Seven-membered cyclic compounds

Russell and coworkers147 had found that treatment of dimsyl anion 88 or of a similar methylsulfonyl carbanion with 1,2-, 1,3- and 1,4-dicarboxylic acid esters can give five- to seven-membered cyclic compounds. By this type of cyclization, they prepared ninhydrin hydrate 106 from diethyl phthalate148,149. 

The five- and six-membered isopropylidene 2-azacycloalkylidenemalo-nates (468, n = 0 and 1, R2 = R4 = H) were prepared in 94% and 76% yields, respectively, in the reactions of Meldrum s acid (421) and the appropriate cyclic lactim ether (465, n = 0 and 1, R2 = H, R5 = OMe) in the presence of triethylamine in boiling benzene overnight (79JOC3089). Under these conditions, caprolactim methyl ether did not react, but if the latter reaction was carried out in the presence of acetic acid and piperidine in boiling benzene overnight, a seven-membered cyclic compound (468, n = 2, R2 = R4 = H) was obtained in 58% yield (79JOC3089). 

The physical properties of the borepins mentioned above have been compared with those of other seven-membered cyclic compounds. It was concluded that a ring current is present in (56), causing a deshielding of its protons in the NMR spectrum. Benzo and dithieno fused borepins have UV spectra very similar to the correspondingly fused tropones, thus suggesting similar electronic structures. 

Cohydrolysis of 1,2-diethoxytetramethyldisilane with dimethyldiethoxy-silane yields as the major product a seven-membered cyclic compound (XI) in which two dimethylsiloxy units are incorporated, but no traces of a five-membered product (XII) (109). 

The syn- versus anti- displacements and the stereoselectivity of the 5 1 reactions (5 2 reactions with an internal nucleophile), which are widely used for making three- to seven-membered cyclic compounds, " and a critical discussion of the factors affecting the chemical glycosylation reaction, which concludes that the kinetic anomeric effect is not responsible for the selectivity in these reactions, have been reviewed. 

An important application of the potential for bis-alkylation is the use of a dihalide 7 as alkylating agent. This variant allows for the synthesis of cyclic compounds 8 by this route, mainly five- to seven-membered ring compounds have been prepared ... 

Mullins71 have shown that the seven-membered cyclic sulfone (38) can be converted photochemically at 254 nm, as well as by thermolysis, into a mixture of 39 and 40. Interestingly, in this series, compound 40, the result of hydrogen transfer (disproportionation) in the presumed intermediate biradical, remained the major product when different solvents and different wavelengths were employed for the irradiation. 

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

Similar to S2C12 or Se2Cl2, which react with [Ti(C5H5)2S5] and [Ti(C5H5)2Se5] to produce cyclic seven-membered chalcogen compounds (S7, l,2-Se2S5, and... 

Synthesis ofSeven-membered Cyclic Nitronates Cyclic nitronates containing more than four carbon atoms in the ring remain virtually unknown. Convenient procedures for the synthesis of these compounds are lacking. In particular, intramolecular alkylation of 5-bromo-l-nitropentane affords nitrocy-clopentane rather than the corresponding seven-membered cyclic nitronate (169) (Scheme 3.48). 

Desymmetrization of a seven-membered cyclic meso compound, followed by a metallo-ene reaction, provides ready access to the trans-hydroazulene skeleton (Scheme 8E.15) [69]. By using BINAP in preference to BINAPO ligand, which gave a lower enantioselectivity (70% ee), two alkylation products were obtained in differential enantioselectivities. The high enantiopurity of the major product 106 may be the consequence of a subsequent kinetic resolution because the second ionization, followed by proton loss from enf-106, involved a matched event. 

Seven-membered rings with four and more heteroatoms attract attention because of their biological activity. An important class of compounds is that of the seven-membered cyclic polysulfides with five sulfur atoms, which are well known as lenthionine and varacin. 

With adiponitrile, an open-chain dinitrile, however, such cyclization leading to a seven-membered cyclic imine occurs to a much lesser extent (see, e.g., eq. 7.25). The hydrogenative cyclizations have been utilized for the synthesis of pyrrolidine and piperidine derivatives from 1,2- and 1,3-dicyano compounds.118,119... 

In the case of McycKc systems (133—140) there are not yet enough data available for a detailed discussion to be given. The barriers obtained for the bicyclo [2.2.2]octane (133, 134) and the bicyclo[3.3.1]nonane (139, 140) compounds are in the range expected for the corresponding mono-cyclic systems. In the case of the bicyclo[3.2.2]nonane derivatives 135 and 136 the inversion barriers are larger than in the seven-membered ring compounds 127 and 128. 

We shall illustrate this with Prestwich s synthesis11 of the natural anti-cancer compound (—)-aplysistatin 69. This interesting compound with a seven-membered cyclic ether and a bromine atom proclaiming its marine origin is probably made in nature by a polyolefin cyclisation and that strategy was used in the synthesis. The alkene must be removed 70 before the cyclisation can be reversed. The stereochemistry of the extra centre in 70 is unimportant until the realisation that it can be made by alkylation of a hydroxylactone 71 whose stereochemistry must be anti. 

The 1,3-dipolar cycloaddition follows with the regiochemistry shown 146a and the product is a bicyclic compound 147 with an N-0 single bond that is easily reduced to give a seven-membered cyclic aminoketone 148 with stereochemistry. 

Preparation of the seven-membered cyclic model compounds is outlined in Eq. 3. Racemic 2,4-pentanediol was first converted to the racemic ditosylate, which was then treated with catechol... 

We next became interested in the possibility of extending this to a seven-membered cyclic ketal. It was immediately recognized that if the yield of the cyclic compound were not nearly quantitative, the resulting polymer would be cross-linked. In our previous work (16) the cis- and trans-l,2-bis (hydroxymethyl)-cyclohexane were prepared. When either the cis- or trans-diol was condensed with 1,4-cyclohexanedione, a 92% yield of the corresponding model compound was obtained. 

In such syntheses of -lactams a seven-membered cyclic a-adduct (133) is formed from (133) the 3-lactam system (134) results by transannular acyl transfer. As a consequence, the Ugi reaction has been used in numerous syntheses of 3-lactam antibiotics and related compounds." ... 

The ease of ring formation helped us to make five-membered cyclic acetals from ketones and a seven-membered heterocyclic compound (see Chapter 6). In this chapter we have seen how three-membered epoxides are formed. Ring formation is generally preferred to bimolecular reactions forming open chain compounds providing that the ring is three-, five-, six-, or seven-membered. Four-membered ring are a special case discussed in Chapter 29 where all these points are developed more fully. 

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