Unexpected Rearrangement Research Articles

Synthesis of difluorinated β- and γ-amino acids: Investigation of a challenging deoxyfluorination reaction

Backbone-homologated amino acids containing the vicinal difluoride motif have been synthesised in a highly stereoselective manner. The key synthetic transformation is the DeoxoFluor®-mediated fluorination of a vicinal fluorohydrin. The synthetic route is amenable to the production of all possible stereoisomers of α,β-difluoro-γ-aminobutyric acid. In addition, a novel difluoromethyl-substituted β-amino acid is accessed via an unexpected rearrangement process.

ChemInform Abstract: Unexpected Rearrangement: A Novel Route to 3‐Thiazoline.

AbstractThe attempt to prepare 1,4‐thiazine products is unsuccessful and the title compounds are formed instead via a rearrangement process.

Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines

3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N-methyl-benzimidazole with the cyanoanhydride formed by condensation of cyanoacetic acid with acetic anhydride, leads to the formation of 2-(1,3-diacetyl-2,3-dihydro-1H-benzo[d]-imidazol-2-yl)acetonitrile (5), whose structure was confirmed by X-ray crystallographic analysis. 3-Oxoalkanenitriles 3a,b were observed to undergo condensation reactions with dimethylformamide dimethyl acetal (DMFDMA) to afford the corresponding enamino-nitriles, which react with malononitrile to give 2-dialkylaminopyridines through a pathway involving a new, unexpected rearrangement process. Reactions of 3-oxoalkanenitriles with ethyl acetoacetate were found to afford 2-oxopyran-3-carbonitriles, also occurring via this unexpected rearrangement process. Mechanisms to account for both rearrangement reactions are suggested. In addition, reactions of 3-oxoalkanenitriles with acetylacetone in acetic acid in the presence of ammonium acetate result in the formation of pyridine-3-carbonitriles. Finally, upon heating in the presence of zeolite 3-oxoalkanenitriles 3b,c self-trimerized to produce the corresponding aniline derivatives 23b,c.

Regioselective synthesis of pyrimido[1,2-a][1,3,5]triazin-6-ones via reaction of 1-(6-oxo-1,6-dihydropyrimidin-2-yl)guanidines with triethylorthoacetate: observation of an unexpected rearrangement

A novel thermal rearrangement, involving pyrimidine ring opening and subsequent ring closure leading to recyclization of the system, was identified in the reaction of (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 (where NR(1)R(2) = NH(2), NH alkyl, NH aralkyl, NHCH(2)Ph(R)) with triethyl orthoacetate, affording 4-substituted-2-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 6 and their ring opened products. However, no such rearrangement was observed with (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 bearing a tertiary amino or anilino substituent (i.e. where NR(1)R(2) = N(CH(3))(2), indoline, morpholino, NHAr). As expected, 2-substituted-4-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 4 were obtained as the final products. Experimental structural determination and theoretical studies were carried out to get an understanding of the observed thermal rearrangement. In addition, an attempt to obtain similar pyrimido[1,2-a][1,3,5]triazin-6-ones using N,N-dimethylacetamide dimethyl acetal (DMA-DMA) as one carbon inserting synthon had furnished triazine ring annulated product 14 bearing N,N-dimethyl enamino substituent at position 4 as a result of further reaction with a second molecule of DMA-DMA.

ChemInform Abstract: Unexpected Cycloisomerizations of Nonclassical Carbocation Intermediates in Gold(I)‐Catalyzed Homo‐Rautenstrauch Cyclizations.

AbstractTreatment of propargylic esters of type (I) and (IV) with gold(I) catalysts results in unexpected rearrangement to cyclohexadiene derivatives like (II).

Peterson Olefination: Unexpected Rearrangement in the Overcrowded Polycyclic Aromatic Ene Series

AbstractAn attempted synthesis of the angularly annelated 9‐(11′‐benzo[a]fluoren‐11′‐ylidene)‐9H‐fluorene (3) through a Peterson olefination reaction between (9H‐fluoren‐9‐yl)trimethylsilyl anion (5a) and 11H‐benzo[a]fluoren‐11‐one (6) led to the linearly annelated 9‐(11′‐benzo[b]fluoren‐11′‐ylidene)‐9H‐fluorene (4), due to an unexpected rearrangement. The proposed mechanism of the rearrangement is illustrated. The core of the mechanism is an intramolecular Haller–Bauer cleavage of the naphthyl C11a′–C11′ bond in the β‐oxysilane anion 11 (formed from 5a and 6) to give the 1‐naphthyl anion (E)‐12, followed by E/Z isomerization to (Z)‐12 and by proton migration to give the 3‐naphthyl anion (Z)‐14. The intramolecular nucleophilic addition of the naphthyl anion at C‐3′ of (Z)‐14 to the carbonyl carbon gives the β‐oxysilane anion 15, a benzo[b]fluorenylidene derivative. The mechanism is supported by the results of DFT calculations. The synthesis of 3 was achieved by application of Barton's double extrusion diazo–thione coupling method.

Unexpected Rearrangement; A Novel Route to 3-Thiazoline

Unexpected Rearrangement; A Novel Route to 3-Thiazoline

Sn(OTf)2 as an Effective Lewis Acid in Reactions of Cyclopropyl Ketones with Acetic Anhydride: Application in the Synthesis of a 19‐Nor‐B‐homo Steroid

AbstractAttempts to convert 3β‐acetoxy‐5,19‐cyclo‐pregna‐6,20‐dione (8) into a cyclocitrinol‐related steroid with a bicyclo[4.4.1]‐undecane AB‐ring substructure through a Lewis acid‐assisted fragmentation failed. Instead, treating 8 with an excess of Ac2O and BF3·Et2O afforded B‐homo steroid 9 in 90 % yield. This unexpected rearrangement is assumed to proceed via an intermediate bicyclobutonium cation. Remarkably, tricyclo[4.4.1.0]undecane‐1‐one (rac‐13), prepared as a model substrate, did not react under the same conditions. However, by screening various Lewis acids, stannous triflate was identified as a particularly efficient reagent for this and related Lewis acid‐assisted ring‐opening reactions of cyclopropyl ketones in the presence of Ac2O, and even catalytic amounts of Sn(OTf)2 (5 mol‐%) proved to be effective.

Genetic dosage compensation in a family with velo‐cardio‐facial/DiGeorge/22q11.2 deletion syndrome

Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome showed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carried a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as shown by fluorescence in situ hybridization and array comparative genome hybridization analyses. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for recurrence risks for the dose-compensated mother.

ChemInform Abstract: An Unexpected Skeletal Transformation of 1,4‐Dihydroxythioxanthen‐9‐one on Treatment with Iodic Acid: The First Construction of the 2‐(5‐Oxofuran‐2‐ylidene)‐1‐benzothienyl‐3‐one Core.

AbstractTreatment of substrate (I) with HIO3 results in formation of the corresponding trione and an unexpected rearrangement product (II).

ChemInform Abstract: Rearrangement of 5‐Phenylthiazolidine‐2,4‐diones to Chiral α‐Ketoamides via α‐Elimination.

AbstractBased‐mediated reaction of thiones (I) in the presence of acetyl chloride gives diones (III) which undergo unexpected rearrangement in basic media to produce aryl‐α‐ketoamides (IV).

An unexpected rearrangement of the benzofurobenzazepine skeleton of galanthamine-type alkaloids

Attempted cyclisation of N-methylated spiro benzazepine–cyclohexenone ( 5) into the corresponding N-methyl tetracyclic unit of galanthamine-type alkaloids ( 6) instead gave an unexpected rearrangement to yield a cyclopentanoisoquinolinone derivative ( 7). Methylation of the tetrahydrobenzofurobenzazepine tetracycle resulted in the expected N-methyl derivative 6, and the anomalous product 8, with structure similar to that of 7.

ChemInform Abstract: An Unexpected Acyloin Rearrangement and Oxidation of a Camphor Derivative.

The trimethylsiyl ether 7 derived in two steps from camphor underwent ring expansion via an acylion rearrangement to afford two products (8 and 9) when desilylation was attempted. Compound 9 was stable but 8 was oxidized in air to homocamphoric acid anhydride 11. Key words: camphor, acyloin rearrangement.

Non‐innocent Behaviour of Dithiocarboxylate Ligands Based on N‐Heterocyclic Carbenes

Not so innocent: Sterically tuneable dithiocarboxylate ligands derived from N-heterocyclic carbenes act as excellent bidentate chelates for ruthenium(II) σ-alkenyl complexes. However, the most sterically demanding member of the ligand family causes a fascinating and unexpected rearrangement to occur (see figure; ICy=1,3-dicylohexylimidazolium, IDip=1,3-bis(2,6-diisopropylphenyl)imidazolium). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ChemInform Abstract: The Alkylation of a Novel Acetal Derived from (2R,3R)-(+)-Tartaric Acid: An Unexpected Rearrangement.

Abstract The novel chiral bis -acetal dioxane 2a derived from (2 R ,3 R )-(+)-tartaric acid was shown to undergo an unexpected rearrangement upon treatment with lithium amide base to give the chiral dioxolane 3a in optically active form. Alkylation and aldol studies were performed on the diisopropyl ester of this dioxolane 3b .

Unexpected Rearrangement Leading to Formation of a 1,3‐Bis(triphenylphosphonio)prop‐1‐en‐3‐idyl Carboxylate

AbstractWhereas biphenyl‐4,4′‐dicarbonyl dichloride reacts with methylenetriphenylphosphorane to give the expected bis(acylylide) 1, the same reaction of biphenyl‐2,2′‐dicarbonyl dichloride results in a multistep rearrangement leading to the zwitterionic 2‐[1,3‐bis(triphenylphosphonio)prop‐1‐en‐3‐id‐2‐yl]biphenyl‐2′‐carboxylate 2. X‐ray crystal structures of both 1 and 2 are reported.

Reactions of Germenes with Somepara-Quinones: Formation of a Tricyclic Compound from 1,4-Benzoquinone Undergoing an Unexpected Rearrangement

Germenes Mes2Ge═CR2 1a (Mes = 2,4,6-trimethylphenyl; CR2 = fluorenylidene) and Mes2Ge═CR′2 1b (CR′2 = 2,7-di-tert-butylfluorenylidene) react with 1,4-benzoquinone and 2,3,5,6-tetramethyl-1,4-benzoquinone to give compounds 3a, 3b, and 5a, containing a 1,4-cyclohexadiene unit as central ring. Upon prolonged storage in diethyl ether or THF solution, compounds 3a and 3b undergo a double 1,3-hydrogen shift, leading to their structural isomers 4a and 4b. Theoretical calculations performed on the model compound H2Ge═CH2 1H postulate that the first steps of its reaction with 1,4-benzoquinone are a double [2+2] cycloaddition between the Ge═C and C═O double bonds, leading to a transient dispiro compound containing two oxagermetane rings, followed by its isomerization to derivative 3H. Between 1a and 9,10-anthraquinone, a double [2+4] cycloaddition is observed involving the oxygens and the ortho-carbon atoms of one adjacent aromatic ring system, to generate the dioxadigermabenzopyrene derivative 2a.

Alkylations ofN4-(4-Pyridyl)-3,5-di(2-pyridyl)-1,2,4-triazole: First Observation of Room-Temperature Rearrangement of anN4-Substituted Triazole to theN1Analogue

Attempts to use alkylation to introduce a positive charge at the nitrogen atom of the 4-pyridyl ring in the bis(bidentate) triazole ligand N(4)-(4-pyridyl)-3,5-di(2-pyridyl)-1,2,4-triazole (pydpt) were made to ascertain what effect a strongly electron-withdrawing group would have on the magnetic properties of any subsequent iron(II) complexes. Alkylation of pydpt under relatively mild conditions led in some cases to unexpected rearrangement products. Specifically, when benzyl bromide is used as the alkylating agent, and the reaction is carried out in refluxing acetonitrile, the N(4) substituent moves to the N(1) position. However, when the same reaction is performed in dichloromethane at room temperature, the rearrangement does not occur and the desired product containing an alkylated N(4) substituent is obtained. Heating a pure sample of N(4)-BzpydptBr to reflux in MeCN resulted in clean conversion to N(1)-BzpydptBr. This is consistent with N(4)-BzpydptBr being the kinetic product whereas N(1)-BzpydptBr is the thermodynamic product. When methyl iodide is used as the alkylating agent, the N(4) to N(1) rearrangement occurs even at room temperature, and at reflux pydpt is doubly alkylated. The observation of the lowest reported temperatures for an N(4) to N(1) rearrangement is due to this particular rearrangement involving nucleophilic aromatic substitution: a possible mechanism for this transformation is suggested.

ChemInform Abstract: Difluorophosphoryl Nitrene F2P(O)N: Matrix Isolation and Unexpected Rearrangement to F2PNO.

AbstractChemInform 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 varicella-zoster virus mutant impaired for latency in rodents, but not impaired for replication in cell culture

While trying to generate a site-directed deletion in the ORF63 latency-associated gene of varicella-zoster virus (VZV) Oka, we constructed a virus with an unexpected rearrangement. The virus has a small deletion in both copies of ORF63 and two copies of a cassette inserted between ORFs 64/65 and 68/69 containing (a) truncated ORF62, (b) ORF63 with a small deletion, and (c) full-length ORF64. The virus was not impaired for growth in human cells, induced higher levels of neutralizing antibodies in guinea pigs, and was impaired for latency in cotton rats compared with parental virus (p=0.0022). Additional mutants containing the same truncation in ORF62, with or without the ORF63 deletion, were less impaired for latency. A VZV Oka mutant, replicating to similar titers and inducing a comparable immune response as parental virus, but impaired for latency, might serve as a safer vaccine and be less likely to reactivate to cause zoster.