Dihydropyrones as dienophiles in the Diels-Alder reaction: Application to the synthesis of 1-oxadecalones
Dihydropyrones as dienophiles in the Diels-Alder reaction: Application to the synthesis of 1-oxadecalones
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DOI：
10.1021/jo982488g
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发表时间：
1999-03-19
影响因子：
3.6
通讯作者：
Totah, NI
中科院分区：
文献类型：
--
作者：
Chen, DQ;Wang, JQ;Totah, NI
1-氧十氢萘单元是许多天然化合物的结构核心，包括还原的呋喃苯并二氢吡喃甲苷 A (1，图 1)、1 以及各种二萜类化合物，例如毛喉素 (2)、2 jamesonilide E (3)、3 和 scutorientalin D (4)。 4 其中许多化合物表现出令人着迷的生物特性，尽管这些系统中存在的多种结构特征使它们对合成目标具有挑战性。我们对开发合成复杂底物的新策略的兴趣，特别是对 PAF 拮抗剂 phomactin A 的制备的兴趣，促使我们考虑合成高度功能化的 1-oxadecalone 衍生物的通用方法。 5 我们的目标是开发一种进入基本 6、6 环系统的便捷方法，同时提供足够的功能以允许后续的合成操作。为此，我们设想适当官能化的 2, 3-二氢-4-吡喃酮与二烯的 Diels-Alder 反应将有效满足这些标准。尽管已经出现了在[4+2]环加成反应中使用色酮6和吡喃酮7衍生物作为亲二烯体的几个相关例子，但据我们所知，这种类型的二氢吡喃酮以前没有在该应用中使用过。在此，我们报告了该策略的成功实施，用于合成高功能化的1-氧杂十酮衍生物。在实践中，我们选择探索在C5（例如5）处含有吸电子取代基的2, 3-二氢-4-吡喃酮的反应性。 8 我们预计需要这种功能来增强这些底物作为亲二烯体相对于母体二氢吡喃酮的反应性。 9 由于二氢吡喃酮的 C5 取代基最终位于 1-氧杂十酮单元的环连接处，因此在该位置加入不同的官能团将为该方法合成更复杂系统的应用提供更大的灵活性。如图所示，
The 1-oxadecalin unit serves as the structural core for a number of naturally occurring compounds, including the reduced furochroman phomactin A (1, Figure 1), 1 as well as a variety of diterpenoids such as forskolin (2), 2 jamesoniellide E (3), 3 and scutorientalin D (4). 4 Many of these compounds exhibit intriguing biological properties, though the diverse array of structural features present in these systems make them challenging synthetic targets. Our interest in the development of new strategies for the synthesis of complex substrates, in particular toward the preparation of the PAF antagonist phomactin A, led us to consider a general approach to the synthesis of highly functionalized 1-oxadecalone derivatives. 5 Our goal in this endeavor was to develop an expedient entry to the basic 6, 6-ring system, while at the same time providing sufficient functionality to allow for subsequent synthetic manipulation. Toward this end, we envisaged that the Diels-Alder reaction of a suitably functionalized 2, 3-dihydro-4-pyrone with a diene would effectively meet these criteria. Though several related examples have appeared using chromone6 and pyrone7 derivatives as dienophiles in [4+ 2] cycloaddition reactions, to the best of our knowledge, dihydropyrones of this type have not previously been utilized in this application. Herein we report the successful implementation of this strategy for the synthesis of highly functionalized 1-oxadecalone derivatives.In practice, we chose to explore the reactivity of 2, 3-dihydro-4-pyrones that contain an electron-withdrawing substituent at C5 (eg, 5). 8 We anticipated the need for this functionality to enhance the reactivity of these substrates as dienophiles relative to that of the parent dihydropyrones. 9 As the C5 substituent of the dihydropyrone would ultimately be located at the ring junction of the 1-oxadecalone unit, incorporation of diverse functionality at this position would provide added flexibility in the application of this method to the synthesis of more complex systems. As shown,