Ether cyclization

Benzene- 1,2-diacetonitriles e.g. 19, in the presence of hydrogen bromide in acetic acid, or in diethyl ether, cyclize to 4-bromo-l //-3-benzazepin-2-amines, e.g. 20a.41,42 l//-Naphtho[2,3-t/]azepines, e.g. 22a, are prepared in a similar manner from naphthalene-2,3-diacetonitriles, e.g. 21.41 Replacement of hydrogen bromide by hydrogen iodide yields the corresponding 4-iodo derivatives, e.g. 20b and 22b. 

Related O-TBS and O-benzyl ethers cyclize with loss of the ether substituent. 

Scheme 18 Synthesis of C-glycals based on oxocarbenium ion-enol ether cyclization.

Boger and co-workers performed a detailed study on the effect of substrate structural features on the 17-membered ring macrolactamization. It was found that the substituent at the remote C4 aryl position had a profound effect on the rate and yield of the cyclization. Substrates bearing either a free phenol or no substituent were found to cyclize more efficiently, whereas those bearing methyl or benzyl ethers cyclized considerably less efficiently (Table 1)J5 ... 

The mechanism of the trimethylsilyl enol ether cyclization may involve formation of a palladium enol-ate which adds to the double bond. However, another mechanism is also possible involving attack of a palladium(II)-alkene complex upon the silyl enol ether double bond. 

Iodolactonization of y, o-unsaturated alcohols results in preferential formation of tram-2, 5-disubstituted tetrahydrofuranes. However, the corresponding benzyl ethers cyclize preferentially to the cis-isomers. The alkyl group must be bulky enough to exert a steric effect, but not to prevent cyclization. Substituted benzyl ethers are particularly useful. Examples of this steric control are illustrated for the preparation of tram- and c/s-linalyl oxide (equations I and II).10... 

Fukuzawa A, Aye M, Takasugi Y, Nakamura M, Tamura M, Murai A (1994) Enzymatic Bromo-ether Cyclization of Laurediols with Bromopeioxidase. Chem Lett 2307... 

Benzyl esters, cyclization-hydrosilylation, 11, 386-387 Benzyl ethers, cyclization-hydrosilylation, 11, 386-387 Benzyl groups, C-H bond silylation, 10, 240 Benzylic alcohols, catalytic alkylation, 11, 146 Benzylic carbon-hydrogen bonds borylation, 9, 174... 

Scheme 10.13 Dialkylammonium and crown ether cyclizations via alkene metathesis.

Iodocyclization. y,8-Unsaturated alcohols or ethers cyclize to tetrahydrofuranes on... 

Vinyl ethers cyclize with ketenes to cyclobutanones (239). 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

Figure 11-16. Thermal ether cyclizations Lewis acid catalyzed ether cyclizations,...

Other researchers have also investigated the involvement of zwitterions in the cyclization of the dienone (162) to give bicyclic products in the presence of electron-rich ethenes. The key reaction is the c/Xtran -isomerism of the enone to afford the highly reactive dienone (163) which cyclises to an oxyallyl intermediate that reacts with the ethenes e.g. vinyl ethers). Cyclization within the resultant intermediate, possibly a zwitterion e.g. 164), can account for the formation of both the tricyclic ether (165) or the bridged ketone (166). The yields obtained are shown for the appropriate structures. The reaction also takes place with alkenes and, for example, using 2-methylpropene the adduct (167) is formed. 

X. fran.v-Pd(NH3)2Cl2/f-BuOH isomerizes allyl ethers to vinyl ethers that can then be hydrolyzed in 90% yield, but in the presence of an a-hydroxy group the intermediate vinyl ether cyclizes to an acetal. This reagent does not affect benzylidene acetals. 

Oxazolidines are obtained in good to excellent yields by the palladium(II)-catalyzed cyclization of A-Boc protected iV-allyl-A -hydroxymethylamines (191) <94CC357>. The palladium species is regenerated by molecular oxygen in DMSO (Scheme 94). Allyl carbamoylmethyl ethers cyclize to oxazolidines by reaction with mercuric acetate <89H(28)663>. Silver triflate catalyzes the cyclization of (9-propargyl isoureas to 4-alkylidene-oxazolidines with high diastereoselectivity <88CC1175>. 

Included in this chapter are ring-forming reactions between an azide and a thio ether. Cyclizations involving azides have been reviewed [35IS]. 

In the case of (bromomcthyl)dimethylsilyl allyl ethers, cyclization of 4-substituted derivatives gives l,5-/rw .f-disubstituted products in accord with the theoretical prediction1. Treatment of the ethers with tributyltin hydride in a free-radical process, followed by successive oxidation with hydrogen peroxide, gives the corresponding 1.3-diols with high stereoselectivity30. The stereoselectivity improves if the bulk of the C-4 substituent is increased. 

On treatment with PtCl2 under CO in toluene o-alkynylaryl alkoxymethyl ethers cyclize to afford benzofurans, by transfer of the alkocymethyl group to C-3 ... 

The Naito group has also prepared pyrrolidines [23] on solid phase by a combination of intermolecular radical addition to alkene 43 (Scheme 10) followed by intramolecular oxime ether cyclization to yield 44. These reactions proceeded sluggishly with triethylborane at room temperature, while the analogous solution-phase process was kinetically much faster. Radical additions to the phenylsulfonyl oxime ether 45 were reported by Jeon et al. [24]. Yields were better with primary and secondary alkyl iodides, and the tandem cyclization sequence with iodide 46 to afford bicyclic 47 was also accomplished, albeit in modest yield. 

Pyrolysis of tri-, tetra-, and penta-chlorobenzenes affords mixtures of chlorinated dibenzofurans and dibenzo-p-dioxins, " and chlorinated diphenyl ethers cyclize in the presence of palladium acetate to polychloro-dibenzofurans/ The action of malononitrile on tetrahydroxy-p-benzoquinone leads to the benzo-difuran (79), contrary to a previous report/ The acid-catalysed condensation of quinones with phenols has been studied p-benzoquinone and resorcinol, for example, afford compound (80)/ Naphtho[2,3- >]furan-4,9-diones (81 R = Me or Ph R = Ac, Bz, C02Et, or CN) are obtained from 2,3-dichloronaphtho-1,4-quinone and compounds R COCHaR in DMF that contains potassium fluoride/ The action of mineral acids on p-benzoquinone produces a mixture of complex benzofurans, which includes (82) and (83)/ Bases convert the ben-zofuranone (84) into the tetrameric compound (85), contrary to an earlier... 

Scheme 13 shows additional examples of constructions of four-carbon chains functionalized appropriately for condensation to pyrroles. Af,Af-bis(trimethylsilyl)propargyl amines can be converted to ketones or esters by lithiation and acylation. These compounds then undergo cuprate addition. The resulting allenyl silyl ethers cyclize to pyrroles on treatment with acid <93T4603). 

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