Diversity-oriented synthesis of azaspirocycles.
Multicomponent condensation of N-diphenylphosphinoylimines, alkynes, zirconocene hydrochloride, and diiodomethane provides a rapid access to omega-unsaturated dicyclopropylmethylamines. These novel building blocks are converted into heterocyclic 5-azaspiro[2.4]heptanes, 5-azaspiro-[2.5]octanes, and 5-azaspiro[2.6]nonanes by means of selective ring-closing metathesis, epoxide opening, or reductive amination. The resulting functionalized pyrrolidines, piperidines, and azepines are scaffolds of considerable relevance for chemistry-driven drug discovery.
Department of Chemistry, Center for Chemical Methodologies & Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf@pitt.edu
Peter
P
Wipf
Corey R J
CR
Stephenson
Maciej A A
MA
Walczak
D001372:Aza Compounds / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D003500:Cyclization; D007202:Indicators and Reagents; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis*
D001372:Aza Compounds; D007202:Indicators and Reagents; D013141:Spiro Compounds