Ring closing alkyne metathesis.: Comparative investigation of two different catalyst systems and application to the stereoselective synthesis of olfactory lactones, azamacrolides, and the macrocyclic perimeter of the marine alkaloid nakadomarin A
Ring closing alkyne metathesis.: Comparative investigation of two different catalyst systems and application to the stereoselective synthesis of olfactory lactones, azamacrolides, and the macrocyclic perimeter of the marine alkaloid nakadomarin A
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DOI：
10.1021/ja992074k
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发表时间：
1999-12-08
影响因子：
15
通讯作者：
Seidel, G
中科院分区：
文献类型：
--
作者：
Fürstner, A;Guth, O;Seidel, G
描述了以前未知的二炔的闭环复分解反应，如果所得环炔产物进行Lindlar还原，则该反应打开了有效的和立体选择性的进入大环（Z）-烯烃的入口。这种新的两步策略提供了显着的优势，在立体化学方面超过传统的RCM的二烯，通常会导致（E，Z）-混合物时，适用于形成大环。钨次烷基络合物（tBuO）（3）W drop CCMe 3（1a）及其类似物以及由Mo（CO）（6）和对氯苯酚原位形成的结构未知物质以高效的方式影响关键的炔复分解反应，其中前一种催化剂对底物和极性官能团的结构变化更耐受。应用于嗅觉化合物ambrettantine 23和柚子内酯24，驱虫剂azamacrolides epilachnene 31和homoepilachnene 33的立体选择性合成，以及细胞毒性生物碱nakadomarin A 51的全合成所需的全功能构建单元64，突出了这种新概念与天然产物化学的相关性。在后一种情况下，闭环炔复分解所需的二炔底物62通过依赖于乙烯基环氧化物的钯催化的打开，随后杂环的氧化环化的新型呋喃合成获得。
Previously unknown ring closing metathesis reactions of diynes are described which open an efficient and stereoselective entry into macrocyclic (Z)-alkenes if the resulting cycloalkyne products are subjected to Lindlar reduction. This new two-step strategy offers significant advantages in stereochemical terms over conventional RCM of dienes which usually leads to (E,Z)-mixtures when applied to the formation of large rings. The tungsten alkylidyne complex (tBuO)(3)W drop CCMe3 (1a) and analogues thereof as well as a structurally unknown species formed in situ from Mo(CO)(6) and p-chlorophenol effect the crucial alkyne metathesis reactions in a highly efficient manner, with the former catalyst being more tolerant toward structural variations of the substrates and polar functional groups. Applications to the stereoselective synthesis of the olfactory compounds ambrettolide 23 and yuzu lactone 24, the insect repellent azamacrolides epilachnene 31 and homoepilachnene 33, as well as to the fully functional building block 64 required for a total synthesis of the cytotoxic alkaloid nakadomarin A 51 highlight the relevance of this new concept for natural product chemistry. In the latter case, the diyne substrate 62 necessary for ring closing alkyne metathesis was obtained via a novel furan synthesis relying on a palladium-catalyzed opening of a vinyl epoxide followed by an oxidative cyclization of the heterocyclic ring.