Catalytic asymmetric synthesis of 8-oxabicyclooctanes by intermolecular [5+2] pyrylium cycloadditions.
Highly enantioselective intermolecular [5+2] cycloadditions of pyrylium ion intermediates with electron-rich alkenes are promoted by a dual catalyst system composed of an achiral thiourea and a chiral primary aminothiourea. The observed enantioselectivity is highly dependent on the substitution pattern of the 5π component, and the basis for this effect is analyzed using experimental and computational evidence. The resultant 8-oxabicyclo[3.2.1]octane derivatives possess a scaffold common in natural products and medicinally active compounds and are also versatile chiral building blocks for further manipulations. Several stereoselective complexity-generating transformations of the 8-oxabicyclooctane products are presented.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138 (USA).
Michael R
MR
Witten
Eric N
EN
Jacobsen
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic
asymmetric catalysis; conformational analysis; cycloaddition; hydrogen bonds; organocatalysis