DIRENICC · Direct Enantioselective N-Acyl Iminium Cyclisation Cascades
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2010-03-01 → 2011-12-31
- Финансиране от ЕС
- 171 741 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Нови химични методи за създаване на сложни азотсъдържащи молекули, като тетрациклични съединения, се разработват чрез специфични катализатори. Те помагат за по-прецизното синтезиране на сложни структури, които са основа за много биологично активни вещества.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Direct Enantioselective N-Acyl Iminium Cyclisation Cascades
The main objectives of the project were to develop new highly enantioselective powerful methodologies, such as asymmetric Bronsted acid catalysed cyclisation cascades in order to access to complex heterocyclic core structures. During the fellowship we successfully developed three new cyclisation cascades catalysed by chiral Bronsted Binol phosphoric acids. These methodologies allowed us to access to a large variety of complex azacyclic compounds as summarised in scheme 1. Starting from an amine bearing a β-ketoester 1 and a lactone 2, we were able to synthesise new tetracyclic compounds 3 via a N-acyl iminium cyclisation cascade with good yield and moderate enantioselectivity (scheme 1, a)). Using a similar methodology but starting from a tryptamine urea derivative 4 and a vinyl ketone 5 we successfully prepared a range of azabicycles 6 in good yield and excellent enantioselectivity, via an enantioselective Michael addition, iminium cyclization cascade (scheme 1 b)). This work has been submitted for publication to Angewandte Chemie International Edition. In addition, we developed the first asymmetric nitro-Mannich / lactamisation cascade, starting from nitroester 7 and an imine 8 with moderate to good yields and enantioselectivities (scheme 1, c)). Furthermore, we synthesised some new chiral phosphoric acid derivatives and evaluated their efficiency in a range of asymmetric transformations. The best results were obatained for the cyclisation of nitrones (scheme 2).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
We wish to develop new asymmetric Brønsted acid catalysed cyclisation reactions through direct condensation that will allow the efficient and highly enantioselective construction of azabicyclic and azaspirocyclic structures from readily available starting materials. This will constitute a new, powerful and broadly applicable organocatalytic asymmetric strategy to such target molecules. The concept of our proposal is to generate and exploit reactive N-acyl iminium ions in cyclisation reactions whereby the chiral environment of an associated chiral conjugate base of a Brønsted acid HA* governs enantioselectivity. The starting materials for the reaction sequence would be readily available ketoesters (or ketoacids) and a primary amine tethered to a suitable pi-nucleophilic trap. Initial condensation of the starting materials would an enamide intermediate. On protonation by HA* in a low polarity solvent, tight ion pairing of the N-acyl iminium ion with the chiral conjugate base of the Brønsted acid should occur. Provided there is sufficient ordering and effective facial differentiation in this ion pair, attack of the pendant pi-nucleophile will give rise to enantioselectivity in the (irreversible) cyclisation step. With at least three points of diversity, numerous multicyclic structures bearing additional functionality and spectator groups can be readily accessed. This will enable the repeated application of the method in target synthesis. During the course of the Fellowship, through physical organic chemistry techniques and molecular modelling calculations we would like to elucidate the mechanistic pathway and origins of stereocontrol. Finally we wish to apply the methodology in the formal synthesis of an alkaloid natural product. Therefore this multidisciplinary Fellowship project will involve the development of innovative asymmetric organic methods, physical organic chemistry, computational chemistry and target oriented 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