Ring closures seven-membered

Finally, examine the transition states for closure of the Ci enolate to the 7-membered ring product, and of the C3 enolate to the 5-membered ring product. Calculate activation energy barriers from their respective enolates. Which ring closure (to the five or the seven-membered ring) occurs more readily ... 

The intramolecular variant of the Friedel-Crafts alkylation is also synthetically useful, especially for the closure of six-membered rings, e.g. the synthesis of tetraline 8 but five- and seven-membered ring products are also accessible ... 

This method has been used to close rings of from three n = 0) to seven members, although five-membered ring closures proceed in highest yields. Another ringclosing method involves internal alkylation. ... 

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. 

This methodology has been applied to the diastereoselective synthesis of the pyrrolizidine alkaloid 196 from 194 via 195 (Scheme 15.62) [123], Furthermore, the diastereoselectivity of these reactions for different dipolarophiles has been investigated in detail [124] and could be extended to a ring closure to seven-membered nitrogen heterocycles [125,126]. 

Another case of an or//io-substituent steric-assistance effect has been described (90JOC3891) for the rather rare situation of a ring-chain equilibrium involving a seven-membered ring closure. The equilibrium was ob-... 

Structurally similar seven-membered dihydro-l,2,7-thiadiazepine 69 and l,2,7-thiadiazepan-3,6-dione 70 were obtained by an unexpected dimerization of acetoxime 71 (1997BSB605) and a ring closure of dicarboxamide 72 (1995CC1449). Curiously, the reaction of sulfur monochloride containing two sulfur atoms in both cases led to the insertion of one sulfur atom to the seven-membered ling or three sulfur atoms to the by-product 73 in the second reaction, but not two sulfurs (Scheme 36). 

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. 

The product is omega-caprolactone, a seven membered lactone that cannot be made by an intramolecular ring closure. 

In the synthesis of the marine neurotoxin hemibrevetoxin B 121, dienetriol 119 was used as an RCM substrate for elaboration of the seven-membered A ring in 121 (Scheme 21). While catalyst B was ineffective in this case, the ring closure occurred smoothly with catalyst G providing the tetracyclic intermediate 120 in high yield. 

The seven membered core of iboga alkaloids has also been constructed in an intramolecular Heck reaction. Insertion of a pendant olefin into the indolylpalladium complex, formed from iodoindole, followed by / -hydride elimination gave the complex framework of the natural product (5.5.), Although the insertion step could have led to the formation of a six membered ring, the formed palladium complex would have contained a quaternary carbon center in the -position, blocking the closure of the catalytic cycle under the applied conditions.5... 

The palladium catalyzed intramolecular nucleophilic substitution of allyl alcohol derivatives (Tsuji-Trost reaction) has successfully been extended to the closure of a seven membered ring. The coupling of the allyl alcohol unit and the enamide was the key step in the preparation of the natural product claviciptic acid (5.14.),14... 

Tethering an iodobenzene and a furane moiety through a y0-lactam led to the formation of a unique tetracyclic y0-lactam derivative (5.17.). Oxidative addition followed by the carbopalladation of the furane ring resulted in the closure of the seven membered core in a so called heteroaryl Heck reaction "... 

The palladium catalysed ring closure of the A-(2 -bromobcnzyl)-naphthylamine derivative shown in 5.18. could in principle occur either in the 2-position or in the 8-position of the naphthalene ring giving rise to the formation of a six or a seven membered ring respectively. Surprisingly the latter case is favoured in most cases, unless there is a bulky substituent in position 7 of the naphthalene ring. This finding, where preference of the observed reaction path is explained by the intramolecular coordination of the benzylamino function to the palladium, has been successfully exploited in the preparation of a series of naphthobenzazepines.17... 

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