Development of a protocol for eight- and nine-membered ring synthesis in the annulation of sp(2),sp(3)-hybridized organic dihalides with keto esters.
A protocol has been developed in which annulation reactions of various dihalides with keto esters can be carried out to provide entry to eight- and nine-membered carbocycles. In this process wherein one alkenyl- or aryl bromide and a tethered alkyl chloride comprise the organic dihalide, a selective metal-halogen exchange reaction between the sp(2)-hybridized bromide and an organolithium initiates the process. Transmetalation to an organoytterbium reagent generates a species that undergoes selective carbonyl addition to the ketone of the keto ester, creating a lactone intermediate. Subjection of the resulting chloroalkyl lactone to intramolecular reductive coupling with samarium(II) iodide completes the desired annulation.
Molander
G A
GA
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA. gmolandr@sas.upenn.edu
Köllner
C
C
D003500:Cyclization; D004952:Esters / Q000737:chemistry; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D012493:Samarium; D015018:Ytterbium
D004952:Esters; D006846:Hydrocarbons, Halogenated; D007202:Indicators and Reagents; D007659:Ketones; D007783:Lactones; D009942:Organometallic Compounds; D012493:Samarium; D015018:Ytterbium