Studies Towards the Total Synthesis of Populusone: Stereoselective Construction of Functionalized 2-Oxa-bicyclo[2.2.2]octenes

A short and efficient synthetic access to functionalized compounds displaying major structural elements of the natural product populusone is elaborated by exploiting a diastereoselective Mukaiyama aldol addition followed by a triflic anhydride-induced oxa-Michael addition to construct the sensitive 2-oxa-bicyclo[2.2.2]octene unit as an enol triflate, which is directly used in a subsequent Suzuki cross -coupling. While attempts to close the strained 10-membered ring by means of Ru-catalyzed ring-closing metathesis were not successful, the developed synthetic scheme opens a rapid synthetic access to advanced intermediates, which may allow the completion of the total synthesis of populusone in the future.

Automated summary

This paper presents a short and efficient synthetic access to functionalized compounds with major structural elements of the natural product populusone. By utilizing a diastereoselective Mukaiyama aldol addition and a triflic anhydride-induced oxa-Michael addition, the sensitive 2-oxa-bicyclo[2.2.2]octene unit is constructed and directly used in a subsequent Suzuki cross-coupling. Although attempts to close the strained 10-membered ring were not successful, the developed synthetic scheme allows the rapid synthesis of advanced intermediates, which may lead to the total synthesis of populusone in the future.