Development of the di-tert-butylphosphinyl directed metalation group, application to the synthesis of aromatic phosphines, substituted ferrocenes and 7-substituted indoles ; Studies directed towards the total synthesis of biruloquinone

Abstract

A new directed metalation group (DMG) has been investigated and developed. The di-tert-butylphosphinyl substituent has been shown to be effective in directing aromatic metalation reactions to the ortho position providing direct access to 1, 2-disubstituted aromatic phosphine oxides in high yield. A preliminary determination of the relative position in the DMG hierarchy has been established. In addition, access to aromatic phosphines has been demonstrated through reduction of the phosphine oxide, and access to hindered biaryls has been demonstrated through homocoupling. Similar reactivity was demonstrated for ferrocenyl substrates, in which deprotonation occurs adjacent to the di-tert-butylphosphinyl substituent.

A new and efficient route for the synthesis of 7-substituted indoles has been established. N-Di-tert-butylphosphinylindole was smoothly metalated in the presence of n-butyllithium to provide 7-lithio-N-di-tert-butylphosphinylindole, which reacted with electrophiles to furnish 7-substituted indoles in high yield. Using the new methodology, a preliminary investigation of the total synthesis of asterriquinone CT4 was performed.

Progress has been made towards the total synthesis of the naturally occurring 9,10-phenanthraquinone biruloquinone. The synthetic strategy involved the combined use of directed ortho metalation and transition metal catalyzed cross coupling protocols in the synthesis of key intermediates.