Gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes featuring tandem cyclization and [3,3]-sigmatropic rearrangement
Gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes featuring tandem cyclization and [3,3]-sigmatropic rearrangement
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DOI：
10.1002/anie.200705117
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Rhee, Young H.
中科院分区：
文献类型：
--
作者：
Bae, Hyo J.;Baskar, Baburaj;Rhee, Young H.
过渡金属催化的1，6-烯炔环异构化反应是合成高官能度碳环化合物的有效途径之一。[1]金和铂催化的环化异构化反应由于其产物的结构多样性而备受关注。[2]通过使用结构简单的1，6-烯炔前体已经组装了许多碳环框架。在许多反应中，内烯烃与金属活化的炔的加成被认为是关键反应。[3]与上述结构简单的1，6-烯炔不同，3-烷氧基-1，6-烯炔1提供了另一种反应模式，如方案1所示。在这种情况下，氧原子可以作为竞争性亲核试剂参与到金属活化的炔的加成中。所得的环状氧鎓离子2具有用于[3，3]-σ迁移重排的结构平台，其产生环庚烯基阳离子3。[4]阳离子金属物质的消除以催化方式产生1-烷氧基-1，4-环庚烯4。基于最近关于刘易斯酸促进（或催化）环烯醇醚的Claisen重排的报道，[5]我们设想氧鎓离子中间体2的参与可以促进关键的[3，3]-σ迁移过程。此外，4中的烯醇醚部分可以化学选择性地转化为各种其他官能团。因此，我们设想，所提出的反应将提供高效获得具有不同官能团的环庚烯框架的途径，所述环庚烯框架是各种生物活性天然产物中的重要构件。[6]根据提出的催化循环，潜在的竞争途径是金属催化的烷氧羰基化（方案2;途径B）。[7]该替代途径将导致由烯丙基阳离子5形成的环庚烯4和环戊烯4 '的混合物，而所提出的σ迁移途径的协同性质导致4的选择性形成（方案2;途径A）。[8]为了研究这一机制建议，我们最初使用6作为底物检测了各种铂和金络合物（表1）。使用铂催化剂（表1，条目1）[7 c，d]或中性[Au {P-（C6 H5）3} Cl]（表1，条目2）的初步研究未能得到所需的双环庚二烯7a。令我们高兴的是，在CH 2Cl 2中切换到预生成的阳离子金络合物8a（5mol%）在室温下10分钟内以55%的产率产生环异构化产物7a，并且没有形成碳环五元环的证据（表1，条目3）。[9]值得注意的是，使用更亲电的催化剂（8b）[10]几乎立即以92%的产率得到7a
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 cycloisomerizations 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 functional groups. Thus, we envisaged that the proposed reaction would provide highly efficient access to cycloheptene frameworks 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 (Table1, entry1)[7c, d] or neutral [Au {P-(C6H5) 3} Cl](Table1, entry2) failed to give the desired bicyclic heptadiene 7a. To our delight, switching to pregenerated cationic gold complex 8a (5mol%) in CH2Cl2 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