Regioselective Ring Expansion Research Articles

ChemInform Abstract: Construction of Dibenzazocine Skeleton by Regiocontrolled Ring Expansion Reaction of Cyclic Oxime with DIBAL‐H: Facile Synthesis of 17β‐Hydroxysteroid Dehydrogenase Type 3 Inhibitor.

AbstractKey step in the synthesis of the title compound is the regioselective ring expansion of oximes (I).

Synthesis of a D Ring‐Functionalized Derivative of the Epiwelwistatin Tetracyclic Core

AbstractA 14‐oxo derivative of the tetracyclic core of the alkaloid 3‐epi‐welwistatin was prepared by a regioselective ring expansion of Kornfeld's ketone followed by a Michael‐intramolecular aldol anionic domino process to generate a tetracyclic system that contained a bicyclo[4.3.1]decane fragment fused to an indole. Treating this compound with N‐bromosuccinimide in tert‐butyl alcohol diastereoselectively generated the oxindole ring that is inherent to the natural product.

Synthesis of Fused Bromofurans via Mg-Mediated Dibromocyclopropanation of Cycloalkanone-Derived Chalcones and Cloke–Wilson Rearrangement

A convenient two-step sequence for the conversion of alkylidenecycloalkanones to bromofurans is reported. The steps involve Mg-mediated diastereoselective dibromocyclopropanation of alkylidenecycloalkanone followed by acidic alumina-mediated regioselective ring expansion of the cyclopropyl ketone. The scope of the reaction was investigated using alkylidenecycloalkanones derived from tetralone, indanone, and benzosuberone to afford 2-aryl-3-bromofurans fused to various benzocycloalkanes. Representative examples of stereoconvergent dibromocyclopropanation and total aromatization of the furobenzocycloalkane are also reported.

Ring expansion of alkynyl cyclopropanes to highly substituted cyclobutenes via a N-sulfonyl-1,2,3-triazole intermediate

Regioselective ring expansion of alkynyl cyclopropanes to highly substituted cyclobutenes was developed. The reaction involves a copper-catalyzed cycloaddition of an alkyne with an arylsulfonyl azide and a silver-catalyzed carbene formation followed by ring expansion of a cyclopropyl carbene intermediate.

ChemInform Abstract: Regioselective Ring Expansion of 2,4‐Diiminoazetidines via Cleavage of C—N and C(sp3)—H Bonds: Efficient Construction of 2,3‐Dihydropyrimidinesulfonamides.

A highly regioselective base-mediated ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp(3))-H bonds is achieved for the first time to afford efficiently 2,3-dihydropyrimidinesulfonamides. The mechanism of the ring expansion via tandem 4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing is well confirmed by the trapping experiments of two key intermediates and deuterium labeling studies.

Stereoselective preparation of cyclobutanes with four different substituents: total synthesis and structural revision of pipercyclobutanamide A and piperchabamide G.

A general strategy was developed for the diastereo- and enantioselective synthesis of cyclobutanes with four different substituents. It consists of three transition metal-catalyzed reactions — a RhII-catalyzed cyclopropanation, a AgI-catalyzed regioselective and stereospecific ring expansion, and a RhI-catalyzed addition reaction. Structures of pipercyclobutanamide A and piperchabamide G were synthesized and revised.

Regioselective Ring Expansion of 2,4-Diiminoazetidines via Cleavage of C–N and C(sp3)–H Bonds: Efficient Construction of 2,3-Dihydropyrimidinesulfonamides

A highly regioselective base-mediated ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp(3))-H bonds is achieved for the first time to afford efficiently 2,3-dihydropyrimidinesulfonamides. The mechanism of the ring expansion via tandem 4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing is well confirmed by the trapping experiments of two key intermediates and deuterium labeling studies.

Synthesis of substituted α-tetralones and substituted 1-naphthols via regioselective ring expansion of 1-acyl-1-indanol skeleton

Substituted 1-acyl-1-indanols were prepared using the corresponding readily commercially available substituted indanones as starting materials. Treatment of each 1-acyl-1-indanol derivative with sodium methoxide in hot methanol furnished a regiospecific 2-hydroxy-α-tetralone derivative, which was an α-keto rearrangement product. Each substituted 2-hydroxy-α-tetralone then underwent dehydration to afford the corresponding 1-naphthol derivative.

Synthesis of (±)‐Merrilactone A and (±)‐Anislactone A

The first synthesis of anislactone A (I) (22 steps, 5.7% overall yield) and a formal synthesis of merrilactone A (II) (22 steps to known intermediate III in 2.4% overall, 24 steps to the natural product) through a common route has been completed. The synthesis describes a direct approach to all-chiral carbon-B ring cyclopenatne IV [TBDMS = SiMe2CMe3] using a [2+2] photocycloaddn., regioselective Tiffeneau-Demjanov ring expansion and stereoselective 1,2-addn. as key C-C-bond forming steps. The defining transformation is then the reductive epoxide cleavage-cyclization to form the C9 quaternary center at the heart of the sesquiterpene structure. [on SciFinder(R)]

Catalytic and Regioselective Ring Expansion of Arylcyclobutanones with Trimethylsilyldiazomethane. Ligand-Dependent Entry to β-Ketosilane or Enolsilane Adducts

Divergent reactivity is uncovered in the homologation of arylcyclobutanones with trimethylsilyldiazomethane. With Sc(OTf)(3) as catalyst, enolsilanes are obtained with a high preference for methylene migration. By contrast, Sc(hfac)(3) gives beta-ketosilanes with both regio- and diastereocontrol. Each adduct affords the cyclopentanone upon hydrolysis.

ChemInform Abstract: Diastereoselective Cycloaddition of Alkylidenecyclopropane Nitrones from Palladium(0)-Catalyzed Nucleophilic Substitution of Asymmetric 1-Alkenylcyclopropyl Esters by Amino Acids.

Abstract The asymmetric construction of perhydropyrrolo[3,4- b ]pyridine derivatives was performed by chemo- and regioselective formation of enantiopure alkylidenecyclopropane nitrones, followed by diastereoselective intramolecular 1,3-dipolar cycloaddition. The resulting spirocyclopropane isoxazolidines then underwent thermally induced regioselective ring expansion into optically active diazaheterocycles.

Lewis Acid-mediated Highly Regioselective Ring-expansion of Methyl 2-Phenyl-1-(arylhydroxymethyl)cyclopropanecarboxylates

Abstract A novel ring-expansion of methyl (arylhydroxymethyl)cyclopropanecarboxylates 1 using Sc(OTf)3 or BF3·OEt2 afforded 1,2-dihydronaphthalene-3-carboxylic acid ester 2 in high to excellent yields. In the reaction, highly regioselective ring opening of cyclopropane and sequential cyclization occurred.

Novel access to azaphosphiridine complexes and first applications using Brønsted acid-induced ring expansion reactions

Synthesis of azaphosphiridine complexes 3a-e was achieved via thermal group transfer reaction using 2H-azaphosphirene complex 1 and N-methyl C-aryl imines 2a-e (i) or via reaction of transient Li/Cl phosphinidenoid complex 5 (prepared from dichloro(organo)phosphane complex 4) using 2a-c (ii), respectively. Reaction of complexes 3a,d and trifluoromethane sulfonic acid in the presence of dimethyl cyanamide led to a highly bond- and regioselective ring expansion yielding 1,3,4sigma3lambda3-diazaphosphol-2-ene complexes 8a,d after deprotonation with NEt3. 31P NMR reaction monitoring revealed that protonation of complex 3a yields the azaphosphiridinium complex 6a, unambiguously identified by NMR spectroscopy at low temperature. All isolated products were characterized by multinuclear NMR spectroscopy, IR and UV/Vis (for 3a,d, 6a, 8a,d), MS and single-crystal X-ray crystallography in the cases of complexes 3b-d, 8a and 8d. DFT studies on the reaction mechanism and compliance constants of the model complex of 6a are presented.

ChemInform Abstract: Regioselective Ring Expansion of 3,3‐Dimethylaziridin‐2‐carboxylate and a Photochemical Entry to the Penem Nucleus.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Protonation of 2H‐Azaphosphirene Complexes: PN Bond Activation and Ring‐Expansion Reactions

P-N bond activation of 2H-azaphosphirene complexes 1 and 2 by using triflic acid led to ring expansion in the presence of nitriles. In the absence of nitriles, the reaction surprisingly afforded two haptomeric N-protonated 1-aza-3-phospha-butadiene complexes in the case of complex 1, whereas the N-protonated 2H-azaphosphirene complex [H-2](+) was characterized by NMR spectroscopy.Protonation of 2H-azaphosphirene complexes 1 and 2 using trifluoromethanesulfonic acid in the presence and in the absence of nitriles was studied. Reactions with nitrile derivatives of different nucleophilicity and steric demand (3 a-f) led to highly bond- and regioselective ring-expansion reactions of complexes 1 and 2 and yielded 2H-1,4,2-diazaphosphole complexes 4 a-f and 5 a after deprotonation with NEt(3). Upon protonation of complex 1 in the absence of nitriles a mixture of two haptomeric N-protonated 1-aza-3-phosphabuta-1,3-diene complexes 13 and 14 was obtained, which upon addition of Me(2)NCN (3 a) and NEt(3) afforded 2H-1,4,2-diazaphosphole complex 16 a bearing a P-substituent with only one SiMe(3) group. Protonation of complex 2 led to the 2H-azaphosphirenium complex [H-2](+), unambiguously identified by NMR spectroscopy at low temperature. All isolated products were characterized by multinuclear NMR spectroscopy, IR, MS, and single-crystal X-ray crystallography in the cases of complexes 4 a, 4 e, 6 a, and 16 a. Furthermore, ESI-MS/MS studies on primarily formed reactive intermediates and DFT studies on the reaction mechanism are presented.

Regioselective Ring Expansion of 3,3-Dimethylaziridin-2-carboxylate and a Photochemical Entry to the Penem Nucleus

3,3-Dimethylaziridin-2-carboxylates undergo ring expansion with thiocyanates to give a 4,4-dimethylthiazolidin-5-carboxylate as the major product. Irradiation of a N-cysteinyl-3,3-dimethylaziridin-2-carboxylate was found to give a penem in low yield, presumably via a transient thioaldehyde which added across the aziridine N-C(3) bond.

Stereospecific and Regioselective Ring Expansion of Cyclopropanes

Stereospecific and Regioselective Ring Expansion of Cyclopropanes

Selective tandem enyne metathesis for the synthesis of functionalized cycloheptadienes

The regio- and site-selective ring expansion of dienes and the regioselective ring expansion of substituted cyclopentenes provide 1,3-cycloheptadienes by enyne metathesis under methylene-free conditions. Site-selectivity results from differential ring strain among two different cycloalkenes in diene reactants. The high regioselectivity found in the ring expansion of tetrahydroindene (THI) is explained on the basis of a selective ring opening by the second generation Grubbs' ruthenium carbene complex. The ring opening of substituted cyclopentenes and cyclopentene contained in a bicyclic ring system was also achieved. The ring expansion of bicyclic dienes provided seven-membered dienes contained in the bicyclo[5.2.0]nonane ring system. Details of the structural analysis are also discussed. A mechanistic analysis is provided to account for the data presented herein.

Enantioselective Synthesis of the Hydroazulene Core of 3α‐Hydroxy‐15‐rippertene

AbstractAs part of a project directed toward the total synthesis of the tetracyclic diterpene 3α‐hydroxy‐15‐rippertene, a constituent of the defense secretion of higher termites, a fast access to two advanced hydroazulene key intermediates has been achieved by starting from (–)‐isopulegol. A regio‐ and diastereoselective formal hydromethallylation and a regioselective ring expansion served as the key steps in the formation of the seven‐membered ring. Completion of the bicyclic title compounds was then achieved by cyclopentene annulation through diastereoselective conjugate addition of organocuprates and subsequent intramolecular aldol condensations.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Synthesis of Unsymmetrically and Highly Substituted Thiophenes Utilizing Regioselective Ring‐Expansion of gem‐Dichlorocyclopropyl Ketones with Lawesson′s Reagent.

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.