Enantioselective synthesis of bicyclo[6.1.0]nonane-9-carboxylic acids via Me2AlOTf-promoted intramolecular Friedel-Crafts alkylation of arenes with the gamma-lactone moiety of 3-oxabicyclo[3.1.0]hexan-2-ones.
A strategy to rapidly assemble enantiomerically pure bicyclo[6.1.0]nonane-9-carboxylic acids via Me2AlOTf-promoted intramolecular Friedel-Crafts alkylation of tethered pi-nucleophiles with the gamma-lactone moiety of 3-oxabicyclo[3.1.0]hexan-2-ones is described. The approach begins with the enantioselective synthesis of 3-oxabicyclo[3.1.0]hexan-2-ones bearing a tethered pi-nucleophile at the 6-position by intramolecular Rh(II)-catalyzed cyclopropanation of allylic diazoacetates, prepared from the corresponding (Z)-allylic alcohols. Me2AlOTf-induced intramolecular Friedel-Crafts cyclization provides medium-sized carbocycles and heterocycles in high yields without requiring high-dilution or slow substrate addition techniques. The scope and limitations of this synthetic methodology are presented.
Fillion
Eric
E
Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. efillion@uwaterloo.ca
Beingessner
Rachel L
RL
D000478:Alkylation; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D006588:Hexanones / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D002264:Carboxylic Acids; D006588:Hexanones; D006841:Hydrocarbons, Aromatic; D007783:Lactones