Diels-Alder Approach for the Construction of Halogenated, o-Nitro
Biaryl Templates and Application to the Total Synthesis of the
Anti-HIV Agent Siamenol
Michael R Naffziger,Bradley O. Ashburn,Johanna R. Perkins, andRich G. Carter*
Department of Chemistry, 153 Gilbert Hall, Oregon State University, Corvallis, Oregon 97331
rich.carter@oregonstate.edu
Received April 11, 2007
Abstract:
A rapid Diels-Alder approach to halogenated biaryl templates is described. These biaryl templates are
available in two steps from the corresponding aromatic aldehydes. The scope of subsequent Suzuki
couplings on the biaryl chlorides is explored. Good tolerance for both electron-donating and electron-withdrawing groups in the coupling process can be achieved. Further functionalization of the biaryl
templates is described. Hydrogenation of the nitro moiety with concomitant removal of the benzyl ether
yields the o-anilino, o-phenolic polyaryls. Selective reduction of the nitro group can be accomplished.
Alternatively, the benzyl ether can be selectively removed under Lewis acidic conditions. The utilization
of the Diels-Alder adducts for the synthesis of a series of chlorinated carbazoles via the Cadogan
cyclization is also demonstrated. Finally, application of this technology to the total synthesis of siamenol,
an anti-HIV agent, is reported.
