Synthesis of nitrogen heterocycles by condensation of the conjugate base of open-chain reissert compound analogs with vinyltriphenylphosphonium bromide (schweizer's salt)

Reaction of the conjugate base of several open-chain Reissert compound analogs with vinyltriphenylphosphonium bromide is shown to afford a convenient route to substituted pyrroles. The condensation is a two-step process involving an initial reversible addition to form an unstabilized Wittig reagent followed by an intramolecular Wittig reaction upon the carbonyl group of the tertiary amide functionality with concomitant elimination of HCN. Several applications to the synthesis of 1,2,5-trisubstituted pyrroles are presented, together with attempts to expand this methodology to the synthesis of other heterocyclic systems.     

Catalytic enantioselective pyrrole alkylations of alpha,beta-unsaturated 2-acyl imidazoles

[reaction: see text] Enantioselective additions of pyrroles to alpha,beta-unsaturated 2-acyl imidazoles catalyzed by the bis(oxazolinyl)pyridine-scandium(III) triflate complex (1) have been accomplished. The alpha,beta-unsaturated 2-acyl imidazoles were synthesized in high yields through Wittig olefination. A short, enantioselective synthesis of the alkaloid (+)-heliotridane has been accomplished utilizing this methodology and a 2-acyl imidazole cleavage and cyclization. This methodology was then extended to the one-pot asymmetric synthesis of 2-substituted indoles.     

Stereoselective synthesis of the densely functionalized C1-C9 fragment of amphidinolides C and F

The synthesis of the C1-C9 subunit of amphidinolides C and F is described. Key steps include tandem Sharpless asymmetric dihydroxylation-S_N2 cyclization reaction, Lewis acid-mediated epoxide opening, Wittig reaction, and Wacker oxidation.     

保幼激素类似物11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯的简便全合成

从价廉的丙酮出发,首先经羟醛缩合、脱水、氧化、酯化、溴代反应合成了4-溴-3-甲基-2-丁烯酸异丙酯,继而与亚磷酸三乙酯反应得到了Wittig-Homer试剂,随后与香茅醛发生Wittig-Horner反应,最后在阳离子树脂催化作用下与甲醇醚化,成功地全合成了具有保幼激素活性的昆虫生长调节剂11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯.所得标题化合物的四种异构体中,具有较高生物活性的(2E,4E)-异构体的含量达66%.各步所合成化合物的结构经1H NMR,IR,MS分析确证.     

昆虫信息素的研究(Ⅵ)——家蝇性信息素组分4,8-二甲基二十七烷的合成

我们曾报道了家蝇性诱剂(Z)-9-二十三碳烯的合成,这个药剂对舍蝇表现出一定的诱引作用,Vebel等认为引起雄蝇交尾行为的不只是单一的(Z)体,他们从雌蝇的表皮类脂物中还检测出4,8-二甲基二十七烷等饱和烃组分,后者与(Z)烯混合能促使雄蝇产生最强烈的交尾撞击反应,迄今为止,有关4,8-二甲基二十七烷的合成报道甚少,我们从廉价易得的2-甲基戊-1-醇(1)出发按以下合成路线制备了标题化合物。     

Diol desymmetrization as an approach to the synthesis of unsymmetrical dienyl diesters

The tandem oxidation/Wittig olefination of unactivated diols utilizing manganese dioxide produces α,β-unsaturated hydroxy esters in high yields in a highly effective desymmetrization process. The formation of small quantities of the corresponding lactones suggests that the reaction may proceed through a lactol intermediate in some cases. The α,β-unsaturated hydroxy esters are transformed into symmetrical or unsymmetrical dienyl diesters using a second oxidation/Wittig olefination sequence mediated by PCC.     

Concise and facile synthesis of (R,R)-dexmethylphenidate hydrochloride and its three stereoisomers

A new and concise route is reported for the first time for the preparation of four stereoisomers of dexmethylphenidate hydrochloride starting from a single reactant, 2-benzyolpyridine, through an eight-step reaction process, which includes hydrogenation, protection, oxidation, chiral separation, Wittig reaction, hydroboration, pyridinium dichromate oxidation, and methyl esterification. The absolute configuration of the two chiral centers of each stereoisomer was confirmed by X-ray and chiral HPLC analyses.     

Enantioselective synthesis of tertiary alcohols through a zirconium-catalyzed Friedel-Crafts alkylation of pyrroles with α-ketoesters

Chiral complexes of 1,1'-bi-2-naphthol-based ligands with zirconium tert-butoxide catalyze the Friedel-Crafts alkylation of pyrroles with α-ketoesters to afford tertiary alcohols in good yields and ee up to 98%. The reaction is also of application to 4,7-dihydroindole to give C2-alkylated indoles after oxidation with p-benzoquinone.     

Tandem Reaction of Deprotonation-Oxidation-Wittig Reaction: Stereoselective Synthesis of (E)-α,β-Unsaturated Enoates

Ｓｉｎｃｅｉｔｓｄｉｓｃｏｖｅｒｙ ,Ｗｉｔｔｉｇｒｅａｃｔｉｏｎｈａｓｂｅｃｏｍｅｏｎｅｏｆｐｒｉｍａｒｙｍｅｔｈｏｄｓｆｏｒｔｈｅｆｏｒｍａｔｉｏｎｏｆｃａｒｂｏｎ ｃａｒｂｏｎｄｏｕｂｌｅｂｏｎｄｓａｎｄｂｅｅｎｗｉｄｅｌｙｕｓｅｄｉｎｔｈｅｓｙｎｔｈｅｓｉｓｏｆｎａｔｕｒａｌｐｒｏｄｕｃｔｓ .1,2 Ｒｅｃｅｎｔｌｙ ,ｉｔｗａｓｆｏｕｎｄｔｈａｔｐｒｉｍａｒｙａｌｃｏｈｏｌｓｃａｎｕｎｄｅｒｇｏｔｈｅｔａｎｄｅｍｒｅａｃｔｉｏｎｏｆｏｘｉｄａｔｉｏｎ Ｗｉｔｔｉｇｒｅａｃｔｉｏｎｗｉｔｈｐｈｏｓ…     

Electrochemical oxidation of 2,4,5-triaryl-substituted pyrroles. II. Oxidative dimerization of 4,5-diphenyl-2-mesitylylpyrrole

2,4,5-Triaryl-substituted pyrroles lead, upon chemical or electrochemical oxidation, to an intermediate β-β'-dimer, which, in the course of the reaction, undergoes further oxidation to a tetracyclic derivative. To improve the selectivity towards the uncyclized dimer the oxidation of a triarylpyrrole in which the ortho positions of the phenyl group in position 2 are hindered by the presence of methyl groups was attempted. The cyclization was hindered, but an α-β'-dimer was obtained as the major product. An unexspected isomeric α-β'-dimer, in which the mesitylyl group is shifted into the β position of the pyrrole ring which undergoes the oxidation, was obtained in minor amounts. Electroanalytical data indicate that the process goes through the formation of a monomeric radical cation, followed by a slow chemical reaction.     

An alternative stereoselective total synthesis of (-)-pyrenophorol

The total synthesis of 16-membered C₂–Symmetric dilactone (-)-Pyrenophorol was accomplished starting from commercially available (S)-epoxide prepared by hydrolytic kinetic resolution of (±) – epoxide with key steps of Grignard reaction, Swern oxidation, Wittig reaction and cyclization was achieved by intermolecular Mitsunobu cyclization. The synthesis of (-)-Pyrenophorol accomplished from cheaply available starting material, easily work-up procedures and reduction of cost in industrial process were major advantages of this route.     

Syntheses and properties of liquid crystalline N-substituted pyrroles and their polymers

Three liquid crystalline N-substituted pyrroles were synthesized from 6-(1-pyrrolyl)hexanol with phenolic derivatives having a mesogenic core of cyclohexylbenzene or biphenyl by Mitsunobu reaction. These pyrroles had two anodic peaks at 1.4 and 1.8 V (vs. SCE). The former was due to an oxidation of the pyrrole moiety and the latter was due to an oxidation of the mesogenic moiety. These pyrrole monomers were polymerized by electrochemical and chemical methods. The potentiostatic method and the chemical method using FeCl₃ gave a soluble and fusible polymer, respectively. A polymer having a mesogenic core of cyclohexyl benzene obtained by the chemical method and a polymer having a mesogenic core of biphenylketone obtained by the potentiostatic method had a liquid-crystalline phase. The phase was identified as smectic A by polarizing microscopy and XRD analysis. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2691–2698, 1998     

Synthesis of highly substituted pyrroles via oxidative free radical reactions of β-aminocinnamates

Oxidative free radical reactions of β-aminocinnamates are described. Imine radicals produced by tetra-n-butylammonium cerium(IV) nitrate (TBACN) oxidation of enamines undergo efficient addition to the C-C double bond of β-aminocinnamates. This TBACN mediated free radical reaction between β-aminocinnamates and enamines provides a novel method for the synthesis of highly substituted pyrroles. The direct TBACN oxidation of β-aminocinnamates gave the dimerization products effectively.     

(±)-19-去甲基-4(18),8,11,13-四烯-松香烷-7-酮的全合成

以间异丙基溴苯1为起始原料,通过进攻环氧乙烷及溴代两步制得溴化物3.溴化物3与Hagemann′s酯发生偶联反应,水解后生成偶联产物5.再以路易斯酸BF3·Et2O催化化合物5进行分子内环化为关键步骤得到反式稠合中间体6,最后通过与三苯基膦碘甲烷季盐发生Wittig反应及氧化,合成了(±)-19-去甲基-4(18),8,11,13-四烯-松香烷-7-酮[19-nor-abieta-4(18),8,11,13-tetraen-7-one](8).     

β-胡萝卜素的合成工艺改进

以呋喃为原料,经水解、原位水解-Wittig反应、还原、氧化四步反应合成了β-胡萝卜素的关键中间体2,7-二甲基-2,4,6-辛三烯-1,8-二醛(5);5与季鏻盐经Wittig反应合成了β-胡萝卜素,总收率43%,其结构经1H NMR确证。     

Direct cyanation of heteroaromatic compounds mediated by hypervalent iodine(III) reagents: In situ generation of PhI(III)-CN species and their cyano transfer

Hypervalent iodine(III) reagents mediate the direct cyanating reaction of a wide range of electron-rich heteroaromatic compounds such as pyrroles 1, thiophenes 3, and indoles 5 under mild conditions (ambient temperature), without the need for any prefunctionalization. Commercially available trimethylsilylcyanide is usable as a stable and effective cyanide source, and the reaction proceeds in a homogeneous system. The N-substituent of pyrroles is crucial to avoid the undesired oxidative bipyrrole coupling process, and thus a cyano group was introduced selectively at the 2-position of N-tosylpyrroles 1 in good yields using the combination of phenyliodine bis(trifluoroacetate) (PIFA), TMSCN, and BF3.Et2O at room temperature. In the reaction mechanism, cation radical intermediates of heteroaromatic compounds are involved as a result of single electron oxidation, and the key to successful transformations seems to depend on the oxidation potential of the substrates used. Thus, the reaction was also successfully extended to other heteroaromatic compounds having oxidation potentials similar to that of N-tosylpyrroles such as thiophenes 3 and indoles 5. However, regioisomeric mixtures of the products derived from the reaction at the 2- and 3-positions were obtained in the case of N-tosylindole 5a. Further investigation performed in our laboratory provided insights into the real active iodine(III) species during the reaction; the reaction is induced by an active hypervalent iodine(III) species having a cyano ligand in situ generated by ligand exchange reaction at the iodine(III) center between trifluoroacetoxy group in PIFA and TMSCN, and effective cyanide introduction into heteroaromatic compounds is achieved by means of the high cyano transfer ability of the hypervalent iodine(III)-cyano intermediates. In fact, the reaction of N-tosylpyrrole 1a with a hypervalent iodine(III)-cyano compound (e.g., (dicyano)iodobenzene 8), in the absence of TMSCN, took place to afford the 2-cyanated product 2a in good yield, and an effective preparation of the intermediates is of importance for successful transformation. 1,3,5,7-Tetrakis[4-{bis(trifluoroacetoxy)-iodo}phenyl]adamantane 12, a recyclable hypervalent iodine(III) reagent, was also comparable in the cyanating reactions as a valuable alternative to PIFA, affording a high yield of the heteroaromatic cyanide by facilitating isolation of the cyanated products with a simple workup. Accordingly, after preparing the active hypervalent iodine(III)-CN species by premixing of a recyclable reagent 12, TMSCN, and BF3.Et2O for 30 min in dichloromethane, reaction of a variety of pyrroles 1 and thiophenes 3 provided the desired cyanated products 2 and 4 in high yields. The iodine compound 13, recovered by filtration after replacement of the reaction solvent to MeOH, could be reused without any loss of activity (the oxidant 12 can be obtained nearly quantitatively by reoxidation of 13 using m-CPBA).     

Reaction of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones with ethyl(triphenylphosphoranylidene)acetate

The Wittig reaction of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones 2 with ethyl (triphenyl-phosphoranylidene)acetate 3 proceeds stereoselectively to give E-4-carbethoxymethylene-1,2,3,4-tetra-hydro-2-quinolones 4 , which were hydrolyzed to corresponding acids 6 Butenolides 5 were detected and, in some cases, isolated as a minor product of the Wittig reaction.     

Copper- or phosphine-catalyzed reaction of alkynes with isocyanides. Regioselective synthesis of substituted pyrroles controlled by the catalyst

The copper-catalyzed reaction of isocyanides (CNCH2EWG1) 1 with electron-deficient alkynes (RC[triple bond]CEWG2) 2 gave the 2,4-di-EWG-substituted pyrroles 3 selectively, whereas the phosphine-catalyzed reaction of 1 with 2 afforded the 2,3-di-EWG-subsituted pyrroles 4. Accordingly, regioselective synthesis of substituted pyrroles has been achieved by merely choosing the catalyst.     

Synthesis and stereochemistry of ω-azolylalkenes [1]

ω-Azolylalkenes 3, 4, and 5 were synthesized by N-alkylation of C-alkylation of ω-bromoalkenes 2, which were obtained either by phase transfer Wittig reactions of ω-bromoalkylphosphonium salts 1 with aldehydes or by Wittig reactions of ω-hydroxyalkylphosphonium salts 6 with aldehydes and subsequent bromination. ω-Azolylalkenes 3 were also directly prepared by the Wittig reaction of ω-azolylalkyltriphenylphosphonium salts 8 with aromatic aldehydes. The stereochemistry of these Wittig reactions was studied. © 1997 John Wiley & Sons, Inc.     

A Synthesis of (+)-Oblongolide

The absolute configuration of natural oblongolide is reassigned as (3aS,5aR,7S,9aS,9bS)-3a,5a,6,7,8,9,9a,9b-octahydro-7,9b-dimethylnaphtho[1,2-c]furan-1(3H)-one 2 by a 7-stage synthesis of its enantiomer 1 from (+)-citronellol involving a regioselective reduction and an intramolecular Diels-Alder reaction (IMDA) as the key steps. (+)-Citronellol was converted into methyl (2E,4E,10E)-(S)-(+)-11-tert-butoxycarbonyl-7-methyl-undeca-2,4,10-trienoate 7 by sequential Lemieux-Johnson oxidation, Wittig reaction, pyridinium chlorochromate oxidation, and Wadsworth-Emmons-Homer alkenation. A regioselective reduction of the methoxycarbonyl group in 7 afforded tert-butyl (2.E,8E,10E)-(S)-(+)-2,6-dimethyl-12-hydroxy-dodeca-2,8,10-trienoate 8 from which (+)-oblongolide was readily obtained via an IMDA reaction.