New approach to the synthesis of functionalized fluoroalkenes

Moscow South-Eastern School named after V.I. Chuikov
Anastasia A. Andrianova; Yulia D. Maslova


Fluorine has a big influence on physical, chemical and biological properties of organic structures. Organofluorine compounds are widely used in modern medical chemistry to develop new drugs. Insertion of fluorine atom into organic molecules can improve their reactivity in biological systems, increase their metabolic stability, lipophilicity and permeability through membranes. As a consequence, in recent years, the percentage of drugs containing one or more fluorine atoms has increased rapidly up to 40%. The fluoroallylic fragment is also able to change properties of bioactive molecules. Its introduction into such structures as inhibitors of histonedeacetylase, inhibitors of matrix metalloproteinase, asparagine, glutamine, etc. increases their biological activity and electronic properties. We propose a new method for the synthesis of functionalized fluoroalkenes, based on the generation of fluoroallyl nucleophiles from silyl- and boronyl-substituted fluorocyclopropanes and their further usage in the allylation of carbonyl compounds or their derivatives. Due to the fact that the cyclopropanation of alkenyl boronates is not possible under conditions of alkaline dehydrohalogenation of dibromofluoromethane, we have developed a new method for the preparation of silyl- and boronyl-substituted cyclopropanes, which consist of carbene cyclopropanation of multiple C=C bonds by sodium dibromofluoroacetate catalyzed by (IPr)AgCl. The new method is effective for the cyclopropanation of not only boronyl- and silyl-substituted olefins, but also for low-reactivity alkenes, such as monoalkyl substituted alkenes, allyl alcohol ethers and α,β-unsaturated carbonyl compounds. The conditions for isomerization of silyl- and boronyl-substituted fluorohalocyclopropanes in the presence of catalytic amounts of copper (I) bromide in acetonitrile was selected. It was shown that the regioselectivity of the process is determined by the thermodynamic control. Thus, the formation of fluorovinylsilanes or fluorovinylboranes in the isomerization of α-silyl- or α-boronyl-gem-bromofluorophenylcyclopropanes and fluoroallylsilanes upon isomerization of β-silyl-gem-bromofluorophenylcyclopropanes was observed. Thus, new types of fluorinated reagents were obtained that are not previously described in the literature (...)

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