Preparation of functionalized organofluorine compounds toward drug discovery

根据含氟有机分子的特点，我们的研究包括以下两个部分：(1)面向药物化学的多种有机氟化合物合成方法的开发；(2)面向普通合成反应的高效催化的新型碳酸化学。针对前者，我们成功地完成了以下反应：(1)通过铜催化的二氟烯丙基醇的格氏反应或无铜的烷基铝反应进行脱氟烯丙基化反应，区域和立体选择性地合成氟代烯烃，并进一步阐述了相应的二肽异构体的制备。(2)利用低价铬化学高效制备1-氟烯基酯及其作为双酰化试剂的反应活性研究。(3)三氟乙醛N，O-缩醛与烷基锂试剂的独特反应合成α，α-二氟酮衍生物。在第二个课题中，我们发现tetrakis(1，1，3，3-trifluoromethanesulfonyl)propane是一种非常有效的催化剂，用于烯醇硅基醚作为亲核剂与碳酰基化合物如α，β-不饱和酮、α，β-不饱和醛和空间受阻酮的碳碳键形成反应。

On the basis of characteristic features of fluorinated organic molecules our research project consists of the following two parts ; (1) development of versatile synthetic methods for organo fluorine compounds directed to medicinal chemistry and (2) new carbon acid chemistry toward efficient catalysis of common synthetic reactions. Concerning the former subject we have successfully achieved the following reactions : (1)Regio and stereoselective synthesis of fluorinated olefins through the defluorinative allylic alkylation of difluorohomoallylic alcohols by copper mediated Grignard reaction or by copper free alkylaluminium reaction, and the further elaboration for the preparation of the corresponding dipeptide isosteres. (2)An efficient preparation of 1-fluoroalkenyl ester utilizing low valent chromium chemistry and the investigation of their reactivity as double acylating reagents. (3)Preparation of α,α-difluoroketone derivatives through the unique reaction of trifluoroacetaldehyde N,O-acetals with alkyllithium reagents. In the latter subject, we found that tetrakis(1,1,3,3-trifluoromethanesulfonyl)propane works as an extremely effective catalyst for the carbon-carbon bond forming reactions of enol silyl ethers as nucleophiles with carobonyl compounds such as α,β-unsaturated ketones, α,β-unsaturated aldehydes and sterically hindered ketones.