Synthesis of new tropinone derivatives by palladium-catalyzed couplings of 8-azabicyclo[3.2.1]oct-2-enyl nonaflates

Whereas tropinone derived nonaflate was no suitable precursor for Heck-reactions, the related carbamate was an excellent substrate for palladium-catalyzed processes. Nonaflate was either isolated in excellent yield by LDA treatment of ketone followed by trapping with NfF (nonafluorobutanesulfonyl fluoride) or generated in situ by fluoride-catalyzed reaction of silyl enol ether with NfF. The desired 1,3-diene was prepared by conventional Heck-reaction of nonaflate with methyl acrylate in almost quantitative yield. Alternatively, the one-pot nonaflation-Heck protocol starting from silyl enol ether provided in good yield. The couplings of acrylonitrile or phenyl vinyl sulfone were also performed with in situ generated and they afforded the expected 1,3-dienes and in good yields. The Sonogashira-reaction with phenylacetylene also started from silyl enol ether and provided enyne via in good yield. A Diels–Alder reaction of 1,3-diene with N-phenyl maleimide at 100 °C furnished tetracyclic adduct in good yield, with excellent diastereofacial selectivity, but with low endo–exo-selectivity. Nonaflate was easily obtained from the corresponding unsaturated bicyclic ketone . It behaved differently in an attempted Heck-reaction and mainly led to fragmentation products and , whereas the expected 1,3-diene was formed only as minor component. However, could successfully be used in a Sonogashira-reaction with phenylacetylene to afford compound . These transformations demonstrate the great potential of tropinone derived alkenyl nonaflates for diversity oriented syntheses of interesting compounds containing an 8-azabicyclo[3.2.1]octane scaffold.