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.

Automated summary

In this study, both aryne 1,4-disubstitution and 1,2,4-trifunctionalization were achieved by using tertiary amines with a penta-2,4-dien-1-yl moiety. The reactions resulted in the incorporation of a C-N and a C-C bond para to each other on an aryne intermediate through sequential nucleophilic addition and [5,5]-sigmatropic rearrangement. When arynes with 3-tethered electrophiles were used, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]-sigmatropic rearrangement process were observed. Density functional theory (DFT) calculations revealed that the remote diastereoselective control in this reaction system is due to 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.