Molecular and crystalline structure of furfural diacetate nitration intermediate

X-ray crystallography established the structure of the acetyl nitrate adduct to furfural diacetate (H. Gilman and G.F. Wright (1930)) as trans-2-acetoxy-5-nitro-2,5-dihydro-2-furfural diacetate (1a). The furanoid ring is essentially planar, its geometry being similar to that of 2,5-dihydrofuran molecule, except for the interatomic distance C(3)-C(4) which is shorter than the corresponding length of double C-C bond in alkenes. The C(5)-N 1.52 Å bond significantly exceeds the standard C-N bond lengths in nitroalkanes and nitrobenzene.     

Reaction of 1-bromovinyl and 1-bromo-2-phenylvinyl sulfones with some CH acids

Benzyl, methyl, and phenyl α-bromovinyl sulfones reacted with malononitrile and dimethyl malonate sodium enolates in THF to give sulfonyl-substituted cyclopropanes. Reactions of the same sulfones with methyl acetoacetate sodium enolate afforded the corresponding sulfonyl-substituted cyclopropanes as mixtures of cis and trans isomers with a small impurity of 5-sulfonyl-4,5-dihydrofuran derivative. Phenyl and p-tolyl 1-bromo-2-phenylvinyl sulfones reacted with methyl acetoacetate sodium salt to produce a mixture of trans-isomeric 5-sulfonyl-4,5-dihydrofuran and Michael adduct of the CH acid with activated acetylene generated by concurrent 1,2-dehydrobromination of the initial α-bromovinyl sulfone.     

Stereoselective hetero-Diels-Alder reaction of 3-nitro-2-trihalomethyl-2H-chromenes with 2,3-dihydrofuran and ethyl vinyl ether under solvent-free conditions

3-Nitro-2-trifluoro(trichloro)methyl-2H-chromenes undergo heterodiene cycloaddition to 2,3-dihydrofuran and ethyl vinyl ether under solvent-free conditions producing novel cyclic nitronates with high stereoselectivity and in good yields. 3,6-Dinitro-2-trifluoromethyl-2H-chromene reacts with two molecules of ethyl vinyl ether to give the tandem [4+2]/[3+2] cycloaddition adduct in 48% yield. The stereochemistry of the products was established based on 2D COSY, NOESY, HSQC, and HMBC experiments and an X-ray diffraction study.     

Enantioselective synthesis of 2-ethyl-2,3-dihydrobenzofuran carboxylic acid, direct precursor of (+)-efaroxan, from a Baylis-Hillman adduct

We describe herein a new and straightforward enantioselective approach to R-(+)-2-ethyl-2,3-dihydrofuran carboxylic acid, the direct precursor of (+)-efaroxan, an α₂ adrenoreceptor antagonist, which is indicated to be used for the treatment of neurodegenerative diseases (Alzheimer and Parkinson), migraine and type II diabetes. Our goal was accomplished using a Baylis-Hillman adduct as starting material. The dihydrobenzofuran acid was obtained in eight steps with an overall yield of 14%.     

The Reaction of 2,5-Dimethoxy-2,5-Dihydrofuran with Dichloroketene

2,5-Dimethoxy-2,5-dihydrofuran (DDF) reacts with dichloroketene to give 7,9-dimethoxy-3,3,5,5-tetrachloro-8-oxabicyclo[4,3,0]-noan-2,4-dione (I), and methyl chloro-(2,5-dihydro-5-methoxy-2-furanylidene) acetate (II). The reactions of 2,5-dihydrofuran and 2,5-dimethoxy-tetrahydrofuran with dichloroketene were also-studied for comparison. Compound II was derived from the insertion of a molecule of dichloroketene into the C-O bond of DDF with subsequent dehydrochlorination. Compound I resulted from the cycloaddition of two molecules of dichloroketene to the C=C bond of DDF. A mechanism involving a 1,5-dipolar intermediate is proposed to account for this novel reaction.     

Synthesis and thermal reactions of 3-trimethylsilyl-1-pyrazoline

The compound 3-trimethylsilyl-1-pyrazoline has been synthesized by addition of diazomethane to vinyltrimethylsilane at room temperature. In contrast, addition of trimethylsilyldiazomethane to ethylene at 55°C yields 1-trimethylsilyl-2-pyrazoline exclusively. The thermal isomerization of 3-trimethylsilyl-1-pyrazoline to 1-trimethylsilyl-2-pyrazoline has been followed kinetically by proton NMR spectroscopy and the reverse reaction has been detected by gas phase pyrolysis. Thermal elimination of nitrogen from either pyrazoline leads to cyclopropyltrimethylsilane, allyltrimethylsilane and E- and Z-1-propenyltrimethylsilane. The relative rates of methylene-H migration to radical centers α and γ to silicon are approximately equal.     

PdI2-catalyzed coupling-cyclization reactions involving two different 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives

Transition-metal-catalyzed dimeric coupling-cyclization reactions of two different 2,3-allenols afforded 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives 3. 2-Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the 2-unsubstituted 2,3-allenols 2 provided the 1,3-diene unit at the 4-position. The reaction is proposed to proceed through an oxypalladation, insertion, and beta-hydroxide elimination process. The C=C double bond was formed with high E stereoselectivity by beta-hydroxide elimination.     

Weak interactions in furan dimers

Dimers of furan, 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran were investigated with the use of theoretical methods to determine the interactions that keep the molecules together. The QTAIM and NCI methods confirmed that for furan dimers the C–H?O hydrogen bond and stacking interactions can form the dimers with similar energy. For 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran, the decisive mechanism of dimer formation is the stacking interaction between the furan rings.     

Stereoselective synthesis of vinylsilanes from alkynylsilanes by reductive alkylation via hydroboration,transmetallation and carbodemetallation

Hydroboration of 1-trimethylsilyl-1-alkynes with dicyclohexylborane gives 1-trimethylsilylvinylboranes regio- and stereoselectively whose successive treatment with methyllithium, cuprous iodide and alkyl halides affords (Z)-1,2-dialkylvinylsilanes in high yields. Functionalized 1-trimethylsilyl-1-alkynes give analogous results. Successive treatment of the intermediary 1-trimethylsilylvinylboranes with methyllithium and methyl iodide gives 2-trimethylsilyl-2(Z)-alkenes. Allyl halides give 4-trimethylsilyl-1,4(Z)-alkadienes analogously.     

Reaction of trimethylsilyl azide with bridged bicyclic olefins

Bridged bicyclic olefins were found to undergo facile 1,3-cycloaddition reaction with trimethylsilyl azide. Norbornene produced cis,exo-1-trimethylsilyl-4,7-methano-3a,4,5,6,7,7a-hexahydrobenzotriazole, while norbornadiene formed a diadduct with cis,exo-stereochemistry, together with 2-trimethylsilyl-1,2,3-triazole produced by a retro-Diels—Alder reaction of an intermediate mono-adduct. Dicyclopentadiene reacted only at the norbornene position while α-pinene did not react with trimethylsilyl azide. In contrast to aryl- and sulfonyl-azide adducts of norbornene derivatives, which decompose upon heating the present adducts were recovered unchanged after prolonged treatment at 205°C.     

1,3-dipolar cycloaddition of trimethylsilyl azide to propynals and dimerization of 1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-5-carbaldehydes to tricyclic bis-hemiaminals

Reactions of trimethylsilyl azide with 3-trimethylsilyl-2-propynal and 2-propynal were studied. X-Ray analysis of the molecular structure of 4-trimethylsilyl-1H-1,2,3-triazole-5-carbaldehyde showed that the carbonyl group appears in the s-cis conformation with respect to the double C=C bond in the heteroring. The effect of the temperature and polarity of the medium on the ability of 1H-1,2,3-triazole-5-carbaldehyde to undergo dimerization to tricyclic bis-hemiaminals was examined by IR and ¹H NMR spectroscopy.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 12, 2004, pp. 1852–1857.Original Russian Text Copyright © 2004 by Demina, Novopashin, Sarapulova, Larina, Smolin, Fundamenskii, Kashaev, Medvedeva.     

Reaction of phenyl and 4-methylphenyl phenylethynyl sulfones with methyl acetoacetate

Stereoselective anti-addition of methyl acetoacetate at the triple C≡C bond of phenyl- and 4-methylphenyl phenylethynyl sulfones in the presence of sodium hydride yields the corresponding Michael adduct containing an impurity of arylsulfonylacetophenone. In the reaction with 4-methylphenyl phenylethynyl sulfone, methyl (Z)-2-acetyl-4-(4-methylphenylsulfonyl)-3-phenylbut-3-enoate was also obtained.     

Synthesis of 2,6-disubstituted dihydropyrans via an efficient BiBr3-initiated three component, one-pot cascade

The rapid synthesis of cis-2,6-disubstituted dihydropyrans is achieved in a three-component, one-pot cascade reaction. BiBr₃-mediated addition of ketene silyl acetals or silyl enol ethers to β,γ-unsaturated cis-4-trimethylsilyl-3-butenal provides a Mukaiyama aldol adduct containing a vinylsilane moiety tethered to a silyl ether. Addition of a second aldehyde initiates a domino sequence involving intermolecular addition followed by an intramolecular silyl-modified Sakurai (ISMS) reaction. Isolated yields of this one-pot reaction vary from 44 to 80% and all compounds were isolated as the cis-diastereomers (10 examples).     

Synthesis of a novel family of water-soluble 2H,3H-[1,3]thia- and -selenazolo[3,2-a]pyridin-4-ium heterocycles by annulation reactions

Regioselective synthesis of a novel family of water-soluble 2H,3H-[1,3]chalcogenazolo[3,2-a]pyridin-4-ium derivatives was developed based on 2-pyridinesulfenyl and -selenenyl halides and unsaturated compounds. The annulation reactions with divinyl sulfide, selenide and N-vinylpyrrolidin-2-one led to addition of the chalcogen atom to the terminal carbon of the double bond whereas the reaction with tetravinylsilane proceeded with opposite regiochemistry. Tricyclic condensed heterocycles were obtained from 2,3-dihydrofuran and cycloalkenes. The products represent novel promising scaffolds for organic synthesis and possible drug discovery.     

Al/P- and Ga/P-Based Frustrated Lewis Pairs and Electronically Unsaturated Substrates: Ring Cleavage and Ring Closure,C−C and C−N Bond Formation

Al/P- and Ga/P-based frustrated Lewis pairs (FLPs) reacted with an azirine under mild conditions under cleavage of the heterocycle on two different positions. Opening of the C−C bond yielded an unusual nitrile–ylide adduct in which a C−N moiety coordinated to the FLP backbone. Cleavage of a C−N bond afforded the thermodynamically favored enamine adduct with the N atom bound to P and Al or Ga atoms. Ring closure was observed upon treatment of an Al/P FLP with electronically unsaturated substrates (4-(1-cyclohexenyl)-1-aza-but-1-en-3-ynes) and yielded by C−N bond formation hexahydroquinoline derivatives, which coordinated to the FLP through P−C and Al−C bonds. Diphenylcyclopropenone showed a diverse reactivity, which depending on steric shielding and the polarizing effect of Al or Ga atoms afforded different products. An AltBu₂/P FLP yielded an adduct with the C=O group coordinated to P and Al. The dineopentyl derivative gave an equilibrium mixture consisting of a similar product and a simple adduct with O bound to Al and a three-coordinate P atom. Both compounds co-crystallize. The Ga/P FLP only formed the simple adduct with the same substrate. Rearrangement resulted in all cases in C₃-ring cleavage and migration of a mesityl group from P to a former ring C atom by C−C bond formation. Diphenylthiocyclopropenone (evidence for the presence of P=C bonds) and an imine derivative afforded similar products.     

V/P复合氧化物上C-H键活化的密度泛函研究

选择氧化催化剂通常为多组分复合氧化物.一般认为,高价过渡金属的端末双键氧(M=O)是烷烃活化的中心,而非金属端氧(NM=O)与烷烃活化无关.但近期的理论研究发现,复合氧化物中非金属端氧也可能参与烷烃活化.本文采用密度泛函方法(B3LYP)对比V=O和P=O的脱氢活性,并深入揭示二者的差异. H脱除反应可以视为是质子偶联电子传递的过程.对于V/P复合氧化物, V5+充当电子的受体,而V=O和P=O均可接受质子.由于P=O具有更强的质子化能力,导致PO–H键能比VO–H有利6–10 kcal/mol.对于烷烃活化, V=O和P=O脱氢的能垒均可与反应焓变很好地关联,但二者线性回归的截距相差6.2 kcal/mol,说明在相同的焓驱动下, P=O脱氢需要克服更高的能垒.根据Marcus模型,反应的能垒不仅取决去反应焓变,还与内部重组能有关.计算表明,在脱氢过程中, P=O需克服的重组能为128–140 kcal/mol,比V=O过程高出21–23 kcal/mol.这很好地解释了前面的计算结果.应该指出的是,除了反应热力学驱动和重组能外,在势能曲线相交处的电子耦合作用(?HAB?)亦对能量有一定的影响.丁烷选择氧化制顺酐可能经过2-丁烯,丁二烯,2,5-二氢呋喃和丁烯酸内酯等一系列中间体,共有8个H原子在反应过程中需要脱除.对于丁烷的脱氢, P=O的能垒仅比V=O低1.3 kcal/mol,说明初始反应时二者是竞争的.但对于2-丁烯和2,5-二氢呋喃,二者活化能的差距增加为6–7 kcal/mol,说明这时P=O脱氢将占主导.而对丁烯酸内酯活化,二者活化能的差异又缩小到2.5 kcal/mol,表明V=O又具有一定的竞争力.事实上,这种能垒的差异与端氧的亲核性密切相关.P=O更具亲核性,因此有利于被更具酸性的C–H键进攻.根据Evens的估计,烷烃C–H键的pKa为50左右,而烯丙基性C–H为43.这就很好地解释了为什么2-丁烯和2,5-二氢呋喃更容易和P=O发生反应,而丁烷脱氢二者差异不大的原因.这些理论研究可以加深我们对复合氧化物催化剂上活性位点的认识,并为催化剂的理性设计提供理论支撑.     

Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 2. Structures of catalyst‐alkoxyborane adduct with a four‐membered ring and succeeding reaction intermediates

Quantum chemical ab initio computations of the structures and properties of oxazaborolidine‐alkoxyborane adduct with a B? N? B? O four‐membered ring and succeeding reaction intermediates are carried out in the current work by means of the Hartree–Fock (HF) and the density functional methods. All the structures are optimized completely at the HF/6‐31G(d) and Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP)/6‐31G(d) levels. As shown in the obtained results, the oxazaborolidine‐alkoxyborane adduct with a B? N? B? O four‐membered ring may be formed during the reduction of the carbonyl bond of the catalyst‐borane‐keto oxime ether adduct. The breakdown of the B? N? B? O four‐membered ring results in the formation of the adduct with a B? N? B? O? C? C? N seven‐membered ring and an oxime bond. The reduction of the oxime bond leads to the adduct with a chiral oxime carbon. The B(2)? N_{C? N} bond in the B? N? B? O? C? C? N seven‐membered ring of the adduct with a reduced oxime bond is weaker comparatively and thus may be more easily broken down. All the adducts have four stable structures. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 294–306, 2003     

Organosilicon compounds XV. Cleavage of the silicon-carbon bond of 2-trimethylsilyl-1-methylimidazole and 2-trimethylsilyl-1-methylbenzimidazole

Cleavage of the aryl-silicon bond of 2-trimethylsilyl-1-methylimidazole (Ia) and 2-trimethylsilyl-1-methylbenzimidazole (Ib) has been effected by five carbonyl reagents, i.e. aldehydes, acid halides, chloroformates, anhydrides and isocyanates, to provide a novel synthetic route to a host of functionally substituted heterocycles. Compound Ia reacted exothermically at room temperature, with four of the, five carbonyl reagents.     

Synthesis and cationic polymerization of substituted 2,3-dihydrofurans

Cationic polymerization of substituted 2,3-dihydrofurans has been performed to investigate the substituent effect on the ring-opening polymerization. 2-Phenyl-2,3-dihydrofuran ( III ), 2-methoxy-5-phenyl-2,3-dihydrofuran ( V _a), and 2-ethoxy-5-phenyl-2,3-dihydrofuran ( V _b) were synthesized and polymerized with BF₃ etherate and AlCl₃ as acid catalysts. V _a and V _b ring-opening polymerized well to give the polymers with benzoyl as pendant group which were formed via cationic rearrangement during the ring-opening process, while III polymerized via simple opening of ethylenic double bond to form a polymer with the retention of tetrahydrofuran ring in the main chain. The nature of substituted cyclic vinyl ethers depending on substituents was also discussed.     

Carbon [bond] hydrogen bond activation by titanium imido complexes. Computational evidence for the role of alkane adducts in selective C [bond] H activation

This paper reports calculations that probe the role of R (hydrocarbon) and R' (ligand substituent) effects on the reaction coordinate for C [bond] H activation: Ti(OR')(2)(=NR') + RH --> adduct --> transition state --> (OR')(2)Ti(N(H)R')(R). Compounds with R = H, Me, Et, Vy, cPr, Ph, Cy, Bz, and cubyl are studied using quantum (R' = H, SiH(3), SiMe(3)) and classical (R' = Si(t)Bu(3)) techniques. Calculated geometries are in excellent agreement with data for experimental models. There is little variability in the calculated molecular structure of the reactants, products, and most interestingly, transition states as R and R' are changed. Structural flexibility is greatest in the adducts Ti(OR')(2)(=NR')...HR. Despite the small structural changes observed for Ti(OR')(2)(double bond] NR') with different R', significant changes are manifested in calculated electronic properties (the Mulliken charge on Ti becomes more positive and the Ti [double bond] N bond order decreases with larger R'), changes that should facilitate C [bond] H activation. Substantial steric modification of the alkane complex is expected from R [bond] R' interactions, given the magnitude of Delta G(add) and the conformational flexibility of the adduct. Molecular mechanics simulations of Ti(OSi(t)Bu(3))(2)([double bond] NSi(t)Bu(3))...isopentane adducts yield an energy ordering as a function of the rank of the C [bond] H bond coordinated to Ti that is consistent with experimental selectivity patterns. Calculated elimination barriers compare very favorably with experiment; larger SiH(3) and TMS ligand substituents generally yield better agreement with experiment, evidence that the modeling of the major contributions to the elimination barrier (N [bond] H and C [bond] H bond making) is ostensibly correct. Calculations indicate that weakening the C [bond] H bond of the hydrocarbon yields a more strongly bound adduct. Combining the different conclusions, the present computational research points to the adduct, specifically the structure and energetics of the substrate/Ti-imido interaction, as the main factor in determining the selectivity of hydrocarbon (R) C [bond] H activation.