Asymmetric Diels-Alder reactions of chiral 1-amino-3-siloxy-1,3-butadiene: Application to the enantioselective synthesis of (-)-alpha-elemene
Asymmetric Diels-Alder reactions of chiral 1-amino-3-siloxy-1,3-butadiene: Application to the enantioselective synthesis of (-)-alpha-elemene
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DOI：
10.1021/ja971272d
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发表时间：
1997-07-30
影响因子：
15
通讯作者：
Rawal, VH
中科院分区：
文献类型：
--
作者：
Kozmin, SA;Rawal, VH
发展有效的方法来制备结构复杂的对映体纯的分子是现代有机合成的一个基本挑战。在能够控制最终产物的绝对立体化学的各种过程中，不对称Diels-Alder反应可能是最强大的。关于这一主题的绝大多数研究都利用了手性修饰的亲双烯体1来诱导环加成反应中的不对称性，尽管手性刘易斯酸催化剂的使用最近也受到了相当大的关注。[2]相比之下，手性二烯用于狄尔斯-阿尔德反应的例子很少。3-5我们最近开发了一种制备1-氨基-3-丁二烯的有效方法，并证明了它们在各种[4+ 2]环加成反应中的有用性（方程式1）。6在该方法的一个重大进展中，我们报道了手性修饰的氨基甲硅烷氧基二烯的形式以高至优异的面选择性进行Diels-Alder环加成，并提供了一种简单、可靠的路线，以获得具有高对映体过量（ee）的取代的环己烯酮。氨基甲硅烷氧基二烯的一个重要优点，除了它的高反应性外，6是氨基取代基开辟了使用手性胺的可能性。预期共振相互作用导致胺上的取代基与烯烃保持在同一平面中，使得手性部分将阻断二烯周围的一个象限。我们选择检查C2-对称胺，希望规避潜在的旋转异构体问题，从而减少可能的非对映体过渡态的数量，并使不对称诱导步骤更可预测。
The development of efficient methods for the preparation of structurally complex molecules in enantiomerically pure form is a fundamental challenge of modern organic synthesis. Among various processes capable of controlling the absolute stereochemistry of the final product, the asymmetric Diels-Alder reaction is perhaps the most powerful. The vast majority of investigations on this topic have taken advantage of chirallymodified dienophiles1 to induce asymmetry in the cycloaddition reaction, although the use of chiral Lewis acid catalysts has also received considerable attention of late. 2 By contrast, there are very few examples of the use of chiral dienes for the Diels-Alder reaction. 3-5 We recently developed an efficient method for the preparation of 1-amino-3-siloxybutadienes and demonstrated their usefulness in various [4+ 2] cycloadditions (eq 1). 6 In a significant advance in this methodology, we report that chirally-modified versions of the amino siloxy dienes undergo Diels-Alder cycloadditions with high to excellent facial selectivity and provide a simple, reliable route to substituted cyclohexenones having high enantiomeric excesses (ee). An important advantage of the amino siloxy diene, aside from its high reactivity, 6 is that the amino substituent opens up the possibility of using a chiral amine. Resonance interactions were expected to cause the substituents on the amine to be held in the same plane as the alkene, such that the chiral portion would block one quadrant around the diene. We elected to examine a C2-symmetric amine, in the hope of circumventing a potential rotomer issue, thereby reducing the number of possible diastereomeric transition states and making the asymmetry-inducing step more predictable.