Mild and efficient Sonogashira couplings of 8-oxa- and 8-thiabicyclo[3.2.1]octanone derived alkenyl nonaflates

Abstract

We demonstrate in this report that bicyclic alkenyl nonaflates (nonafluorobutanesulfonates) generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives are excellent substrates for Sonogashira couplings with alkynes. Employing CuI, Pd(OAc) 2, PPh 3 in DMF/ i-Pr 2NH as standard reagents structurally diverse bicyclic nonaflates were coupled with phenyl acetylene in generally high yields. Particularly efficient are transformations of precursors 16, 18, and 20 bearing methyl groups at the bridgehead carbons, which furnished the expected enynes 17, 19, and 21 in approximately 90% yield. With respect to the alkyne component the scope of this palladium-catalyzed reaction seems also to be fairly broad. Thus, trimethylsilyl acetylene and propargyl alcohol could also be used, affording coupling products 22, 23, and 25 with high efficacy. The protocol of Grieco was applied to induce a domino coupling of tricyclic alkenyl nonaflate 14 with trimethylsilyl acetylene affording product 26 in moderate yield and as 1:1 mixture of the expected two diastereomers.