Synthesis of Carbazole Alkaloids by Ring‐Closing Metathesis and Ring Rearrangement–Aromatization

Abstract

Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring-closing metathesis (RCM) and ringrearrangement-aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2-diallyl 3-oxindole derivatives through a 1,2-allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel class of spirocyclopentene-3-oxindole derivatives, which underwent a novel RRA reaction to afford carbazole derivatives. The synthetic sequence to carbazoles was shortened by combining the RCM and RRA steps in an orthogonal tandem catalytic process. The utility of this methodology was further demonstrated by the straightforward synthesis of carbazole alkaloids, including amukonal derivative, girinimbilol, heptaphylline, and bis(2-hydroxy-3-methylcarbazole).

Access to 3‐Oxindoles from Allylic Alcohols and Indoles

“…As expected, the use of allylation catalyst Ru‐1 led to the formation of corresponding diallylated pseudoindoxyls 7 in 55–98 % yield (Scheme ). Rapid screening of the reaction conditions demonstrated that the Hoveyda–Grubbs II precatalyst allowed the formation of the tricyclic adducts in up to 84 % yield . Owing to the rigid structure of the tricyclic adducts, diastereoisomers of 8 ab , 8 ac , and 8 ae were easily separated after isolation by column chromatography.…”

“On Water” Direct Organocatalytic Cyanoarylmethylation of Isatins for the Diastereoselective Synthesis of 3-Hydroxy-3-cyanomethyl Oxindoles

“…Unless otherwise noted, analytical grade solvents and commercially available reagents were used without further purification. N-protected isatins 1 (GP-1) 16 : N-alkylated isatin derivatives were prepared from commercially available isatins with different alkyl halides in the presence of K2CO3 in DMF at room temperature. MeI or BnBr (10.2 mmol, 3.0 equiv) was added to a stirred solution of isatin (3.4 mmol, 1.0 equiv) and K2CO3 (8.5 mmol, 2.5 equiv) in DMF and stirred for 12 h at room temperature.…”

Synthesis of Tetranuclear Palladium(II) Complexes and Their Catalytic Activity for Cross‐Coupling Reactions

“…[42,43] approach, Dash et al obtained 1 by ac opper(II) chloride-catalyzed coupling of 14. [46] In our originalp ublication, 2-hydroxy-3-methylcarbazole (14)w as synthesized by reactiono ft he arylamine 13 with ac yclohexadienylmolybdenum salt followed by oxidative cyclization and cleavage of the methyl ether. [25] Since then, variouss ynthetic approaches to 14 have been developed.…”

“…[25] Since then, variouss ynthetic approaches to 14 have been developed. [10,18,[46][47][48][49] Our approach using aB uchwald-Hartwig coupling of the aniline 13 and iodobenzene followed by palladium(II)-catalyzed oxidative cyclization and methyl ether cleavage provided 2-hydroxy-3-methylcarbazole (14)i nt hree steps and 85 %o verall yield on gram scale. [40,48,49] Using 14 as model compound, we screened the performance of variousr eagents for the oxidative coupling to the 1,1'-bicarbazole 1 ( Table 1).…”

“…[59] Under these conditions, the 1,1'-bicarbazole 1 was obtained in 77 %y ield. As eparation of the atropisomers of 1 was not attempted, since we did not expect ac onfigura- [46] tional stability of the pure enantiomerso f1 at room temperature (vide infra). Moreover, Furukawa et al did not report any chiroptical data for the naturalp roduct.…”