Masked 3-aminoindan-1-ones by a palladium-catalyzed three-component annulation reaction.
A new palladium(0)-catalyzed three-component reaction involving a set of salicylic aldehyde triflates, ethylene glycol vinyl ether, and various secondary nucleophilic amines has been developed. Through systematic optimization experiments using multivariate design, the conditions effecting robust and convenient one-pot generation of protected 3-aminoindan-1-ones were identified. A reaction route involving an initial internal Heck arylation of the hydroxyalkyl vinyl ether, iminium ion formation, and subsequent tandem cyclization is invoked to explain the selective formation of the isolated tertiary 3-aminoindan acetals. Hydrogenolysis of orthogonally blocked 3-aminoindan-1-ones delivered primary or secondary amines after 10-20 min of microwave heating.
Arefalk
Anna
A
Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, BMC, Box-574, SE-751 23 Uppsala, Sweden.
Larhed
Mats
M
Hallberg
Anders
A