Syncom BV , Kadijk 3, Groningen 9747 AT, The Netherlands.
Acc Chem Res. 2017 Apr 18;50(4):905-914. doi: 10.1021/acs.accounts.6b00630. Epub 2017 Mar 1.
The relationship between fundamental and applied is often uneasy, particularly in modern political climates. A familiar political view, aimed negatively at the scientific community, is that the former is a waste of money whereas the latter gives value for investment. The answer that fundamental is required as the basis for practical suffers from the fact that the timelines between fundamental and practical are often long and the routes contorted and unexpected. This has been my experience. In this Account, examples are given from the research in which I have been involved wherein quite fundamental considerations have led to various applications. The longer the time, the clearer and broader the relationship. Fundamental can and does lead to application. They need and depend on each other. I have seen this both from the side of academia and from small companies. In the course of the past 40 plus years, I have been involved in various aspects of stereochemistry and, in particular, chirality. It has been rewarding to see that several of the developments, most originally grounded in fundamental research considerations, have been used in the chemical community and given new dimensions and often practical applications by others. In this Account, a path-not planned deliberately by me-from orbital symmetry and Woodward-Hoffmann rules through crown ethers to conformational analysis to diastereomeric resolutions to deracemizations powered by Ostwald ripening and the Gibbs-Thomson effect to nucleation to helicenes is described. In order of discussion, the orbital symmetry aspects have via an unusual and unpredicted path has resulted in, among other things, a synthesis of hindered alkenes useful for the production of molecular motors. The crown ether aspects led to discovery of the utility of cesium salts particularly for racemization sensitive nucleophilic substitutions. Work on diastereomeric resolutions has concentrated on the mechanistic as well as practical/commercial aspects of the use of multiple resolving agents (Dutch resolution). During this work the complex relationship between nucleation and chirality in diastereomeric resolutions began to reveal itself. In general, nucleation, especially with involvement of chirality, is a topical challenge that has attracted the attention of many groups. The contribution of this knowledge to the development of attrition driven deracemizations of racemizable conglomerates is described. This remarkable technology allows, without intervention of chiral aids, conversion of certain racemates in quantitative yield and absolute enantiomeric excess to a single enantiomer. From a practical standpoint, this methodology has been used for the production in enantiomerically pure form of commercially interesting compounds like naproxen and clopidogrel (Plavix). Finally an STM investigation of the nucleation behavior of a helicene, prepared via a remarkably short and efficient route, on a metal surface is described.
基础研究和应用研究之间的关系往往很紧张，尤其是在现代政治氛围下。一种常见的针对科学界的负面政治观点认为，前者是浪费金钱，而后者则有投资价值。而基础研究作为实践基础的答案，其问题在于基础研究和应用研究之间的时间线往往很长，而且路线曲折且出人意料。这是我的经验。在本报告中，我给出了一些例子，这些例子来自于我参与的研究，其中一些非常基础的考虑因素导致了各种应用。时间越长，关系就越清晰和广泛。基础研究确实可以带来应用。它们相互需要，相互依存。我从学术界和小公司两个方面都看到了这一点。在过去的 40 多年里，我一直从事立体化学的各个方面的研究，特别是手性。看到一些原本基于基础研究考虑的发展，在化学界得到了应用，并被其他人赋予了新的维度和实际应用，这是非常有意义的。在本报告中，我描述了一条路径——不是我故意规划的——从轨道对称性和伍德沃德-霍夫曼规则，通过冠醚，到构象分析，到手性对映体的拆分，再到手性外消旋体的动力学拆分，这得益于奥斯特瓦尔德成熟和吉布斯-汤姆逊效应，最后到成核，再到螺旋。按照讨论的顺序，轨道对称性方面的研究通过一条不寻常且无法预测的路径，除其他外，合成了有用的受阻烯烃，用于生产分子马达。冠醚方面的研究发现了铯盐在对映体敏感的亲核取代反应中的用途。手性对映体拆分的研究工作集中在手性对映体拆分的机械和实际/商业方面，使用了多种拆分试剂（荷兰拆分）。在此过程中，手性对映体拆分中的成核和手性之间的复杂关系开始显现出来。一般来说，成核，特别是涉及手性时，是一个热门的挑战，吸引了许多研究小组的关注。本报告描述了这方面知识对消旋化动力学拆分可消旋化外消旋体的发展的贡献。这项引人注目的技术可以在无需手性助剂的情况下，将某些外消旋体以定量产率和绝对对映体过量转化为单一对映体。从实际的角度来看，这种方法已用于以对映体纯的形式生产具有商业价值的化合物，如萘普生和氯吡格雷（波立维）。最后，描述了一种通过一条非常短而有效的路线制备的螺旋烯在金属表面上的成核行为的 STM 研究。
