ИСТИНА

Ожидается разработка нового улучшенного метода каталитического асимметрического аллилборирования иминов, характеризующегося беспрецедентно высокой скоростью и атомной эффективностью. Поскольку разработка затрагивает фундаментальный процесс аллилборирования, применяемый во многих областях синтетической химии ожидается, что результаты могут найти широкое применения в лабораторном и индустриальном синтезе. В частности, в ходе проекта будет продемонстрировано использование метода для получения гомоаллиламинов ряда аминофосфонатов, перспективных для применения в медицинской химии.

Chemistry of organoboranes is an intensively developing area of chemical science. Now there is no one sphere of organic synthesis where boron derivatives are not used as reagents or intermediates, including asymmetric synthesis and catalysis. Allylboration of carbonyl compounds and imines is the most mild and selective way of building up of carbon skeleton of molecules, keeping in mind the possibility of its further multiple functionalization, especially upon construction of heterocyclic system of alicyclic types. To date, two main classes of allylborating reagents have been constituted – allylic triorganoboranes and boronate derivatives, which differ drastically in their properties. The very first, historically, and unprecedentedly active allylborating agents are allylic triorganoboranes (instant reaction with C=O and C=N bonds even at -100 C). However, their high sensitivity to oxygen of air, water, and functional groups prevents their widespread use. At the same time, boronate derivatives are practically free of these disadvantages - they are not sensitive to atmospheric oxygen (with the exception of allylboronic acids and boroxins in pure form), water (alcohols), compatible with many functional groups, and can be used in a variety of catalytic reactions. Along with these advantages, the fundamental drawback of boronate derivatives is their low reactivity associated with the lowered Lewis acidity of boron. The second drawback is low atomic efficiency, for example, the ballast part of the molecule of commonly used and most affordable allylboron pinacol esters reaches 75%! The use of allylborate derivatives with poor atom-economy in industrial or pilot synthesis is extremely unlikely; moreover, it requires significant costs for the extraction of boron from waste water. Therefore, the need in development of allylboration reagents that would include the advantages of both classes and would not have known disadvantages is an urgent and even “insolent” task, because it is a challenge to an established system. Recently we discovered that adducts of triallylborane with ammonia, primary and secondary amines possess a complex of valuable chemical properties (stability in air, low sensitivity to proton-donor compounds (water, alcohols, amines), excellent compatibility with functional groups), which in fact , put them on a par with the most popular derivatives of allylboronic acids. The advantage of our reagents is that, possessing the aforementioned properties, they retain the high reactivity inherent in free allylic triorganoboranes, and triallylic derivatives also retain their atomic efficiency surpassing any known allyl metals or metalloids. Our recent data indicate the possibility of effective use of amine adducts in allylation reactions catalyzed by cheap and affordable copper(I) complexes, which is an unprecedented property for allylic derivatives of triorganoboranes. The discovered properties show an order of magnitude greater efficiency of amine adducts of allylboranes comparing with boronates in transallylation processes with copper catalysts and make these reagents promising for other types of catalysis. Therefore, the next stage of our research and the main goal of this project will be the development of effective methods for the catalytic asymmetric allylboration of imines using complexes of copper(I) with chiral ligands, phosphorus(III) derivatives (phosphines, phosphites) and N-heterocyclic carbenes. It should be emphasized the complete priority and novelty of our developments. The products of allylboration of imines are homoallylamines, which are of considerable interest for the preparation of many biologically active molecules and drugs. When using our method, the cost of these compounds will be significantly reduced and ensure their easy availability. To demonstrate the capabilities of the method developed during the project, homoallylamines of a number of alfa-, beta-, and gamma-aminophosphonates will be synthesized. Aminophosphonate derivatives are phosphorus analogs of the corresponding amino acids and are used as antibiotics, enzyme inhibitors, anti-HIV agents, etc.