Enantioselective total synthesis of (-)-acutumine.
Enantioselective total synthesis of (-)-acutumine.
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DOI：
10.1021/jo902006q
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发表时间：
2009-12-04
影响因子：
3.6
通讯作者：
Castle, Steven L.
中科院分区：
文献类型：
--
作者：
Li, Fang;Tartakoff, Samuel S.;Castle, Steven L.
报道了四环生物碱(−)-乌头胺的全合成。由于自由基环化反应中不正确的区域选择性，第一代螺环亚单位的方法不成功。然而，这项工作催生了第二代策略，其中螺旋循环是通过自由基极性交叉反应形成的。这个过程融合了分子内自由基共轭加成和烯酸酯羟基化，并产生了两个具有良好的非对映选择性的立体中心。该反应在太阳灯的照射下得到促进，芳基自由基的形成需要二锡试剂。这些事实表明，底物可以作为增敏剂，从而促进ditin试剂的均溶裂解。然后，将目标的螺旋桨基元通过将吡咯烷环环化到螺旋循环上来安装。反应顺序包括酚氧化、中村手性烯丙基锌试剂催化的不对称酮烯丙基化、阴离子氧合重排、一锅臭解还原胺化以及路易斯酸促进胺在α，β不饱和二甲缩酮上的环化反应。对不对称酮烯丙基化的进一步研究表明，Nakamura试剂能够在不匹配的情况下很好地发挥作用。TiCl4催化的1，3-二酮的区域选择性甲烯醇醚化反应完成了合成。
An account of the total synthesis of the tetracyclic alkaloid (−)-acutumine is presented. A first-generation approach to the spirocyclic subunit was unsuccessful due to incorrect regioselectivity in a radical cyclization. However, this work spawned a second-generation strategy in which the spirocycle was fashioned via a radical–polar crossover reaction. This process merged an intramolecular radical conjugate addition with an enolate hydroxylation, and created two stereocenters with excellent diastereoselectivity. The reaction was promoted by irradiation with a sunlamp, and a ditin reagent was required for aryl radical formation. These facts suggest that the substrate may function as a sensitizer, thereby facilitating homolytic cleavage of the ditin reagent. The propellane motif of the target was then installed via annulation of a pyrrolidine ring onto the spirocycle. The sequence of reactions used included a phenolic oxidation, an asymmetric ketone allylation mediated by Nakamura’s chiral allylzinc reagent, an anionic oxy-Cope rearrangement, a one-pot ozonolysis–reductive amination, and a Lewis acid promoted cyclization of an amine onto an α,β-unsaturated dimethyl ketal. Further studies of the asymmetric ketone allylation demonstrated the ability of the Nakamura reagent to function well in a mismatched situation. A TiCl4-catalyzed regioselective methyl enol etherification of a 1,3-diketone completed the synthesis.
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影响因子：
2.1
作者：
CAMICI, L;DEMBECH, P;TADDEI, M
通讯作者：
TADDEI, M
影响因子：
15
作者：
GEMAL, AL;LUCHE, JL
通讯作者：
LUCHE, JL
影响因子：
3.6
作者：
GARDNER, JN;CARLON, FE;GNOJ, O
通讯作者：
GNOJ, O
影响因子：
3.6
作者：
Ahmad, Nadia M.;Rodeschini, Vincent;Blake, Alexander J.
通讯作者：
Blake, Alexander J.
DOI：
10.1039/j39680000929
发表时间：
1968-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC
影响因子：
--
作者：
BARTON, DHR;KIRBY, AJ;KIRBY, GW
通讯作者：
KIRBY, GW