Regio- and stereochemistry of Michael addition of methanol to Thiele's ester

Acid‐promoted esterification of Thiele's acid with methanol was found to afford three products. In addition to the expected major product (i.e. the corresponding dimethyl ester, 2a), two minor products are obtained, one of which, 3, results from subsequent Michael addition of methanol to the norbornene CC double bond in 2a. Analysis of its one‐ and two‐dimensional NMR spectra indicates that this minor product possesses structure 3a in which the (C‐5)—OCH3 and (C‐6)—CO2CH3 bonds are exo and endo, respectively. This conclusion is reinforced by the results of thermodynamics calculations and associated chemical shift calculations. In addition, theoretical analysis of competing transition states for Michael addition of methanol to 2a suggests that exo approach of methanol towards the (C‐5)(C‐6) double bond in the substrate is preferred kinetically over the corresponding endo reaction pathway. Copyright © 2004 John Wiley & Sons, Ltd.