The domestication of ortho-quinone methides.
The domestication of ortho-quinone methides.
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DOI：
10.1021/ar500330x
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发表时间：
2014-12-16
影响因子：
18.3
通讯作者：
Pettus, Thomas R. R.
中科院分区：
文献类型：
--
作者：
Bai, Wen-Ju;David, Jonathan G.;Feng, Zhen-Gao;Weaver, Marisa G.;Wu, Kun-Liang;Pettus, Thomas R. R.
邻苯二酚甲醚(o-QM)是一种高活性的化学基元，被自然界用于各种目的。鉴于其非凡的反应性和生物学重要性，令人惊讶的是，有机合成中的应用如此之少。我们推测，由于其前体的制备、苛刻的生成方法以及由于其短暂的性质而从计算机数据库中遗漏了这一策略，它们的广泛使用已经放缓。大约十年前，我们发现了一种温和的阴离子触发过程，可以在低温下从容易获得的水杨醛，特别是OBoc衍生物中产生短暂的o-QMS。这种新颖的反应级联反应既包括邻位QM的生成，也包括随后的消耗反应。整个转化是通过添加有机金属试剂来启动的，通常是格氏试剂，这导致了苄氧基醇氧化物的形成。BOC从邻近的苯酚迁移生成了苯氧镁，我们认为它经过了转移的BOC残基的β消除，形成了o-QM，用于立即进行进一步反应。此外，事实证明，通过仔细操纵金属和温度杠杆，级联是可控的，因此可以在不同的中间和阶段暂停、停止或重新启动。这一新的驯化水平使我们能够首次在包括非对映控制反应在内的一系列应用中部署o-QMS。该序列最终可在多锅或单锅工艺中进行。转瞬即逝的o-QM中间体的后续反应包括导致未支化或支化的邻烷基取代酚的1，4-共轭加成，以及提供4-未取代或4-取代的苯并吡喃和色满酮的Diels-Alder反应。后者为首次得到的环加合物，具有良好的非对映控制性能。此外，新生成的立体中心在后续的色满酮和缩醛反应中的空间效应也被研究并被证明是可预测的。通过使用手性助剂，Diels-Alder产物被应用于许多不对称反应中，包括几个复杂的天然产物的合成。在这篇文章中，我们总结了我们的努力，我们希望这些努力为这个古老物种的人工复兴做出了贡献。
An ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature. About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a magnesium phenoxide that we supposed underwent β-elimination of the transferred Boc residue to form an o-QM for immediate further reactions. Moreover, the cascade proved controllable through careful manipulation of metallic and temperature levers so that it could be paused, stopped, or restarted at various intermediates and stages. This new level of domestication enabled us to deploy o-QMs for the first time in a range of applications including diastereocontrolled reactions. This sequence ultimately could be performed in either multipot or single pot processes. The subsequent reaction of the fleeting o-QM intermediates included the 1,4-conjugate additions that led to unbranched or branched ortho-alkyl substituted phenols and Diels–Alder reactions that provided 4-unsubstituted or 4-substituted benzopyrans and chroman ketals. The latter cycloadducts were obtained for the first time with outstanding diastereocontrol. In addition, the steric effects of the newly created stereocenters in subsequent reactions of chroman ketals and acetals were studied and proved predictable. Through the use of a chiral auxiliary, Diels–Alder products were deployed in numerous enantioselective reactions including several complex natural products syntheses. In this Account, we summarize our efforts, which we hope have contributed to the synthetic renaissance for this venerable species.
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影响因子：
3.6
作者：
Bai, Wen-Ju;Green, Jason C.;Pettus, Thomas R. R.
通讯作者：
Pettus, Thomas R. R.
影响因子：
5.2
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3.6
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影响因子：
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影响因子：
3.2
作者：
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通讯作者：
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