Catalytic, Regioselective 1,4‐Fluorodifunctionalization of Dienes
You‐Jie Yu, Michael Schäfer, Constantin G. Daniliuc, Ryan Gilmour
Abstract
Abstract A catalysis‐based regioselective 1,4‐fluorofunctionalization of trifluoromethyl substituted 1,3‐dienes has been developed to access compact, highly functionalized products. The process allows E , Z ‐mixed dienes to be processed to a single E ‐alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4‐difluorination is disclosed and subsequently evolved to enable 1,4‐hetero‐difunctionalization, which allows δ‐fluoro‐alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp 3 )−F and C(sp 3 )−CF 3 groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post‐reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.