Unexpected ring contraction and oxidation rearrangement reactions of securinine

The bromination and oxidation of securinine were studied. An interesting and surprising rearrangement was observed during the reaction of securinine with tribromo-isocyanuric acid or 1,3-dibromo-5,5-dimethylhydantoin in methanol, yielding a stereoselective ring contraction norsecurinine derivative. Meanwhile two oxidation rearrangement products were also reported. Some preliminary discussions on the reactivity of securinine were conducted from these rearrangements; it is believed to be induced by alkaline nitrogen atom of the molecule.     

Selective ring contraction of 5-spirocyclopropane isoxazolidines mediated by acids

Thermolysis of 3,4-cis ring-fused 5-spirocyclopropane isoxazolidines 16, 18-21, 33, 34, 38a, and 61, in the presence of a protic acid at 70-110 degrees C, yielded 3,4-cis ring-fused azetidin-2-ones 22-26,41, 42, 46, and 62 with concomitant extrusion of ethylene, in good yields. So far, the collected evidences strongly support a mechanism started by a homolytic cleavage of the protonated N-O bond for the rearrangement of 5-spirocyclopropane isoxazolidines to beta-lactams. Some different competitive pathways can then follow depending on the stability or the stereoelectronic properties of cationic diradical intermediates. The two-step process, intramolecular 1,3-dipolar cycloaddition/thermal rearrangement under acidic conditions, represents a general synthesis of a new class of 3,4-cis-fused bicyclic azetidin-2-ones starting from easily available compounds such as amino acids, hydroxy acids, and dicarbonyl or amino alcohol derivatives.     

Five vs six membered ring formation in the vinyl radical cyclization

The ratio of methylenecyclopentane to methylenecyclohexane derivatives observed in the vinyl radical cyclization increases with the concentration of substrate and tin hydride. This is interpreted to mean that these cyclizations are under thermodynamic control at low concentrations.     

Concomitant ring contraction cyclization strategy for the synthesis of novel 4-oxo-4,5-dihydro-pyrroloquinolines

The synthesis of novel substituted pyrroloquinolinones is described by concomitant ring contraction cyclization form 2-(2-amino-5-nitro-phenyl)-[4H]-1,3-thiazines, which were derived from N-substituted 5-nitro-anthranilonitrile. An easy access to novel 4-thiono-1,4-dihydro-1,3-quinazoline heterocycles is also mentioned.     

An unprecedented 7-membered ring enamide cyclization through hypervalent iodine phenolic oxidation

An unprecedented 7-membered ring cyclization of an enamide to a phenol through hypervalent iodine phenolic oxidation was discovered. In the process a molecule of solvent is incorporated on the cycle forming an unusual and stable hemi-aminal ether.     

3H-Indol-3-ols by a novel ring contraction

Treatment of α-hydroxy-α-phenyl-o-toluidide with phosphorus tribromide afforded a series of 4H-3,1-benzoxazines. These last, when reacted with potassium amide in liquid ammonia, ring contracted to 2,3-disubstituted 3H-indol-3-ols. The scope of this rearrangement was examined. The indolols on treatment with hot base were found to rearrange to indoxyls. Several of these as well as their N-alkylation products are described.     

Reaction of thallium(III) salts with homoallylic alcohols: ring contraction vs. dimethoxylation

The oxidation of 2-(3,4-dihydronaphthalen-1-yl)-ethanol (1) with a variety of thallium(III) salts was investigated. An indan, formed by a ring contraction reaction, was obtained in good to moderate yields under a variety of reaction conditions: i) thallium triacetate (TTA) in aqueous AcOH; ii) thallium tris-trifluoroacetate (TTFA) in aqueous TFA; iii) TTFA in CH(2)Cl(2); iv) thallium tripropionate (TTP) in aqueous propionic acid and v) thallium tris-[(S)-(-)-triacetoxypropionate] in aqueous (S)-(-)-2-acetoxypropionic acid. On the other hand, the reaction of compound 1 with TTA in methanol led to a 2:1 mixture of the corresponding cis- and trans-dimethoxylated compounds, respectively.These compounds were formed by a thallium-promoted addition of methanol to the double bond.     

Medium ring ethers by ring expansion-ring contraction: synthesis of lauthisan

[reaction: see text] A new general method for the construction of medium ring ethers has been developed. This involves the ring expansion of halo-O,S-acetals followed by a Ramburg-B?cklund ring contraction reaction with concomitant extrusion of the sulfur atom. This methodology has been utilized for the synthesis of cis- and trans-lauthisan.     

A convenient synthesis of the β-lactam ring by 3 + 1 cyclization

A new synthetic method for the β-lactam ring formation using the 1,3-dianion (II) of the α-phenylthioacetamide derivative (I) and methylene iodide is described. The episulfonium intermediate (III) is proposed for the reaction.     

Ring contraction/transannular cyclization of chiral bicyclo[3.3.1]nonanediones mediated by thallium(III) nitrate

The reaction of several chiral bicyclo[3.3.1]nonane ketones mediated by thallium(III) nitrate to afford ring contraction products is investigated. The effect of solvent on the oxidation is discussed, and the use of thallium(III) nitrate for the oxidative rearrangement of regioisomers of bicyclononanones is outlined. In compounds with proximately located carbonyl groups in the bicyclic framework, unexpected transannular ring closure was observed.     

Triphenylphosphine-induced ring contraction of 1,2-dioxines

Triphenylphosphine inserts into the peroxide bond of 1,2-dioxines, initiating ring contraction with loss of triphenylphosphine oxide. This process yields dihydrofuran oxides in 54-97% yield from oxirenyl[2,3-c][1,2]dioxines and dihydrofurans from 3,6-dihydro-1,2-dioxines with inversion of stereochemistry at either the 2 or 5 position in the furan product.     

Intramolecular rearrangement with ring contraction of 1,4-dihydroxy-3-bromo-2,2,6,6-tetramethylpiperidine

Conclusions 1,4-Dihydroxy-3-bromo-2,2,6,6-tetramethylpiperidine on treatment with bases rearranged with ring contraction to 1,3-dihydroxy-2-(2-propenyl)-5,5-dimethylpyrrolidine.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1582–1587, July, 1987.     

Ortho-substitution of the benzene ring in 3-arylsydnones mediated by butyllithium

C(4), C′(2)-Double substitution was achieved in good yields by reacting 3-arylsydnones with BuLi and then with a suitable electrophile in THF at −50°C. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:549–552, 1998     

Synthesis and ring contraction reactions of polyazamacrolides

The synthesis of three analogues of the single most abundant component of a ladybird beetle (Epilachna borealis) defensive secretion, the trimeric 42-membered polyazamacrolide PAML 681, is described. Construction of the nonnatural macrocyclic trimers began with the preparation of the corresponding monomeric segments, followed by their oligomerization and a final macrolactonization step of the activated linear trimeric hydroxy acid. The relative rates of the O-to-N acyl migrations that are characteristic of PAML 681 itself, as well as of the synthetic analogues, were investigated. These studies showed that changes in the substitution pattern adjacent to the nucleophilic nitrogen atom, along with changes in the size of the oxaazacyclic intermediates, have substantial effects on the polyazamacrolide rearrangement rates.     

An unusual samarium diiodide mediated reductive ring contraction of a tricyclic oxazine to a highly-functionalized cyclopentane and cyclobutane

[reaction--see text] Samarium diiodide mediated reductive ring contraction of a substituted tricyclo[2.2.2]oxazine at 25 degrees C leads to a mixture of cyclopentane and cyclobutane rearrangement products with complete diastereoselectivity in each case. At -78 degrees C, the anticipated amidocyclohexanol reduction product is obtained exclusively, while the cyclopentane is the sole product at reflux in THF.     

Zinc halide-promoted cyclization of propargyl amide enynes: novel six-membered ring formation

Highly unusual zinc halide-promoted cyclization of propargyl amide enynes in the presence of an alcohol or a Brønsted acid afforded novel six-membered rings.