Polymethylhydrosiloxane (PMHS)/trifluoroacetic acid (TFA): a novel system for reductive amination reactions

Polymethylhydrosiloxane (PMHS)/trifluoroacetic acid (TFA) was discovered as a novel metal-free system for reductive amination reactions. A variety of (het)aryl amines as well as a representative carbamate and urea were successfully alkylated by benzaldehyde in the presence of PMHS and TFA in dichloromethane at room temperature in moderate to excellent yields (28-87%). Furthermore, this reaction protocol was successfully applied to the alkylation of p-nitroaniline with a wide range of aldehydes, ketones, and a representative acetal to obtain the alkylated products in yields ranging from 40% to 92%. The current work represents one of the very few examples of PMHS being activated by a Brønsted acid.     

Zur Photochemie von 3,5-Diaryl-2-isoxazolinen. 30. Mitteilung über Photoreaktionen

Irradiation of 3,5-diphenyl- or 3-(p-tolyl)-5-phenyl-2-isoxazoline ( 12 and 13 , respectively) in benzene with a high-pressure mercury lamp yields 4,5-diphenyl- or 4-(p-tolyl)-5-phenyl-3-oxazoline ( 17 and 19 , respectively) and the β-amino-chalcones 18 or 20 in addition to benzaldehyde, benzonitrile and p-tolunitrile, respectively (scheme 6 and ‘Anmerkg.’ p. 2600). The 3-oxazolines 17 and 19 are formed by route a (scheme 8) via 3-phenyl- or 3-(p-tolyl)-2H-azirine ( 23 , R = H and CH₃, respectively) and their photochemically rearranged successors, the nitrile methylides 24 , as intermediates. The discovery of this reaction has served as a basis for the quickly developing photochemistry of 3-aryl-2H-azirines [2] [24]. Photolysis of the 2-isoxazoline 13 in methanol leads to the formation of a mixture of syn/anti-p-tolyl trans-styryl ketoximes (syn/anti, trans- 30 ) and anti, cis- 30 , 2-(p-tolyl)-quinoline ( 29 ), the 4-hydroxymethylated derivative 32 of the latter (in small amounts), besides the β-aminochalcone 20 , benzaldehyde, p-tolualdehyde and p-tolunitrile (scheme 9). It could be shown that the stereoisomeric ketoximes 30 are photochemically interconvertible (scheme 12) and that at least one mechanism of formation of 2-(p-tolyl)-quinoline ( 29 ) is the photo-induced cyclisation of p-tolyl-cis-styryl ketoximes (cis- 30 ) (scheme 13). A tentative mechanism for the formation of p-tolual-dehyde is given in scheme 10; the crucial step is the protonation of p-tolunitrile methylide ( 24 , R = CH₃) by methanol at the nitrile carbon atom, after which hydrolysis yields the aldehyde.     

Reductive monoalkylation of nitro aryls in one-pot

The scope of the serendipitous reductive monoalkylation of ethyl (4-methoxy-3-nitrophenyl) acetate taking place during reduction of the nitro functionality to the corresponding primary amine when treated with hydrogen (1 atm) over Pd/C (10%) in ethanol is investigated. Upon prolonged reaction time the reaction conducted in ethanol and methanol yields significant amount of the corresponding secondary amines, while when performed in n-butanol and i-propanol it only resulted in the formation of a small amount of the corresponding secondary amines. Further development of the reductive monoalkylation reaction provided conditions that facilitate conversion of a range of different nitro aryls in one-pot to the corresponding secondary benzyl amino aryls in mostly good to excellent yields. This is accomplished by using hydrogen (1 atm) over Pd/C (10%) as reducing agent and benzaldehyde as the benzyl source combined with a stepwise reaction sequence. This chemistry was further extended to the formation of substituted benzyl amino aryls. The yields of the latter products varied dramatically depending on the substitution patterns associated with the benzaldehyde. However, by altering the reaction conditions it was possible to improve the yields of the benzylated products.     

A mild and efficient method for the oxidation of benzylic alcohols by two-phase electrolysis

Electrochemical oxidation of benzylic and substituted benzylic alcohols by two-phase electrolysis yields the corresponding aldehydes as products. The reaction was carried out in a single compartment cell with platinum electrodes at room temperature in chloroform using an aqueous sodium bromide solution (25%) containing a catalytic amount of HBr. The two-phase electrolysis resulted in high yields (74-96%) of benzaldehyde from primary alcohols and secondary alcohols were oxidized to the corresponding ketone but only in low yields under these conditions.     

The role of the planar chirality of iron tricarbonyl substituted homochiral amino alcohols in the asymmetric alkylation of aldehydes with diethylzinc

Homochiral amino alcohols bearing an iron tricarbonyl moiety were prepared from 2-amino-1,1-diphenylethanol derivatives 4a–d and [(3S,4S)-η^4,7-octa-4,6-dien-3-ol]Fe(CO)₃ complex 2. The addition of diethylzinc to aldehydes bearing electron donating substituents in the presence of these chiral ligands gave the alkylated products in good enantiomeric excess (up to 93% e.e.), whereas the addition to aldehydes bearing electron withdrawing substituents resulted in low yields and poor enantiomeric excesses.     

A new protocol for the in situ generation of aromatic,heteroaromatic, and unsaturated diazo compounds and its application in catalytic and asymmetric epoxidation of carbonyl compounds. Extensive studies to map out scope and limitations,and rationalization of diastereo- and enantioselectivities

A variety of metalated tosylhydrazone salts derived from benzaldehyde have been prepared and were reacted with benzaldehyde in the presence of tetrahydrothiophene (THT) (20 mol %) and Rh(2)(OAc)(4) (1 mol %) to give stilbene oxide. Of the lithium, sodium, and potassium salts tested, the sodium salt was found to give the highest yield and selectivity. This study was extended to a wide variety of aromatic, heteroaromatic, aliphatic, alpha,beta-unsaturated, and acetylenic aldehydes and to ketones. On the whole, high yields of epoxides with moderate to very high diastereoselectivities were observed. A broad range of tosylhydrazone salts derived from aromatic, heteroaromatic, and alpha,beta-unsaturated aldehydes was also examined using the same protocol in reactions with benzaldehyde, and again, good yields and high diastereoselectivities were observed in most cases. Thus, a general process for the in situ generation of diazo compounds from tosylhydrazone sodium salts has been established and applied in sulfur-ylide mediated epoxidation reactions. The chiral, camphor-derived, [2.2.1] bicyclic sulfide 7 was employed (at 5-20 mol % loading) to render the above processes asymmetric with a range of carbonyl compounds and tosylhydrazone sodium salts. Benzaldehyde tosylhydrazone sodium salt gave enantioselectivities of 91 +/- 3% ee and high levels of diastereoselectivity with a range of aldehydes. However, tosylhydrazone salts derived from a range of carbonyl compounds gave more variable selectivities. Although those salts derived from electron-rich or neutral aldehydes gave high enantioselectivities, those derived from electron-deficient or hindered aromatic aldehydes gave somewhat reduced enantioselectivities. Using alpha,beta-unsaturated hydrazones, chiral sulfide 7 gave epoxides with high diastereoselectivities, but only moderate yields were achieved (12-56%) with varying degrees of enantioselectivity. A study of solvent effects showed that, while the impact on enantioselectivity was small, the efficiency of diazo compound generation was influenced, and CH(3)CN and 1,4-dioxane emerged as the optimum solvents. A general rationalization of the factors that influence both relative and absolute stereochemistry for all of the different substrates is provided. Reversibility in formation of the betaine intermediate is an important issue in the control of diastereoselectivity. Hence, where low diastereocontrol was observed, the results have been rationalized in terms of the factors that contribute to the reduced reversion of the syn betaine back to the original starting materials. The enantioselectivity is governed by ylide conformation, facial selectivity in the ylide reaction, and, again, the degree of reversibility in betaine formation. From experimental evidence and calculations, it has been shown that sulfide 7 gives almost complete control of facial selectivity, and, hence, it is the ylide conformation and degree of reversibility that are responsible for the enantioselectivity observed. A simple test has been developed to ascertain whether the reduced enantioselectivity observed in particular cases is due to poor control in ylide conformation or due to partial reversibility in the formation of the betaine.     

Preparation of SF5 aromatics by vicarious nucleophilic substitution reactions of nitro(pentafluorosulfanyl)benzenes with carbanions

Vicarious nucleophilic substitutions (VNS) of hydrogen in 1-nitro-4-(pentafluorosulfanyl)benzene with carbanions provide 2-substituted 1-nitro-4-(pentafluorosulfanyl)benzenes in good to high yields. VNS of 1-nitro-3-(pentafluorosulfanyl)benzene gives a mixture of 6- and 4-substituted 1-nitro-3-(pentafluorosulfanyl)benzenes in 85:15 to >98:2 ratio and good to high yields. In basic media, the VNS reactions lead to the formation of carbanions that can be alkylated by alkyl halides affording the corresponding alkylated products in moderate yields. Transformation of primary products to substituted (pentafluorosulfanyl)anilines and 3- or 4-substituted (pentafluorosulfanyl)benzenes is also described.     

Vanadium(IV)-oxo Corrole Catalyzed Selective Oxidative Cleavage of Alkenes to Aldehydes

A practical and efficient protocol for oxidative cleavage of olefinic bonds especially in arylated olefins has been demonstrated. Herein, an oxo[5,10,15-tris(4-nitrophenyl)corrolato]vanadium (IV) complex (cat.), has been successfully synthesized and the existence of two tautomeric forms of this complex in solution has been established. Oxo[5,10,15-tris(4-nitrophenyl)corrolato]vanadium (IV) (cat.) in the presence of H₂O₂ cleaves olefinic bonds to yield the corresponding aldehyde compounds. In general, a high valent, oxo-(porphyrinoid)-metal complex catalyzes the epoxide formation reactions, however, in the present case, we have observed the exclusive formation of aldehydes. The reaction offered aryl aldehydes with good yields and excellent selectivity. A mechanism was also proposed for these catalysis reactions.     

Some chemical transformations of alkyl (4-aminophenyl)carbamates

Azo coupling of diazonium salts derived from alkyl (4-aminophenyl)carbamates with ethyl α-methylacetoacetate gave ethyl 5-alkoxycarbonylamino-1H-indole-2-carboxylates. The condensation of aminophenylcarbamates with aromatic aldehydes in ethanol afforded the corresponding Schiff bases. Cyclohexyl {4-[(4-methoxyphenyl)methylidene]aminophenyl}carbamate reacted with chloroacetyl chloride in dioxane in the presence of triethylamine to produce cyclohexyl {4-[3-chloro-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]phenylcarbamate, and the reaction of benzyl {4-[(4-nitrophenyl)methylidene]aminophenyl}carbamate with sulfanylacetic acid in DMF led to the formation of benzyl {4-[2-(4-nitrophenyl)-4-oxo-1,3-thiazolidin-3-yl]-phenyl}carbamate.     

A facile solvent free Claisen-Schmidt reaction: synthesis of α,α'-bis-(substituted-benzylidene)cycloalkanones and α,α'-bis-(substituted-alkylidene)cycloalkanones

Solvent-free Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes (aryl aldehydes) using solid NaOH (20 mol%) and applying a grinding technique were studied. Quantitative yields (96-98%) of α,α'-bis-(substituted-benzylidene)cycloalkanones were obtained. Aliphatic aldehydes also provided α,α'-bis-(substituted-alkylidene)cycloalkanones in very good yields with minor amounts of a-(substituted-alkylidene)cycloalkanones. The catalytic performance of solid NaOH was examined. The molar ratio of NaOH was optimized. The catalytic effect of solid NaOH was also evaluated by comparing it with KOH, NaOAc, and NH(4)OAc and it turns out that 20 mol% of solid NaOH was good enough to catalyze the Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes. Additionally, the regioselectivity of the Claisen-Schmidt reaction of acetone with benzaldehyde was examined. Using the same method, we could synthesize the corresponding bis-benzylidene- and mono-benzylideneacetone separately in 98% and 96% yields, respectively.     

((3-(3-硅胶丙基)硫基)丙基)硫酸酯作为可回收催化剂用于合成4,4'-芳亚甲基-双(1H-吡唑-5-醇)(英文)

Sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl)ester is employed as a recyclable catalyst for the condensation reaction between aromatic aldehydes and 3-methyl-l-phenyl-5-pyrazolone. This condensation reaction was performed in ethanol under refluxing conditions giving 4,4'-alkylmethylene-bis(3-methyl-5-pyrazolones) in 74-90% yields. The heterogeneous catalyst was recycled and used in eleven runs for the reaction between benzaldehyde and 3-methyl-l-phenyl-5-pyrazolone without losing catalytic activity.     

Reactivity of Zirconocene Azametallacyclobutenes: Insertion of Aldehydes, Carbon Monoxide, and Formation of alpha,beta-Unsaturated Imines. Formation and Trapping of [Cp(2)Zr=O] in a [4 + 2] Retrocycloaddition(1)

Azametallacyclobutene Cp(2)ZrN-t-BuCEt=CEt (1) underwent an insertion reaction with CO to form the acyl complex 2 (Cp(2)Zr(N-t-BuCEtCEtCO), 67% yield). The addition of acetone to azametallacyclobutene 3 (Cp(2)Zr(NArCMeCPh), Ar = 2,6-dimethylphenyl) yielded the N-bonded enamine and O-bonded enolate complex of zirconocene 4 (Cp(2)Zr(NArCMeCPhH)(OCMeCH(2)), 76% yield). The addition of aldehydes RCOH to metallacycle 3 resulted in the insertion of the aldehyde into the Zr-C bond to form complexes Cp(2)Zr(NArCMeCPhCRHO) (8a) and Cp(2)Zr(NArCMeCPhC(i-Pr)HO (9) in 85% (R = Ph) and 73% yields, respectively. Similarly, treatment of metallacycle 10 (Cp(2)Zr(NArCEtCEt)) with benzaldehyde yielded the insertion product 11 (Cp(2)Zr(NArCEtCEtCPhHO)) in 56% isolated yield. The structure of complex 11 was confirmed by an X-ray crystallographic study. Heating the insertion products 8a and 9 led to elimination of the alpha,beta-unsaturated imines 13 and 14a (ArN=CMeCPh=CRH) in 53% and 72% yields, respectively, and the formation of oxozirconocene oligomer (Cp(2)ZrO)(n)(). The oxozirconocene monomer was trapped by dimethylzirconocene, preventing the formation of oligomer and resulting in the isolation of product 15. A kinetic study of this retrocycloaddition produced the following activation parameters: DeltaH() = 26.5 kcal/mol, DeltaS() = 3.48 eu. A Hammett sigma/rho study showed that electron-donating groups alpha to the metallacycle oxygen accelerate the retrocycloaddition (rho = -0.8).     

Regio- and stereoselective nickel-catalyzed homoallylation of aldehydes with 1,3-dienes

Ni(acac)(2) catalyzes homoallylation of aldehydes with 1,3-dienes in the presence of triethylborane. Triethylborane serves as a reducing agent delivering a formal hydride to the C2 position of 1,3-dienes, thus generating a formal homoallyl anion species and enabling the novel homoallylation of aldehydes. The reaction proceeds smoothly at room temperature in the absence of any phosphane or nitrogen ligands and is highly regioselective and stereoselective for a wide variety combination of aldehydes and 1,3-dienes: e.g., isoprene and benzaldehyde combine to give a mixture of anti- and syn-1-phenyl-3-methyl-4-penten-1-ol (2.2) in a ratio of 15:1 in 90% yield. Under the conditions, sterically congested aliphatic aldehydes and ketones show low yields. In such cases, diethylzinc serves as a substitute for triethylborane and yields the expected products in good yields with similarly high regio- and stereoselectivity. 1,3-Cyclohexadiene is one exception among 24 kinds of dienes examined and undergoes allylation (not homoallylation) selectively.     

A synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes by the magnesium carbenoid 1,2-CH and 1,2-CC insertion as the key reaction

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from aldehydes, with lithium enolate of tert-butyl acetate at −78 °C in THF gave adducts in high yields. Treatment of these adducts with Grignard reagents resulted in the formation of magnesium carbenoids via the sulfoxide-magnesium exchange reaction. When the adducts were derived from alkyl aldehydes or electron-deficient aromatic aldehydes, carbenoid 1,2-CH insertion reaction took place from the magnesium carbenoids to afford β,γ-unsaturated butyric esters having a substituent at the β-position. On the other hand, when the adducts were derived from electron-rich aromatic aldehydes, carbenoid 1,2-CC insertion reaction took place from the magnesium carbenoids to give β,γ-unsaturated butyric esters having the aromatic group at the γ-position. Highly stereospecific 1,2-CC insertion reactions were observed in the latter reactions. When the addition reactions were quenched with iodoalkanes, the alkylated adducts were obtained in quantitative yields. Tri-substituted β,γ-unsaturated esters, or in some case γ,δ-unsaturated esters, were obtained by the treatment of the alkylated adducts with EtMgCl. These procedures provide a good way for a new synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes with two or three carbon-carbon bond-formations.     

Highly enantioselective synthesis of (E)-allylic alcohols

The asymmetric addition of alkenylzincs to aromatic and alpha-branched aliphatic aldehydes catalyzed by 1 generated the corresponding (E)-allylic alcohols with >95% ee and good to excellent chemical yields, especially >99.5% ee was observed in the case of 4-CF3-benzaldehyde. Notably, 1 is an effective ligand to catalyze the addition of disubstituted (R2 = R3 = ethyl) and bulky substituted (R2 = H, R3 = tert-butyl) alkenylzincs to benzaldehyde, affording the corresponding allylic alcohols both with 96% ee.     

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for acetal formation

Commercially available copper(II) tetrafluoroborate hydrate has been found to be a highly efficient catalyst for dimethyl/diethyl acetal formation in high yields from aldehydes and ketones by reaction with trimethyl/triethyl orthoformate at room temperature and in short period. Acetalisation was carried out under solvent-free conditions with electrophilic aldehydes/ketones. For weakly electrophilic aldehydes/ketones (e.g., benzaldehyde, cinnamaldehyde and acetophenone) and for aldehydes having a substituent that can coordinate with the catalyst, the corresponding alcohol was used as solvent.     

Alkylations of Resorcarenes and Calix[4]pyrroles in Phase Transfer Catalytic Systems

Calixlnlarenesarecyclicoligomersmadeupofphenolsandformaldehyde.Thisversatileclassofcompoundshasbeenextensivelystudiedinthelastdecademainlyinordertoobtainnewcomplexingagentsbyappropriatefuntionalizationoftheparentmoleculel.ResorcarenesZandcall-c[4]pyrroles'aretwosubgroupmembersofthefamilyofcalixarensandalsoattractedincreasinginterests.Aspartofaprogrammeaimedatthesynthesisofneweasy-to-makecalixarenemolecules,wedecidedtoinvestigatethealkylationofsomecalixarensinPhaseTransferCatalysis(PTC)condi…     

Regiocontrolled, palladium-catalyzed bisfunctionalization of allenyl esters. Multicomponent coupling approaches to highly substituted alpha,beta-unsaturated delta-lactones

A palladium-catalyzed regioselective bisfunctionalization of allenyl esters with boronic acids (nucleophiles) and aldehydes (electrophiles) was demonstrated. The three-component coupling afforded alpha,beta-unsaturated delta-lactones under mild conditions and with excellent chemo-, regio-, and diastereoselectivity. Aromatic, heteroaromatic and vinylic boronic acids (R1B(OH)2) reacted with ethyl 2,3-butadienoate and benzaldehyde to afford the corresponding 4-R(1),6-Ph-disubstituted alpha,beta-unsaturated delta-lactones in 62-78% yields. Lactones derived from aromatic, heteroaromatic, and vinylic aldehydes were isolated in 51-58% yields, while aliphatic aldehydes were less reactive. The regiochemistry of bisfunctionalization of allenyl ester homologues remained controlled by the ester substituent, and the reactions afforded cis-4,5,6-trisubstituted alpha,beta-unsaturated delta-lactones and esters of (Z)-syn-3,4,5-trisubstituted-5-hydroxy-2-pentenoic acids in combined 47-65% yields. The superior performance of a pi-allylpalladium(II) dimer catalyst featuring an auxiliary allyl ligand derived from beta-pinene, among diverse palladium(II) catalysts, was demonstrated. A catalytic cycle involving an unsymmetrical bis-pi-allylpalladium complex as the key intermediate was proposed, and the communication highlights the synthetic potential of such intermediates. However, the efficiency of asymmetry transfer remained low (<20%).     

The influence of terminal push-pull substitution on the electronic structure and optical properties of pentacenes

The synthesis of 2,3-R(2)-9,10-(OMe)(2)-substituted pentacenes (R=OMe, F, Br, CN; 1-4) from 2,3-R(2)-9,10-dimethoxy-6,13-dihydro-6,13-ethanopentacene-15,16-diones (α-diketone-bridged precursors) by photochemically induced bis-decarbonylation (Strating-Zwanenburg reaction) is described. Under matrix-isolation conditions (solid Ar, 10 K) the S(1) transitions of 1 and 2 undergo hypsochromic and those of 3 and 4 bathochromic shifts compared to parent pentacene. The S(1) transition wavelengths correlate well with the difference of substituent parameters σ(p). A computational analysis of the excited states at the CAM-B3LYP/6-311+G** level of theory provides an assignment of the electronic transitions. Photolysis in solution at room temperature yields red [R=OMe (1)], blue [R=Br (3), F (2)], and green [R=CN (4)] pentacenes. The compounds are oxygen-sensitive and have low solubility, but their formation can be monitored by UV/Vis and, in the case of R=CN, also by (1)H NMR spectroscopy. The S(1) transition in 4 does not show the typical pentacene fine structure in the electronic absorption spectrum. Photogeneration in the presence of oxygen leads to a number of photoproducts that could be identified by monitoring the reaction by (1)H NMR spectroscopy for R=OMe.     

Photolysis of organopolysilanes. Reactions of trimethylsilylphenylsilylene with carbonyl compounds

Photolysis of tris(trimethylsilyl)phenylsilane (I) in the presence of acetone, diethyl ketone and cyclohexanone resulted in formation of the respective 2,2,2-trimethylphenyldisilanyl enol ethers in moderate yields. UV-irradiation of I in the presence of methyl acrylate, followed by treatment of the reaction mixture with isopropyl alcohol, afforded methyl 3-(1′-isopropoxy-1′-phenyltrimethyldisilanyl)propionate, in addition to an adduct arising from addition of a silicon-carbon double-bonded intermediate to the carbon-carbon double bond.