New Methods for Construction of Enantiomerically Enriched Tertiary Alcohols via Nucleophilic Reactions of Enediolates

密歇根大学教授约翰·P·沃尔夫在化学系化学合成计划的支持下，开展了开发用于立体控制组装α-羟基叔酯的新化学反应的研究。这些官能团存在于许多生物活性分子中，也是合成复杂分子的重要构件。这项研究的重点是发明产生反应性二元醇的新技术，以及研究二元烯二醇酸盐的新的亲核反应，以制备含有1-2个四元立体中心的分子。此外，本研究还针对亲核烯二醇酸酯与碳心亲电体之间的新的碳-碳键形成反应用于合成复杂的碳环和杂环分子。这些新反应将提供获得有价值的有机化合物的途径，这些化合物不容易用现有方法以立体控制的方式制备。新反应的发展使化学家能够缩短合成序列，节省时间、金钱和自然资源。这最终使社会受益，因为它以负担得起的成本和环境友好的方式提供重要的化学品，如药品。这项研究将使通向具有已知用途的化合物的路线变得更加流畅，也将使人们能够获得用现有方法无法轻易制备的新化合物。这将为发现新的、有用的分子提供许多机会，这些分子在制药、农用化学品或材料等领域有应用。上述研究也将为研究生和本科生提供极好的培训，他们将掌握有机合成和合成方法开发的概念和技能。完成培训后，这些学生将成为工业、政府或学术实验室的高产科学家。

Professor John P. Wolfe of the University of Michigan is supported by the Chemical Synthesis Program in the Division of Chemistry to carry out research on the development of new chemical reactions for the stereocontrolled assembly of tertiary alpha-hydroxy esters. These functional groups are found in many biologically active molecules as well as important building blocks for complex molecule synthesis. The research is focused on the invention of new techniques to generate reactive enediolates and the investigation of new nucleophilic reactions of enediolates for the preparation of molecules that contain 1-2 quaternary stereocenters. In addition, the research is also directed towards the utilization of new carbon-carbon bond-forming reactions between nucleophilic enediolates and carbon-centered electrophiles for the synthesis of complex carbocyclic and heterocyclic molecules. These new reactions will provide access to valuable organic compounds that cannot easily be prepared in a stereocontrolled fashion with existing methods. The development of new reactions allows chemists to shorten synthetic sequences, saving time, money, and natural resources. This ultimately benefits society by providing important chemicals such as pharmaceuticals at an affordable cost and in an environmentally friendly manner. This research will lead to streamlined routes to compounds with known utility, and will also give access to new compounds that cannot be easily prepared with existing methods. This will afford many opportunities for the discovery of new, useful molecules with applications in fields such as pharmaceuticals, agrochemicals, or materials. The research described above will also provide excellent training to both graduate and undergraduate students, who will master concepts and skills in organic synthesis and synthetic methods development. Upon completion of their training, these students will be well positioned to enter the workforce as productive scientists in industrial, government, or academic laboratories.