Indoles synthesis from indolines

The Hegedus indole synthesis involves one of the earlier (formal) examples of olefin hydroamination. An ortho-vinyl or ortho-nllyl aniline derivative 1 is treated with palladium(II) to deliver an intermediate resulting from alkene aminopalladation. Subsequent reduction and/or isomerization steps then provide the indoline or indole unit 2, respectively. 

The Fischer indole synthesis. The Fischer acid-catalyzed conversion of an 7V-arylhydrazone 42 into an indole is one of the most powerful and versatile methods for the preparation of indoles . The mechanism involves a [3,3] sigmatropic Claisen-type rearrangement of a protonated enehydrazine tautomer 43 to give intermediate 44, which spontaneously cyclizes by loss of ammonia, probably via indoline 45, to an indole 46 (Scheme 27). For unsymmetrical ketones, two isomeric indoles are possible and the general result is that the indole derived from the more stable (usually the more highly substituted) enehydrazine is formed. 

Recently, Cook s group described their Mori-Ban indole synthesis of substrate 10, easily assembled from 9 [23]. The intramolecular cyclization gave a 1 1 mixture of indole 11 and exo-3-methylene-indoline 12, which was readily converted to 11 upon treatment with acid. By changing the base from K2CO3 to Ag2C03, the Mori-Ban reaction gave exo-3-methylene-indoline 12 exclusively in 90% yield. 

This reaction can be traced back to the initial work of Cadogan for the preparation of car-bazole by the reductive cyclization of aromatic nitro compounds with triethyl phosphite. This reaction was then extended by Sundberg to the fornnation of indoles by the treatment of o-nitrostyrene with triethyl phosphite or the formation of indolines from the o-alkyl nitrobenzenes. Thus the formation of indole from the reduction of o-nitfostyrenes is referred to as the Cadogan-Sundberg indole synthesis." ... 

Reddy, K. H. V., Satish, G., Ramesh, K., Kamakar, K., and Nageswar, Y. V. D. 2012. An efficient synthesis of N-substituted indoles from indoline/indoline carboxylic acid via aromatization followed by C-N cross-coupling reaction by using nano copper oxide as a recyclable catalyst. Tetrahedron Lett. 53(24) 3061-3065. 

A novel procedure for the synthesis of an indole skeleton 81 was developed by Mori s group (Scheme 13).16e,16f Enantioselective allylic amination of 78 with A-sulfonated < r/ < -bromoaniline 79 followed by Heck cyclization of 80 provided chiral indoline 81. The treatment of a cyclohexenol derivative 78 with 79 in the presence of Pd2(dba)3-GHGl3 and ( )-BINAPO gave compound 80 with 84% ee in 75% yield. Total syntheses of (—)-tubifoline, (—)-dehydrotubifoline, and (—)-strychnine were achieved from compound 80. 

JPS 62,490(1973) gives an indoline synthesis which can be carried one step further (dehydrogenation described in this chapter) to give DMT derivatives. See JOC 41,1118(1976) for indoles from betaketosulfoxides. 

Sakamoto et al. reported the synthesis of hyellazole (245) and carazostatin (247) based on the benzannulation of indoles. This method involves an electrocyclization of the 3-(l,3-butadienyl)indoles 685, which derive from the indolin-3-one 686 and the phosphorus ylides 687 (Scheme 5.59). 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

Indolines are useful intermediates for the synthesis of indoles with substituents in the carbocyclic ring. In electrophilic substitutions, they behave like anilines the example shows A -acetylindoline undergoing regioselective 7-thallation. Indolines can be obtained easily from indoles by reduction (see section 17.8) and can be cleanly oxidised back to indoles using a variety of methods, including oxygen with cobalt catalysis (salcomine), hypochlorite/dimethylsulfide, Mn(III), and Au(III) compounds. 

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