Arene Trifunctionalization with Highly Fused Ring Systems through a Domino Aryne Nucleophilic and Diels–Alder Cascade

Abstract

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.

Concise Synthesis of Chromene/Chromane-Type Aryne Precursors and Their Applications

“…Encouraged by the above results, we sought the use of the OTf group to serve as both a guiding group to control regioselectivity and a leaving group to generate aryne, thereby achieving 1,2,3-trifunctionalization of chromane. Inspired by the methodologies developed by Li and Hosoya, we envisioned that the development of domino aryne precursors is of significant value for organic synthesis (Scheme ). To our delight, the domino chromane-type precursor was prepared according to the procedure described in Scheme .…”

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

“…Both the experimental studies and the DFT calculations suggested a concerted aryne ene process. Moreover, examples of aryne ene reactions involved in cascade transformations were reported. ,, …”

“…Moreover, domino aryne nucleophilic/Diels–Alder reaction processes were independently realized by the groups of Hoye and Li . As shown in Scheme b, Hoye et al demonstrated that substrate 11-42 could participate in domino aryne nucleophilic addition, intramolecular hexadehydro-Diels–Alder (HDDA) reaction with either TPBT 11-28 or TTPM 11-37 to generate a naphthalyne intermediate 11-43 , which was then trapped by various arynophiles to afford polysubstituted naphthalenes 11-44 .…”

“…As shown in Scheme b, Hoye et al demonstrated that substrate 11-42 could participate in domino aryne nucleophilic addition, intramolecular hexadehydro-Diels–Alder (HDDA) reaction with either TPBT 11-28 or TTPM 11-37 to generate a naphthalyne intermediate 11-43 , which was then trapped by various arynophiles to afford polysubstituted naphthalenes 11-44 . On the other hand, Li and co-workers disclosed that cinnamyl sulfonamides 11-46 could also realize a nucleophilic, Diels–Alder reaction cascade process, furnishing a variety of [6, n ,6,6]-tetracyclic and [6,5,6,6,6]-pentacyclic ring structures 11-47 in a highly efficient manner (Scheme c) . In this study, a series of domino aryne precursors 11-45 were systematically investigated, and 11-45 with a 2,6-difluorophenylsulfonate (Ar = 2,6-difluorophenyl) as the second LG was identified to serve as an ideal domino aryne precursor.…”

The Stannum–Ene Reactions of Benzyne and Cyclohexyne with Superb Chemoselectivity for Cyclohexyne

“…At last, a domino aryne nucleophilic and stannum–ene reaction was examined. As shown in Scheme 6c, when compound 15 was treated with domino aryne precursor 16 , [4h] the desired product 17 was obtained in 38 % yield [22] . Although the yield was not satisfied yet, it demonstrates the possibility of stannum–ene reaction in domino 1,2‐benzdiyne process.…”