Aryne 1,4‐Disubstitution and Remote Diastereoselective 1,2,4‐Trisubstitution via a Nucleophilic Annulation‐[5,5]‐Sigmatropic Rearrangement Process.

Both aryne 1,4‐disubstitution and 1,2,4‐trifunctionalization were accomplished from tertiary amines bearing a penta‐2,4‐dien‐1‐yl moiety. These transformations could directly incorporate a C−N and a C−C bond para to each other on an aryne intermediate via a sequential nucleophilic addition and [5,5]‐sigmatropic rearrangement. When arynes bearing 3‐tethered electrophiles were employed, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]‐sigmatropic rearrangement process was observed. Our density functional theory (DFT) calculations revealed that hydrogen‐bonding interactions between two C−H hydrogens on the penta‐2,4‐dien‐1‐yl chain and the oxygen anion generated upon N‐nucleophilic annulation reaction in the [5,5]‐sigmatropic rearrangement step is responsible for the remote diastereoselective control in this reaction system. [ABSTRACT FROM AUTHOR]