Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

Herein, we report a multistep synthesis of polycyclic tetrahydro­isoquinolines and tetrahydro­benzo­[d]­azepines starting from Wang resin-immobilized allylglycine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides, Mitsunobu alkylation with various phenylalkynols yielded the corresponding (phenylprop-2-yn-1-yl)-sulfonamides. “Interior” ring-closure enyne metathesis (RCEM) using a Grubbs catalyst second generation (Ru2) yielded functionalized tetrahydro­isoquinoline/tetrahydro­benzo­[d]­azepine intermediates. “East-side” [4 + 2] cycloaddition with representative dienophiles was followed by the “west-side” construction of different heterocycles using various electrophiles to finally furnish a set of novel molecular frameworks bearing fused [6 + 6] or [6 + 7] rings. The developed methodology enables the facile parallel synthesis of novel, pharmacologically promising compounds derived from privileged scaffolds.