Cyclization reactions in synthetic organic chemistry

有机合成化学中的环化反应

• 批准号: 1480-2012
• 负责人: Burnell, Jean
• 金额: $ 5.1万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=568193
• 关键词: Cyclization; reactions; synthetic; organic; chemistry

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.

拟议研究的五个领域有一个共同点。 它们都旨在制造环状有机化合物。 环状分子在自然界中极为常见，绝大多数具有有趣且有益的生物活性的有机分子都至少含有一个环状部分。 1. 第一个研究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突破性研究的基础上，在这些研究中我们确定了烯基乙烯基酮是非常有用的环化底物，并且在同一操作中形成了额外的键。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. 我们已经在第二个领域（孪生酰化）领域活跃多年，但我们提出通过使用制造所有螺桨烷环的工艺来展示孪生酰化的合成潜力，令人印象深刻。此外，我们还大大扩展了孪生酰化的范围，以合成对映体富集/纯形式的六元杂环。 3. 我们开发了用阻碍底物实现 Pauson-Khand 环化的程序。 我们的结果将被用来合成一种复杂的二萜生物碱，这是一类生物活性化合物，但现在我们的重点将转向另一种类型的环化，一种几乎没有优先权的环化，但仍有待实现。 4. 将开辟两个新的调查领域。据报道，源自环状 1,3-二硫化合物的阳离子会环化。我们将研究该反应以确定合成范围并深入了解其机制。一些产品可能会转化为手性环丙烷/环丙酮。 5. 第二个新领域涉及高活性物质环己炔。取代环己炔的环化从未被探索过。当反应能够以可预测的区域选择性和立体选择性进行时，这种环化将具有巨大的合成价值。所有这些研究都将成为培养研究生的严格训练场，使他们成为工业界和学术界职位的理想人选。