Efficient synthesis of γ-keto sulfones by NHC-catalyzed intermolecular Stetter reaction

The N-heterocyclic carbene-catalyzed intermolecular Stetter reaction of aldehydes with α,β-unsaturated sulfones allows the atom-economic and selective formation of γ-keto sulfones in good yields. Key to the success of this unique transition-metal-free carbon-carbon bond-forming reaction is the right choice of the NHC precursor and base. The reaction tolerates a broad range of different aldehydes.     

A new reaction of diazomethane with norbornyl α-diketones

A new reaction of diazomethane with norbornyl α-diketones in MeOH as solvent leading regioselectively to ketals is described. The mechanistic details of this intriguing reaction were investigated employing d₄-MeOH, EtOH and d₆-EtOH. The surprising observation of complete deuterium incorporation in the diazomethane-derived methoxy group was accounted for by sequential deuterium exchange between the initially formed hemiketal d₄-18 and diazomethane in the presence of d₄-MeOH as solvent.     

Copper-catalyzed diversified annulations between α-diketones and alkynyl α-diketones

Copper-catalyzed divergent annulations between α-diketones and alkynyl α-diketones have been achieved, delivering a series of highly functionalized and biologically important cis-hexahydro-2Hcyclopenta[b]furan(HCPF) and 2-hydroxydihydrofuran-3(2H)-one(HDFO) products with high levels of stereoselectivity under identical conditions. The protocol features the use of earth-abundant copper catalyst, mild conditions, shortening synthetic routes in constructing different molecular frameworks, and reduc...     

Catalytic chemodivergent annulations between α-diketones and alkynyl α-diketones

Four types of unprecedented and chemodivergent reactions between α-diketones and alkynyl α-diketones have been achieved under the catalysis of phosphine and Br?nsted base, respectively, leading to the rapid construction of four different classes of biologically important but synthetically challenging molecular scaffolds including 2-hydroxyfuran-3(2H)-ones, 4-hydroxy-2-oxabicyclo[2.2.1]heptan-3-ones, 1,3-diaryl cyclobutanes, and 4-(furan-2(3H)-ylidene)cyclopent-2-enones. The formation of the products includes two novel rearrangement processes, and further transformations on the products can be easily achieved to deliver value-added substances such as highly functionalized cyclopentanes. Moreover, the 2-hydroxyfuran-3(2H)-one products display promising photophysical properties such as green luminescence under UV light and aggregation-induced emission effect,showing the practical application value of this work. The great potential of α-diketones in both synthetic chemistry and material science has been unambiguously demonstrated.     

Exploring the metal-catalyzed reaction of furans with alkyl α-diazomethanesulfonate and α-diazomethanephosphonate: synthesis of ω-acyl-substituted sulfono- and phosphonobutadienes

The metal-catalyzed reactions of neopentyl α-diazomethanesulfonate (DAMS) and diisopropyl α-diazomethanephosphonate (DIDAMP) with furan, 2-methylfuran and 2-methoxyfuran are reported. The products consist mostly of ω-acyl-substituted sulfono- or phosphonobutadienes and exo-cyclopropane derivatives. Treatment of the multicomponent reaction mixtures with iodine afforded exclusively the corresponding (E,E)-sulfono- and phosphono-ω-acylfunctionalized dienes, thus providing a short and efficient synthetic route to these hitherto unreported classes of compounds.     

Intra- and intermolecular reaction selectivities of γ-substituted adamantanylidenes

A study of adamantanylidenes having a γ-substituent (R) was undertaken to gauge how inductive and steric effects of remotely positioned functional groups influence intra- and intermolecular product selectivity. 3H-Diazirines were thermolyzed or photolyzed to generate the corresponding carbenes. On rapid heating, the resulting carbenes isomerized to 2,4-didehydroadamantanes by intramolecular 1,3-CH insertions. When R was an electron donor (R(D)) mostly asymmetric 1-substituted derivatives were produced but when it was an electron acceptor (R(A)) the symmetric 7-substituted ones were formed. When solutions were exposed to UV-A light, intermolecular adducts from the carbenes and solvent predominated with lesser amounts of intramolecular product being formed. Valence isomerization of 3H-diazirines also afforded diazo compounds. In methanol, protonation of diazo compounds to give the corresponding 2-adamantyl cations exceeds their coupling. This diversion was controlled with fumaronitrile by trapping the diazo compounds. The adducts possessed mostly anti configurations with R = R(D) and syn arrangements with R = R(A). The connection between as- and anti-product formation and that of s- and syn-products was deemed to be the consequence of a rapid equilibrium between two distinct carbene conformations. This was qualified and quantified using ab initio calculations and NBO analyses.     

Synthesis of indenoindene-fused α-methylene-γ-butyrolactones via a tandem intra- and intermolecular Friedel-Crafts reaction

An efficient synthesis of indenoindene-fused α-methylene-γ-butyrolactones was carried out via a tandem intra- and intermolecular Friedel-Crafts reaction from the spiro-lactone, which can be easily prepared from ninhydrin by indium-mediated Barbier reaction of cinnamyl bromide.     

Microwave-assisted synthesis of fused pyrazolo[3,4-b]pyrazines by the reaction of ortho-aminonitrosopyrazoles and cyclic β-diketones

Novel fused pyrazolo[3,4-b]pyrazines 3 were prepared by assisted microwave cyclocondensation reaction of ortho-aminonitrosopyrazoles 1 and cyclic β-diketones 2 in dimethylformamide. This protocol provides a simple procedure for the synthesis of the title compounds with the advantages of easy work-up, mild reaction conditions and good yields.     

Highly enantioselective intermolecular Stetter reactions of β-aryl acceptors: α-ketoester moiety as handle for activation and synthetic manipulations

The use of β,γ-unsaturated-α-ketoesters in the intermolecular Stetter reaction furnishes 1,2,5-tricarbonyl compounds in high yield and excellent enantioselectivity. The α,δ-diketoesters generated using this methodology serve as useful synthetic building blocks via chemo- and diastereoselective transformations.     

Synthesis of cis,cis-diunsaturated α-meromycolic acid by a palladium-catalysed alkyl–alkyl Negishi reaction

The first total synthesis of cis,cis-diunsaturated α-meromycolic acid has been accomplished using a convergent strategy and a palladium-catalysed alkyl–alkyl Negishi reaction as the key step.     

The asymmetric synthesis of chiral cyclic α-hydroxy phosphonates and quaternary cyclic α-hydroxy phosphonates

A highly practical, catalytic enantioselective cyclic phosphite addition to aldehydes and ketones was developed. The reaction rate of the asymmetric hydrophosphonylation was significantly enhanced by the addition of silver carbonate. Particularly, significant improvement has been achieved on the asymmetric hydrophosphonylation of unactivated ketones, giving quaternary α-hydroxy phosphonates with excellent enantioselectivity (up to 99% ee).     

Additions of free dimethylgermylene to vinyl ketones and α-diketones

Derivatives of 1-oxa-2-germacyclopent-4-ene are obtained from germylenes with a number of cyclic or acyclic vinyl ketones, and 1,3-dioxa-2-germacyclopent-4-enes with different non-enolizable α-diketones. Structure-mechanism relationships are discussed.     

A new approach to the synthesis of cyclic ethers via the intermolecular allylation of α-acetoxy ethers and ring-closing metathesis

A concise synthesis of the isolaurepinnacin skeleton 6 was achieved via the intermolecular allylation of the α-acetoxy ether 3 followed by ring-closing metathesis. This methodology was successfully applied to the convergent synthesis of the oxocene 15, an advanced synthetic intermediate for the total synthesis of laurencin.     

Synthesis of symmetrical α-alkyl- and α-arylalkylbenzyl and diarylmethyl ethers by HCl-catalyzed intermolecular dehydration

α-Alkyl-, α-arylalkyl-, and α-aryl-substituted benzyl alcohols were converted into the corresponding symmetrical dibenzyl ethers in the presence of a catalytic amount of 10% aqueous HCl both in methylene chloride and under solvent-free conditions. Analogous reactions in dioxane and on heating afforded mainly the corresponding arylalkenes, whereas symmetrical dibenzyl ethers were formed as minor products.     

Rh-catalyzed intermolecular reactions of cyclic α-diazocarbonyl compounds with selectivity over tertiary C-H bond migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C-H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X-H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described.     

Vibrational spectra and intermolecular potential of the α-form crystal of glycine

Polarized Raman and far i.r. spectra of glycine and N-deuterated glycine crystallized in the α-form were recorded. The normal coordinate analysis of the optical active intra- and intermolecular vibrations of the α-form crystal of glycine was carried out. A modified Urey—Bradley type intramolecular potential was adopted. The observed factor group splittings were elucidated fairly well by using the intermolecular potential including the exchange repulsion—dispersion interaction between non-bonded atoms and the Coulomb interaction. The stretching potential for the hydrogen bonds was found to contribute appreciably to the lattice frequencies.     

Phosphorescence of α-diketones from ozone-olefin reactions

Phosphorescence spectra of α-diketones in the gas phase have been measured at 3 to 12 Å resolution, and are compared with equally well resolved chemiluminescence spectra from ozone-olefin reactions. Glyoxal phosphorescence could be identified in the chemiluminescence spectra of propene, 1-butene, cis- and trans-2-butene, and cyclohexene. Methylglyoxal phosphorescence results from the reactions of isobutene, trimethyl-ethylene, tetramethyl-ethylene. Biacetyl phosphorescence most probably does not contribute to the chemiluminescence of ozone-olefin reactions. The pressure dependence ofthe phosphorescence from the ozone-tetramethyl-ethylene reaction yields rate constants of 2.6 × 10⁻¹⁵ and 2.5 × 10⁻¹⁶ cm³ molecule⁻¹ s⁻¹ for the quenching of methylglyoxal phosphorescence by O₂ and N₂. The relative pressure dependences of formaldehyde fluorescence, glyoxal phosphorescence and methylglyoxal phosphorescence, as well as their excitation mechanisms are briefly discussed.