Tuning Oxocarbenium Ion and Acyl Iminium Ion Reactivity and Stereoelectronics

在这个由化学部化学合成项目资助的项目中，William & Mary学院的Robert J. Hinkle教授将探索高活性亲核试剂攻击环氧羰基离子的立体化学偏好。虽然通过氧羰基离子形成c -糖苷已被用于许多全合成，但控制表面选择性的因素尚不清楚，高活性烯醇醚和烯酮硅基缩醛亲核试剂会显著降低选择性。对电子偏置的、完全取代的氧羰基碳原子进行研究，以确定反应是通过sn1类还是sn2类机制发生的。更广泛的影响主要包括培训学生，同时通过将众多本科生和硕士研究人员纳入该项目来扩大参与。这些活动将继续在威廉玛丽学院培养一个强大的、包容的、以本科生为主的项目。确定亲核试剂对环氧羰基离子的表面选择性的影响因素，可以在有价c -糖苷的合成中实现更大、更可预测的立体控制。这些环状结构是大量具有抗癌、抗生素和其他生物活性的化合物中的常见元素。在本研究中发展的技能将适用于各种各样的化学工作，如与制药和农业工业有关的研究，以及改进催化剂和开发生物探针的研究；所有这些活动都需要有机分子的受控合成。最后，该项目将为本科生和硕士生提供优秀的机械和综合训练，包括那些来自历史上在物理科学领域代表性不足的群体的学生。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Robert J. Hinkle of the College of William & Mary will explore the stereochemical preferences for attack of highly-reactive nucleophiles on cyclic oxocarbenium ions. Although formation of C-glycosides via oxocarbenium ions has been utilized in a number of total syntheses, the factors governing facial selectivity are not clear and significant erosion of selectivity occurs with highly-reactive enol ether and ketene silyl acetal nucleophiles. Studies on electronically biased, fully-substituted oxocarbenium carbon atoms will be undertaken to determine if the reactions are occurring via SN1-like, or SN2-like mechanisms. The broader impacts primarily involve training students while broadening participation through the inclusion of numerous undergraduate and Master's researchers on the project. The activities herein will continue to foster a strong, inclusive, predominantly undergraduate program at the College of William & Mary. Establishing the factors which govern facial selectivity in the approach of nucleophiles on cyclic oxocarbenium ions could lead to greater, and more predictable, stereocontrol in the synthesis of valuable C-glycosides. These ring structures are common elements in a vast number of compounds possessing anti-cancer, antibiotic and other biological activities. The skills developed in this research will be applicable to a wide variety of chemical endeavors such as those relating to the pharmaceutical and agricultural industries as well as research to improve catalysts and develop biological probes; all of these activities require the controlled syntheses of organic molecules. Finally, this project will provide excellent mechanistic and synthetic training for undergraduate and Master's students, including those from groups historically underrepresented in the physical sciences.