Indoles quinolizines

In a somewhat different approach, Asahi Glass KK have claimed [132] that the addition of a transition metal salt (e. g., cobalt-, copper-, lead-, cerium-, bismuth-, manganese-, chromium-, iron- chloride, or cobalt fluoride, etc.) greatly improves the ECF production of perfluorobicyclic compounds, derived from naphthalene, indene, benzofuran, phthalimide, indole, quinolizine, benzotriazole, and quinoline. 

CN (2a,6a,8a,9aa)-l/7-Indole-3-carboxylic acid octahydro-3-oxo-2,6-methano-2/f-quinolizin-8-yl ester base... 

Enamine fragments present in quinolizine systems show their expected behavior as nucleophiles. For example, reaction of the indoloquinolizine derivative 78 with formaldehyde at room temperature afforded the unstable hydroxymethyl derivative 79, while reflux of 78 with formaldehyde under acidic conditions led to indole deprotection and allowed the isolation of the pentacyclic derivative 80 (Scheme 4) <2001TL7237>. 

The quinolizine derivative 276 was obtained through a Friedel-Crafts acylation reaction onto the C-3 indole position of 275. This precursor was obtained by a sequence comprising a Fischer cyclization leading to 5-methyl-2-(2-pyridyl)indole 274, catalytic hydrogenation, N-alkylation with ethyl bromoacetate, and hydrolysis of the ester group (Scheme 59) <1999FA479>. 

Utilizing Wenkert s cyclization process, a number of new approaches have been elaborated for the synthesis of simple indolo[2,3-a]quinolizine derivatives. For example, treatment of JV-[2-(indol-3-yl)ethyl]piperidine (V-oxide (134) with trifluoroacetic anhydride gave piperideinium intermediate 135 in a Polonovski-type reaction, which could be cyclized in acidic medium to ( )-l (101). 

Results and data gathered on mass spectroscopy of various indole alkaloids have been summarized by Hesse (320). The derivation of the characteristic fragments of indolo[2,3-a]quinolizidines has been interpreted by Gribble and Nelson (321), who investigated C-3, C-5, C-6, C-20, and C-21 deuterated derivatives of octahydroindolo[2,3-a]quinolizine (1). Kametani et al. have observed and proved, with labeled compounds, a methyl transfer from the ester function of reserpine derivatives to the basic nitrogen atom during mass-spectroscopic measurement (322). 

A vinylogous indole derivative like 264 reacts with DMAD to give a phenanthridone derivative (267) (Scheme 42). An interesting case of the reaction of an enamine system is observed in the case of the 2H-pyrrolizine (268), which gives a mixture of the azepino[2,l,7-crflpyrrolizine derivative (271) and the 1 1 adduct (275) (Scheme 43) 164,165 reaction of 3-ethoxycarbonylmethylene-3 -pyrrolizine, on the other hand, yields a pyrrolo[2,l,5-croom temperature, the primary adduct (278) is isolated and undergoes thermal cyclization to 281 (Scheme 44). ... 

Indolizine is an important ring system in view of its similarity to indole. Like indole, it has a delocalized 10ir-electron system that confers aromaticity, in contrast to its analogs, pyrrolizine and quinolizine. Consequently, it has a theoretical and practical interest. 

The 13C shifts of the octahydroindolo[2,3-a]quinolizine [363] provide an important basis for the analysis of the 13C NMR spectra of the yohimbine and related group of alkaloids. The shifts shown in [363] (208) represent a revision of those originally made for C(9) and C(10) (225) since these were based on misassigned signals in the spectrum of indole itself (see Section XII.A). In addition, Wenkert (226) has suggested the interchange of the shifts for C(4) and C(6) and the correction has been made in [363]. 

C23H30Oy, 23637-79-8) sec Gestrinone cis-l-ethyl-l-(2-hydroxy-2-ethoxycarhonylethyl)-l,23,4,6,7,12,12b-octahydroindolo 23-o]quinolizine (C22Hk,N20, 43184-10-7) see Vinburnine 5- ethyI(2-hydroxyethyl)amino]-2-pentanone (C,2Hh,N02 74509-79-8) see Hydroxychloroquine 7-ethyl-3-(2-hydroxyethyl)indole (Ci2H,5NO 41340-36-7) see Etodolac... 

Tetrabenazine or 2-oxo-3-isobutyl-9,10-dimethoxyhexahydrobenzo-[a]quinolizine (LVI) (229), which has apparently emanated from work related to the synthesis of emetine, has obtained much attention recently. In spite of the absence of an indole ring system, it seems to possess sedative reserpine-like activity. Tetrabenazine has been pharmacologically studied in great detail (230). 

Ortho lithiation of 2-substituted indoles occurs readily, but fragmentation to an alkynylanilide may occur in some instances. The use of a 2-pyridyl group to facilitate the 3-lithiation of an indole was recently used in a synthesis of some indolo[2,3-a]quinolizine alkaloids an example is the synthesis of flavopereirine (22 Scheme 29). 

Often indolo[2,3-fl]quinolizines (e.g., 109) form the skeletal basis for work in the indole and oxindole alkaloid field. These are most often prepared from pyridinyl- (108) or quinolinylindolethanes via reduction with metal hydrides. The tetrahydropyridines then undergo acid-catalyzed ring closure, often giving mixtures of several compounds (109,110, 111). 

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