title: Asymmetric [3+2] Annulation Approach to 3-Pyrrolines: Concise Total Syntheses of (-)-Supinidine, (-)-Isoretronecanol, and (+)-Elacomine.
abstract: An asymmetric [3+2] annulation reaction to form 3-pyrroline products is reported. Upon treatment with lithium diisopropylamide, readily available ethyl 4-bromocrotonate is deprotonated and trapped with Ellman imines selectively at the α-position to yield enantiopure 3-pyrroline products. This new method is compatible with aryl, alkyl, and vinyl imines. The efficacy of the method is showcased by short asymmetric total syntheses of (-)-supinidine, (-)-isoretronecanol, and (+)-elacomine. This novel annulation approach also works for an aldehyde, thus providing access to a 2,5-dihydrofuran product in a single step from simple precursors. By modifying the structure of the carbanion nucleophile, an asymmetric vinylogous aza-Darzens reaction can be realized.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson AZ 85721 (USA) http://www.cbc.arizona.edu/njardarson/group.
authors.forename: Isaac
authors.initials: I
authors.lastname: Chogii
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson AZ 85721 (USA) http://www.cbc.arizona.edu/njardarson/group. njardars@email.arizona.edu.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Njardarson
mesh_terms: D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry*; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D007211:Indoles; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; D013141:Spiro Compounds; C487224:elacomine; C013231:pyrroline; C051740:isoretronecanol; C011549:supinidine
keywords: annulation; heterocycles; reaction mechanisms; synthetic methods; total synthesis