SusChEM: The Use of Ti-C Bonds for RNC Insertions and Dynamic Kinetic Resolutions

在这个由美国国家科学基金会化学结构、动力学和机制B项目资助的项目中，哥伦比亚大学的Jack R. Norton教授带领一个团队探索有机钛化学的基本问题。钛既便宜又无毒，为各种化学转化提供了可持续的途径。该项目旨在使用廉价的钛基试剂来合成有价值的有机化合物，不仅包括杂环化合物，还包括对制药工业至关重要的对映体富集化合物。该项目涉及无机化学、有机金属化学和有机化学的混合，因此是培养年轻工作者从事科学事业的理想选择。研究小组的学生被鼓励与学术和工业科学家互动，更好地为学术/工业鸿沟两边的永久职位做好准备。更具体地说，该项目解决了有机钛化学中的三个基本问题：(1)在钛碳（Ti-C）键中插入异腈。在Ti-C键中插入一氧化碳（CO）是一种强大的合成工具。原则上，CO可以被任何等电子异腈（RNC）所取代，从而产生与CO插入一样有用的转化；(2)动态动力学不对称变换。手性钛氮吡啶和钛氧烷可以进行快速的对映体相互转化，这一特性使它们在动态动力学不对称转化中具有潜在的用途。原则上，这种方法可以从廉价的外消旋起始材料生成富集对映体的化学物质；(3)用更便宜、更丰富的烷氧基配体Ti试剂取代环戊二烯基Ti试剂。

In this project, funded by the Chemical Structure, Dynamics, & Mechanisms B Program of the National Science Foundation, Professor Jack R. Norton at Columbia University leads a team exploring fundamental issues in organotitanium chemistry. Titanium, inexpensive and nontoxic, offers sustainable ways of carrying out a variety of chemical transformations. This project aims to use inexpensive titanium-based reagents for the synthesis of valuable organic compounds - not only heterocycles but also the enantioenriched compounds essential to the pharmaceutical industry. This project involves a mixture of inorganic, organometallic, and organic chemistry, and is therefore ideal for training young workers for careers in science. Students in the research group are encouraged to interact with both academic and industrial scientists, better preparing themselves for permanent positions on either side of the academic/industrial divide. More specifically, the project addresses three fundamental questions in organotitanium chemistry: (1) The insertion of isonitriles into titanium-carbon (Ti-C) bonds. The insertion of carbon monoxide (CO) into Ti-C bonds has served as a powerful synthetic tool. In principle CO can be replaced by any of the isoelectronic isonitriles (RNC), giving transformations that could be as useful as CO insertion; (2) Dynamic kinetic asymmetric transformations. Chiral titanaaziridines and titanaoxiranes undergo rapid enantiomer interconversion, a property which makes them potentially useful for dynamic kinetic asymmetric transformations. In principle, this approach can generate enantioenriched chemicals from inexpensive racemic starting materials; and (3) Replacement of cyclopentadienyl ligand based Ti reagents with less expensive and more abundant alkoxy ligand based Ti reagents.