A Domino Amidation Route to Indolines and Indoles:  Rapid Syntheses of Anhydrolycorinone, Hippadine, Oxoassoanine, and Pratosine

Abstract

[reaction: see text] When subjected to palladium-catalyzed amidation conditions, 2-triflyloxy phenethyl carbonates undergo, in addition to the expected aryl cross-coupling, an additional amidation with net displacement of the carbonate. The result is a one-step synthesis of indolines which may be oxidized to indoles. The utility of the procedure is illustrated by the two- or three-step syntheses of anhydrolycorinone, hippadine, oxoassoanine, and pratosine.

The attempted stereoselective synthesis of chiral 2,2′-biindoline

“…16 2-Allylphenol (1.00 g, 7.46 mmol) was added to a stirred mixture of N-phenyltriflimide (3.4 g, 11.18 mmol) and K 2 CO 3 (2.06 g, 14.9 mmol) in THF (50 mL). The reaction mixture was heated at reflux and after 48 h was partitioned between CH 2 Cl 2 and satd NaCl.…”

“…The crude product was subjected to gravity silica gel column chromatography (1% EtOAc/hexanes) to afford the triflated phenol 19 (1.648 g, 83%) as a colourless, volatile liquid. 16 Grubbs' II catalyst (48 mg, 0.057 mmol, 5 mol %) was added to a solution of 2-allylnitrobenzene 22 (185 mg, 1.14 mmol) in CH 2 Cl 2 (5 mL), and the flask was flushed with Ar(g) and heated at reflux for 7 h. The reaction mixture was washed with water, and the aqueous layer was extracted with CH 2 Cl 2 (3Â20 mL). Charcoal was added to the combined organic layers and filtered.…”

“…16. The diol (R,R)-16b was synthesised by General procedure A using alkene 15(80 mg, 0.19 mmol, E/Z 8.5:1), ADmix b (267 mg), methanesulfonamide (18 mg, 0.19 mmol), sodium sulfite (238 mg) in t…”

Transition metals in organic synthesis: Highlights for the year 2005

“…A double N-arylation of 2,2 -biphenylene triflates with primary amines to give carbazoles was reported and this reaction was used in a synthesis of mukonine [213]. Related reactions were used to prepare hetero [7]helicenes [554], indoles [555], murrastifoline A [206] and anhydrolycorine, hippadine, oxoassonine, and pratosine [556].…”

One-pot synthesis of highly substituted indolines

“…These (Scheme 1) include reduction of indoles, [6][7][8][9][10][11][12][13][14][15][16][17][18] anionic, [19][20][21][22][23] radical, [24][25][26] and metal-mediated [27][28][29][30] intramolecular cyclizations, as well as several other approaches. [31][32][33] As part of our efforts in developing therapeutic agents for CNS diseases, we desired a convenient and versatile synthesis of 3,3-disubstituted indolines with potential substitution at alternate positions of the scaffold. We recently reported the synthesis of indoles 1 34 and oxindoles 2 35 from indolenines 3, which could be readily synthesized from arylhydrazines 4 (Scheme 2).…”