Synthesis of the insect antifeedant CDE molecular fragment of 12-ketoepoxyazadiradione and related compounds

A diastereoselective synthesis of the model insect antifeedant 29 a CDE molecular fragment of 12-ketoepoxyazadiradione has been achieved in ten steps from indenone 9 in 44% overall yield. Several of the compounds obtained along the synthesis related to model compound 29 show significant antifeedant activity against Spodoptera littoralis and Spodoptera frugiperda.     

A stereoselective synthesis of squalamine

Squalamine (1) was synthesized stereoselectively in 14 steps and 19% overall yield from 3-keto-5-chenodeoxycholanate (2) by using a modified Sharpless asymmetric dihydroxylation as the key step.     

Optically active nitroalkenes—synthesis, addition reactions and transformation into amino acids

Optically active nitroalkenes 4 were synthesized via Henry reaction. Conjugate addition of vinylmagnesium bromide to 4 gave nitroalkane syn-5 while cyclopropanation with sulfur ylides or dibromocarbene afforded nitrocyclopropanes 8, 10 and 11 in a diastereoselective manner. These products were used to synthesize optically active β-amino acids 7 and 16 as well as cyclopropane γ-amino acids 19 and 20 by reduction of the nitro group and oxidative cleavage of the dioxolane substituent.     

Application of organolithium and related reagents in synthesis. Part 25: Novel specific synthesis of the 4-arylisochroman-3-acetic acids via conversion of benzoic acids

The transformation of the benzanilides 1 into 4-arylisochroman-3-acetic acids 8 applying the following sequence of reactions is described. At first, the 3-arylphthalides 3 were obtained via metallation [n-BuLi] of benzanilides 1 and subsequent treatment of the generated bis-lithiated anilides 2 with aromatic aldehydes. Next, the 3-arylphthalides 3 were reduced [LiBH₄] to phthalanes 5 and then, via reductive metallation [Li/C₁₀H₈] and reaction of the generated bis-lithiated species 6 with dimethylformamide, 3-hydroxy-4-arylisochromans 7 were produced. In the final step the isochromans 7 were treated with 1-methoxy-1-trimethylsilyloxyethene in the presence of titanium tetrachloride and furnished 4-arylisochromans-3-acetic acid methyl esters 8 as trans stereoisomers (Ψ-e/e).     

Pyrazole-tethered arylphosphine ligands for Suzuki reactions of aryl chlorides: how important is chelation?

Pyrazole-derived bidentate ligands (P,N-donor) with bulky substituents at the 3-position of the pyrazole, 1b–d, were used with Pd₂(dba)₃ to carry out efficient Suzuki coupling reactions with both aryl bromides and chlorides. Enhanced catalytic activity on account of steric crowding in the metal complex suggested participation of a chelated structure in the intermediate catalytic steps.     

A ring-fission/C–C bond cleavage reaction with an N-alkyl-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine

The reaction of N-(3,4-dichlorophenethyl)-N-methylamine (1) with 3-chloromethyl-5-phenyl-1,2,4-oxadiazole (2) was investigated. Employment of an equimolar amount of 1 and 2 in the presence of potassium carbonate led to the expected tertiary amine 3 (N-[(3,4-dichlorophenyl)ethyl]-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine), whereas an excess of 1 and prolonged reaction time resulted in ring fission of the oxadiazole system in 3 and finally in the formation of N′-benzoyl-N-[(3,4-dichlorophenyl)ethyl]-N-methylguanidine (4) and N,N′-bis[(3,4-dichlorophenyl)ethyl]-N,N′-dimethylmethanediamine (5). The structures of products 3–5 were determined by means of ¹H and ¹³C NMR-spectroscopy, mass spectrometry and IR-spectroscopy, for 3 (as picrate) and 4 also X-ray structure analysis was employed. A possible mechanism of the reaction pathway leading to compounds 4 and 5 is proposed.     

Unprecedented cyclisations of calix[4]arenes under the Mitsunobu protocol. Part 3: Thiacalix[4]crowns versus dimers

Intermolecular couplings versus intramolecular ring closures were observed in the reaction of p-tert-butylthiacalix[4]arene and diethylene glycols affording dimers 2 and/or the inherently chiral 1,2-thiacalix[4]crown-3 derivatives 5 under the Mitsunobu protocol. The enantiomeric separation of 5a was achieved by chiral HPLC. The reaction of thiacalix[4]monocrowns 1 with diethylene glycols failed to give crowned thiacalix-tubes 7, instead biscrowns 8 were formed. Partially alkylated double thiacalix[4]arenes 10, 11 were obtained via the base promoted alkylations of a thiacalixarene dimer 2a containing diethyleneoxy linkers.     

Synthesis of helianane, an unusual marine sesquiterpene employing ring-expansion by flash vacuum thermolysis

A total synthesis of the marine sesquiterpene helianane 1 is described involving the thermal rearrangement of the benzoxabicyclo[4.2.0]octenone 4 to generate the dienone 5 incorporating the benzoxocane ring system of 1. This dienone was converted to the key ketone 11, which on interaction with methylmagnesium iodide followed by hydrogenation of the resulting alkene 18 furnished helianane 1.     

Synthesis of tripodal aza crown ether calix[4]arenes and their supramolecular chemistry with transition-, alkali metal ions and anions

Tripodal aza crown ether calix[4]arenes, 5a, 5b, 6a and 6b, have been synthesized. The structure of protonated 5a was elucidated by X-ray crystallography to be a self-threaded rotaxane. Complexation studies of 5a and 5b towards anions using Na⁺ as countercation were carried out by ¹H NMR titration in dimethylsulfoxide-d₆ and the mixture of chloroform-d and methanol-d₄, respectively. Ligands 5a and 5b were able to form 1:1 complexes with Br⁻, I⁻ and NO₃⁻ and the complexation stability varied as follows: NO₃⁻>I⁻>Br⁻. The effect of countercation on anion complexation was also investigated. The results showed that the association constants of 5a towards Br⁻ in the presence of various cations varied as K⁺>Bu₄N⁺>Na⁺. The enhancement in anion complexation ability of 5a may result from the rearrangement of the tripodal ammonium unit in the presence of K⁺. The neutral forms, 6a and 6b, were able to form complexes with transition metal ions such as Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺. The stability of the complexes followed the sequence: Ni²⁺2+Cu²⁺Zn²⁺. Compounds 6a and 6b may, therefore, potentially be used as either transition metal ion or anion receptors that can be controlled by pH of the solution.     

New dense fluoroalkyl-substituted imidazolium ionic liquids

New mono and polyfluoroalkyl-substituted ionic liquids have been synthesized and characterized. The neat reaction of 1-methylimidazole (1a) with 1,1,1-trifluoro-3-iodopropane (2a) at 80°C formed the quaternary salt, 1-methyl-3-trifluoropropylimidazolium iodide (3), in 90% yield. Similarly, sodium imidazole (1b) gave good yields of the quaternary salts, 1,3-bis(trifluoropropyl)imidazolium iodide (3b) with an excess of 2a, and 1,3-bis(monofluoropropyl)imidazolium bromide (3c) with an excess of 1-fluoro-3-bromopropane (2b). In water as solvent, metathesis reactions of 3 with KPF₆, LiN(SO₂CF₃)₂ and KSO₃CF_3, and of 3b and 3c with KPF₆ and LiN(SO₂CF₃)₂ led to 4a–c, 4d,e, and 4f,g, respectively, in good isolated yields. Some of the di(polyfluoroalkyl)imidazolium salts are liquids with densities in excess of 1.8 g/cm³.     

A novel extension of the Stork–Jung vinylsilane Robinson annelation procedure for the introduction of the cyclohexene of guanacastepene

A new annelation procedure has been developed in a model system to introduce the cyclohexene ring of guanacastepene. Cyclohexenone 16 is prepared by sequential methylation and alkylation with allylic iodide 15. One-pot epoxidation, protodesilylation and hydrolysis of the THP forms dione 19, which cyclizes with NaOMe to 24 in 57% overall yield. Reduction, Mitsunobu inversion, and selective oxidation of the primary alcohol forms model 29. Phenyldimethylsilyl allylic iodide 36 is easier to make and more stable than trimethylsilyl allylic iodide 6 used by Stork.     

Unexpected sulfonylamino migration in the reactions of carbazole derivatives with fluoroalkanesulfonyl azides

The reactions of fluoroalkanesulfonyl azides 1 with carbazole derivatives have been studied in detail. At room temperature 1 reacted with 1,2,3,4-tetrahydrocarbazole 2 readily to afford ring-contraction spiroindole derivatives 3 together with an unexpected 4a-fluoroalkanesulfonylamino-1,2,3,4-tetra-hydrocarbazoles 4. However, in the case of 9-methyl-1,2,3,4-tetrahydrocarbazole 5, unexpected sulfonylamino migration occurred and a similar product 9-methyl-1-fluoroalkanesulfonylamino-2,3,4,9-tetrahydro-1H-carbazoles 6 were obtained as major products in moderate yields. These new products were fully characterized by spectral methods and single X-ray diffraction analyses. Possible mechanisms for these reactions were proposed.     

Synthesis and photochromic reactivity of macromolecules incorporating four dithienylethene units

Two macrocycles bearing four dithienylethene units were synthesized. Upon irradiation of the macrocycles 5 and 6 with ultraviolet light, only one or two photo-induced cyclization reaction occurs. Each isomers were isolated and analyzed by ¹H NMR spectrum. The quantum yield of 5 and 6 are 0.58 and 0.64, respectively. The high value is due to the presence of enforced antiparallel conformation in the macrocycles 5 and 6.     

Formation of 1,2,4-trioxolanes via 9,10-dicyanoanthracene(DCA)-sensitized photo-oxygenation of 2,2-diaryl-3-(2,2-diarylvinyl)oxiranes

9,10-Dicyanoanthracene-sensitized photo-oxygenation of 2,2-diaryl-3-(2,2-diarylvinyl)oxiranes 3 in acetonitrile did not afford the corresponding 1,2,4-trioxepines 4, but 1,2,4-trioxolanes 7. The structural assignment of 7 was reported, and the mechanism of the formation of 7 was proposed.     

Synthesis of new 1,2,4-oxadiazolidin-3-ones by cycloaddition of 2-alkyl-3-aryloxaziridines with chlorosulfonylisocyanate

2-Alkyl-4-chlorosulfonyl-5-aryl-1,2,4-oxadiazolidin-3-ones 5 were prepared via cycloaddition of 2-alkyl-3-aryloxaziridines 3 with chlorosulfonylisocyanate. The structure of 5 was proved by a crystal X-ray analysis. Hydrolysis of 5 in the presence of triethylamine afforded 2-alkyl-5-aryl-1,2,4-oxadiazolidin-3-ones 6.     

Stereoselective synthesis of hyptolide and 6-epi-hyptolide

The first stereoselective syntheses of the naturally occurring, ,β-unsaturated lactone hyptolide 1 and of its nonnatural epimer at C-6 are described. Ethyl l-lactate was the chiral starting material. Key steps of these syntheses were a Brown's asymmetric allylation, a Carreira's asymmetric ethynylation and a ring closing metathesis.     

Novel sesquiterpenes and a lactone from the Jamaican sponge Myrmekioderma styx

Two novel sesquiterpenes, styxone A (1) and styxone B (2), and a novel lactone, styxlactone (3), were isolated from the Jamaican sponge Myrmekioderma styx. Their structures were elucidated by detailed ¹H, ¹³C and 2D NMR data and the absolute stereochemistry of styxone A and B was determined by CD spectra. Styxone A represents a novel sesquiterpene skeleton. (S)-(+)-Curcuphenol (4), (S)-(+)-curcudiol (5), and abolene (6) were also isolated. An activity enhancement by cyanthiwigin B (7) to curcuphenol was observed in the antimicrobial assays when the two compounds were administered together.     

The first synthesis of tetraglucosyl glucitol having phytoalexin-elicitor activity in rice cells based on a sequential glycosylation strategy

We describe a highly convergent approach for the synthesis of the tetraglucosyl glucitol 1 and its derivatives 4, 5 and 6 which exhibit phytoalexin-elicitor activity in rice cells based on sequential glycosylation.     

Site-recognition of one of the two alkoxy carbonyl groups present in the dienophile for Diels–Alder reaction

Recognition of one alkoxy carbonyl group from the two in a molecule by a Lewis acid was investigated using 1a–e in the Diels–Alder reaction with diene 6. Combination of 1a and BF₃·OEt₂ provided the highest efficiency to afford 7a, thus showing evidence for the site-selective coordination of BF₃·OEt₂ to the MOM-oxy carbonyl group in 1a. Furthermore, the generality and high reactivity of this combination were confirmed with dienes 11–14.     

5-Aminocyclopentadienes by intramolecular addition of enolether to aminoallene functionalities

3-(1-Alkoxyvinyl)-1-aminoallenes 6 were generated by conjugate addition of acyclic and cyclic (1-alkoxyvinyl)cuprates with the semicyclic propyne iminium salt 4. They isomerized smoothly into spiroannellated cyclopentadienes 7 through a 1,5-cyclization that in some cases occurred already at ≤20°C. (1-Methoxyallenyl)cuprates reacted with salt 4 in a 2:1 ratio to give the 5,5-dimethoxy-4-methylenepentalene-1-spiro-2′-dihydroindole derivative 10. The thermal isomerization of morpholinoallene 12 into cyclopentadiene 13 indicates that the novel 1,5-cyclization can be extended to other 3-(1-alkoxyvinyl)-1-aminoallenes as well.