Tandem Reactions DOI: 10.1002/anie.200705117 Gold(I)-Catalyzed Cycloisomerization of 3-Methoxy-1,6-enynes FeaturingTandemCyclizationand[3,3]-SigmatropicRearrangement** HyoJ.Bae,BaburajBaskar,SangE.An,JaeY.Cheong,DanielT.Thangadurai,In-ChulHwang, and YoungH. Rhee* The transition-metal-catalyzed cycloisomerization of 1,6- enynes is one of the most powerful strategies for the synthesis of highly functionalized carbocyclic compounds. [1] Recent studies on the gold- and platinum-catalyzed cycloisomeriza- tions are particularly noteworthy because of the structural diversity of the products provided by these reactions. [2] Numerous carbocyclic frameworks have been assembled by using structurally simple 1,6-enyne precursors. In many reactions, addition of internal olefins to the metal-activated alkynes has been proposed as the key event. [3] Unlike the structurally simple 1,6-enynes mentioned above, 3-alkoxy-1,6-enynes 1 offer an alternative mode of reaction as depicted in Scheme 1. In this case, the oxygen atom can participate as a competing nucleophile in the addition to the metal-activated alkynes. The resulting cyclic oxonium ion 2 has a structural platform for a [3,3]-sigmatropic rearrangement, which generates cycloheptenyl cation 3. [4] Elimination of the cationic metal species produces 1-alkoxy- 1,4-cycloheptadiene 4 in a catalytic manner. On the basis of the recent reports on Lewis acid promoted (or catalyzed) Claisen rearrangement of cyclic enol ethers, [5] we envisioned that the involvement of the oxonium ion intermediate 2 could facilitate the key [3,3]-sigmatropic process. Moreover, the enol ether moiety in 4 can be chemoselectively transformed into a variety of other func- tional groups. Thus, we envisaged that the proposed reaction would provide highly efficient access to cycloheptene frame- works having diverse functional groups, which are important building blocks in a variety of bioactive natural products. [6] In light of the proposed catalytic cycle, a potentially competing pathway is the metal-catalyzed carboalkoxylation (Scheme 2; pathway B). [7] This alternative pathway would result in a mixture of cycloheptadiene 4 and cyclopentene 4’ formed from allylic cation 5, whereas the concerted nature of the proposed sigmatropic pathway leads to the selective formation of 4 (Scheme 2; pathway A). [8] To investigate this mechanistic proposal, we initially examined various platinum and gold complexes by using 6 as the substrate (Table 1). Preliminary investigations using a platinum catalyst (Table 1, entry 1) [7c,d] or neutral [Au{P- (C 6 H 5 ) 3 }Cl] (Table 1, entry2) failed to give the desired bicyclic heptadiene 7a. To our delight, switching to pregen- erated cationic gold complex 8a (5mol%) in CH 2 Cl 2 produced the cycloisomerized product 7a in 55% yield within 10 minutes at room temperature, and there was no evidence of the formation of carbocyclic five-membered rings (Table 1, entry 3). [9] Notably, employing a more electrophilic catalyst (8b) [10] gave 7a almost instantaneously in 92% yield Scheme 1. Proposed mechanism for the gold(I)-catalyzed cycloisomeri- zation of 3-alkoxy-1,6-enynes. Scheme 2. Sigmatropic rearrangement (pathway A) versus carboalkox- ylation (pathway B). [*] H. J. Bae, B. Baskar, S. E. An, J. Y. Cheong, D. T. Thangadurai, Prof. Dr. Y. H. Rhee Department of Chemistry POSTECH (Pohang University of Science and Technology) Pohang, 790-784 (Korea) Fax: (+ 82)54-279-3399 E-mail: yhrhee@postech.ac.kr Dr. I.-C. Hwang Department of Chemistry Center for Superfunctional Molecules Center for Basic Sciences POSTECH (Pohang University of Science and Technology) (Korea) [**] This work was supported by the Korea Science and Engineering Foundation (KOSEF), which is funded by the Korean government (R01-2007-000-10889-0). H.J.B. thanks the BK21 program for a fellowship. We thank Prof. Dr. Kwang S. Kim for the supporting crystal structure analysis. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 2263 Angew. Chem. Int. Ed. 2008, 47, 2263 –2266 # 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim