Seven-membered rings Friedel-Crafts reaction

These reactions are most successful for the preparation of six-membered rings, though five- and seven-membered rings have also been closed in this manner. For other Friedel-Crafts ring-closure reactions, see 11-13, 11-14, and 11-23. 

The total synthesis of frodosin B, which is a potentially useful drug for HIV, has been reported (Scheme 8.8). The key steps in the synthesis are a Friedel-Crafts reaction to form the seven-membered ring and a Diels-Alder reaction of nitroethylene to build the six-membered ring, thereby fixing the double bond in the proper position.44... 

This reflects a rather general tendency for the formation of six-membered rings in preference to five- and seven-membered rings in ring closure by intramolecular Friedel-Crafts reactions.38,39 Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. Entries 5-7 in Scheme 11.3 are examples of this type of reaction. 

Nearly all of the cyclization reactions covered in this section aim at formation of the seven-membered ring. A distinction can be made between acylations at pyrrole rings and Friedel-Crafts type cyclizations at benzene rings. 

Although the Friedel-Crafts reaction failed to produce the seven-membered ring in the 1-benzazepine series, the method has been successfully used to prepare 2-benzazepines. The first study by von Braun et al.,M however, showed that the reaction carried out with A-(2-phenylethyl)-glycine chloride (71, n = 2 R1 = S02Ph R2 = Cl) and aluminum chloride in nitrobenzene proceeded exothermically with evolution of carbon monoxide and hydrogen chloride to give 72 (R = S02Ph). Consequently,... 

Fovmlation can be carried out by means of the Gattermann reaction [98] or the Vilsmeier reaction [121 - 123], or by using ethyl orthoformate in the presence of a Friedel-Crafts catalyst [124]. In each case the 1-aldehyde is obtained. Azulene-l-aldehyde is less reactive than benzene aldehydes towards nucleophiles, presumably because any charge developed on the carbonyl carbon atom can be delocalised into the seven-membered ring [111,125 - 127]. 

In this work, the combination of cinchona-alkaloid-derived primary amine and Au(I) phosphine complex has been employed to effect two consecutive Friedel-Crafts-type reactions of pyrrole in one pot to furnish 2,3-annulated pyrroles containing a seven-membered ring (eq 1) This reaction proceeds through initial asymmetric 1,4-addition of p)rrole to enones catalyzed by the primary amine followed by an intramolecular 7-c/ido-dig cycliza-tion catalyzed by the Au(I) phosphine complex. 

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