Aza-Nazarov cyclization cascades

Benzamides with tethered acetal groups undergo reactions in CF₃SO₃H to give ring-fused isoindolinones by a cyclization cascade. The reaction initially forms an N-acyliminium ion which then gives the isoindolinone by the aza-Nazarov reaction. An unusual variant also cyclizes at the allylic position.     

Acid-catalyzed cyclization of epoxyallylsilanes. An unusual rearrangement cyclization process

[reaction: see text]. A new route for the synthesis of epoxyallylsilanes bearing the phenyldimethylsilyl group is reported that involves silylcupration of allene, conjugate addition to enones, and sulfur-ylide-mediated epoxidation. The Lewis acid-catalyzed cyclization of these substrates is presented. The expected normal products derived from 5-exo and/or 6-endo attack are not observed; instead, methylenecyclohexanols resulting from a tandem rearrangement-cyclization process are formed.     

Unexpected Prins cyclization: iron-promoted cyclization/hydration of alkynyl-dimethyl acetals

Unexpected products containing acyl-substituted unsaturated seven-membered carbocycle were synthesized by FeCl₃-promoted intramolecular Prins cyclization of alkynyl-dimethylacetals in good yields. It is remarkable that the synthesized 7-exocyclic vinyl cations generated as a result of Prins-type cyclization were trapped by H₂O (no halogen ion) in CH₂Cl₂ to give the corresponding enol derivatives. Those enol derivatives underwent enol-keto tautomerism and then eliminated one molecule of MeOH to give the corresponding acyl-substituted unsaturated seven-membered carbocycle.     

Polyene cyclization : cyclization studies on an acyclic furanoditerpene and its epoxide

Reaction of an acyclic diterpene alcohol 1c with chlorotrimethylsilane and sodium iodide or SnCl₄ furnishes compounds 7 and 8. This cyclization is reminiscent of the biosynthesis of pallescensins E-G - an analogous compounds in sesquiterpenoids. Reaction of the epoxide 2 with SnCl₄ furnishes only the acyclic compounds 12, 13, 14a, 14 c and 15a. Photolysis of 2 results in the formation of (4+2) photocycloaduct 21.     

An unusual reductive cyclization

Li-NH₃ reduction of 1α-Ethynyl-1β-hydroxy-6-oxo-8a-methyl-1,2,3,4,6,7,8,8a octahydronaphthalene 5 furnishes, in addition to reported products, the tricyclic compound $\text{8}$.     

Organomediated Morita-Baylis-Hillman cyclization reactions

We have developed the Morita-Baylis-Hillman reaction to include, for the first time in a completely organomediated process, intramolecular examples bearing allylic leaving groups as the electrophilic partner providing a facile, high yielding, straightforward synthesis of densely functionalized cyclic molecules.     

Conjugate addition-initiated Nazarov cyclization

A reaction sequence involving the 1,6-conjugate addition of a nucleophile to a dienyl diketone followed by Nazarov cyclization is described. Several nucleophiles are identified as competent initiators for the sequence. A different reaction outcome is observed when catalytic amounts of nucleophile are employed, involving elimination of the nucleophile after the electrocyclization.     

The 5-hexenyl cyclization

The cyclization of the 5-hexenyl radical to form the cyclopentylmethyl radical has been reexamined by kinetic EPR spectroscopy at temperatures between 183 and 232°K in cyclopropane solvent. The rate constant, k_c for this important radical rearrangement can be represented by where Θ = 2.3RT kcal/mol.     

Oxidative cyclization of morusin

Oxidative cyclization of morusin (I) by using one-electron transfer oxidizing agents (manganese dioxide, silver oxide) afforded morusin hydroperoxide (II). A similar reaction was carried out in the presence of 2,4,6-tri-t-butylphenol, a radical quencher, to give compounds (IV, V, VI and VII) coupled with the 2,4,6-tri-t-butylphenoxy radical. On the basis of above results, the possible mechanism of this oxidative cyclization was discussed. In addition, morusin hydroperoxide (II) was also obtained by photo-sensitized oxidation of morusin (I) in the presence of sensitizers (Rose Bengal, hematoporphyrin). To elucidate the reaction mechanism similar reactions were carried out in the presence of radical quencher (2,4,6-tri-t-butylphenol) or singlet oxygen quencher (triethylenediamine). From these results, the possible mechanism of the formation of morusin hydroperoxide (II) from morusin (I) was discussed.     

Thiol-mediated radical cyclization: regioselective formation of indole-annulated sulfur heterocycles by tandem cyclization

Indole-2-yl-prop-2-ynyl sulfides, under thiophenol-mediated alkenyl radical cyclization conditions, afforded exclusively 4-thiophenyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indoles or 3-thiophenylmethyl-2,3,8-trihydrothieno[2,3-b]indoles depending on the substituent at the indole nitrogen.     

Triflic acid-catalyzed cascade cyclization of arenyl enynes via acetylene-cation cyclization and Friedel-Crafts type reaction

A novel triflic acid-catalyzed cascade cyclization of arenyl 1,7-enynes through acetylene-cation cyclization followed by Friedel-Crafts reaction has been described. Various fused poly carbocycles can be obtained in good to high yields under mild reaction conditions.     

Heteroareno-annelated estranes by triene cyclization

17-Thienyl-and 17-benzo[b]thienyl-3-hydroxyestra-1,3,5(10),16-tetraenes were synthesized by either sequential or one-pot Suzuki cross-coupling and Wittig olefination reactions. At 160 °C, heteroaryl substituted steroids were observed to undergo thermal intramolecular cyclization to produce E-ring heteroareno-annelated estranes.     

Biomimetic cyclization of hedycaryol derivatives. Unexpected cyclization of phenyl sulfides with methyl iodide

Four isomeric hedycaryol phenyl sulfides, when reacted with Mel, yielded eudesmol derivatives with different stereochemistry from that of the acid cyclization products of the corresponding hedycaryols. New stereoisomers of α- and β-eudesmols, β-dehydroparadisiol and a defensive substance of termite were synthesized. Nephthenol phenyl sulfide yielded a 14-membered tetraene.     

Intramolecular cyclization in hyperbranched polyesters

The effect of monomer structure and catalyst on the synthesis of hyperbranched polyesters based on 4,4-(4′-hydroxyphenyl)pentanoic acid has been examined. The nature of the ester group and the catalyst have a significant effect on the molecular weight of the hyperbranched polyester but do not effect the degree of branching for these materials. The fate of the single ester group at the focal point of these hyperbranched macromolecules is probed by the synthesis and polymerization of ¹³C labeled methyl 4,4-(4′-hydroxyphenyl)pentanoate. Comparison of the molecular weights determined by ¹H- or ¹³C-NMR spectra with those determined by osmometry suggest that intramolecular cyclization does not occur to a significant extent in these systems. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 1627–1633, 1997     

Intramolecular cyclization of 2-hydroxycinnamaldehydes

The effect of substituents on the intramolecular cyclization of 2-hydroxycinnamaldehydes was studied. It was established that aldehydes that contain bulky groups in the side chain and in the 3 position of the benzene ring are readily converted to intramolecular hemiacetals or bimolecular acetals either spontaneously at the moment of isolation or in solutions in DMF or DMSO, as well as on heating. An increase in the lability of the phenolic proton favors the cyclization.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 460–465, April, 1988.