Cyclization reactions in synthetic organic chemistry

拟议研究的五个领域有一个共同的主线。它们都是为了制造环状有机化合物。环分子在自然界中极为常见，绝大多数具有有趣和有益生物活性的有机分子至少含有一个环部分。1. 第一个调查领域是基于纳扎罗夫反应。这项工作将在很大程度上建立在我们过去四年的开创性研究的基础上，在这些研究中，我们确定了烯基乙烯基酮是非常有用的底物，可以在相同的操作中形成额外的键。这项新工作最令人兴奋的方面将是纳扎罗夫中间体的分子内捕获以及该过程在天然产物合成中的应用。2. 我们在第二个领域，双酰基化，已经活跃了很多年，但我们正在提出一个令人印象深刻的双酰基化的合成潜力的演示，通过使用这个过程来制造所有的螺旋桨环。此外，我们正在将双烷基化的范围大大扩展到以对映异构富集/纯形式合成6元杂环。3. 我们已经开发出了用累加底物影响Pauson-Khand环化的程序。我们的研究结果将用于合成一种复杂的二萜生物碱，一种生物活性化合物家族中的一种，但现在我们的重点将转移到另一种类型的环化上，这种环化几乎没有优先权，但仍有待实现。4. 将开辟两个新的调查领域。从1,3-二硫代环化合物中衍生的阳离子有环化的报道。我们将研究这一反应，以建立合成范围，并深入了解其机理。有些产物可转化为手性环丙烷/环丙烷酮。5. 第二个新领域涉及一种高活性物质——环己炔。取代环己炔的环化从未被探索过。当反应具有可预测的区域选择性和立体选择性时，这种环化反应将具有很大的合成价值。所有这些研究都将成为培养研究生的严格训练基地，这些研究生将成为工业界和学术界职位的理想人选。

The five areas of proposed research have a common thread. They are all aimed at making cyclic organic compounds. Cyclic molecules are extremely common in Nature, and the vast majority of organic molecules with interesting and beneficial biological activities contain at least one cyclic portion. 1. The first area of investigation is based on the Nazarov reaction. This work will build considerably on our groundbreaking research of the past four years in which we established that allenyl vinyl ketones are very useful substrates for cyclizations with additional bond formation in the same operation. The most exciting aspects of the new work will be the intramolecular trapping of Nazarov intermediates and the application of this process to the synthesis of natural products. 2. We have already been active in the second area, geminal acylation, for many years, but we are proposing an impressive demonstration of geminal acylation's synthetic potential by using the process for making all the rings of propellanes. Also, we are extending considerably geminal acylation's scope to the synthesis of 6-membered heterocycles in enantiomerically enriched/pure form. 3. We have developed procedures for effecting the Pauson-Khand cyclization with encumbered substrates. Our results will be exploited to synthesize a complex diterpene alkaloid, one of a family of biologically active compounds, but now our focus will shift to a different type of cyclization, one with little precedence, that is still to be achieved. 4. Two new areas of investigation will be opened. Cations derived from cyclic 1,3-dithia-compounds have been reported to cyclize. We will investigate this reaction to establish the synthetic scope and to gain insights into the mechanism. Some products may be transformed into chiral cyclopropanes/cyclopropanones. 5. The second new area involves a highly reactive species, cyclohexyne. Cyclizations of substituted cyclohexynes have never been explored. This cyclization will have great synthetic value when the reaction can be carried out with predictable regio- and stereoselectivity. All this research will serve as a rigorous training ground to educate graduate students who will become ideal candidates for positions in industry and academia.