A concise synthesis of (-)-aplyviolene facilitated by a strategic tertiary radical conjugate addition.
A concise synthesis of (-)-aplyviolene facilitated by a strategic tertiary radical conjugate addition.
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通过战略三级自由基共轭物促进的（ - ） - 丙烯的简洁合成。
DOI：
10.1002/anie.201204977
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发表时间：
2012-09-17
影响因子：
16.6
通讯作者：
Overman, Larry E.
中科院分区：
文献类型：
--
作者：
Schnermann, Martin J.;Overman, Larry E.
阿普利维拉烯(1)和马法兰素E(2，图式1A)是重排的天然产物中更复杂的二萜类成员的代表。[1，2]这些二萜的结构定义为连接的顺式全氢天青烯和6-乙酰氧基-2，7-二氧双环[3.2]。1]Octan-3-one片段。组装这些结构的实质挑战集中在敏感的双环内酯亚基的构建和连接两个环系的C8-C14σ-键的形成上，这一挑战因C8的四元性质而增加。[3]我们先前报道了通过合成截断的同系物3和4制备1和2的内酯亚基(方案1 A)、[4]以及首次全合成紫罗兰烯(在方案1B中概述)。关键的C8-C14σ键是通过Michael将叔烯醇酯5加成到烯酮6上形成的。[6]随后对产物7的精制提供了中间体8，它沿着我们先前合成3的路线被转化为(±)-Aplyviene。这种第一代合成的不希望的方面是顺氢天青烯单元的长时间准备和需要从裂解偶联步骤的产物中去除外来的酮羰基。如随附的通信中所描述的，[7]我们最初试图通过在关键偶联片段中使用从顺式-全氢唑烯腈9衍生的叔基有机铜酸盐来简化合成，但由于排除了加合物11的形成而阻止了我们最初的尝试在关键的四碳立体中心(图式1C)，它与紫罗兰烯是同向异构体。有机铜共轭加成反应的这种意想不到的立体化学结果引发了对另一种策略的考虑，在该策略中，C8-C14σ-键将通过叔基12和烯酮13的结合形成
Aplyviolene (1) and macfarlandinE (2, Scheme1A) are representative of the more complex members of the rearranged spongian diterpene class of natural products.[1, 2] These diterpenes are structurally defined by attached cis-perhydroazulene and 6-acetoxy-2, 7-dioxabicyclo [3.2. 1] octan-3-one fragments. The substantial challenge in assembling these structures centers on the construction of the sensitive bicyclic lactone subunit and the formation of the C8–C14 σ-bond joining the two ring systems, a challenge augmented by the quaternary nature of C8.[3] We previously reported preparation of the lactone subunits of 1 and 2 by the synthesis of truncated congeners 3 and 4 (Scheme 1 A),[4] as well as the first total synthesis of aplyviolene (outlined in Scheme 1B).[5] In this latter effort, the key C8–C14 σ-bond was formed by Michael addition of tertiary enolate 5 to enone 6.[6] Subsequent elaboration of product 7 provided intermediate 8, which was converted to (À)-aplyviolene along the lines of our earlier synthesis of 3. Undesirable aspects of this firstgeneration synthesis are the lengthy preparation of the cisperhydroazulene unit and the need to remove the extraneous ketone carbonyl group from the product of the fragmentcoupling step.As described in the accompanying Communication,[7] our initial attempt to streamline the synthesis by using a tertiary organocuprate derived from cis-perhydroazulene nitrile 9 in the key fragment coupling was prevented by exclusive formation of adduct 11, which is epimeric to aplyviolene at the critical quaternary carbon stereocenter (Scheme1C). This unexpected stereochemical outcome of the organocuprate conjugate addition reaction provoked consideration of an alternative strategy in which the C8–C14 σ-bond would be formed by the union of the tertiary radical 12 and enone 13
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影响因子：
1.8
作者：
KOZIKOWSKI, AP;MUGRAGE, BB;XU, ZB
通讯作者：
XU, ZB
影响因子：
15
作者：
Ischay, Michael A.;Anzovino, Mary E.;Yoon, Tehshik P.
通讯作者：
Yoon, Tehshik P.
影响因子：
15
作者：
CURRAN, DP
通讯作者：
CURRAN, DP
影响因子：
15
作者：
MUKAIYAMA, T;HOSHINO, T
通讯作者：
HOSHINO, T
影响因子：
2.1
作者：
Cossy, J;Bouzbouz, S;Hakiki, A
通讯作者：
Hakiki, A