Synthetic studies toward (-)-FR901483 using a conjugate allylation to install the C-1 quaternary carbon.
Two approaches to the aza-tricyclo dodecane skeleton of (-)-FR901483 are reported. Both routes utilized a Grignard addition to an N-acylpyridinium salt to establish the absolute stereochemistry at C-6 and a highly diastereoselective conjugate allylation reaction to form the quaternary center at C-1 of the natural product in an excellent yield. Although the desired polysubstituted piperidine intermediates were prepared regio- and stereoselectively, the construction of the C-8/C-9 bond connectivity could not be achieved. All attempts at a pinacol cyclization or an intramolecular 6-exo-tet epoxide opening were unsuccessful because of an unfavorable A(1,3) strain inherent in the molecule.
Gotchev
Dimitar B
DB
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
Comins
Daniel L
DL
D002244:Carbon / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C098358:FR 901483; D009943:Organophosphorus Compounds; D002244:Carbon