A concise synthesis of eupomatilones 4, 6, and 7 by rhodium-catalyzed enantioselective desymmetrization of cyclic meso anhydrides with organozinc reagents generated in situ
A concise synthesis of eupomatilones 4, 6, and 7 by rhodium-catalyzed enantioselective desymmetrization of cyclic meso anhydrides with organozinc reagents generated in situ
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DOI：
10.1002/anie.200700816
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Rovis, Tomislav
中科院分区：
文献类型：
--
作者：
Johnson, Jeffrey B.;Bercot, Eric A.;Rovis, Tomislav
交叉偶联方法作为过渡金属催化反应的一个分支，已经彻底改变了复杂分子的构建方法。[1]尽管最近取得了一些进展，但在这一领域仍然存在重大挑战，包括有选择地建造和界定立体中心。[2]虽然许多活化的酰基物种已被用于酮的形成，[3]羧酸酐只是最近才被研究作为金属介导反应中的酰化剂。[4]本课题组致力于过渡金属催化的羧酸酐交叉偶联反应的研究，并报道了镍催化的环酐与有机锌亲核试剂的烷基化反应，生成1，4-或1，5-酮酸。[5]这种方法的力量在于能够将环状羧酸酐转化为具有立体定向骨架的酮酸衍生物。我们最近公开了由Pd（0Ac）2和Josiphos（1）催化的琥珀酸酐的对映选择性去对称化（方案1）。[6]作为利用该反应快速组装复杂分子的努力的一部分，我们利用官能化的有机锌亲核试剂靶向2，3-二甲基琥珀酸酐的对映选择性去对称化。尽管用市售的二有机锌试剂获得了优异的结果，但原位形成的锌亲核试剂的使用与钯催化的方法不相容，这在涉及有机锌试剂的不对称催化中并不少见。[7，8]有机锌亲核试剂也不能以可观的产率产生所需的酮酸，进一步限制了可用的亲核试剂的数量。铑络合物已经被证明可以耐受刘易斯碱的存在，如在水中进行的铑催化的不对称共轭加成反应所示，[9]因此它们承诺不太容易受到卤化物存在所引起的并发症的影响。此外，RhI/RhIII氧化还原对的使用具有不同于镍和钯催化反应的机制的前景。[10]在此，我们提出了铑催化的琥珀酸酐与各种锌亲核试剂原位形成的去对称化的发展。该方法的实用性证明了与eupomatilone家族的天然产物的三个成员的简明合成。
Cross-coupling methodology, as a subset of transition-metalcatalyzed reactions, has revolutionized the means by which complex molecules are constructed.[1] Despite recent advances, significant challenges remain in this area, including the selective construction and definition of stereocenters.[2] Although numerous activated acyl species have been utilized in the formation of ketones,[3] carboxylic acid anhydrides have only recently been investigated as acylating agents in metalmediated reactions.[4] Our group is engaged in the development of the transition-metal-catalyzed cross-coupling reactions of carboxylic anhydrides and has reported the nickelcatalyzed alkylation of cyclic anhydrides with organozinc nucleophiles to produce 1, 4-or 1, 5-keto acids.[5] The power of this methodology lies in the ability to transform cyclic carboxylic anhydrides into keto acid derivatives with stereodefined backbones. We have recently disclosed the enantioselective desymmetrization of succinic anhydrides catalyzed by Pd (OAc) 2 and Josiphos (1)(Scheme 1).[6] As part of an effort to utilize this reaction for the rapid assembly of complex molecules, we targeted the enantioselective desymmetrization of 2, 3-dimethylsuccinic anhydride utilizing functionalized organozinc nucleophiles. Despite the excellent results obtained with commercially available diorganozinc reagents, the use of zinc nucleophiles formed in situ is not compatible with the palladium-catalyzed methodology, an observation not uncommon in asymmetric catalysis involving organozinc reagents.[7, 8] Organozinc nucleophiles also fail to produce the desired keto acids in appreciable yields, further limiting the number of available nucleophiles.Rhodium complexes have been documented to tolerate the presence of Lewis bases, as illustrated by rhodiumcatalyzed asymmetric conjugate addition reactions run in water,[9] and thus they promise to be less susceptible to complications arising from the presence of halides. Furthermore, the use of the RhI/RhIII redox couple holds the promise of a mechanism distinct from that of the nickel-and palladium-catalyzed reactions.[10] Herein, we present the development of the rhodium-catalyzed desymmetrization of succinic anhydrides with a variety of zinc nucleophiles formed in situ. The utility of this methodology is demonstrated with the concise synthesis of three members of the eupomatilone family of natural products.