Dihydroindole derivative

The photocyclization of N-aryl enamines derived from cyclic or acyclic ketones proceeds under mild conditions to produce 2,3-dihydroindole derivatives (178b). The stereochemistry of the products is predominantly trans, which follows from a photochemical electrocyclic process which should take place in a conrotatory manner (178c,I78d). However, the presence of some cis products is not as easily explained. 

The copper catalyzed formation of carbon-nitrogen bonds was exploited in the conversion of 2-(3 -aminopropyl)-bromobenzene to tetrahydro-isoquinoline (4.17.), The coupling, which proceeded readily already at 40 °C in the presence of diethyl salicylamide, was also efficient in the formation of dihydroindole derivatives.20... 

Some synthetically useful reactions not covered in the above sections should be mentioned. An unusual heterocyclization to form indole derivatives is found in the aminomercuration of allylenaminones (equation 130).261 Palladium(II)-catalyzed cyclizations of o-allyl- and -vinyl-anilines and amino-quinones are discussed elsewhere.30 Other electrophiles used to form dihydroindole derivatives include phenylselenenyl chloride216 and methyl(bismethylthio)sulfonium salts.231... 

CB2029). The analogous cyclization is characteristic also of 2,3-dihydroindole derivatives (189 — 190) (60CB2029). 

Keywords /7-phenyl enaminone, inclusion complex, photocyclization, dihydroindole derivative... 

Rezaie and Bremner reported the synthesis of tricyclic 1,4-thiazepines by ring contraction. OT-Cyclophane lactam 237 was treated with Ar-bromosuccinimide and azoisobutyronitrile to yield 47% of dihydroindole derivative 238, as the major product next to side products 239-242 (Scheme 42). The same reaction condition was applied for the ester derivative of 237 (X = COOCH3>, but with longer reaction time. This resulted in indole analogues 240-242 (X = COOCH3) without the formation of dihydroindole derivatives. Bromination on the aromatic ring was observed prior to the intramolecular cyclization. The exact mechanism has not been resolved, but a possible reaction sequence could be... 

The zero-bond in a bicyclic system with certain structural features can be cleaved by the von Braun degradation. In this case a nitrogen atom must be in a bridgehead position. For example, ring cleavage of the dihydroindole derivative, VIII/118, gives benzazocines VIII/119 and VIII/120 in good yields [70] [71], Scheme VIII/22. 

NHCH2), which exhibits a typical dihydroindole UV-spectrum, and which, in contrast to mitraphylline, couples with diazotized sulfanilic acid. The formation of a dihydroindole derivative, and not an indole derivative, in this reduction is an indication, though not perhaps a conclusive one, that the molecule is a 3,3-disubstituted oxindole hence, structure V is invalidated (57). 

The first, and hitherto only, synthesis of lysergic acid was effected by the research group of Kornfeld et al. (50, 26). In this particular synthesis a X-acyl-2,3-dihydroindole derivative was used as starting material, thus allowing the formation of rings C and D by classical methods. Dehydrogenation of the 2,3-dihydroindole system to the indole system was only effected in the last stage so that the formation of the benz[c,d]-indoline system was prevented. 

In the partial synthesis of Khuong-Huu and co-workers (205), corynan-theidine (105) was reduced with NaBFL, in the presence of trifluoroacetic acid (TFA) to the corresponding 2a,7a-dihydro derivative 106, which by NaOMe/MeOH treatment was transformed to the corresponding acetal 107. Benzenesulfonylation of compound 107 afforded compound 108. Photosensitized oxidation of 108 in the presence of rose bengal and KCN yielded compound 109, which, via the corresponding iminium ion, was claimed to cyclize to Afa-benzenesulfonyl-2a,7a,19,20a-tetrahydro-10-de-soxysarpagine (110) (a dihydroindole derivative, which, however, could not be transformed to an indole derivative) (Scheme 6). It is noteworthy that... 

The periwinkle plant (Vinca rosa), which is indigenous to Florida, has yielded several indole alkaloids. Two with antineoplastic properties are the dimeric indole-dihydroindole derivatives vinblastine (Velban ) and vincristine (Oncovin ). These agents bind to tubulin, arresting mitosis at the metaphase. 

Samarium diiodide-induced intermolecular coupling of aldehydes and ketones to indoles with an electron-withdrawing group at the 3-position of the indole have also been reported [19]. Carbonyl compounds including acetone, acetophenone, benzophenone, pivaldehyde, and isobutyraldehyde added to the C-2 position of the indole to give the thermodynamically stable trani-dihydroindole derivatives 27. 

Blot V, Reissig HU (2006) Highly substituted dihydroindole derivatives by intermolecular couplings of samarium ketyls and indoles. Synlett 2763-2766... 

Luo and Wang [65] showed that the intermediate palladium(II) species can be trapped by a variety of organozinc chlorides to give exclusively the corresponding (Z)-3-methylene-2,3-dihydroindole derivatives 62-69 in fair to good yields (Scheme 6.18). 

Condensation of tryptamines (14,44) with indole-3-acetic acid (45) provides N-[2-(indol-3-yl)ethyl]indole-3-acetamides (46a, 81% 46b, 98%). Reduction of 46a with EtsSiH/TFA produces bis-2,3-dihydroindole derivative (47a, 90%), while the reduction with NaBHsCN gives rise to 47a (42%) and 48 (45%), a product reduced selectively at the tryptamine pyrrole part. 

Raper suggested that the red product obtained on oxidation of 3,4-dihydroxyphenylalanine (DOPA, 3) was a cyclic 2,3-dihydroindole derivative, namely indoline-5,6-quinone-2-carboxylic acid (4)[14]. It was originally believed that (4) was identical with hallachrome, a red pigment that can be isolated from the marine worm Halla parthenopaea Costa [15]. 

These novel dihydroindole derivatives have been isolated from plants of the genus Kopsia, and have proven to be rich sources of novel alkaloids with intriguing carbon skeletons that display a wide variety of interesting activities. ... 

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