<p>In this manuscript we describe a modular pathway
to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC
derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub>
and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts
alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling
reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we
demonstrate using extensive NMR evidence that similar halide-substituted
Friedel-Crafts alkylation/cyclization products in previous articles were
wrongly assigned as the para-isomers, which also has consequence for the
assignment of the subsequent cross-coupled products and interpretation of their
biological activity. </p>
<p>Considering the importance of the availability
of THC derivatives in medicinal chemistry research and the fact that previously
synthesized compounds were wrongly assigned, we feel this research is describing a
straightforward pathway into new cannabinoids.</p>
Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes via one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions