Highly Selective Diels-Alder Reactions of Directly Connected Enyne Dienophiles

The paper describes the course of cycloadditions of Diels−Alder dienophiles containing linked
enyne sites, each substituted with activating groups. Consistently, it was found that in the enyne cases the
Diels−Alder reaction occurred specifically at the acetylenic center. Furthermore, it was found that the
regiochemical sense of the cycloaddition was apparently determined by the remote activating group bound
to the olefinic site. This remote acrylyl group totally dominated the course of the cycloaddition, relative to
the activating group bound directly on the acetylene site. Explanations for these findings at the computational
level are provided. The computations also rationalize the strong preference for cycloaddition to occur at
the acetylene linkage and encompass the otherwise surprising regiochemical dominance by the remote
ester on the olefinic site. The high selectivities available through such reactions provide important new
opportunities in the synthesis of orsenillate type substructures that are found in a variety of natural products
of contemporary interest.