Swern Conditions Research Articles

Selective Synthesis of Interlocked Molecules with Topological Chirality

Mechanically interlocked molecules can be chiral if each of the rings has no bilateral symmetry. Although chiral catenanes have been isolated from racemic mixtures via chromatographic techniques, these optically active molecules have not been directly synthesized until now. In this issue of Chem, Goldup and co-workers describe an auxiliary approach for the stereoselective synthesis of the topological enantiomers of chiral [2]catenanes. This methodology enables exploration of the potential applications of these chiral molecules in areas such as medicine and materials science.

Direct oxidation of Δ2-isoxazolines synthesis by metal ion-mediated diastereoface-selective 1,3-dipolar cycloaddition with “activated” DMSO

A series of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one derivatives was prepared by magnesium ion-mediated diastereoface-selective 1,3-dipolar cycloaddition of aromatic nitrile oxides with pyrrolidinone derivatives. The reaction of 4-hydroxyl-Δ2-isoxazol-6(6aH)-one derivatives with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a Δ2-isoxazole-4,6(5H,6aH)-dione.

Chemo- and Regioselective 1,3-Dipolar Cycloaddition of 2-Diazopropane over 1,4-Benzoquinone: Synthesis of New Pyrazoloquinones

1,3-Dipolar cycloaddition reaction of 2-diazopropane 1 with 1,4-benzoquinone 2 carried out at −20 °C led to a minor mono-cycloadduct 4 and mixture of bis-cycloadducts 6 and 7. The same addition realized with 3H-pyrazole 7 at −60 °C for 2 h yields a mixture of compounds 8 and 9 and results in O-alkylation. The reaction of 3H-pyrazoles 4 and 7 with dimethylsulfoxide and oxalyl chloride under Swern conditions led to pyrazolenines 11 and 12.

The Swern Oxidation: First example of direct oxidation of 2-pyrazolines with “activated” DMSO

1,3-Dipolar cycloaddition of 2-diazopropane to conjugated dienes 1 and α,β-unsaturated ketones 5 is taking place regiospecifically to give cycloadduit 4 and 6. The reaction of 2-pyrazolines derivatives with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a pyrazolenines 7 and 8.

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

AbstractThe 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one (1) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF3⋅Et2O under anhydrous conditions. Intermediate 10 was available from the known enone 8, either via direct epoxidation (60% H2O2, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH4, THF), followed by epoxidation ([VO(acac)2], tBuOOH) and reoxidation under Swern conditions, in 37% total yield.

Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine

Tetrabenazine (1) was reduced with NaBH4 to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (−)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (−)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.

Synthesis of Surfactants Based on Pentaerythritol. I. Cationic and Zwitterionic Gemini Surfactants

Simple strategies for the synthesis of five series of cationic gemini surfactants and one series of zwitterionic gemini surfactants from pentaerythritol have been developed. Two lipophilic groups were introduced onto pentaerythritol by alkylation of the known compound, O-benzylidenepentaerythritol, with 1-bromooctane, 1-bromodecane, 1-bromododecane, and 1-bromotetradecane. Hydrogenolysis of the benzylidene acetals gave diols which were converted into three different series of trimethylammonium derivatives. The diiodides derived from the diols could be displaced by dimethylamine, even though they are adjacent to a quaternary carbon atom. Alkylation with methyl iodide gave the first series. The iodides were easily displaced by cyanide ion and the resulting dinitriles were hydrolyzed, converted to N,N-dimethylamides, and reduced to give a second series. Oxidation of the diols to dialdehydes under Swern conditions followed by Horner-Wadsworth-Emmons reactions with diethyl N,N-dimethylcarbamoylmethylphosphonate followed by two-stage reduction gave a third series. The dialkoxides derived from the four di-O-alkylpentaerthritol diols were reacted with 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride in neighboring-group assisted double Williamson ether syntheses to give precursors to two more series. As expected because the neighboring group participation occurs through a four-membered-ring intermediate, considerably more vigorous conditions were required for the reactions with 3-dimethylaminopropyl chloride. 2-Diethylaminoethyl bromide was found to be less reactive than 2-dimethylaminoethyl chloride. The products were alkylated with methyl iodide and, in some cases, other alkyl halides to give cationic gemini surfactants. Alkylation of one series with ethyl bromoacetate followed by anion exchange resin catalyzed ester hydrolysis gave zwitterionic gemini surfactants. The members of all series have superior surfactant properties.

Efficient, one-pot transformation of indoles into functionalized oxindole and spirooxindole systems under Swern conditions

The reaction of indole derivatives bearing a 3- or 4-hydroxyalkyl chain with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a one-pot, three-component process involving three different synthetic transformations, namely oxidation of indole to oxindole, introduction of a chlorine substituent at the oxindole C-3 position and substitution of the hydroxyl group in the side chain by chlorine, in good to excellent overall yields. The same conditions, applied to a 2-methylindole, afforded a 2-formylindole derivative oxidized at its side chain. The reaction starting from one indole with a 2-hydroxyalkyl chain furnished 3-(2-hydroxyalkyl)oxindoles. Finally, application of the Swern conditions to derivatives of indole-3-propionic or -butyric acid afforded 3-spirooxindole lactones.

One-Pot Synthesis of Highly Functionalized Oxindoles under Swern Oxidation Conditions

The reaction of indole derivatives bearing a 3- or 4-hydroxyalkyl chain with dimethyl sulfoxide and oxalyl chloride under Swern conditions led to a one-pot process involving three different synthetic transformations, namely oxidation of indole to oxindole, introduction of a chlorine substituent at the oxindole C-3 position, and substitution of the hydroxyl group in the side chain by chlorine. In spite of its mechanistic complexity, this synthetically useful process proceeded in good to excellent overall yield.

Synthesis of Symmetrical and Unsymmetrical Pyrazines.

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.

Synthesis of symmetrical and unsymmetrical pyrazines.

Opening of representative epoxides with 1,2-amino alcohols delivered the amino diols. The product amino diols were then oxidized under Swern conditions. The amino diketones so prepared were not isolated, but were condensed directly with hydroxylamine to give the substituted pyrazines.

Synthetic studies directed toward the total synthesis of dolabriferol

Herein we report our results towards the total synthesis of (−)-dolabriferol, describing the synthesis of fragments C1–C9 and C10–C21. This convergent asymmetric approach relies on the use of a common Weinreb amide precursor for the preparation of both fragments, an efficient anti-aldol reaction followed by Zn(BH 4) 2 reduction to give a 1,3- syn diol, a selective oxidation of a triol under Swern conditions with concomitant lactol formation, and a diastereoselective epoxidation of an allylic alcohol with m-CPBA followed by an efficient epoxide opening with Me 2CuCNLi 2.

ChemInform Abstract: Oxidation of Carbamate‐Protected Alkylhydrazines to the Corresponding Hydrazones under Swern Conditions.

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.

Oxidation of carbamate-protected alkylhydrazines to the corresponding hydrazones under Swern conditions

Carbamate protected alkylhydrazines have been found to oxidize cleanly to the corresponding hydrazone under Swern conditions. The reaction works on hydrazines with primary, secondary, and branched alkyl groups.

Total synthesis of 12(R)-HETE, 12(S)-HETE, 2H2-12(R)-HETE and LTB4 from racemic glycidol via hydrolytic kinetic resolution

The total synthesis of 12(R)-HETE, 12(S)-HETE (Samuelsson's HETE), [14,15-2H2]-12(R)-HETE and Leukotriene B4 from racemic glycidol is described. The key steps are the hydrolytic kinetic resolution of racemic TES-glycidol with salen-Co catalyst and the selective oxidation of primary silyl ethers, in the presence of secondary ones, under Swern conditions to give a short entry to both enantiomers of 12-HETE and LTB4.

Selective oxidation of primary silyl ethers and its application to the synthesis of natural products

Primary TMS or TES ethers, in the presence of secondary TMS or TES ethers, are selectively oxidized to the corresponding aldehydes under Swern conditions. A short synthesis of key intermediates towards various natural products has been achieved.

Total synthesis of cytochalasin D: total synthesis and full structural assignment of cytochalasin O

A total synthesis of cytochalasin D 3 is reported in which the key step is an intramolecular Diels–Alder reaction used to close the 11-membered ring simultaneously introducing the required stereochemistry at four of the stereogenic centres, C(4), C(5), C(8) and C(9). The precursor 21 for the Diels–Alder reaction was prepared from the aldehyde 13 by condensation with the dienyl phosphonate 14 to give the triene 15 which, after conversion into the acyl imidazole 17, was used to acylate the pyrrolidinone 18. The unstable pyrrolinone 21 was then generated from the pyrrolidinone by phenylselenation–oxidative elimination and was cyclised by heating in toluene under high dilution conditions to give the macrocyclic triene 22 (25–30%). Selective functionalisation of the double-bonds in this triene was investigated with epoxidation being selective for the 17,18-double-bond and hydroxylation using osmium tetroxide taking place selectively at the 6,7-double-bond. For completion of the synthesis of cytochalasin D 3, the 6,7-diol 26 was converted into the exocyclic alkene 30 by protection and dehydration. Further hydroxylation using osmium tetroxide gave the diol 31 which was taken through to the enone 36 by protection followed by phenylselenation, N-debenzoylation and oxidative elimination. Reduction under Luche’s conditions gave the alcohol 37 which was converted into the acetate 41 by acetylation followed by protecting group exchange. Selective deprotection of the vicinal diol and mild oxidation then gave the ketone 43. Final deprotection gave cytochalasin D 3 so completing the first total synthesis of this natural product.During the course of this work, the Diels–Alder adduct 22 was oxidised using an excess of osmium tetroxide to give the tetraol 28. After protection as its bis-acetonide 46, this was converted into the allylic acetate 51 using the chemistry developed during the synthesis of cytochalasin D 3. Selective hydrolysis of the 17,18-acetonide and oxidation under Swern conditions gave the hydroxyketone 53 which on deprotection gave cytochalasin O 54 so confirming the structure of this natural product.

Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral N-Acylnitroso Dienophile

An asymmetric total synthesis of (−)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels−Alder (D−A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-12f incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in “stacked” position and with the acylnitroso group in the s-cis conformation, wherein π attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 under...

An Intramolecular Prins Double Cyclization Catalyzed by Silyl Triflates1

Several intramolecular Prins double cyclizations are reported. The 2-alkyl 5-hepten-1,2-diols and their analogues, 9−11, were prepared and oxidized to the aldehydes 6−8 under Swern conditions. Treatment of these α-hydroxy aldehydes with TBSOTf and a hindered base gave the products of an intramolecular Prins double cyclization, namely the 7-(silyloxy)-2-oxabicyclo[2.2.1]heptanes, 17−19, in 84−92% yield. These compounds were formed as single diastereomers with only the anti silyl ethers being obtained. The cyclizations occur when five-membered rings are being formed and when the initially formed cation is highly stabilized. Other substrates do not cyclize, e.g., when the α-hydroxy aldehydes 20−22, prepared from 26−28, are treated under similar conditions, none of the corresponding cyclization products, 23−25, were obtained.

ChemInform Abstract: Synthesis and Stereoselective C‐C Bond Forming Reactions of Peptide Aldehydes.

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.