Synthesis of enantiopure 3-quinuclidinone analogues with three stereogenic centers: (1S,2R,4S)- and (1S,2S, 4S)-2-(Hydroxymethyl)-1-azabicyclo[2.2.2]octan-5-one and stereocontrol of nucleophilic addition to the carbonyl group.
The pseudoenantiomeric title compounds have been prepared from quincorine (QCI) and quincoridine (QCD), respectively, in enantiopure form following an efficient six-step pathway. Nucleophilic attack at the carbonyl group proceeds preferentially from the supposedly more hindered endo pi-face, giving quinuclidinols with natural configuration at C5 (up to 97%). pi-Face selectivity is highest in the QCD series with bulky O-protecting groups, involving an unprecedented 1,7-stereoinduction.
Frackenpohl
J
J
Department of Organic Chemistry, University of Hannover, Schneiderberg 1B, D-30167 Hannover, Germany.
Hoffmann
H M
HM
D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011812:Quinuclidines / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D011812:Quinuclidines