Direct synthesis of previously inaccessible bridgehead azabicyclics by intramolecular cyclization of alpha-sulfonamido and alpha-sulfonimido radicals.
Syntheses of the first bridgehead sultams and the only known bridgehead disulfonimide are described. Both approaches capitalize on the electrophilicity of alpha-sulfonyl radicals and their propensity to undergo intramolecular ring closure. Where double bonds are concerned, 5-exo and 6-exo pathways operate preferentially as long as structural strain is not excessive. When the reaction center is a carbon-carbon triple bond, the first cyclization gives rise to vinyl radicals that hold sufficient reactivity to capture solvent benzene. In the case of 45, this sequential reaction leads importantly to the introduction of a styrene functionality sufficiently activated to allow a second ring closure to be kinetically feasible. The solid-state structural features of 12 and 17 have been elucidated by X-ray crystallographic methods. Despite key differences from the norm in the alignment of the nitrogen lone pair relative to the adjacent sulfonyl groups, these compounds exhibit good hydrolytic stability. For 13, generation of the alpha-sulfonamide carbanion is possible and regiospecific oxidation with chromyl acetate has been achieved.
Paquette
L A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, OH 43210, USA. Paquette.l@osu.edu
Ra
C S
CS
Schloss
J D
JD
Leit
S M
SM
Gallucci
J C
JC
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis; D018360:Crystallography, X-Ray; D003500:Cyclization; D005609:Free Radicals; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry
D000890:Anti-Infective Agents; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D005609:Free Radicals; D013449:Sulfonamides