title: Fully substituted carbon centers by diastereoselective spirocyclization: stereoselective synthesis of (+)-lepadiformine C.
abstract: Reductive lithiation of N-Boc alpha-amino nitriles generated alpha-amino alkyllithium reagents with unexpected selectivity. The intermediate radical prefers to align with the nitrogen lone pair, and this interaction leads to an A(1,3)-strain effect that biases the conformation of the radical. In cyclohexane rings with alpha-substituents the net effect is an inversion of configuration on reductive lithiation. In the presence of a tethered electrophile the alkyllithium cyclizes to produce a spiro compound, again with inversion of configuration. The overall result is retention of configuration in the cyclization reaction. The same overall selectivity is found with alpha-oxygen alkyllithium cyclizations, but in this case both steps proceed with retention. The difference can be explained by careful consideration of the intermediate geometries. The alpha-amino spirocyclization was utilized in a concise and stereoselective synthesis of lepadiformine C.
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Perry
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Morin
authors.forename: Brian W
authors.initials: BW
authors.lastname: Slafer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wolckenhauer
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rychnovsky
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; C431548:lepadiformine; D002244:Carbon