Azepinoindoles

H-Azepinium perchlorate, 6,7-dihydro-formation, 7, 512 Azepinoindoles synthesis, 7, 537 Azepin-2-one, hexahydro-chlorination, 7, 517 synthesis, 7, 530 Azepin-2-one, 3-hydroxy-methylation, 7, 518... 

Intramolecular oxidative palladium couplings of alkenylamino indoles allow the preparation of azepinoindole derivatives in high yields (2005MI707). 

The preparation of lactams 68 and 69 from the corresponding dichloramides 66 and 67 in acetonitrile under UV light in 43% and 42% yields, respectively, has been reported. But with dichloramide 67, carried out under similar conditions in aqueous acetonitrile, in addition to the mixture of diastereoisomers of azocinoindole 70 (54%), azepinoindole 71 (25%) was also obtained (92JCS(P1)823, 92JCS(P1)797 Scheme 21). 

Formation of l-aryl-l//-azepines is rare and occurs only with those arylnitrenes made sufficiently electrophilic by an electron-withdrawing, e.g. CN, N02 or CF3, ortho or para substituent. Even so, these docile nitrenes attack only electron-enriched arenes (e.g. mesity-lene or Af,Af-dimethylaniline) and are of minor synthetic importance (B-73MI51600). More reactive are 7r-deficient heteroarylnitrenes, and moderate yields (15-40%) of 1-heteroaryl-l//-azepines, e.g. (228 R=4,6-dimethoxy-l,3,5-triazin-2-yl), may be obtained by the photodecomposition of 2-azido-4,6-dimethoxy-l,3,5-triazine in a variety of aromatic substrates (81BCJ301). Interestingly, intramolecular insertion of arylnitrenes into arenes is more common and has been used for the synthesis of fused azepines, e.g. the azepinoindoles (229) from o-azidodiphenylmethanes (81JCS(P1)1132). 

TMS)3SiH-mediated 7-ewdo-trig cyclization of bromides was employed as the key step for the construction of the azepinoindole tricyclic core of the Stemona alkaloid94. 

Benzo-fused azoniaazulenes were also reported. o-Benzylphenyl azide 260 (92%) was obtained by diazotization of 259 followed by treatment with sodium azide. Decomposition of the azide 260 at 190°C gave azepinoindole 261, which was hydrolyzed to afford dihydroazepinoindolone 262 (90%). Dehydrogenation of262 with dichlorodicyanobenzoquinone yielded azepi-... 

An asymmetric version of the total synthesis of clavicipitic acid was reported by Yokoyama et al. [82-84]. As illustrated in Scheme 29 asymmetric hydrogenation of the known 4-bromodehydrotryptophan 163 was best achieved (94% ee) using the optically active Monsanto bidentate phosphine, DIPAMP. The Heck vinylation in the presence of Ag,CO, gave the C(4)-vinylated product 168 without racemization. Treatment of 168 with HCl-EtOAc effected the cyclization to give the tricyclic azepinoindole 170 (62%), al.- ig with diene 169 (29%). Cleavage of the sulfonamide (Mg/MeOH) afforded 171 which underwent saponification (KOH) to give optically active clavicipitic acid (167). 

As described in Section 4.1. (Scheme 29), in the frequently reviewed synthesis of N-acetyl ( )-clavicipitic acid methyl ester (167) by Hegedus [80, 81], intramolecular aminopalladation of 164 was accomplished by a Pd(n)-catalyzed process lo give the tricyclic azepinoindole 16S. 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Bennasar also recently extended their interest in the cyclization of A -alkenyl substituted 2-indolylacyl radicals towards the annulation of larger rings [126]. A 7-endo-mg closure was observed when brotnovinyl substituted seleno ester 237 was treated with excess tin hydride in EtaB. In addition to the desired azepino[3,2-I>] indole 238, the 6-exo cyclization product 239 was observed as the minor product, with both products showing no evidence of the bromine atom in their strucmres. Previous attempts at this cyclization using a tethered allyl moiety, rather than the 2-bromo-2-propenyl tether, also gave the azepinoindole but only as the minor product. 

A number of azepinoindole syntheses have been described. Reaction of tryptamine or N -methyl-tryptamine with methyl chloropyruvate affords the /S-carbolines (274 R = H, Me) which on heating or treatment with sodium acetate in acetic acid rearrange to respectively, (276 R = H, Me) and... 

King GS, Waight ES, Mantle PG, Szczyrbak CA (1977) The Structure of Clavicipitic Acid, an Azepinoindole Derivative from Claviceps fusiformis. J Chem Soc Perkin Trans 1 2099... 

The enantiomers of azepinoindole and its 7V-desmethyl metabolites were well resolved on a 8-cyclodextrin-modified silica column (A = 231 run). A 1/99 r-butyl alcohol/water (10 mM sodium phosphate buffer at pH 7 with 15 mM jS-cyclodextrin and 2 mM triethylamine) mobile phase was used to generate the chiral separation. The assay calibration range covered 100-500 ng/mL. Peaks were somewhat tailed. Elution was complete in 25 min [584]. 

An example of a rhodium(I)-catalyzed cycloisomerization of nitrogen-tethered indole-alkylidenecyclopropanes 13 was reported allowing for ready access to azepinoindole derivatives 14, which are tetrahydro-P-carboline homologs (13CEJ13668). 

An interesting transannular reductive rearrangement of bridged cyclic a-amino ketone 18 under classic Clemmensen conditions was developed, which provided the all-tram ring-fused azepinoindole derivative 19 as the sole isolated product (13JOC6154). 

Aube and Golden (dJ) have demonstrated the utility of a combined intramolecular Diels-Alder/intramolecular Schmidt reaction to construct the azepinoindole intermediate 110 (Scheme 5). The Lewis add-catalyzed tandem intramolecular Diels-Alder/Schmidt reaction required azidodiene 109, which was prepared after five steps as a 85 15 mixture of diastereoisomers from diene 108 via a modified Julia olefination between aldehyde... 

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