) Krafft, M. E.; Hallal, K. M.; Vidhani, D. V.; Cran, J. W. Org.
Biomol. Chem. 2011, 9, 7535. (b) Wei, H.; Wang, Y.; Yue, B.; Xu, P.-F.
Adv. Synth. Catal. 2010, 352, 2450.
r
10.1021/ol4011129
XXXX American Chemical Society