Gold(I)-catalyzed cyclizations of silyl enol ethers: Application to the synthesis of (+)-lycopladine A
Gold(I)-catalyzed cyclizations of silyl enol ethers: Application to the synthesis of (+)-lycopladine A
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DOI：
10.1002/anie.200602035
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Toste, F. Dean
中科院分区：
文献类型：
--
作者：
Staben, Steven T.;Kennedy-Smith, Joshua J.;Toste, F. Dean
第5991章化学。国际。埃德。 2006, 45, 5991–5994 2006 Wiley-VCH Verlag GmbH & Co. KGaA，Weinheim 将烯醇化 β-酮酯和 β-二酮附加到炔烃上作为环戊烯形成的方法。 [2]尽管广泛适用于各种环状和双环系统的非对映选择性形成，但该方法仅限于合成带有两个羰基官能团的季碳原子。我们提出的这些转化机制包括将酮酯的烯醇互变异构体加成到金 (I) 络合炔烃上，然后对所得乙烯基-金 (I) 物质进行质子解作用。基于这一假设，我们设想利用硅烯醇醚先有的亲核性作为金 (I) 催化环化反应中的“冷冻烯醇等价物”。 [3, 4] 本文描述了金 (I) 催化硅烯醇醚在炔烃和丙二烯上环化的发展以及这种碳-碳的应用 成键反应以方便地全合成 (+)-lycopladine A.[5]在金 (I) 催化反应中使用甲硅烷基烯醇醚时必须面对几个问题。首先，与烯醇亲核试剂不同，硅烷化对应物缺乏乙烯基-金 (I) 中间体质子解所需的质子源。因此，需要外部质子源来完成催化循环。必须避免该质子源 [6, 7] 和亲电阳离子金 (I) 物质 [8] 与高度亲核的硅烯醇醚发生竞争反应。考虑到这一点，我们研究了以水作为外部质子源，金 (I) 催化的硅烯醇醚 1 5-外环化的可行性。催化量的[Ph3PAuCl]/AgBF4在10:1二氯甲烷/水混合物中于408℃反应30分钟提供双环酮2，分离产物的产率为78％[式(1)； OTf=三氟甲磺酸盐]。抗衡离子的身份被证明是关键，因为其他配合物（即 ClO4、SbF6 和 OTf 盐）可产生具有不同量的水解烯醇醚的所需环化产物。此外，我们发现甲醇可以替代作为质子源，而分离产物 2 的产率仅略有下降。在这些条件下，金 (I) 催化的 exo-dig 环化被证明是通用的（表 1，条目 1-8）。在双环系统的完全非对映选择性形成中，α-位允许烷基、芳基和氢取代。例如，金（I）催化烯醇醚3的环化得到双环产物4，其含有三个连续的全碳季立体中心
5991 Angew. Chem. Int. Ed. 2006, 45, 5991–5994 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim enolizable β-keto esters and β-diketones onto appended alkynes as a method for cyclopentene formation.[2] Although broadly applicable to the diastereoselective formation of a variety of cyclic and bicyclic systems, the method is limited to the synthesis of quaternary carbon atoms that bear two carbonyl functionalities. Our proposed mechanism for these transformations involves the addition of the enol tautomer of the keto ester to a gold (I)-complexed alkyne and the subsequent protonolysis of the resulting vinyl–gold (I) species. On the basis of this hypothesis, we envisioned taking advantage of the well-precedented nucleophilicity of silyl enol ethers as “frozen enol equivalents” in gold (I)-catalyzed cyclization reactions.[3, 4] Described herein is the development of the gold (I)-catalyzed cyclization of silyl enol ethers onto alkynes and allenes and the application of this carbon–carbon bond-forming reaction to an expedient total synthesis of (+)-lycopladine A.[5] Several issues must be confronted in employing silyl enol ethers in gold (I)-catalyzed reactions. First, unlike enol nucleophiles, the silylated counterparts lack the proton source necessary for the protonolysis of the vinyl–gold (I) intermediate. Thus, an external proton source is required to complete the catalytic cycle. The competitive reaction of this proton source [6, 7] and the electrophilic cationic gold (I) species [8] with the highly nucleophilic silyl enol ether must be avoided. With this in mind, we examined the feasibility of the gold (I)-catalyzed 5-exo cyclization of silyl enol ether 1 with water as the external proton source. A catalytic amount of [Ph3PAuCl]/AgBF4 in a 10: 1 dichloromethane/water mixture at 408C for 30minutes provided bicyclic ketone 2 in 78% yield of the isolated product [Eq.(1); OTf= trifluoromethanesulfonate]. The identity of the counterion proved to be key as other complexes (namely, ClO4, SbF6, and OTf salts) produced the desired cyclized product with varying amounts of hydrolyzed enol ethers. Additionally, we found that methanol could be substituted as the proton source with only a slight deterioration in the yield of the isolated product 2.Under these conditions, the gold (I)-catalyzed exo-dig cyclization proved to be general in scope (Table 1, entries 1–8). Alkyl, aryl, and hydrogen substitution was tolerated at the α-position in the completely diastereoselective formation of bicyclic systems. For example, the gold (I)-catalyzed cyclization of enol ether 3 afforded bicyclic product 4, which contains three consecutive all-carbon quaternary stereocen-