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

Abstract

Whereas tropinone derived nonaflate 3 was no suitable precursor for Heck-reactions, the related carbamate 7 was an excellent substrate for palladium-catalyzed processes. Nonaflate 7 was either isolated in excellent yield by LDA treatment of ketone 5 followed by trapping with NfF (nonafluorobutanesulfonyl fluoride) or generated in situ by fluoride-catalyzed reaction of silyl enol ether 6 with NfF. The desired 1,3-diene 8 was prepared by conventional Heck-reaction of nonaflate 7 with methyl acrylate in almost quantitative yield. Alternatively, the one-pot nonaflation-Heck protocol starting from silyl enol ether 6 provided 8 in good yield. The couplings of acrylonitrile or phenyl vinyl sulfone were also performed with in situ generated 7 and they afforded the expected 1,3-dienes 9 and 10 in good yields. The Sonogashira-reaction with phenylacetylene also started from silyl enol ether 6 and provided enyne 11 via 7 in good yield. A Diels–Alder reaction of 1,3-diene 8 with N-phenyl maleimide at 100 °C furnished tetracyclic adduct 12 in good yield, with excellent diastereofacial selectivity, but with low endo– exo-selectivity. Nonaflate 14 was easily obtained from the corresponding unsaturated bicyclic ketone 13 . It behaved differently in an attempted Heck-reaction and mainly led to fragmentation products 15 and 16 , whereas the expected 1,3-diene 17 was formed only as minor component. However, 14 could successfully be used in a Sonogashira-reaction with phenylacetylene to afford compound 18 . 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.