Synthetic studies toward halichlorine: complex azaspirocycle formation with use of an NBS-promoted semipinacol reaction.
The investigations of a synthetic route incorporating a NBS-promoted semipinacol rearrangement to the 6-azaspiro[4.5]decane fragment within halichlorine ( 1) are presented. A convergent approach was pursued, utilizing two chiral, enantiomerically enriched building blocks, 2-trimethylstannyl piperidene 10 and substituted cyclobutanone 19. Noteworthy synthetic operations in this study include the following: (a) a highly diastereoselective NBS-promoted semipinacol reaction that established four stereogenic centers in ketone 25 and (b) the use of a N- p-toluenesulfonyl-2-iodo-2-piperidene as a precursor to a basic organometallic reagent, which was critical to the success of the coupling of fragments 10 and 19.
Hurley
Paul B
PB
Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, B.C., Canada.
Dake
Gregory R
GR
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry*; D003500:Cyclization; D053138:Cyclohexenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D013055:Spectrophotometry, Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D000470:Alkaloids; D001372:Aza Compounds; D053138:Cyclohexenes; D013141:Spiro Compounds; C412666:halichlorine; C519041:semipinacol