CHIRALTIPOCAT · Chiral Triamino Iminophosphorane Organocatalysts and their Reactions
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2010-05-03 → 2012-05-02
- Финансиране от ЕС
- 172 741 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Нов клас органични катализатори се изследва за по-бързо създаване на химични връзки, например при добавяне на нитрометан към кетимини. Тези вещества помагат за по-ефективното синтезиране на важни структури като аминокиселини, които са основа за много химични съединения.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Chiral Triamino Iminophosphorane Organocatalysts and their Reactions
Bifunctional organocatalysts1 offer unlimited opportunities for the discovery of powerful new asymmetric carbon-carbon and carbon-heteroatom bond forming reactions due to their capacity of simultaneously organizing and activating electrophilic substrates (through H-bonding interactions) and pro-nucleophilic reagents (through deprotonation), thereby catalysing their stereocontrolled union. However, despite the surge of interest over the last decade, low reaction rates and high catalyst loadings remain the major limitations within the field. Furthermore low acidity pro-nucleophiles or low energy electrophiles often do not react at all in the presence of the existing best bifunctional organocatalysts, owing to negligible activation of the pro-nucleophile by the weak and untunable organic base. During this project, we have developed a new class of modular bifunctional iminophosphorane/thiourea catalysts which offer much broader scope and tunability whilst providing new and enhanced reactivity and maintaining high levels of enantiocontrol. We have used these new bifunctional systems in the first catalytic asymmetric metal-free scalable addition of nitromethane to ketimines (nitro-Mannich or aza-Henry reaction),2 a transformation in which the best-in-class bifunctional organocatalysts or even metal catalysts need high temperatures and/or long reaction times to perform. The resulting enantioenriched α-nitroamines allow the construction of important building blocks for asymmetric synthesis such as 1,2-diamines or α-amino acids bearing at least one fully substituted carbon atom. Triaminoiminophosphoranes ((R1N)3P=NR 2 ) have been used extensively as organic bases for synthetic transformations. 3 However, to the best of our knowledge, trialkyl- or triaryliminophosphoranes have not, despite also possessing a strongly basic nitrogen. Hence, we envisaged that key to the success of our novel bifunctional catalyst design would be the presence of a strongly Brønsted basic and variable/tunable iminophosphorane (whose basicity could be modified by the use of different phosphines) linked to a variable/tunable H-bond donor group via a variable/tunable chiral scaffold (Fig. 2). Therefore, the overall objective of this work is to develop (by design, synthesis and testing) a new family of potent asymmetric iminophosphorane organocatalysts which can efficiently catalyse a broad range new of synthetically useful asymmetric reactions between pro-nucleophiles (NuH) and weakly electrophilic reagents with exceptionally high enantioselectivity. Furthermore the catalysts can be made in situ via a ‘Click’-type Staudinger reaction of an organoazide and a phosphine to generate the strongly Brønsted basic iminophosphorane from catalytically inactive precursors thus providing a combinatorial method for best catalyst identification and facilitating rapid optimization in any reaction of interest (Fig. 2).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
We wish to develop new families of chiral single enantiomer triamino iminophosphorane bases and exploit their high basicity in a series of new organocatalytic asymmetric methodologies for providing ready access to desirable chiral products with high enantio- and diastereocontrol from readily available starting materials. This would constitute a new, powerful and broadly applicable organocatalytic asymmetric strategy to such target molecules. The development of new readily accessible and modular designs for tunable single enantiomer triamino iminophosphorane bases will be carried out via two complementary routes that could allow the synthesis of focused libraries of tens of catalysts for screening in a range of important synthetic transformations. In the first, stereochemically pure azides are heated with phosphorous triamides, which upon release of nitrogen yields the target base in just one simple transformation. As azides can be readily prepared from parent enantiopure alcohols via Mitsunobu inversion or from amines through diazo transfer, the route benefits from a broad-based simple design which can allow much structural variation to the target triamino iminophosphorane bases. An alternate route would employ commercially available or readily prepared chiral ethylene diamines reacting with PCl5 followed by triple N-alkylation. The performance of these new highly basic chiral organocatalysts will then be assessed in a range of addition reactions of methylene and methine pronucleophiles to a range of low reactivity electrophiles. Furthermore, through molecular modelling we would like to elucidate the mechanistic pathway and origins of stereocontrol and finally apply the chemistry in the total asymmetric synthesis of the natural product (R,R)-elacomine. The work will therefore be multidisciplinary, involving the development of innovative catalytic asymmetric organic methods, computational chemistry and target synthesis.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз