Stereoelectronic Influence of a "Spectator" Propargylic Substituent Can Override Aromaticity Effects in Radical Peri-Cyclizations en Route to Expanded Polyaromatics.

Computational analysis quantifies key trends in " peri"-radical cyclizations, a recently developed type of ring-forming reaction for the expansion of polyaromatic systems at the zigzag edge. Comparison of vinyl radical attack on the peri-position versus a topologically similar six-membered ring formation at the armchair edge reveals that the barriers for the peri-ring closure are slightly higher, even though the peri-attack is more exergonic. On the other hand, the intramolecular competition between the formation of a five-membered ring by ortho-attack at the armchair edge and formation of a six-membered ring by peri-attack at the zigzag edge clearly favors six-membered ring formation. The key novel finding is the unprecedented sensitivity of peri-cyclization to the presence and spatial orientation of a "spectator" propargylic -OMe substituent. Remarkably, formation of cis-products proceeds, in general, through a significantly (∼2-4 kcal/mol) lower barrier than formation of the trans-products, even when the cis-products are less stable. The origin of this unexpected effect is clearly stereoelectronic. These findings identify such remote substitution as a conceptually new tool for the control of rate and selectivity of radical reactions. The correlations of activation barriers for vinyl radical attack with aromaticity of the target show the expected relationship in phenanthrenes and pyrenes but not in anthracenes. In the latter case, the attack at the less aromatic ring corresponds to a higher barrier because a steric penalty on the stereoelectronically favorable cis-TS negates the accelerating influence of the properly aligned C-O and C-Sn bonds.