Sustainable Phosphorus Chemistry: Catalytic Asymmetric SN2 Reactions

可持续磷化学：催化不对称 SN2 反应

基本信息

批准号：
EP/J000868/1
负责人：
Ross Denton
金额：
$ 43.85万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FJ000868%2F1
关键词：
Sustainable Phosphorus Chemistry Catalytic Asymmetric

项目摘要

This proposal describes innovative new chemistry that will transform phosphorus-mediated substitution reactions by rendering them catalytic in the phosphorus component and, therefore, devoid of phosphorus waste. This will substantially reduce the economic and environmental footprint of phosphorus-mediated processes that are used by academic and industrial chemists on a daily basis and allow the full commercial potential of the chemistry to be realized. Furthermore, the world's supply of phosphate rock, the material from which most organophosphorus compounds are derived, is running out and the new catalytic reactions represent a sustainable alternative to current methods. Despite over one hundred years of progress many of the transformations that underpin chemical synthesis, e.g SN2 reactions of activated alcohols, are inherently wasteful. Since the 1960s organic chemists have used phosphorus-mediated reactions, such as the Mitsunobu reaction, for the synthesis of important fine chemicals including pharmaceuticals. However, at present, this chemistry generates at least one molecule of phosphorus waste for every molecule of product produced. This impacts heavily on the environmental and economic footprint of the chemistry and for over a decade industry has been asking for a solution to this problem. For example, a recent report authored by process chemists from GlaxoSmithKline, Pfizer, Merck, Lilly, Schering-Plough and AstraZeneca stated that "the ideal Mitsunobu reaction would be catalytic in nature" and, most significantly, "future research towards making this transformation green is required to realize its full potential in commercial applications". To meet these demands new sustainable phosphorus chemistry is urgently required. This adventurous programme, that is aligned with the "Dial-a-Molecule" grand challenge, will deliver highly sought after substitution reactions that are catalytic in phosphorus. This will dramatically reduce downstream waste and open up a range of new applications in pharmaceutical and agrochemical synthesis that will benefit UK industry. Moreover, new fundamental chemistry of phosphine oxides, incorrectly assumed by many to be unreactive compounds, will be explored. Finally, the new strategy described is applicable to many other important phosphorus-mediated reactions and, therefore, forms a new platform for catalysis. This proposal benefits from: (a) exciting preliminary results that indicate the chemistry proposed is deliverable; (b) a collaborative experimental, theoretical and mechanistic approach and (c) the PI's reduced teaching load (as a new academic) allowing him to closely monitor progress and drive the project forward.

该提案描述了创新的新化学反应，该化学将通过在磷成分中催化磷介导的替代反应，因此没有磷废物。这将大大减少学术和工业化学家每天使用的磷介导过程的经济和环境足迹，并允许化学的全部商业潜力。此外，世界上磷酸盐岩的供应，大多数有机磷化合物的材料已经耗尽，新的催化反应代表了当前方法的可持续替代品。尽管有一百多年的进步，许多基于化学合成的转化，例如激活醇的Sn2反应本质上是浪费的。自1960年代以来，有机化学家已经使用了磷介导的反应，例如三菱反应，用于合成包括药物在内的重要细胞化学物质。但是，目前，该化学为每种产生的产物分子产生至少一个磷废物的分子。这对化学的环境和经济足迹产生了重大影响，并且十多年来，行业一直在要求解决这个问题。例如，一份由葛兰素史克，辉瑞，默克，礼来，Schering-plough和阿斯利康的工艺化学家撰写的最新报告指出，“理想的Mitsunobu反应本质上将是催化性的”，并且最重要的是，未来的研究需要使这种转型绿色具有在商业应用中实现其全部潜力。为了满足这些要求，迫切需要新的可持续磷化学。这个冒险的计划与“拨号”大挑战保持一致，它将提供高度追捧的替代反应，这些反应在磷中催化。这将大大减少下游浪费，并为制药和农业化学合成中开放一系列新应用，这将使英国行业受益。此外，将探讨许多被许多人认为是无反应化合物的磷酸氧化物的新基本化学。最后，所描述的新策略适用于许多其他重要的磷介导的反应，因此构成了催化的新平台。该提案受益于：（a）令人兴奋的初步结果，表明提出的化学是可交付的；（b）一种协作的实验，理论和机械方法，以及（c）PI减少的教学负载（作为新学者），使他能够密切监视进度并推动项目前进。