Synthesis of allylamides from allyl halides, carbon monoxide, and titanium-nitrogen complexes prepared from molecular nitrogen

4-Phenylbut-3-enamide could be synthesized from corresponding 3-chloroprop-2-enylbenzene, carbon monoxide (1 atm), and titanium-nitrogen complexes, prepared from Ti(OⁱPr)₄, Li, TMSCl, and molecular nitrogen (1 atm), using a palladium catalyst. The reaction proceeds via transmetalation of the titanium-nitrogen complex to an acylpalladium complex. P^tBu₃ as a ligand of the palladium catalyst, afforded a good result, and the amounts of Li and TMSCl affected the yield of amide. When the reaction was carried out using a bidentate ligand on the palladium complex under an atmosphere of argon instead of carbon monoxide, an allylamine derivative was obtained.     

One-Pot Synthesis of N-Boc-2, 5-bis(trimethylsilyl)pyrrolidine

Since Daly reported the structure of epibatidine and its potent analgesic activity in 19921, study on the synthesis of epibatidine and its derivatives and relationships between the structure and activity of epibatidine has received much attention2. During the course of our research for the synthesis of epibatidine derivatives, N-boc-2, 5-bis(trimethylsilyl)pyrrolidine 4 was used as the key intermediate to construct the skeleton of epibatidine via the 1, 3-dipolar cycloaddition (Scheme 1). Ac…     

Synthesis of substituted pyrimidine using ZnFe2O4 nanocatalyst via one pot multi-component reaction ultrasonic irradiation

A highly efficient, eco-friendly, recyclable heterogeneous ZnFe₂O₄ nanocatalyzed synthesis of 2-amino-4-substituted 1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carbonitrile (4a-j) derivatives via one pot multicomponent reaction of benzimidazole ( 1 ), substituted aromatic aldehyde ( 2a-j ) and malononitrile ( 3 ) under ultrasonic irradiations. Significance of this synthetic approach is short reaction time, easy handling, simplicity, efficiency, high yield, and recoverable catalyst.     

Palladium-catalyzed mono-N-allylation of unprotected anthranilic acids with allylic alcohols in aqueous media

Palladium-catalyzed N-allylation of anthranilic acids 1a-j with allyl alcohol 2a in the presence of Pd(OAc)(2), sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) in THF-H(2)O at room temperature gave only mono-N-allylated anthranilic acids 3a-j in good yields (70-98%). The reactions of 4-bromoanthranilic acid 1i with 2-methyl-3-buten-2-ol 2b showed complete chemoselectivity in N-allylation (neutral conditions) and C-vinylation (basic conditions). In our catalytic system, the keys to success are use of an unprotected anthranilic acid as a starting material and the presence of water in the reaction medium. The carboxyl group of anthranilic acid and water may play important roles for the smooth generation of the π-allyl palladium species by activation of the hydroxyl group of the allylic alcohol.     

Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octa-5,7-dien-2-ones

The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13), bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a-d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl-2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5-diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively, in good overall yields.     

Synthesis, structure and ethylene polymerization behavior of zirconium complexes with chelating ketoiminate ligands

Mixed ketoiminate/ketoimine/pentamethylcyclopentadienyl (Cp*) complex of zirconium, [(η⁵-Cp*){CH₃C(O)CHC(NHR)CH₃}{CH₃C(O)CHC(NR)CH₃}ZrCl₂] (R=4-CF₃Ph) (3) has been prepared in high yield by the reaction of one equivalent of 4-CF₃-phenyl-β-ketoimine (1a) and one equivalent of lithium 4-CF₃-phenyl-β-ketoiminate (2a) with one equivalent of Cp*ZrCl₃ in Et₂O. Bis(ketoiminate)zirconium dichloride complexes, 4 and 6, have been also prepared in high yield by the reaction of amine elimination of ketoimine ligands, respectively 1a and 1b, with Zr(NMe₂)₄ and followed by chlorination reaction with TMSCl. The X-ray crystallography reveals that the compound 3 is based on distorted octahedral geometry containing a ketoimine and a ketoiminate. The ketoiminate ligand coordinates to the zirconium as a bidentate ligand, leaving the metal center coordinatively unsaturated and thus leading to an additional binding of a ketoimine ligand to the metal to stabilize the complex 3. The zirconium complexes 3, 4 and 6 provide the moderate activity for the polymerization of ethylene in the presence of MMAO cocatalyst. Low molecular weight and high density polyethylene was obtained.     

Nucleophilic additions of arylzinc compounds to aldehydes mediated by CrCl(3): efficient and facile synthesis of functionalized benzhydrols, 1(3H)-isobenzofuranones, benzyl alcohols, or diaryl ketones

In the presence of a stoichiometric amount of CrCl(3) and trimethylchlorosilane (TMSCl), nucleophilic addition of arylzinc compounds 1c-h to arylaldehydes 2a,b,g smoothly proceeded at room temperature to yield corresponding benzhydrols 4a-f in good yields. From arylzinc compounds 1a,b, 3-aryl-1(3H)-isobenzofuranones 3a-f were given by the CrCl(3)-mediated reaction with arylaldehydes 2a-f. Diaryl ketones 5a-e were obtained in good yields by the addition of excess amount of benzaldehyde as an oxidant to the resulting solution after the CrCl(3)-mediated reaction between arylzinc compounds 1c-g and arylaldehydes 2b,g was completed. In the nucleophilic additions of arylzinc compounds 1a,d,f to alkyladehydes 6b-f, the treatment of arylzinc compounds with CrCl(3) was required prior to the addition of the aldehydes in order to prevent the fast protodezincation of arylzinc compounds by the enolizable aldehydes. In these CrCl(3)-mediated nucleophilic additions of arylzinc compounds to aldehydes, arylchromium(III) species are probably reactive intermediates.     

Facile syntheses of oxazolines and thiazolines with N-acylbenzotriazoles under microwave irradiation

Microwave reactions of 2-amino-2-methyl-1-propanol (2) or 2-aminoethanethiol hydrochloride (4) with readily available N-acylbenzotriazoles 1a-j in the presence of SOCl(2) produced 2-substituted 2-oxazolines 3a-j in 84-98% yields and 2-substituted thiazolines 5a-i in 85-97% yields, respectively. With use of this method chiral oxazoline 6, bisoxazoline 7, bisthiazoline 8, and 5,6-dihydro-4H-1,3-oxazines 9 or 10 have also been prepared in 82-96% yields. These results demonstrate a new application of N-acylbenzotriazoles in the preparation of oxazolines and thiazolines under mild conditions and short reaction times with microwave irradiation.     

Synthesis and antimicrobial activity of some novel 5-alkyl-6-substituted uracils and related derivatives

6-chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-c via treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.     

Toward the development of a structurally novel class of chiral auxiliaries. Conformational properties of the aldol adducts of oxadiazinones: observation of unusual shielding effects

Asymmetric aldol reactions were conducted with the titanium enolate of N(3)-hydrocinnamoyl-3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one to afford aldol adducts 5a-j. The dominant product of the asymmetric aldol reaction was the non-Evans syn adduct as determined by (1)H NMR spectroscopy and X-ray crystallography. When evaluating the (1)H NMR spectra of adducts 5a-j, a highly shielded signal with an average chemical shift of 0.05 ppm was observed. This signal was readily determined to be the C(5)-methyl group of the oxadiazinone. It is presumed that the overall conformation adopted by the aldol adducts in solution places an aromatic ring of the N(3)-substituent in close proximity to the C(5)-methyl group. An investigation of this conformational preference is conducted employing (1)H NMR spectroscopy, X-ray crystallography, and computational methods.     

Chemistry of odorants: stereoselective synthesis of octahydronaphthalene-based perfumery Georgywood, (+,−)-1-[(1R,2S)-1,2,3,4,5,6,7,8-octahydro-1,2,8,8-tetramethylnaphthalen-2-yl]ethan-1-one

A straightforward synthesis of octahydronaphthalene-based fragrance, such as Georgywood, is described. The Lewis acid tin (IV) chloride catalyzed efficiently an original one-pot sequential cycloaddition-clyclization process by reaction of myrcene with 3-bromo-but-3-en-2-one, leading directly to the octahydronaphthalene skeleton in very good yields (85%). Then, dehydrohalogenation with DBU gave the key 2,4-dienone intermediate in excellent yield (85%). Regioselective Michael addition gave rise to the formation of the addition product as a trans/cis diastereoisomeric mixture, by reaction either with CH₃Cu·BF₃ (6:1 ratio, 70%) or (CH₃)₂CuLi/TMSCl reagents (3:1 ratio, 80%). The generation of thermodynamically more stable enolate by treatment of the diastereoisomeric mixture with sodium hydride in tetrahydrofuran in the presence of an excess of methyl iodide, allowed stereoselective introduction of the methyl group at C2, leading to the formation of Georgywood in good yield (60%), as the only diastereoisomer, with a trans stereochemistry of the two methyl groups as demonstrated by NMR experiments.     

A simple and eco-friendly method for the aminomethylation of 3-substituted oxindoles via three-component Mannich reaction in aqueous media

A simple and eco-friendly method for the aminomethylation of various 3-substituted oxindoles via three-component Mannich reaction in aqueous media has been established. A variety of oxindoles containing a quaternary carbon center, which comprises an aminomethyl group were obtained smoothly in good yields (up to 93%) with this method. Particularly valuable features, such as employing cheap and readily available formalin as a useful aminomethylation C1 unit and using water as a reaction medium, are embodied in this method.     

JAK2II型抑制剂CHZ868的合成

以廉价易得的1-硝基-3-甲氧基甲苯为原料,依次经硝基还原、保护氨基、硝化、保护氨基后还原硝基、氨基甲基化,再与异硫氰酸酯环化构建2-氨基苯并咪唑环、脱去羟基保护基、成醚、硝基还原和乙酰化反应,合成JAK2II型抑制剂CHZ868,总收率6.24%,其结构经¹H NMR, ¹³C NMR和LC-MS确证。     

Imino ene reaction catalyzed by ytterbium(III) triflate and TMSCl or TMSOTf

A novel combined system of Yb(OTf)(3) with TMSCl or TMSOTf catalyzed an imino ene reaction. The reaction of N-tosylbenzaldimine (1) with alpha-methylstyrene (2) proceeded smoothly to give homoallylic amine 3 in the presence of a catalytic amount of Yb(OTf)(3) and TMSCl. This catalytic system was successfully applied to the imino ene reactions of various aldimines with alkenes. This new imino ene reaction provides a unique method for the three-component coupling reaction of an aldehyde, tosylamide, and alpha-methylstyrene in the presence of Yb(OTf)(3) and TMSOTf, to give the corresponding homoallylic amine.     

Designing the "search pathway" in the development of a new class of highly efficient stereoselective hydrosilylation catalysts

The direct coupling of oxazolines and N-heterocyclic carbenes leads to chelating C,N ancillary ligands for asymmetric catalysis that combine both an "anchor" unit and a stereodirecting element. Reacting various N-substituted imidazoles with 2-bromo-4(S)-tert-butyl- and 2-bromo-4(S)-isopropyloxazoline gave the imidazolium precursors of the stereodirecting ancillary ligands. A library of ten different ligand precursors was obtained by using this simple procedure (65-97 % yield). These protioligands were metalated in a subsequent step by reaction with [{Rh(mu-OtBu)(nbd)}2] (nbd=norbornadiene), generated in situ from KOtBu and [{RhCl(nbd)}2] giving the corresponding N-heterocyclic carbene complexes [RhBr(nbd)(oxazolinyl-carbene)] 4 a-j in good yields. X-ray diffraction studies of two of the rhodium complexes, 4 d and 4 j, established a distorted square-pyramidal coordination geometry with the bromo ligand occupying the apical position. The rhodium-carbene bond length was found to be 2.070(4) A (4 d) and 2.012(3) A (4 j). Complexes 4 a-j were treated with AgBF4 in dichloromethane, giving the active cationic square-planar catalysts for the hydrosilylation of ketones. As a reference reaction for the catalyst optimisation, the hydrosilylation of acetophenone with diphenylsilane was studied and the system optimised with respect to the counterion (BF(4) (-)), solvent (THF) and the silane reducing agent (diphenylsilane). The reaction product (1-phenylethanol) was obtained with the highest enantiomeric excess (ee) by carrying out the reaction at -60 degrees C, whilst the enantioselectivity drops upon going both to lower and higher temperatures. The observation that the temperature dependence of the ee values goes through a maximum indicated a change in the rate-determining step as the temperature is varied. The determination of the initial reaction rate in the hydrosilylation of acetophenone upon varying the catalyst (4 d) and substrate concentrations at -55 degrees C established a rate law for the initial conversion which is first-order in both substrates as well as the catalyst (Vi = k[4][PhCOMe][Ph2SiH2]). The catalytic system derived from complex 4 d was found to afford high yields and good enantioselectivities in the reduction of various aryl alkyl ketones (acetophenone: 92 % isolated yield and 90 % ee, 2-naphtyl methyl ketone: 99 % yield, 91 % ee). The selectivity for the reduction of prochiral dialkyl ketones is comparable or even superior to the best previously reported for prochiral nonaromatic ketones; whereas cyclopropyl methyl ketone is hydrosilylated with an enantioselectivity of 81 % ee, the increase of the steric demand of one of the alkyl groups leads to improved ee's, reaching 95 % ee in the case of tert-butyl methyl ketone. Linear chain n-alkyl methyl ketones, which are particularly challenging substrates, are reduced in good asymmetric induction, such as 2-octanone (79 % ee) and even 2-butanone (65 % ee).     

Synthesis and Fungicidal Activities of 2-Alkylthio-5-(3,4,5-tribenzyloxyphenyl)-l, 3,4-oxadiazoles

Ten novel 2-alkylthio-5-(3, 4, 5-tribenzyloxyphenyl)-1, 3, 4-oxadiazole derivatives (5a-j) were synthesized from methyl 3, 4, 5-trihydroxybenzoate by etherification, hydrazidation, cyclization and thioetherification reactions. The structures of 5a-j were confirmed by 1HNMR, MS spectra and elemental analysis. The results indicated that most of the compounds 5 exhibited good fungicidal activities. The activity of 5h is higher than 90% against Fusarium oxysporum and Botrytis cinereapers in 50 mg/L.     

Studies in the 1,2,4-triazole series. III. Aminomethylation of 4-phenyl-1,2,4-triazolinethione-3

In a study of the aminomethylation of 4-phenyl-1,2,4-triazolinethione-3 (TRIT) it is ascertained that the reaction involves the nitrogen atom of the thioamide group. Salts of TRIT with secondary amines are obtained. It is shown that replacement of N (2) in 1-phenyltetrazolinethione-5 by the=CH- of TRIT leads to a decrease in the acidity of the thione and an increase in the stability of the hydroxymethyl and chloromethyl derivatives.For preceding papers see [1] and [2].     

Lithiation of 1-chloromethylbenzotriazole: generation and elaboration of benzotriazolyloxiranes

1-Benzotriazolylchloromethyllithium generated from 1-chloromethylbenzotriazole (1) and LDA reacts with enolizable and nonenolizable ketones to give benzotriazolyloxiranes 2a-g in good yields. The oxiranyllithiums 4a-d generated from 2a-d and n-BuLi at -78 degrees C were trapped by a variety of electrophiles to give oxiranyl derivatives 5a-j in good to excellent yields. Lewis-acid-promoted nucleophilic ring opening of benzotriazolyloxiranes 2a,f,g with allyltrimethylsilane gave the corresponding 1,7-octadien-4-ols 6a-c in 68-75% yield. Hydrolysis of alpha-acylbenzotriazolyloxiranes 5g,h provided 3-hydroxy-1,2-diones 7a and 7b in 73 and 86% yield, respectively.     

Synthesis of a new (1R)-(-)-myrtenal-derived dioxadithiadodecacycle and its use as an efficient chiral auxiliary

[reaction: see text] The new macrocycle 9 (>70% yield from hydroxythiol 10) was treated with several nucleophilic reagents (RMgX, RLi, and LiAlH4) affording carbinols 12a-j (80-96% yield, >99:1 dr). Oxidative hydrolysis of 12a,c,e, followed by LiAlH4 reduction of the resulting mixture, gave 16a,c,e in >95% ee,16c being a key precursor for the preparation of fungicide 17. The absolute configuration of 9 and 12j (Nu = H) was established by single-crystal X-ray diffraction analyses and chemical correlation.     

Enantioselective Baeyer-Villiger oxidation catalyzed by palladium(II) complexes with chiral P,N-ligands

Asymmetric Baeyer-Villiger reaction of symmetrical cyclobutanones 1a-j with urea-hydrogen peroxide (UHP) can be catalyzed by a complex of Pd(II) and the new terpene-derived P, N-ligand 7. The resulting lactones 2a-j were obtained in high yields and with good enantioselectivity (< or =81% ee).