Two-carbon ring expansion of cyclobutanone skeletons by nickel-catalyzed intermolecular alkyne insertion

The reaction of cyclobutanone with an alkyne in the presence of a nickel(0) catalyst formally achieves intermolecular alkyne insertion between the carbonyl carbon and the α-carbon of a cyclobutanone, providing a six-membered carbocyclic skeleton.     

Cyclopropylcarbinyl radicals as three-carbon insertion units: easy synthesis of C-15 macrocyclic ketones by three-carbon ring expansion

Thermal isomerization of cyclic 3-cyclopropyl ketones under FVP conditions at 620 °C provides a new and convenient route to δ,ε-unsaturated cycloalkanones. The synthetic potential of this novel three-carbon ring expansion has been demonstrated by the synthesis of (±)-muscone from inexpensive C-12 starting material.     

The reactions of dialkyl and diarylethoxysilanes with T6 silsesquioxane cages: X-ray crystallographic studies of the mono-T6D1 and bis-T6D2 insertion ring expansion products

Successful ring-expanding insertion reactions of T₆ silsesquioxane cages using dialkyl and diarylethoxysilanes have been performed to give the first reported mixed T₆D₁ and T₆D₂ silsesquioxane cages. The reactions of hexacyclohexylsilsesquioxane (T₆) with dialkyl and diaryldiethoxysilanes give predominantly T₆D₂ bis-insertion compounds while the reaction of T₆ with dimethylethoxysilane gives one T₆D₁ mono-insertion product and various T₆D₂ bis-insertion products as isolable components. Three of the ring-expanded products are chiral and it has been shown from their X-ray crystal structures that the pairs of enantiomers, formed as racemic mixtures, co-crystallise together. As well as comparing these structures with related ones in the literature, the possible mechanism of their formation is discussed.     

Routes to HIV-integrase inhibitors: efficient synthesis of bicyclic pyrimidones by ring expansion or amination at a benzylic position

Ring expansion of [6,6] bicyclic pyrimidones led, through an aziridinium intermediate, to potent HIV-integrase inhibitors with a [7,6] core. A more flexible and diversity-oriented synthesis of functionalized pyrimidohexahydrodiazepines was then developed; the key benzylic substituent was introduced in one pot by using sequentially DDQ and BnMeNH. Both synthetic routes are described.     

Synthesis of 2-aryl-4-chloropyrroles via ring expansion of 2-aryl-1-chlorocyclopropanecarbaldehydes

An efficient electrophile-induced ring opening of 2-aryl-1-chlorocyclopropanecarbaldehydes is described towards halogenated butanals, which were converted to the corresponding imines. These α,α,γ-trichloroimines proved to be good substrates for a nucleophile-induced ring closure towards 2-pyrrolines as versatile synthons for the synthesis of pyrroles bearing physiologically interesting substitution patterns.     

Grignard reagent-promoted selective ring expansion and alkylation of formyl borneol and isoborneol: a new route to highly substituted cyclopentanes

Formyl borneol, a [2.2.1]-bicyclic carbinol, reacts with various Grignard reagents to produce corresponding alkyl [3.2.1]-bicyclic diols, which can be converted to new highly substituted cyclopentanes, and further to 3-acyl-bornylenes. These ring expansion-alkylation reactions are highly selective. Reaction of formyl isoborneol with methyl magnesium bromide gave ring expansion-only and alkylation-only products.     

Acid-catalyzed reaction of 3-aminopyrrole with s-tetrazines: formation of 1H-1,2,4-(triazol-3-yl)pyrimidines via an unprecedented s-tetrazine-ring contraction and concomitant pyrrole-ring expansion

Initial reaction of 3-aminopyrrole with the conjugate acid of 3,6-diphenyl-1,2,4,5-tetrazine gave an intermediate that rearranged to a 1H-1,2,4-(triazol-3-yl)pyrimidine via an unprecedented cascade. In this cascade, the s-tetrazine-ring opened, contracted to a 1,2,4-triazole-ring, and the pyrrole ring expanded to a pyrimidine. Similar results were obtained with three other electronically different s-tetrazines.     

Insertions‐ und Substitutionsreaktion von Ameisensäuremethylester mit [Cp′2ZrCl(PHTipp)] – Molekülstruktur von meso‐trans‐[Cp′2ZrCl{OCH(PHTipp)2}] (Cp′ = η5‐C5MeH4, Tipp = 2,4,6‐Pri3C6H2)

Insertion and Substitution Reaction of Methyl Formate with [Cp′₂ZrCl(PHTipp)] – Molecular Structure of meso‐trans ‐[Cp′₂ZrCl{OCH(PHTipp)₂}] (Cp′ = η⁵‐C₅MeH₄, Tipp = 2,4,6‐Prⁱ₃C₆H₂) [Cp′₂ZrCl(PHTipp)] ( 1 ) (Cp′ = η⁵‐C₅MeH₄, Tipp = 2,4,6‐Prⁱ₃C₆H₂) reacts with methyl formate with insertion and substitution to give [Cp′₂ZrCl{OCH(PHTipp)₂}] ( 2 ). 2 was characterized spectroscopically (¹H, ³¹P NMR, IR, MS) and by X‐ray structure determination. Only the meso‐trans isomer is present in the solid state.     

Ring Expansion to 6-, 7-, and 8-Membered Benzosilacycles through Strain-Release Silicon-Based Cross-Coupling

The synthesis of silacycles is highly appealing due to their important applications in organic synthesis, medicinal chemistry, and materials chemistry. However, sila-tetralins and sila-benzosuberanes are surprisingly under-represented due to a lack of general methods to access these compounds. We successfully developed a Pd-catalyzed strain-release silicon-based cross-coupling as an unprecedented ring-expansion method, which constitutes a general route for preparing diverse sila-tetralins and sila-benzosuberanes.     

Reduction of 5-(bromomethyl)-1-pyrrolinium bromides to 2-(bromomethyl)pyrrolidines and their transformation into piperidin-3-ones through an unprecedented ring expansion-oxidation protocol

3,3-Dialkyl-5-(bromomethyl)-1-pyrrolinium bromides, prepared via bromocyclization of N-(2,2-dialkyl-4-pentenylidene)amines by means of bromine in dichloromethane, were reduced to 4,4-dialkyl-2-(bromomethyl)pyrrolidines for the first time using borane dimethyl sulfide in dichloromethane. Furthermore, the latter 2-(bromomethyl)pyrrolidines were transformed into the corresponding piperidin-3-ones through an unprecedented ring expansion-oxidation protocol in dimethylsulfoxide in the presence of potassium carbonate. Reduction of 5,5-dialkylpiperidin-3-ones by means of sodium borohydride in methanol afforded 5,5-dialkyl-3-hydroxypiperidines in good yields.     

Palladium(II)-catalyzed ring expansion of a 1-alkenyl cyclopentanol

7,7-Dimethyl-2-methylenenorbornan-1-ol, a strained bicyclic 1-alkenyl cyclopentanol, undergoes Wagner-Meerwein rearrangement to fenchone under treatment with a catalytic amount of PdCl₂(PPh₃)₂ in refluxing N-methylpyrrolidin-2-one. The described reaction constitutes the first example of the palladium(II)-catalyzed ring expansion of 1-alkenyl cyclopentanols to the corresponding cyclohexanones.     

Visible light triggered regioselective ring expansion of N-tosylaziridines: An efficient approach to 2-nitroazetidines

Visible light induced ring expansion of N-tosylaziridines with 1-bromo-1-nitroalkanes to afford 2-nitroazetdines in moderate to excellent yields with high regio- and diastereoselectivity is reported. The salient features of the protocol include the first synthesis of 2-nitroazetidines, operational simplicity, utilization of clean, inexpensive and sustainable resources like visible light and atmospheric oxygen under photoredox catalysis at room temperature in one-pot procedure.     

Unexpected Ring Expansion of the (3aS,6aR)‐γ‐Thiolactone Moiety during the Introduction of the (+)‐Biotin Side Chain

The reaction of vinylmagnesium bromide with the (3aS,6aR)‐γ‐thiolactone 2 in THF afforded, after unexpected ring expansion of the γ‐thiolactone moiety, the seven‐membered‐ring ketone 5 in excellent yield, instead of the expected tertiary alcohol 3 .     

Synthesis of conjugated enynes by assembly of three components, ketones, chloromethyl p-tolyl sulfoxide, and acetylenes, with the magnesium carbenoid 1,2-CC insertion as the key reaction

The reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of magnesium carbenoids by the sulfoxide-magnesium exchange reaction. 1,2-Carbon-carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoids took place to afford conjugated enynes in good to high yields. This procedure provides a good method for the synthesis of multi-substituted conjugated enynes.     

Ag‐Catalyzed Trifluoromethylative Ring Expansion of Isatins and Isatin Ketimines with Trifluorodiazoethane

A general method for the construction of trifluoromethylated 2‐quinolinones has been established herein by using a trifluoromethylative ring expansion of isatin with trifluorodiazoethane. The strategy provides a platform for the rapid synthesis of a wide range of substituted 3‐hydroxy‐4‐trifluoromethyl‐2‐quinolinones. This operationally simple and robust Ag‐catalyzed protocol successfully transforms isatin ketimines to 3‐amino‐4‐trifluoromethylquinolinones in excellent yields. The utility of this novel method is further illustrated by the conversion of the products into various synthetically and medicinally relevant molecules.     

Nucleophile-mediated ring expansion of 4-chloromethyl- and 4-mesyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones: effect of the leaving group and the substituent at C6

A five-step synthesis of 4-chloromethyl- and 4-mesyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones has been developed. The reaction of N-[(2-benzoyloxy-1-tosyl)ethyl]urea with sodium enolates of α-tosylketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-ones, which were transformed into the 4-chloromethyl- or 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as sodium cyanide, sodium diethyl malonate, sodium thiophenolate, or potassium phthalimide, afforded the corresponding 4,7-disubstituted 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones as a result of ring expansion. The effect of the leaving group and the substitution at the position C6 on the reactivity of the pyrimidines is discussed.     

Scandium(III) triflate mediated intramolecular ring expansion of aziridines: a direct access to 4-aryltetrahydroisoquinolines

A novel, high yielding facile synthesis of 4-substituted tetrahydroisoquinolines has been developed by employing scandium(III) triflate mediated intramolecular ring expansion of aziridines. The meta-substituted electron-donating group on the benzene ring facilitates trapping of an in situ generated benzyl carbenium ion cation leading to the formation of tetrahydroisoquinolines.     

General approach to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones via nucleophile-mediated ring expansion of tetrahydropyrimidines

A general six-step approach to 6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones has been developed. The key step involves a ring expansion reaction of 4-mesyloxymethyl- or 4-tosyloxymethyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-one mediated by nucleophilic reagents.