A convenient and efficient domino aryne process was developed under transition‐metal‐free conditions to generate a range of tetra‐ and pentacyclic ring systems. This transformation was realized via a 1,2‐benzdiyne through a nucleophilic and Diels–Alder reaction cascade using styrene as the diene moiety. Three new chemical bonds, namely one C−N and two C−C bonds, and two benzofused rings could be constructed concomitantly, which was made possible by distinct chemoselective control at both the 1,2‐aryne and 2,3‐aryne stages. Moreover, in‐depth studies were carried out on the domino aryne precursors and controlling the diastereoselectivity.

Scheme 1. Backgrounda nd proposal. Nu = nucleophile, Tf = trifluoromethanesulfonyl, TMS = trimethylsilyl.Scheme 3. Substrate scope. [a] Conditions A: slow addition of asolution of 1a (0.6 mmol) in PhCl (10 mL) to asuspension of 5 (0.3 mmol), Cs 2 CO 3 (1.8 mmol), and 18-crown-6 (0.6 mmol) in PhCl (20 mL) at 130 8 8Cover 1h.[b] Yields of isolated products. [c] Conditions B: slow addition of asolution of 1k (0.6 mmol) in toluene (10 mL) to asuspension of 5 (0.3 mmol), Cs 2 CO 3 (1.8 mmol), and 18-crown-6 (0.6 mmol) in toluene (20 mL) at 100 8 8Cover 1h.[ d] 38 %of6n with (1.5:1 d.r.) was obtained using conditions A. Angewandte Chemie Communications