Azepinones, formation

Another example of azepinone formation was in the synthesis of new tetracyclic com-ponnds 418 (eqnation 174). 

H-Azepin-2-one, 3-acetyl-synthesis, 7, 542-543 3/f-Azepin-2-one, 7-acetyl-synthesis, 7, 542-543 3H-Azepin-2-one, 3-acyl-rearrangements, 7, 505 3/f-Azepin-2-one, 3-acyl-2-alkoxy-formation, 7, 542-543 3H-Azepin-2-one, 1-alkyl-rearrangements, 7, 505 3/f-Azepin-2-one, N-alkyl-synthesis, 7, 511 Azepinones... 

A possible mechanism for the observed transformation includes the sequence outlined in Scheme 2.327 (i) propargyl (A) - allene (B) tautomerization, (ii) 8jt-cyclization (C), (iii) N-0 cleavage (diradical D), (iv) diradical recombination (cyclopropanone derivative E), and (v) one or two step cyclizations of the azadienyl cyclopropanone into azepinone F. The occurrence of cyclopropanones (type E), as intermediates, is supported by the formation, in some cases, of isoindoles (type I) (789) as minor products (Scheme 2.327) (139, 850, 851). 

Construction of the azepine ring by C-C bond formation. The Heck-type cyclization of amides 11, easily available by amide bond coupling (EDCI, DMAP) between the corresponding indolo- and pyrrolo-[2,3- 7]p)uidine-carboxylic acids and 2-iodobenzylamine, is effective in the presence of Pd(OAc)2/PPh3 catalyst and silver carbonate base and leads to excellent yields of the corresponding azepinones 12 (Equation (1) (2005TL8177)). 

Several azepine ring constructions have been reported using palladium catalyzed C-C bond formation. Palladium catalyzed cyclizations of substituted tryptamine derivatives 73 lead to benzo[d]pyrrolo[l,2-a]azepinones 74 (Equation (8) (2000JMC1050)). 

Palladium catalyzed reaction of iodo 84 with allene is an example of a 5 + 2 ring formation and gives access to the fused benzo[d]pyrrolo[l,2-fl]azepinone... 

A-Alkylation of azepinones has been discussed in Section 5.16.3.3.3. In many cases alkylation involves prior formation of the amide anion, which is readily generated by treating the lactam with strong base, e.g. NaH or Bu OK. 

Other light-induced ring closures to benzazepines include the intramolecular radical arylation of A-substituted enaminones (224) to hydrodibenz[6,[Pg.536]

The /V-acylaminals 136 can serve as substrates for the formation of fused azepinone derivatives on treatment with a catalytic amount of TiCh, although the reaction is sensitive to the nature of the R group. Thus, 138 was obtained from 136 (R = CH2OAc), but with R = Me in 136, the 6,6-fused system 137 resulted (Scheme 18) <1999TL7939>. 

Fig. 2. Stern-Volmer plot for the quenching of (+) cycloadduct 56, ( ) ene product 5 7, and (0) azepinone 58 formation from photoaddition of 3-ethoxy isoindolenone (50) to tetramethyl-ethylene by di-f- butyl nitroxide (DTBN)...

A key step in the asymmetric synthesis of the angiotensin converting enzyme inhibitor, benazepril HCl 32, was the reduction of the ketoester 28 with baker s yeast to afford the chiral a-hydroxy ester 29 in high chemical yield and ee. Formation of the benz[i]azepinone 31 directly from 29 proceeded in 42% yield (without racemization at C-3) or in 74% yield in two steps via 30, again with no racemization <03TA2239>. 

Electrophilic cyclization of the carbamate 55 resulted in formation, in moderate yield, of the xantheno[l,9-ci5 ]azepinone 56a, which could then be converted to the amine 56b by borane reduction <04SL2331>. 

One challenge of this reaction is the potential lii-electrocyclization of the product to afford the cyclobutene 76. However, by carrying out this reaction in flow the immediate removal of the product from the reactor minimized the unwanted side reaction. After evaluating reaction times between 1 and 200 minutes they observed a direct correlation of time and product ratio. The optimal reaction time was found to be 30 minutes which afforded a 51% yield of 3H-azepinone 61 and nearly no formation of the undesired product. 

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