Saturated oxygen and nitrogen heterocycles oxidative coupling of alkyltrifluoroborates with alkenols, alkenoic acids and protected alkenylamines.

Saturated heterocycles are important components of many bioactive compounds. The method disclosed herein enables a general route to a range of 5-, 6- and 7-membered oxygen and nitrogen heterocycles by coupling potassium alkyltrifluoroborates with heteroatom-tethered alkenes, predominantly styrenes, under copper-catalyzed conditions, in the presence of MnO. The method was applied to the synthesis of the core of the anti-depressant drug citalopram.

Synthesis of Benzyl Amines via Copper-Catalyzed Enantioselective Aza-Friedel-Crafts Addition of Phenols to N-Sulfonyl Aldimines.

A new copper-catalyzed enantioselective aza-Freidel-Crafts reaction between phenols and N-sulfonyl aldimines that provides chiral secondary benzylamines in good to excellent yields and excellent enantioselectivities (up to 99% ee) is disclosed. In particular, excellent scope with alkylimines was observed for the first time. The synthetic utility of the products was demonstrated in the first enantioselective synthesis of a dual orexin receptor antagonist, a compound that contains an amine-bearing stereocenter adjacent to a bis- ortho-functionalized arene.