Nitrogen-ring systems, seven-membered

Methods for the preparation of seven-membered nitrogen-ring systems by the nse of the intramolecular aza-Wittig reaction have increased in the last decade. This heterocycle is quite common in benzodiazepine derived alkaloids. This methodology has been applied for the first total synthesis of (-)-benzomalvin A (142) (Scheme 15.31). Reaction of the starting azide 138 with tributylphosphine leads to the formation of the phosphazene intermediate 139, which under the reaction conditions affords the benzodiazepine 141 in 58% yield via compound 140. Benzodiazepine 141 suffered subsequent transformations to afford (-)-benzomalvin A (142). 

Four tautomeric forms I -4 can be drawn for azacycloheptatriene and of these four tautomers only 1 ff-azepine ( ) is formally a fully conjugated system however, the chemistry of all four tautomers is covered in this section together with the three isomeric, fully conjugated, cyclopentazepines 5-7, in which nitrogen is located in the seven-membered ring, and their indeno analogs. 

This section treats seven-membered ring systems with maximum unsaturation containing within the ring two or more oxygen, sulfur or nitrogen atoms, or a combination of these.1... 

Systems of this type are still dominated by those containing a nitrogen atom, particularly with one or more rings fused to the seven-membered ring. The following material is divided into non-fused and fused examples. 

The central seven-membered ring of the TCAs imposes a 120° angle between the two flanking aromatic rings, in contradistinction to the flat ring system present in phenothiazine type neuroleptics (p. 237). The side chain nitrogen is predominantly proto-nated at physiological pH. 

Current work is focused on the benzoheteropines with the fused pyrrole (or indole), thiophene or furan rings, i.e., ortho-fused 6 + 7 + 5 ring systems with carbons only on the six-membered ring, one heteroatom on the five-membered ring and one or more heteroatoms on the seven-membered ring. The variety of heteroatoms is limited to nitrogen, oxygen and sulfur. Several examples of the related cyclic systems with the other heteroatom distribution or peri-fusion are briefly summarized in Section 4.3. The current first specialized review covers synthetic, reactivity and structural aspects reported from the late 1989 until 2007. 

As in more recent years, the chemistry of seven-membered ring systems has been dominated by the chemistry of oxygen heterocycles in the form of the marine toxins and, to a lesser extent, the antimalarial artemisinin. Indeed, if it were not for the interest in these systems it would have been a sparse year indeed. For this reason the division of this report will be into just three section, nitrogen, oxygen, and other systems. 

The presence of two or three adjacent nitrogen atoms distinguishes 1,2,4- from 1,2,3-triazoles. These systems could be fused with the thiazep-ine ring on the b, c, and d edges, but only the fusion of 1,2,4-triazoles on face d of the seven-membered ring is known. 

The only representative of this seven-membered ring system was obtained by a transamination reaction using a derivative of triazaboradecaline [Eq. (62)]. The boron atom and the two nitrogens of the triazaboradecaline (a system which is most suitable for further reactions, due to its stability) form part of the seven-membered ring 205> as depicted in structure 19. 

Alkaloids are classified according to their heterocyclic rings. For example, cocaine, a central nervous system stimulant, and atropine, a muscle relaxant, are examples of the tropane alkaloids in which a nitrogen appears in a bridge of a seven-membered ring structure. Nicotine, the addictive and toxic component of tobacco, is an example of the pyridine alkaloids in which a nitrogen appears as a member of a six atom aromatic ring. (Nicotine is an effective insecticide.) The addictive... 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

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