Abstract
The β-disubstituted ketone functionality is prevalent in biologically active compounds and in pharmaceuticals. A ruthenium-catalyzed direct synthesis of β-disubstituted ketones by cross-coupling of two different secondary alcohols is reported. This new protocol was applied to the synthesis of variety of β-disubstituted ketones from various cyclic, acyclic, symmetrical, and unsymmetrical secondary alcohols. An amine–amide metal–ligand cooperation in a Ru catalyst facilitates the activation and formation of covalent bonds in selective sequences to provide the products. Kinetic and deuterium-labeling experiments suggested that aliphatic alcohols oxidize faster than benzylic secondary alcohols. A plausible mechanism is proposed on the basis of mechanistic and kinetic studies. Water and H2 are the only byproducts from this selective cross-coupling of secondary alcohols.
1 Introduction
2 Catalytic Self- or Cross-Coupling of Alcohols and Selectivity Challenges
3 Recent Developments in the Synthesis of β-Disubstituted Ketones
4 Scope of Ruthenium-Catalyzed Cross-Couplings of Secondary Alcohols
5 Mechanistic Studies and Proposed Mechanism
6 Conclusion
Key words cross-coupling - alcohols - ketones - ruthenium catalysis - homogeneous catalysis - green synthesis
