HIV protease inhibitors Part 2: [3+2] cycloaddition, isomerization; and ring expansion en route to 4,5-substituted cyclohexenones

4,5-Substituted cyclohexanone 10 and its derivatives are carbocyclic analogues of Indinavir 3 and are expected to have antiviral activity. Early attempts to obtain these compounds via a diastereoselective [3+2] cycloaddition between 19 and 14 failed due to the sensitivity of the cycloadduct 24. It proved possible to obtain 30 from the α,β-unsaturated ester 27: [3+2] cycloaddition, isomerization, and ring expansion provided α,β-unsaturated ketone 31 from ester 26 in good yields. Further transformations of 31 gave the hydroxyethylamino inhibitor analogues of Indinavir 3.