Palladium-Catalyzed Dearomative [4 + 2]-Cycloaddition toward Hydrocarbazoles

Abstract

An efficient method for the construction of hydrocarbazoles bearing three continuous sterically hindered stereocenters, two quaternary and one tertiary, via a highly diastereoselective palladium-catalyzed [4 + 2]-cycloaddition/dearomatization of 3-nitroindoles has been developed. The cycloaddition of 3-nitroindoles occurs at ambient conditions with a 1,4-zwitterionic intermediate, in situ generated from γ-methylidene-δ-valerolactones. The further synthetic utility of this method is demonstrated by the multifaceted transformations possible from the products. The catalytic asymmetric aspect of this transformation has also been explored.

Transition‐Metal Catalyzed [4+2]‐Cycloaddition Reactions: A Sexennial Update

“…[94] hydrocarbazole moieties, Pandit et al in 2023 developed an efficient method for the construction of hydrocarbazoles 97 via a highly diastereoselective palladium-catalyzed [4 + 2]-cycloaddition of 3-nitroindoles 95 and γ-methylene-δ-valerolactones 96 in high yields (Scheme 25). [105] This dearomatization strategy uses mild reaction conditions and is highly atom-economic. Initially, the palladium catalyst reacts with 96 to provide the zwitterionic complex LIV by elimination of CO 2 .…”

Palladium-Catalyzed Cycloaddition Reactions of π–Allylpalladium 1,4-Dipoles with 1,3,5-Triazinanes: Access to Hexahydropyrimidines, 1,3-Oxazinanes, and 1,5-Diazocanes

“…Procedure for the Synthesis of 5-Methyl-1-phenyl-3-tosylhexahydropyrimidine (10). In a reaction tube with a magnetic stirring bar, the solution of 3p (31.4 mg, 0.1 mmol, 1.0 equiv) and NiCl 2 (13.0 mg, 0.1 mmol, 1.0 equiv) in MeOH (2.0 mL) was obtained, and then, NaBH 4 (45.4 mg, 1.2 mmol, 12 equiv) was slowly added at 0 °C.…”

“…The residue was purified by flash column chromatography (petroleum ether/ethyl acetate = 5:1) to afford product 9; white solid, 37.7 mg, 92% yield; mp: 104.7−104.9 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.32−7.26 (m, 4H), 7.26−7.20 (m, 3H), 7.07−6.98 (m, 4H), 6.95−6.87 (m, 1H), 6.58−6.52 (m, 2H), 6.13−6.04 (m, 1H), 5.03 (s, 2H), 3.90 (s, 2H), 3.20 (s, 2H), 2.39 (s, 3H); 13 C { 1 H} NMR (101 MHz, CDCl 3 ) 13 C NMR (101 MHz, CDCl 3 ): δ 144. 8, 143.2, 139.0, 136.1, 129.4, 129.4, 128.7, 128.6, 127.6, 126.6, 125.7, 120.9, 115.5, 111.7, 59.4, 46.1, 39.1, 21.7 Procedure for the Synthesis of 5-Methyl-1-phenyl-3-tosylhexahydropyrimidine (10). In a reaction tube with a magnetic stirring bar, the solution of 3p (31.4 mg, 0.1 mmol, 1.0 equiv) and NiCl 2 (13.0 mg, 0.1 mmol, 1.0 equiv) in MeOH (2.0 mL) was obtained, and then, NaBH 4 (45.4 mg, 1.2 mmol, 12 equiv) was slowly added at 0 °C.…”

“…8b In 2021, a palladium/Lewis acid-catalyzed decarboxylative [5 + 2] annulation of 4methylene-5-vinyl-1,3-dioxolan-2-ones with 1,3,5-triazinanes toward the synthesis of nonfused N-aryl azepane derivatives was discovered by Guo and co-workers (Scheme 1c). 9 Despite the successful construction of heterocyclic compounds through the cyclization reaction of 1,3,5-triazinanes with π-allylpalladium 1,3-dipoles 8,9 and the wide application of π-allylpalladium 1,4-dipoles in the efficient synthesis of heterocyclic compounds through cyclization reactions, 10 the [4 + 2] cycloaddition reaction of π-allylpalladium 1,4-dipole precursors with 1,3,5-triazinane has not yet been achieved. To the best of our knowledge, the 5-methylene-1,3-oxazinan-2-ones could be used for the generation of aza-π-allylpalladium 1,4-dipole species, thereby undergoing allylic alkylation with diverse nucleophiles and further cyclization for the construction of nitrogen-containing heterocycles.…”

Catalytic Intermolecular [4+2]-Cycloaddition toward the Stereo­selective C2–C3 Annulation of Indoles

“…In 2023, Majumdar and co-workers reported a palladiumcatalyzed dearomative [4 + 2]-cycloaddition of 3-nitroindoles with a 1,4-zwitterionic species in situ generated from γmethylidene-δ-valerolactones via decarboxylation (Scheme 23). 33 The reaction occurs at ambient reaction conditions to provide polycyclic indoline derivatives containing three consecutive stereocenters in good yields (up to 96%) and excellent diastereoselectivity (>20:1 dr). A series of substituted indoles and γ-methylidene-δ-valerolactones have been successfully examined.…”