Synthesis of Diverse β-Quaternary Ketones via Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Cyclic Enones
The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields β-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and β-substituent of the enone are highly variable, and a wide variety of β-quaternary ketones can be synthesized. More recently, the use of NH_4PF_6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and β-acyl enone substrates.
Additional Information© 2014 Elsevier B.V. Received 5 October 2014, Revised 15 November 2014, Accepted 17 November 2014, Available online 28 November 2014. Dedicated to Professor Barry M. Trost upon receipt of the 2014 Tetrahedron Prize. We are thankful to the NIH-NIGMS (R01GM080269), Caltech, Amgen, the American Chemical Society Division of Organic Chemistry (predoctoral fellowship to J.C.H.), the Swiss National Science Foundation (postdoctoral fellowship to M.G.), the Japan Society for the Promotion of Science (postdoctoral fellowship to K.K.), and the German National Academy of Sciences Leopoldine (LPDS 2011-12 postdoctoral fellowship to A.N.M.) for financial support. Prof. Theodor Agapie, Prof. Sarah E. Reisman, and Mr. Robert A. Craig, II (Caltech) are thanked for helpful discussions. Dr. David VanderVelde (Caltech) is thanked for invaluable assistance with NMR experiments and helpful discussions. The Varian 400 MHz NMR spectrometer at Caltech was purchased via an NIH grant (RR027690).
Accepted Version - nihms647723.pdf
Supplemental Material - mmc1.pdf