膦启动的极性反转反应

Polarity inversion (umpolung) in organic chemistry is the reversal of the polarity of a center atom through the chemical modification of its substituent or the functional group, enabling polarity switchs between nucleophilicity and electrophilicity. Since the introduction of this concept by D. Seebach and E. J. Corey more than 30 years ago, this strategy has found widespread applications in the development of new reactions and in modern organic synthesis. In contrast to a variety of methods available for the polarity inversion transformations of aldehydes and α,β-unsaturated carbonyl compounds, the umpolung reactions of electrophilic alkylating agents are still limited to the metal approaches, in which the alkylating agents (RX) are converted into the corresponding organometallic compounds (RMXn). However, due to the high reactivity of these organometallic reagents, extremely dry conditions and an innert atmosphere are usually required. The inherent high nucleophilicity and basicity of these metal reagents frequently lead to a low functionality tolerance, cause some side-reactions and thus restrict their application, although this kind of organometallic reagents has being widely employed in organic synthesis. This project will aim at developing a non-metal, green, mild, and general method for the polarity inversion of alkylating agents on the basis of phosphine-initiated, ylide hydrolysis-terminated umpolung reactions. This new approach together with the realization of a catalytic and asymmetric version will bring in a variety of new reactions and novel synthetic routes for the syntheses of important intermediates and biologically active molecules.

有机化学中的极性反转（Umpolung）是通过对取代基进行修饰或转化从而实现中心原子的极性翻转，即其亲核和亲电性的相互转换。此概念从提出到现在的30多年里在反应开发和有机合成中得到了广泛的应用。然而此类极性反转反应大多集中在对醛和不饱和羰基化合物的极性反转，对于亲电烷基化试剂的极性反转（从R+到R-）常用的方法仍然是将其转化为有机金属试剂，但由于这类金属试剂性质极其活泼，常常表现出强亲核性和强碱性，对实验条件要求高，操作不方便，副反应多，虽然在有机合成中得到了广泛应用，但反应类型的拓展仍然很受限制。最近，我们研究发现膦启动经叶立德水解的途径能提供一个很好的对烷基化试剂进行极性反转的方法。本项目将基于对膦盐和膦叶立德水解反应的研究，开发出一个绿色、实用、普适性高的烷基化试剂极性反转的方法，设计一系列新的选择性高的极性反转反应，实现其催化不对称的转化，并进一步将其应用到有用分子的合成中。

项目执行四年来，我们开展了针对膦启动的化学键的极性反转的研究工作：1）利用膦叶立德对亲电试剂发生极性反转，设计了新型的膦催化剂；2）利用膦叶立德对亲电试剂发生极性反转，设计并发展了一系列新型的串联环化反应；3）利用叶立德基团对缺电子烯烃进行活化，成功地实现了对α,β–不饱和羰基化合物中缺电子C=C双键的极性反转，设计并发展了一系列反应新模式。本项目利用膦启动的化学键的极性反转，提供了解决传统化学无法实现的反应的新思路；膦叶立德作为启动试剂或催化剂，也为构建多官能团化杂环化合物提供了有效的合成途径。项目执行以来，共发表文章7篇，其中在Chem. Commun.发表3篇，在Eur.J. Chem. 发表1篇；在Org. Lett. 发表2篇；Org. Chem. Front. 发表1篇; 编写专著1章节。研究人员中有2人取得博士学位；1人获中科院院长奖学金；1人获优秀学生称号。