Catalysis Atropisomerism

A particular case in this category is that of atropisomeric compounds (those where chirality originates from a barrier to rotation over a single bond). In a thermal reaction, racemization occurs unless the temperature is sufficiently low. The peculiar temperature independence of photochemical reactions allows to transform axis chirality into point chirality with no loss. 

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Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

J. Rebek et al. synthesized novel dibenzoheptalene bislactones via a double intramolecular Cannizzaro reaction for condensation polymerization and remote catalysis studies. These bislactones are chiral, atropisomeric molecules. 

Lloyd-Williams, P., Giralt, E. Atropisomerism, biphenyls and the Suzuki coupling peptide antibiotics. Chem. Soc. Rev. 2001, 30,145-157. Dupont, J., de Souza, R. F., Suarez, P. A. Z. Ionic Liquid (Molten Salt) Phase Organometallic Catalysis. Chem. Rev. 2002, 102, 3667-3691. Hassan, J., Sevignon, M., Gozzi, C., Schulz, E., Lemaire, M. Aryl-Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction. Chem. Rev. 2002, 102, 1359-1469. 

When coordinated to the metal, the chiral ligand plays an important role in the control of enantioselectivity during the course of the catalysis reaction. These ligands can contain chirality in the backbone (e.g.. CHIRAPHOS, 1), at the phosphorus atom (e.g., DIP AMP, 2), or atropisomerically from C2 symmetric axial configurations (e.g., BINAP, 3). Typically, most chiral ligands possess di-phenylphosphine moieties (Figure 1). 

P-Phos and its variants as versatile and effective atropisomeric dipyridylphosphine ligands in asymmetric catalysis 06ACR711. 

Despite the prevalence and importance of atropisomerism in organic structures, the field of asymmetric catalysis has not yet recorded extensive success in the development of catalysts, which control this stereochemical feature. Indeed, catalytic reactions of this nature are presently rare and only modest atropi-somer selectivity has been observed. In this context. Miller s group recently developed the DKR of biaryl atropisomers via peptide-catalysed asymmetric bromination. The reaction proceeded via an atropisomer-selective electrophilic aromatic substitution reaction using a simple bromination reagent such as A7-bromophthtalimide. As shown in Scheme 5.27, a series of chiral bromi-nated biaryl compounds could be prepared with excellent enantioselectivities of... 

Wu J, Chan ASC (2006) P-Phos a family of versatile and effective atropisomeric dipyridyl-phosphine ligands in asymmetric catalysis. Acc Chem Res 39 711-720. doi 10.1021/... 

Wang F, Zhang YJ, Wei H, Zhang J, Zhang W. Atropisomeric bisoxazoline ligands with a bridge across the 5,5 -position of biphenyl for asymmetric catalysis. Tetrahedron Lett. 2007 48 4083 086. 

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