Nonracemic bicyclic lactam lactones via regio- and cis-diastereocontrolled C-H insertion. Asymmetric synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol.
The Rh(2)(MPPIM)(4)-catalyzed intramolecular C-H insertion reaction of (S)- and (R)-1-benzyl-5-(alpha-diazoacetoxy)piperidin-2-one and (S)-1-benzyl-4-(alpha-diazoacetoxy)pyrrolidin-2-one proceeds with high regioselectivity and cis-diastereoselectivity to give good yields of chiral nonracemic bicyclic lactam lactones (BLLs). For (S)- and (R)-1-benzyl-5-(alpha-diazoacetoxy)piperidin-2-one, the regioselectivity of the C-H insertion is catalyst-dependent; for example, (S)-1-benzyl-5-(alpha-diazoacetoxy)piperidin-2-one undergoes C-H insertion at C-6 preferentially when Rh(2)(5S-MPPIM)(4) is used, but with Rh(2)(5R-MPPIM)(4), C-H insertion occurs preferentially at C-4. This effect is not observed in the reaction of (S)-1-benzyl-4-(alpha-diazoacetoxy)pyrrolidin-2-one. The utility of the BLLs as chiral building blocks in alkaloid synthesis is exemplified by the synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol.
Wee
Andrew G H
AG
Department of Chemistry and Biochemistry, University of Regina, Regina Saskatchewan, S4S 0A2, Canada. andrew.wee@uregina.ca
Fan
Gao-Jun
GJ
Bayirinoba
Hypolite M
HM
D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry; D007769:Lactams / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D054836:Indolizidines; D007769:Lactams; D007783:Lactones