A New Approach to Atropisomerism

A New Approach to Atropisomerism

Cardoso, Flávio Sêga Pereira; Aponick, Aaron

Abstract:

The design of new chiral ligands is on the cutting-edge of organic synthesis. In particular, the field of atropisomeric ligands has shown to be very successful in asymmetric catalysis, however, the majority of axially chiral biaryl ligands are comprised of six-membered aromatic rings. In this context, creative new atropisomeric ligand scaffolds should advance the field by using other ring sizes. Herein, a novel strategy towards the design of a new family of ligands, which will allow the synthesis of atropisomeric ligands containing a five membered ring in the biaryl backbone is described. We aim to design a new system in which the barrier to rotation of a biaryl bond is increased due to the decrease of the groundstate energy of enantioconfomers. In general, the presence of sterically demanding groups ortho to the atropisomeric axis are employed to increase the barrier to rotation (Figure 1, A), but surprisingly the simple concept of groundstate stabilization proposed herein has not been explored (Figure 1, B). Our model system is a biaryl structure composed of three aromatic units A, B and C designed to π-π stack2 intramolecularly (Figure 2). This system presents two main advantages: 1) the easy calculation of the biaryl bond barrier to rotation using VT-NMR (diastereotopic methylene protons); 2) easily modified A/B rings to the preparations of functional molecules.

The design of new chiral ligands is on the cutting-edge of organic synthesis. In particular, the field of atropisomeric ligands has shown to be very successful in asymmetric catalysis, however, the majority of axially chiral biaryl ligands are comprised of six-membered aromatic rings. In this context, creative new atropisomeric ligand scaffolds should advance the field by using other ring sizes. Herein, a novel strategy towards the design of a new family of ligands, which will allow the synthesis of atropisomeric ligands containing a five membered ring in the biaryl backbone is described. We aim to design a new system in which the barrier to rotation of a biaryl bond is increased due to the decrease of the groundstate energy of enantioconfomers. In general, the presence of sterically demanding groups ortho to the atropisomeric axis are employed to increase the barrier to rotation (Figure 1, A), but surprisingly the simple concept of groundstate stabilization proposed herein has not been explored (Figure 1, B). Our model system is a biaryl structure composed of three aromatic units A, B and C designed to π-π stack2 intramolecularly (Figure 2). This system presents two main advantages: 1) the easy calculation of the biaryl bond barrier to rotation using VT-NMR (diastereotopic methylene protons); 2) easily modified A/B rings to the preparations of functional molecules.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_2013816154041

Referências bibliográficas

• [1] 1. Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691-1693.
• [2] 2. (a) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int. Ed.
• [3] 2003, 42, 1210-1250. (b) Salonen, L. M.; Ellermann, M.; Diederich, F.
• [4] Angew. Chem., Int. Ed. 2011, 50, 4808-4842.

Como citar:

Cardoso, Flávio Sêga Pereira; Aponick, Aaron; "A New Approach to Atropisomerism", p-157-157. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013816154041