Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift of propargylic esters toward substituent naphthylamines

A novel and convenient carboannulation method for the synthesis of highly substituted naphthylamine derivatives has been developed though a Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift and cyclization reaction of propargyl esters.     

Alkatrienyl Sulfoxides and Sulfones. Part I. 3-Methyl-1,2,4-pentatrienyl Phenyl Sulfoxide-Synthesis and Electrophile-Induced Cyclization Reactions

A method for the synthesis of the 3-methyl-1,2,4-pentatrienyl phenyl sulfoxide 3 by [2,3]-sigmatropic rearrangement of the 3-methyl-1-penten-4-yn-3-yl benzenesulfenate 2 , formed in the reaction of the 3-methyl-1-pentene-4-yn-2-ol 1 with phenylsulfenyl chloride has been created. Possibilities and restrictions of the five-membered heterocyclization in electrophile-induced reactions leading to the synthesis of the 5H-1,2-oxathiol-2-ium salts 5 , 7 , and 8 have been explored. Chlorination of the sulfoxide 2 proceeded with formation of the (E)-2-chloro-3-methylene-1,4-pentadienyl phenyl sulfoxide 4 , while the bromination afforded the 4-bromo-5H-1,2-oxathiol-2-ium bromide 5 , which after reflux in 1,2-dichloroethane eliminated hydrogen bromide and was transformed into the (E)-2-bromo-3-methylene-1,4-pentadienyl phenyl sulfoxide 6 .     

Serine-cis-proline and serine-trans-proline isosteres: stereoselective synthesis of (Z)- and (E)-alkene mimics by Still-Wittig and Ireland-Claisen rearrangements

Two new amide isosteres of Ser-cis-Pro and Ser-trans-Pro dipeptides were designed and stereoselectively synthesized to be incorporated into potential inhibitors of the phosphorylation-dependent peptidylprolyl isomerase Pin1, an essential regulator of the cell cycle. The cis mimic, the (Z)-alkene isomer, was formed through the use of a Still-Wittig [2,3]-sigmatropic rearrangement, while the trans mimic, the (E)-alkene, was synthesized through the use of an Ireland-Claisen [3,3]-sigmatropic rearrangement. Starting from N-Boc-Ser(OBn)-N(OMe)Me, both mimics were synthesized in Boc-protected form suitable for peptide synthesis with an overall yield of 20% in 10 steps for the cis mimic and 13% in eight steps for the trans mimic.     

Thermal sigmatropic rearrangements of isopyrazoles and pyrazolenines to pyrazoles

Thermal rearrangement of 4-allyl-, 4-dimethylallyl-, and 4-propargyl-isopyrazoles proceed by [3,3]-sigmatropic processes to pyrazoles. The migration terminus is the C(3) Me group, if present, and the rearrangement is preceded by imine-enamine tautomerism. When enamine formation is not possible the rearrangment is diverted to nitrogen. Thermal rearrangements of 4-alkyl- and 4-benzyl-isopyrazoles also occur although at higher temperatures and evidence is presented suggesting [1,5]-sigmatropic processes are involved. Some pyrazolenine to pyrazole rearrangements involving migration of ester and phenyl groups are also reported.     

Ruthenium-catalyzed cycloisomerization of cis-3-en-1-ynes to cyclopentadiene and related derivatives through a 1,5-sigmatropic hydrogen shift of ruthenium-vinylidene intermediates

We report a new ruthenium-catalyzed cycloisomerization of unactivated cis-3-en-1-ynes, which produces substituted cyclopentadiene and related derivatives. The mechanism of this cyclization is proposed to involve a [1,5]-sigmatropic hydrogen shift of ruthenium-vinylidene intermediates on the basis of deuterium-labeling experiments.     

Five-membered 2,3-dioxo heterocycles. 2. Synthesis and [1,5]-sigmatropic rearrangement of 4-acyl-3-diphenylmethoxy-1,5-diphenyl-2,5-dihydropyrrol-2-ones

4-Acyl-1,5-diphenyltetrahydropyrrole-2,3-diones react with diphenyldiazomethane to give O-alkylation products, which upon heating undergo [1,5]-sigmatropic suprasurface rearrangement to form 4-[methyl- and 4-[-aryl(diphenylmethoxy)-methylene]-1,5-diphenyltetrahydropyrrole-2,3-diones.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 5, pp. 625–628, May, 1987.     

1,3- and 1,5-Sigmatropic Shifts: Insights into the Structure-Reactivity Relationship from ab initio Calculations

Thermal [ 1,n]-sigmatropic rearrangements of hydrogen shift have been of considerable theoretical and experimental interests during the past several decades.[1,2] In this paper, a group of intramolecular proton transfers in hydrocarbons and heteroatom substituted analogues, including twelve 1,3- and twelve corresponding 1,5-sigmatropic rearrangements (Scheme 1), have been investigated at the QCISD(T)/6-3 1 1G(d,p)∥B3LYP/6-311++G(d,p) level of theory.     

Novel furanoid alpha-substitued alpha-amino acid as a potent turn mimic in peptide synthesis

A stereoselective approach has been developed to the new sugar amino acid and potential potent turn mimic 5-O-(tert-butyldimethylsilyl)-3-deoxy-1,2-O-isopropylidene-3-methoxycarbonylamino-alpha-D-xylofuranose 3-C-carboxylic acid (12), via the [3,3]-sigmatropic rearrangement of allylic thiocyanates (Z)-6 and (E)-7, prepared from D-xylose. The synthesis of a new dipeptide 13 is also described.     

Synthesis and antibacterial activities of novel 2,5-diphenylindolo[2,3-e] pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines

The formation of (E)-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-yl)hydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1) and isatin (or isatin derivatives) 2 at room temperature. The (E)-products could be isomerized into corresponding the (Z)-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4-7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H)-thione (11). The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.     

Double diastereoselective [3,3]-sigmatropic aza-Claisen rearrangements

Asymmetric [3,3]-sigmatropic aza-Claisen rearrangement of the (Z)-N-allyl-N,O-silylketene aminal of (3S,4E,alphaR)-1-benzyloxy-3-(N-propionyl-N-alpha-methylbenzylamino)hex-4-ene furnishes (2S,3R,4E,alphaR)-N-alpha-methylbenzyl-2,3-dimethyl-7-benzyloxyhept-4-enamide in > 92% d.e.; rearrangement of the diastereomeric (3R,4E,alphaR)-(Z)-N,O-silylketene aminal proceeds with low diastereoselectivity.     

Direct transformations of ketones to gamma-unsaturated thiols via

The reaction of a series of ketones with dimsylsodium in dimethyl sulfoxide resulting in the formation of gamma-unsaturated thiols was studied experimentally. [2,3]-Sigmatropic rearrangements of beta-unsaturated sulfinyl carbanions are involved at the key step of those transformations. DFT computations at the B3LYP/6-31+G level indicated that such rearrangements, as well as some typical [2, 3]-sigmatropic rearrangements, e.g., thermal rearrangements of allyl sulfoxides and Wittig rearrangements of sulfur ylides and lithiated allyloxy methyl anions, are concerted and moderately synchronous processes. Negative (diatropic) nucleus-independent chemical shifts (NICS) and high diamagnetic susceptibility exaltations indicate that the transition structures of these [2,3]-sigmatropic migrations are aromatic.     

A theoretical study of the sulfenate–sulfoxide rearrangement. Effect of the hydrogen bond complexation

A DFT study of the thermal and radical sulfenate–sulfoxide rearrangement of derivatives of 3‐propenyl sulfoxide has been carried out. The effect of the substitution and hydrogen bond complexation has been analyzed. The results show that without external factors the radical breakdown path is the one preferred by the alkyl and aromatic derivatives while the unsubstituted system proceeds preferentially through a two‐step series of [1,3]‐ and [2,3]‐sigmatropic shifts. The inclusion of a hydrogen bond donor interacting with the oxygen atom increases the stability of all the species except the radical and the final products. Thus, in the dimethyl derivative the radical and two‐step processes present similar limiting steps. The analysis of the electron density of the systems provides some relationships between the properties at the bond critical point and the interatomic distances for the S···C and H···O cases. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2391–2397, 2010     

Total synthesis of (-)-13-oxyingenol and its natural derivative

Ring functionalization: the total synthesis of a natural derivative of (-)-13-oxyingenol, a potent anti-HIV diterpenoid, is reported. The key steps in this synthesis include a ring-closing olefin metathesis and a Mislow-Evans-type [2,3]-sigmatropic rearrangement. This synthesis provides access to (-)-13-oxyingenol and its natural derivative in 21 steps from a synthetic intermediate previously prepared by Kigoshi and co-workers.     

Five-membered 2,3-dioxoheterocycles 15. Synthesis and [1,3]-sigmatropic rearrangement of 1,5-diaryl-3-diphenylmethoxy-4-ethoxycarbonyl-2,5-dihydropyrrol-2-ones

Ethyl oxaloacetate reacts with a mixture of an aromatic aldehyde and an arylamine to give 1,5-diaryl-4-ethoxycarbonyltetrahydropyrrole-2,3-diones, which react with diphenyldiazomethane to give the O-alkylation products. On heating, the latter undergo suprafacial [1,3]-sigmatropic rearrangement to 1,5-diaryl-4-diphenylmethyl-4-ethoxycarbonyltetrahydropyrrole-2,3-diones. The effects of the type of migrating group on the rearrangement are discussed.For Communication 14, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–757, June, 1990.     

Methylene-azaphosphirane as a reactive intermediate

Reaction of the transient phosphinidene complexes R-P=W(CO)5 with N-substituted-diphenylketenimines leads unexpectedly to the novel 2-aminophosphindoles, as confirmed by an X-ray crystal structure determined for one of the derivatives. Experimental evidence for a methylene-azaphosphirane intermediate was found by using the iron-complexed phosphinidene iPr2N-P=Fe(CO)4, which affords the 2-aminophosphindole together with the novel methylene-2,3-dihydro-1H-benzo[1,3]azaphosphole. Analysis of the reaction pathways with DFT indicates that the initially formed methylene-azaphosphirane yields both phosphorus heterocycles by way of a [1,5]- or [1,3]-sigmatropic shift, respectively, followed by a H-shift. Strain underlies both rearrangements, which causes these remarkably selective conversions that can be tuned by changing the substituents.     

Repetierbare Ringerweiterungen durch [2,3]-sigmatropische Umlagerungen in cyclischen Allylsulfonium-allyliden; Synthese von mittleren und grossen Thiacyclen. Vorläufige Mitteilung

Repeatable ring expansions by [2,3]-sigmatropic shifts in cyclic allylsulfonium allylides; synthesis of medium- and large-sized thiacycles Allylation of a 2-vinyl thiacyclus with allyl bromide in 2,2,2-trifluoroethanol followed by ylide generation by use of aqueous potassium hydroxide results in a [2,3]-sigmatropic rearrangement with formation of a new 2-vinyl thiacyclus enlarged by three carbon atoms (Scheme 1). In this way, starting from the 5-membered ring 1 , a series of four ring enlargement sequences leads to the 17-membered thiacycles 9 and 10 via the 8-, 11- and 14-membered rings 4 , 7 and 8 (Scheme 2).     

Studies toward the enantioselective syntheses of oxylipins: total synthesis and structure revision of solandelactone E

An efficient and general entry to unsaturated cyclopropane- and lactone-containing oxylipins of marine origin has been designed and applied to the first enantioselective total synthesis of solandelactone E. The synthesis, which proceeds in a total of 23 steps from commercially available materials, features a diastereoselective acetal-directed cyclopropanation of an electron-deficient diene, a regioselective Sharpless enantioselective dihydroxylation, and a stereoselective [2,3]-sigmatropic rearrangement of a selenoxide to effect a 1,3-transposition of an allylic alcohol. Comparison of spectral data for the synthetic solandelactone, thus prepared, with data in the literature led to a revision of the original structural assignments of the C(11)-epimeric solandelactones.     

Enantioselective synthesis of α-alkyl,α-vinyl amino acids via [2,3]-sigmatropic rearrangement of selenimides

Chiral α-alkyl,α-vinyl amino acids (quaternary vinyl glycine derivatives) are prepared with high levels of enantiomeric purity by [2,3]-sigmatropic rearrangement of allylic selenimides. The required trisubstituted allylic selenides are prepared by an organocatalytic α-selenenylation of aldehydes followed by Horner-Wadsworth-Emmons (HWE) olefination. Both (E)-and (Z)-geometrical isomers are available giving access to both enantiomers of the desired products.     

Stereospecific thermal isomerization of 2, 2-dimethylbenzocyclobutenols to 2-isopropenylphenyl alcohols

Thermolysis of the 1-alkyl-2,2-dimethylbenzocyclobutenol 3 at 160 degrees C gave the 2-isopropenylphenyl alcohol 8 through an (E)-dienol intermediate by a 1,5-sigmatropic hydrogen shift from the isopropylidene methyl group to the carbon bearing hydroxy group. In the thermolysis of each of the diastereomeric 2, 2-dimethylbenzocyclobutenols 6 and 7 which have a hydroxy group on the beta-carbon of the quaternary C(1)-alkyl substituent, the isomerization to the 2-isopropenylphenyl alcohols 10 and 11 took place stereospecifically through a twisted (E)-dienol intermediate. The configuration of the newly formed chiral center in 10 and 11 was the same as that of the ring carbon bearing hydroxy group in the starting 6 and 7.     

Photochemische Reaktionen. 121. Mitteilung. Zur Photochemie von ε,ζ-Methano-α,γ-dienonen und 7,8-Methano-1,3,5-trienen

Photochemistry of ε,ζ-Methano-α,γ-dienones and 7,8-Methano-1,3,5-trienes Irradiation of the δ-cyclopropyl-dienone (E)- 6 (λ ≥ 347 nm) gives (Z)- 6, 10 (1,5-sigmatropic H-shift), (E/Z)- 9 (electrocyclic process involving C(ε), C(ζ)-cleavage) and 11 (ring opening). The corresponding 6-cyclopropyl-triene (E)- 7 gives on singlet excitation (δ > 280 nm) 14 (1,5-sigmatropic H-shift) and, to a smaller extent, the bicyclo [3.2.0] heptenyl-dienes (E/Z)- 13 . However, on triplet excitation (λ ≥ 347 nm, benzophenone) (E)- 7 gives (E/Z)- 13 as the main products. On both ¹π,π*- and ³π,π*-excitation, (Z)- 7 and 15 are formed in small amounts.