Regioselective and Stereoselective [3+3] Annulation of Ketones Derived Azomethine Ylides with 2‐Indolylethylenes: Direct Access to Highly Substituted Tetrahydro‐γ‐Carbolines

Abstract

A highly efficient asymmetric [3 + 3] annulation of ketones derived azomethine ylides with 2indolylethylenes is reported, which is achieved by catalytic Michael addition in the presence of Ag(I)/Ph-Phosferrox complex and subsequent BF 3 · Et 2 O promoted Friedel-Crafts tandem reaction in a one-pot process. This strategy addresses the challenge of selectivity between [3 + 2] cycloaddition and [3 + 3] annulation and exclusively affords a series of [3 + 3] cycloadducts, highly substituted tetrahydro-g-carbolines in excellent yields (up to 99%), with excellent levels of regioselectivities and stereoselectivities (> 20:1 rr, up to > 20:1 dr; up to 99% ee).

Recent Advances in the Synthesis of Fused Heterocyclic Compounds and Their Antitumor Activities

“…Copper catalysis 2018 年, 邓卫平课题组 [37] 同年, 他们课题组 [38] 2018 年, 孔望清课题组 [39] 报道了镍催化 N- ( 2021 年, Lautens 课题组 [40] 报道了铁催化 N-(2-乙烯 2017 年, Chandrasekar 课题组 [42] 发展了邻溴芳胺与 芳基端炔串联环化合成吲哚的反应(Scheme 17a). 该反 应使用一种新型高效的钯-吡啶-氮杂卡宾作为催化剂, 表现出对水氧不敏感和低至 0.1 mol%负载量的优异性 能.…”

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

“…Following their earlier work, Deng described the first example of the Ag(I)/( S , S p )-Ph-FcPHOX ( 289 )-catalyzed regioselective and stereoselective [3 + 3] annulation of ketone-derived azomethine ylides ( 311 ) with 2-indolylethylenes ( 312 ) ( Scheme 90 ). 105 This tandem method involved a Michael addition followed by a BF 3 ·Et 2 O-promoted Friedel–Crafts reaction. Like their earlier report, the traditional [3 + 2] cycloaddition was prevented by using sterically hindered ketone-derived azomethine ylides (>20:1 rr).…”

Arylsulfonylation-Triggered Cyclization of 3-Alkenyl Indoles Enabling Synthesis of Tetrahydro-γ-carboline

“…On the other hand, 2-indolylnitroethylenes have been developed by Deng’s group as substrates for the construction of tetrahydro-γ-carboline skeletons via chemoselective [3 + 3] cycloaddition with azomethine ylides . The same group also reported a strategy via Sc-catalyzed [3 + 3] cycloaddition with β-(indol-2-yl)-α,β-unsaturated ketones and aziridines as substrates . In addition, regioselective [3 + 3] cycloaddition of 2-indolylmethanols with azomethine ylides provided an alternative way to construct tetrahydro-γ-carboline frameworks in high yields and excellent enantioselectivities (Scheme b) .…”