Synthesis of Bicyclo[2.2.2]octanes with a Quaternary Bridgehead Carbon by Diphenylprolinol Silyl Ether-mediated Domino Reaction

Bicyclo[2.2.2]octane derivatives possessing a quaternary bridgehead carbon were synthesized with excellent diastereoselectivity in nearly optically pure form by diphenylprolinol silyl ether mediated domino Michael/Michael reaction of alpha,beta-unsaturated aldehyde and cyclohex-2-en-1-one bearing an electron-withdrawing group at the 3-position. Carbonitrile, alkoxycarbonyl, and sulfonyl substituents were successfully employed as a suitable electron-withdrawing group at the 3-position of cyclohex-2-en-1-one.

Automated summary

Bicyclo[2.2.2]octane derivatives with a quaternary bridgehead carbon were synthesized in nearly optically pure form with excellent diastereoselectivity using diphenylprolinol silyl ether mediated domino Michael/Michael reaction of alpha,beta-unsaturated aldehyde and cyclohex-2-en-1-one containing an electron-withdrawing group at the 3-position. Carbonitrile, alkoxycarbonyl, and sulfonyl substituents proved to be effective electron-withdrawing groups at the 3-position of cyclohex-2-en-1-one.