Catalytic Enantioselective Arylation and Heteroarylation of Ketones with Organotitanium Reagents Generated In Situ

5 years ago

Catalytic Enantioselective Arylation and Heteroarylation of Ketones with Organotitanium Reagents Generated In Situ

Yusuke Kobayashi, Tomoya Ushimaru, Atsushi Matsuda, Toshiro Harada

A practical and useful, catalytic enantioselective method has been developed for the synthesis of tertiary diaryl and aryl heteroaryl carbinols starting from commercially available aromatic ketones and aryl or heteroaryl bromides. In this method, organotitanium reagents are generated in situ from the bromides by lithiation with nBuLi followed by transmetallation of the resulting organolithiums with ClTi(OiPr)3. Treatment of the ketones with the titanium reagents in the presence of (R)-3-(3,5-bistrifluoromehthylphenyl)-1,1′-bi-2-naphthol (BTFP-BINOL) affords the corresponding tertiary alcohols in high enantioselectivities and yields. The reaction can also start with furan and 2-thienyllithium. The method is operationally simple and can be conducted on a 10-mmol scale without any difficulties. Titanium from within: A practical method has been developed for the catalytic enantioselective arylation and heteroarylation of ketones using titanium reagents, prepared in situ from inexpensive bromide or heteroarene precursors. Enantioselective preparation of a variety of tertiary diaryl carbinols and aryl heteroaryl carbinols could be achieved with a chiral titanium catalyst derived from a new ligand (R)-BTFP-BINOL at low loading (2 mol %).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701395