Mediated Ring Expansion Research Articles

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

AbstractWe demonstrate that arylchlorodiazirines serve as photo‐activated halocarbene precursors for the selective one‐carbon ring expansion of N‐substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N‐substituted pyrazoles to pyrimidinium salts. The N‐substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co‐product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring‐expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents.

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment.

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3 ) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing-rather than thermolyzing-these reagents.

Catalyst-Free Synthesis of Oxacyclic Spirooxindoles through Oxonium Ylide Mediated Ring Expansion

Key words photochemistry - ring expansion - oxindoles - oxacycles - spirooxindoles - diazo compounds - carbene generation

The diastereoselective synthesis of 2,3-diaryl-3-cyano-substituted pyrrolidines via the MgI2 mediated ring expansion of aryl cyclopropyl nitriles

The MgI2 mediated reaction of aryl substituted cyclopropyl nitriles with tosyl aldimines to give 2,3-diaryl-3-cyano-substituted pyrrolidines has been demonstrated. In all cases, the trans-diastereoisomer was determined to be the major product. The overall yield and diastereoselectivity of the reaction showed some sensitivity to the electronic and steric demands of the aryl cyclopropyl nitriles and the tosyl aldimines. Substitution with electron withdrawing substituents on both reacting partners proved beneficial in terms of the yield and diastereoselectivity.

Concise Synthesis of Open-Cage Fullerenes for Oxygen Delivery.

Open-cage fullerenes with a 19-membered orifice were prepared in three steps from C60 . The key step for cage-opening is aniline mediated ring expansion of a fullerene-mixed peroxide with a ketolactone moiety on the orifice. Release of ring strain on the spherical fullerene cage served as the main driving force for the efficient cage-opening sequence. Encapsulation of oxygen could be achieved at room temperature under moderate pressure (50 atm) and the encapsulated oxygen could be released slowly under ambient conditions. The activation energy of the oxygen-releasing process is 18.8 kcal mol-1 and the half-life at 37 °C was 73 min, which makes this open-cage fullerene derivative a potential oxygen-delivery material.

Concise Synthesis of Open‐Cage Fullerenes for Oxygen Delivery

AbstractOpen‐cage fullerenes with a 19‐membered orifice were prepared in three steps from C60. The key step for cage‐opening is aniline mediated ring expansion of a fullerene‐mixed peroxide with a ketolactone moiety on the orifice. Release of ring strain on the spherical fullerene cage served as the main driving force for the efficient cage‐opening sequence. Encapsulation of oxygen could be achieved at room temperature under moderate pressure (50 atm) and the encapsulated oxygen could be released slowly under ambient conditions. The activation energy of the oxygen‐releasing process is 18.8 kcal mol−1 and the half‐life at 37 °C was 73 min, which makes this open‐cage fullerene derivative a potential oxygen‐delivery material.

Synthesis of 2,2-bis(pyridin-2-yl amino)cyclobutanols and their conversion into 5-(pyridin-2-ylamino)dihydrofuran-2(3H)-ones.

A two-step protocol is presented for the preparation of 5-(pyridin-2-ylamino)dihydrofuran-2(3H)-ones from 2-hydroxycyclobutanone and some 2-aminopyridines via a catalyst-free synthesis of 2,2-bis(pyridin-2-ylamino)cyclobutanols followed by Dess-Martin periodinane mediated ring expansion.

ChemInform Abstract: BF3·OEt2‐Mediated One Pot Synthesis of 10‐Indolyldibenzo[b,f]azepine Derivatives via Tandem Ring Expansion and C—C Bond Formation.

A simple and efficient one pot protocol was developed for the synthesis of new structurally diverse 10-indolyldibenzo[b,f]azepine derivatives. The reaction involves Lewis-acid mediated ring expansion followed by C–C bond formation through nucleophilic addition of indole moiety.

Synthesis of 2-Substituted 1,3-Cycloheptanedione via a Lewis Acid Mediated Ring Expansion Reaction

The reaction of (Ib) is carried out on a gram scale requiring reflux conditions and affording the product in comparable yield.

ChemInform Abstract: Rh(II)‐Carbenoid Mediated 2H‐Azirine Ring‐Expansion as a Convenient Route to Non‐Fused Photo‐ and Thermochromic 2H‐1,4‐Oxazines.

AbstractFor the first time representatives of monocyclic 2H‐1,4‐oxazine derivatives show photo‐ and thermochromic activity.

Iodine(III)-mediated ring expansion: an efficient and green pathway in the synthesis of a key precursor for the design of aminopeptidase (APN or CD13) inhibitors

Iodine(III)-mediated ring expansion of a methylidenebenzocyclohexane derivative into the corresponding benzosuberone was used as a key reaction for the obtention of an important precursor for the design of aminopeptidase (APN or CD13) inhibitors. It represents the first application of this environmentally friendly rearrangement to medicinal chemistry.

ChemInform Abstract: Free Radical Mediated Ring Expansion Reactions: Endocyclic Cleavage of Cyclopropylcarbinyl Radicals.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Facile Access to Medium- and Large-Size Naphthalenacarbocycles via Lewis Acid Mediated Ring-Expansion Reaction of Bicyclic Vinylidenecyclopropanes

Ring-expansion reactions of bicyclic vinylidenecyclopropanes in the presence of Lewis acid was investigated, providing an efficient method for the synthesis of naphthalenes with annulated carbocycles of various ring sizes in good to excellent yields under mild conditions.

Synthesis Of The Bicyclo-[4.3.0]-Thymidyl-Nucleoside Via Pd(Ii)-Mediated Ring Expansion Chemistry

A variety of modified nucleosides to improve antisense oligodeoxynucleotide properties such as target affinity, nuclease resistance, and pharmacokinetics were developed in the last two decades. In the context of conformational restriction we present here the synthesis of the [4.3.0]-bicyclo-DNA thymine monomer via Pd(II)-mediated ring expansion of an intermediate of the tricyclo-DNA synthesis.

Tandem Staudinger—azaWittig Mediated Ring Expansion: Rapid Access to New Isofagomine‐Tetrahydroxyazepane Hybrids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Tandem Staudinger–azaWittig mediated ring expansion: rapid access to new isofagomine-tetrahydroxyazepane hybrids

New seven-membered iminosugars with potent and selective inhibition towards glycosidases have been prepared as 1-N-iminosugar homologues via a tandem Staudinger-azaWittig mediated ring expansion.

Metal Iodide Mediated Ring Expansion of Cyclopropanecarboxylic Thioesters with Imines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Preparation of Cyclic N‐tert‐Butylsulfonyl Enamines by Rh(II)‐Mediated Ring Expansion of α‐Diazoesters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Metal iodide mediated ring expansion of cyclopropanecarboxylic thioesters with imines

Metal iodide mediated three-component reactions of cyclopropanecarboxylic thioesters 1, aldehydes, and amines were developed. The initial products, pyrrolidines 2 were obtained in 39–73% yields, which could further be converted to lactams 4, via sequential reactions of a retro-aza-Michael addition and an intramolecular cyclization. This methodology provided facile access to analogs of both pyrrolidines 2 and lactams 4.

Preparation of Cyclic N-tert-Butylsulfonyl Enamines by Rh(II)-Mediated Ring Expansion of α-Diazoesters

The anion derived from ethyl diazoacetate adds to N-tert-butylsulfonyl ketimines to give β-tert-butylsulfonylamino α-diazo­esters, which are further transformed into cyclic enamines by treatment with Rh2(OAc)4, through 1,2-C-C bond migration of a Rh(II) carbene intermediate.