Metal‐Catalyzed Regiospecific (4+3) Cyclization of 2‐Indolylmethanols with ortho‐Quinone Methides

Abstract

The first metal‐catalyzed C3‐nucleophilic (4+3) cyclization of 2‐indolylmethanols with stable ortho‐quinone methides has been established, which constructed indole‐based seven‐membered heterocycles in high yields (70 %‐98 %) with regiospecificity. This reaction has tackled the challenges in exploring the C3‐nucleophilicity of 2‐indolylmethanols, which will contribute to the chemistry of 2‐indolylmethanols, especially to metal‐catalyzed cyclizations of 2‐indolylmethanols. In addition, this approach will provide a useful method for constructing indole‐based seven‐membered heterocycles with high efficiency and regioselectivity.

Asymmetric [4 + 3] Annulations for Constructing Divergent Oxepane Frameworks via Cooperative Tertiary Amine/Transition Metal Catalysis

“…Over the past years, [4 + 3] and [5 + 2] annulation reactions emerged as powerful strategies for constructing oxepane derivatives including N -heterocyclic carbene (NHC)-activated homoenolates, Lewis base tethered dipoles, Pd-trimethylenemethane intermediates, and 2-indolylmethanols, , furnishing a broad range of aromatic ring fused oxepane derivatives (Scheme a). On the other hand, vinylethylene carbonates (VECs) proved to be the prevalent five-atom synthons to access oxepane derivatives via [5 + 2] annulations (Scheme b) .…”

Synthesis of C3-functionalized indole derivatives via Brønsted acid-catalyzed regioselective arylation of 2-indolylmethanols with guaiazulene

“…Recently, 2-indolylmethanols have been demonstrated as versatile platform molecules for the synthesis of indole-based heterocycles, through substitution reactions and cycloadditions. 11–22 It is universally acknowledged that 2-indolylmethanols can easily be converted into delocalized cation intermediates with carbocation resonance structures by the use of Brønsted or Lewis acids that act as a catalyst. For this reason, the regioselective substitution reactions of 2-indolylmethanols could lead to benzylic site functionalized 12,19 a ,20,21 or C3-functionalized indole derivatives.…”

“…For this reason, the regioselective substitution reactions of 2-indolylmethanols could lead to benzylic site functionalized 12,19 a ,20,21 or C3-functionalized indole derivatives. 16–22 Moreover, 2-indolylmethanols are also involved in cycloadditions, including [3 + 2], 13 [3 + 3], 14 and [4 + 3] 15 cyclizations, which are efficient methods to synthesize indole-fused cyclic derivatives.…”

PFOA‐Catalyzed Regioselective Alkylation of Indolylmethanols with 2‐Alkylazaarenes**

“…In 2017, Shi group established substrate‐controlled regioselective arylation of 2‐indolylmethanols with indoles, which afforded bisindole derivatives in high yields [10] . The versatile reactivity of 2‐indolymethanols was further highlighted by a number of cycloaddition reactions with diverse partner, such as [4+3] cycloaddition with ortho ‐quinone methides, [11] [3+3] cyclization with vinylcyclopropanes, [12] [3+2] cycloaddition with p ‐hydroxystyrenes [13] . For instance, in 2021, the Shi group achieved the first C3‐nucleophilic asymmetric [3+3] cycloaddition of 2‐indolylmethanol with nitrone by the synergistic catalysis [14] .…”