No abstract

We report here a simple and robust gold-catalyzed annulation reaction, giving N-and O-spirocycles in good to excellent yields. We have prepared a library of protected amines and tertiary alcohols which give, upon cyclization with alkynes, a representative set of heterospirocycles, and illustrate reaction compatibility with diverse functional groups. A change in catalytic activity is possible by modifying the solvent, and two original tricyclic spirocycles were synthesized in a tandem reaction.

Gold-(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza-spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out to demonstrate the robustness of the reaction. An intramolecular Mizoroki-Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK1.