Johnson-Claisen rearrangement of γ-fluoro-γ-(di- or tri-fluoromethyl)allyl alcohols affording stereoselective access to β-fluoro-β-di- or tri-fluoromethylated γ,δ-unsaturated carboxylic acid esters

γ-Fluoro-γ-di- or tri-fluoromethyl-β-(tosyloxy)allyl alcohols smoothly reacted with the orthoacetic acid triethyl ester in the presence of a catalytic amount of propionic acid and hydroquinone at 140 °C for 24 h or 48 h to afford the corresponding (Z)-β-fluoro-β-polyfluoromethyl-γ,δ-unsaturated carboxylic acid esters in fair to good yields.     

高立体选择合成N,N''-取代-双-(反式-β,γ-二取代-γ-丁内酰胺)的简便方法

顺式－1－甲氧羰基－2－芳基－6，6－二甲基－5，7－二氧螺环[2，5]－4，8－辛二酮与联苯二胺（Ⅱ^0）或4，4'－亚甲基二苯胺（Ⅱ^1）在二氯甲烷中，40℃搅拌反应合成得到化合物Ⅲ^0 和Ⅲ^1，干燥后进一步在二甲苯中回流即可得到N，N－取代－双－（反式－β，γ－二取代－γ－丁内酰胺）（Ⅳ^0或Ⅳ^1），得率高，立体选择性好，方便简便。     

Highly stereoselective synthesis of β,γ-disubstituted and α,β,γ-trisubstituted butyrolactones

β,γ-Disubstituted butyrolactones were produced effectively and steroeselectively from arsonium ylides generated in situ and substituted olefins. The transformation could be realized in one-pot or in two steps, which depended on the electronic properties of the olefins. With the adjustment of the solvent and in the presence of EtOH, α,β,γ-trisubstituted butyrolactones were also obtained in high yield from arsonium ylides and substituted olefins.     

Polyformylation of copper(II) porphyrins

Vilsmeier formylation of copper(II) octaethylporphyrin (1) is shown to yield the copper(II) complexes of meso-monoformyloctaethylporphyrin, meso-α,β- and meso-α,γ-diformyloctaethylporphyrins, meso-α,β,γ-triformyloctaethylporphyrin, and meso-α,β,γ,δ-tetraformyloctaethylporphyrin. There is therefore no difference in regioselectivity of meso-diformylation between the octaethylporphyrin and etioporphyrin-I series.     

Asymmetric synthesis of α,β-diamino acid derivatives with an aziridine-, azetidine- and γ-lactone-skeleton via Mannich-type additions across α-chloro-N-sulfinylimines

The efficient asymmetric synthesis of new chiral γ-chloro-α,β-diamino acid derivatives via highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycine esters across a chiral α-chloro-N-p-toluenesulfinylimine was developed. The influence of the base, LDA or LiHMDS, used for the formation of the glycine enolates, was of great importance for the anti-/syn-diastereoselectivity of the Mannich-type reaction. The γ-chloro-α,β-diamino acid derivatives proved to be excellent building blocks for ring closure towards optically pure anti- and syn-β,γ-aziridino-α-amino esters, and subsequent ring transformation into trans-3-aminoazetidine-2-carboxylic acid derivatives and α,β-diamino-γ-butyrolactones.     

Development of methods for the synthesis of libraries of substituted maleimides and α,β-unsaturated-γ-butyrolactams

Synthetic methods for the preparation of maleimide and α,β-unsaturated-γ-butyrolactam compound collections are described. These routes take advantage of Pd cross-coupling and conjugate addition/elimination reactions to permit the facile production of bisaryl-maleimides, anilinoaryl-maleimides, and bisanilino-maleimides while allowing control over the synthesis of symmetrical or nonsymmetrical derivatives. Similarly, the chemistry developed allows for the generation of bisaryl substituted α,β-unsaturated-γ-butyrolactams. The scope and limitations of the approaches are presented.     

Isomerisations acides de cyclobutanones tetrasubstituees

The acid-catalysed rearrangement of substituted cyclobutanones has been studied. The treatment of the the α,α′ - or α,β-tetrasubstituted compounds with trifluoroacetic acid gives α,β- or β,γ-unsaturated ketones, by a succession of Wagner-Meerwein migrations.     

Induced Circular Dichroism and Magnetic Circular Dichroism Spectra of Maleimide and Related Molecules

The induced circular dichroism (ICD) spectra of the inclusion complexes of maleimide, phthalimide, and naphthalene‐2,3‐dicarboximide with β‐ or γ‐cyclodextrin (CDx) have been measured. The structure of the CDx inclusion complexes are interpreted by the signs and shapes of ICD spectra compared with the results of PPP calculations. In maleimide and naphthalene‐2,3‐dicarboximide, the ICD spectra of the β‐CDx inclusion complex are very similar to those of the γ‐CDx inclusion complex in spite of the differences in dimensions between the cavity of β‐CDx and that of γ‐CDx. In phthalimide, the ICD spectra of the β‐CDx inclusion complex are very different from those of the γ‐CDx inclusion complex. The split‐type ICD bands at 220–235 nm show that the dimer of phthalimide is formed in the presence of β‐CDx.     

Nucleoside-5'-phosphorothioate analogues are biocompatible antioxidants dissolving efficiently amyloid beta-metal ion aggregates

Amyloid beta (Aβ) peptide is known to precipitate and form aggregates with zinc and copper ions in vitro and, in vivo in Alzheimer's disease (AD) patients. Metal-ion-chelation was suggested as therapy for the metal-ion-induced Aβ aggregation, metal-ion overload, and oxidative stress. In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we tested a series of nucleoside 5'-phosphorothioate derivatives as re-solubilization agents of Cu(+)/Cu(2+)/Zn(2+)-induced Aβ-aggregates, and inhibitors of Fenton reaction in Cu(+) or Fe(2+)/H(2)O(2) system. The most promising chelator in this series was found to be APCPP-γ-S. This nucleotide was found to be more efficient than EDTA in re-solubilization of Aβ(40)-Cu(2+) aggregates as observed by the lower diameter, d(H), (86 vs. 64 nm, respectively) obtained in dynamic light scattering measurements. Likewise, APCPP-γ-S dissolved Aβ(40)-Cu(+) and Aβ(42)-Cu(2+)/Zn(2+) aggregates, as monitored by (1)H-NMR and turbidity assays, respectively. Furthermore, addition of APCPP-γ-S to nine-day old Aβ(40)-Cu(2+)/Zn(2+) aggregates, resulted in size reduction as observed by transition electron microscopy (diameter reduction from 2.5 to 0.1 μm for Aβ(40)-Cu(2+) aggregates). APCPP-γ-S proved to be more efficient than ascorbic acid and GSH in reducing OH radical production in Fe(2+)/H(2)O(2) system (IC(50) values 85, 216 and, 92 μM, respectively). Therefore, we propose APCPP-γ-S as a potential AD therapy capable of both reducing OH radical production and re-solubilization of Aβ(40/42)-M(n+) aggregates.     

Synthesis of α- and/or γ-benzoyloxy-α,β-enones from α-halo-α,β-enones

Sodium benzoate reacts with α-halo-α,β-enones in the presence of tetrabutylammonium hydrogensulfate or 18-Crown-6 to afford α- and/or γ-benzoyloxy-α,β-enones in good yield. The α/γ and γ/γ′ selectivities are dependent on the substrate and reagent.     

Stereoselective synthesis of (Z)-γ-cyano-β-perfluoroalkyl-β,γ-unsaturated esters

(Z)-γ-Cyano-β-perfluoroalkyl-β,γ-unsaturated esters have been synthesized by the reaction of perfluoroacylated phosphonates with organozinc reagent in 50-71% (three steps) yields.     

Synthesis of Unsaturated F-Alkyl Sulfoxides

The action of p-toluenesulfonyl chloride on β-hydroxy-β-F-alkyl sulfoxides and β-hydroxy-γ-F-alkyl sulfoxides in basic medium leads to the α,β-unsaturated sulfoxides and α,β-δ,γ- unsaturated sulfoxides respectively.     

New chemo and chemo-enzymatic synthesis of β-benzyl-γ-butyrolactones

β-Benzyl-γ-butyrolactones, important intermediates for the synthesis of butyrolactone lignans, have been synthesized by a new route involving preparation of α-β-unsaturated formyl esters. The formyl esters can easily be converted into the desired butyrolactones either through chemical transformations or by enzymatic methods.     

Stereoselective syntheses of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and naturally occurring lipid guggultetrol

γ-Oxo-butyramides derived from tartaric acid serve as excellent precursors for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and for the synthesis of tetrols containing three contiguous stereogenic centres. The methodology presented here is general for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones. Utility of the chiral building block was demonstrated by the synthesis of naturally occurring lipid guggultetrol.     

Study on Inclusion Complexes of Cyclodextrin with Sodium Dodecyl Polyoxyethylenated Sulfonate Using Microcalorimetry and 1H NMR

The association of α‐, β‐ and γ‐cyclodextrin (α‐CD, β‐CD and γ‐CD) with sodium dodecyl polyoxyethylenated sulfonate (C₁₂E_nS n=1, 3) was studied by means of isothermal titration calorimetry and ¹H NMR measurements in aqueous solution at T=298.15 K. The results indicate that the binding processes of β‐CD with the surfactants are characterized by both enthalpy favorable and entropy favorable, while those of α‐CD or γ‐CD with the surfactants are mainly entropy driven. The stoichiometry of β‐CD binding with the surfactants is different with different numbers of oxyethyl groups in surfactant molecules, while that of α‐CD or γ‐CD binding with the surfactants makes no difference. The ¹H NMR spectra reveal that chemical shift data of all protons in α‐CD, β‐CD and γ‐CD molecules move to high field in the presence of C₁₂E_nS, which can be regarded as a microscopic evidence of the occurrence of inclusion interaction.     

Titanium(IV) chloride-mediated ring cleavage and Michael addition of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]-cyclobutanones

β'-Chloro and β',γ'-unsaturated trichlorotitanium enolates, which were formed in situ by titanium(IV) chloride-mediated ring cleavage of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]cyclobutanones, reacted with enones to give Michael adducts with keeping a labile β'-chloro or β',γ'-unsaturated group.     

Conjugate addition of organocopper reagents to n-tosylated α, β-unsaturated amides

N-Tosylated α, β-unsaturated amides and lactams undergo facile conjugate addition with R²CuLi or RMgX/CuI (cat.). Stereoselective synthesis of trans-β,γ-dialkyl-γ-lactams can be achieved by this procedure. The resulting N-tosylamide moiety is further transformed to alcohol and several carbonyl compounds by way of reduction or nucleophillic displacement.     

Syntheses of β- and γ-fluorophenyl cis- and trans-α-methylene-γ-butyrolactones

Preparation of a series of cis-γ-fluorophenyl-β-phenyl-α-methylene-γ-butyrolactones is reported via ‘allylboration’ of fluorobenzaldehydes with (E)-methyl 3-phenyl-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)acrylate. The corresponding trans-γ-fluorophenyl lactones were prepared either (i) via ‘allylboration’ using the (Z)-reagents or (ii) via an indium triflate-mediated isomerization of the cis-products. The difficulty in isomerizing difluorinated cis-products confirms the probable intermediacy of carbocations. Finally, the synthesis of cis-β-fluorophenyl-γ-phenyl-α-methylene-γ-butyrolactones was achieved via an indium-catalyzed allylation–lactonization of aldehydes with (Z)-2-(bromomethyl)-3-(fluorophenyl)acrylates.     

Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides

Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides took place in good yields to give products exclusively with cis-β,γ-olefinic bond.     

Pd-Catalyzed [3+2]-Dehydrogenative Annulation Reactions

The significance of cross dehydrogenative couplings has increased considerably in recent years. This article revisits the [3+2] C−C/N−C, C−C/O−C and C−C/C−C annulation strategy, recently reported by our group, according to a Pd(II) catalyzed dehydrogenative variant. Our original report relied on Pd(0) catalysis, using α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles and resonance-stabilized acetamides or 3-oxoglutarates as C/N and O/C or C/C bis-nucleophiles, respectively. In this more modern and straightforward Pd(II)-catalyzed dehydrogenative approach, β,γ-unsaturated carbonyl derivatives replace α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles. Our study includes experimental optimization and showcases the synthetic versatility in the formation of diverse heterocyclic structures, such as bicyclic lactams, furo-cycloalkanones and bicycloalkane-diones. Furthermore, a mechanism is proposed to elucidate the underlying processes involved in these reactions.