ABACCR · Asymmetric Brønsted Acid Catalysed Cyclisation Reactions
FP7 — People (Marie Curie Actions)
- Duration
- 2009-09-15 → 2011-09-14
- EU contribution
- €178,516
- Participants
- 1
- Scheme
- MC-IIF
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Results in brief
Asymmetric Brønsted Acid Catalysed Cyclisation Reactions
The concept of our proposal is to exploit the high reactivity of N-acyl iminium ions in cyclisation reactions within the chiral environment of an associated chiral conjugate base of a Brønsted acid HA*. Following the preliminary result published by the Dixon Group, during this project our objectives were to: A) explore the the Asymmetric Brønsted acid catalysed N-acyl iminium ion cyclisation Reacions; B) apply the reaction to the enantioselective synthesis of the indole alkaloid Subincanadine B; C) investigate new enantioselective intermolecular reactions using chiral Brønsted acids. We have investigated and found that our previously published reaction can be extended to a wide range of enol lactone substrates bearing substituted aromatic rings in the 5-position. This work is being written up for publication. Paper in preparation: stereoselective Brønsted acid-catalyzed N-acyliminium cyclization cascades for the synthesis of highly substituted β-carbolines Michael E. Muratore, Chloe A. Holloway, Lei Shi, R. Ian Storer and Darren J. Dixon. We have also investigated a dual catalysis method for accessing the beta-carboline products and have found a remarkable compatibility of 3,3'-substituted binol phosphoric acids with certain polymer supported bases, attributed to a size exclusion phenomenon. This is likely to be an important finding which will have impact in a range of asymmetric catalysis programs employing binol phosphoric acids. Paper in preparation: Size Exclusion Annihilation Resistance in Enantioselective Binol Phosphoric Acid Catalysis Michael E. Muratore, Lei Shi, R. Ian Storer and Darren J. Dixon. During this project we made a number of attempts to synthesise the indole alkaloid Subincanadine B. Unfortunately none of these successfully made the natural product, nor the key intermediate we believed would provide us access to the natural product. However, we have succeeded to develop two methods of preparing highly functionalised β-carbolines with moderate to good stereocontrol over a quaternary stereogenic centre. In addition to these successes we also explored other new N-acyl iminium cyclisation reactions using for example tethered imidazoles and a range of intermolecular reactions using the chiral Brønsted acids as catalysts and facilitators. Uploaded, please find the final publishable summary report.
Data: CORDIS, © European Union
Project objective
We wish to develop new asymmetric Brønsted acid catalysed cyclisation reactions that will allow the efficient and highly enantioselective construction of azabicyclic structures from readily available starting materials. This will constitute a new, powerful and broadly applicable organocatalytic asymmetric strategy to such target molecules. Conceptually our proposal is to exploit the high reactivity of N-acyl iminium ions in cyclisation reactions within the asymmetric environment of an associated conjugate base of a chiral Brønsted acid (HA*). For enantioselective N-acyl iminium ion cyclisations, a keto amide starting material with a suitable pi-nucleophile attached to the nitrogen atom of the amide is required. The reaction is technically trivial to perform; a solution of the keto amide starting material is treated with a catalytic quantity of an ‘effective’ chiral Brønsted acid. Loss of water should result in the formation of an N-acyl iminium ion, which, in a low polarity solvent, should be (tight) ion paired with the chiral conjugate base of the Brønsted acid. Provided there is sufficient ordering and effective facial differentiation in the ion pair, attack of the pendant pi-nucleophile will give rise to enantioselectivity in the (irreversible) cyclisation step. 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 in the new catalytic asymmetric methods we are developing. Finally we wish to apply the developed chemistry as a key carbon-carbon bond forming step in the total asymmetric synthesis of an indole alkaloid natural product. Therefore this multidisciplinary Fellowship project will involve the development of innovative asymmetric organic methods, physical organic chemistry, computational chemistry and target synthesis.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union