Planned and unplanned halogenations in route to selected oroidin alkaloids

Highly diastereoselective, substrate-controlled, halogenation/ring contraction sequences delivered the naturally occurring chlorinated and unnatural brominated and iodinated axinellamine core structure. An unexpected azide displacement of the chlorinated cyclopentane, which proceeded with retention of stereochemistry, suggested a modification of the Scheuer/Kinnel proposal that may account for the related natural product massadine. Two unsuccessful routes to access the stereochemistry proposed for palau'amine were S_N2 displacement of the bromo- and iodocyclopentane with excess chloride anion and an intramolecular directed chlorination pathway. Finally, an unexpected chlorination during our phakellstatin synthesis proceeded with retention of stereochemistry during tosylation possibly resulting from neighboring group participation.