Cyclization reactions in synthetic organic chemistry

拟议研究的五个领域有一个共同的主线。它们的目标都是制造环状有机化合物。环状分子在自然界中非常常见，绝大多数具有有趣和有益的生物活性的有机分子至少含有一个环状部分。1.第一个调查领域以纳扎罗夫反应为基础。这项工作将建立在我们过去四年开创性研究的基础上，在过去四年中，我们确定了烯基乙烯基酮是在同一操作中形成额外键的环化反应的非常有用的底物。这项新工作最激动人心的方面将是纳扎罗夫中间体的分子内捕获，以及这一过程在天然产物合成中的应用。2.多年来，我们一直活跃在第二个领域--双子酰化反应，但我们正在提出一个令人印象深刻的示范，通过使用制造所有螺旋桨环的工艺来证明双子酰化反应的合成潜力。此外，我们还将双子酰化反应的范围大大扩展到合成对映体富含/纯净的6元杂环。3.我们已经制定了利用受阻底物实现Pauson-Khandd环化反应的程序。我们的结果将被用来合成一种复杂的二萜生物碱，这是一类具有生物活性的化合物之一，但现在我们的重点将转移到另一种类型的环化反应上，这种环化反应几乎没有先例，这一点仍有待实现。4.将开辟两个新的调查领域。环状1，3-二硫杂环化合物衍生的阳离子已被报道为环化反应。我们将对这一反应进行研究，以确定合成范围并深入了解其机理。部分产物可转化为手性环丙烷/环丙酮。5.第二个新领域涉及高活性物种--环己炔。取代的环己炔的环化反应从未被研究过。当反应能够以可预测的区域和立体选择性进行时，这种环化反应将具有很大的合成价值。所有这些研究都将作为一个严格的培训基础，以培养那些将成为工业和学术界职位的理想候选人的研究生。

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.