In situ vinylindole synthesis. Diels-alder reactions with maleimides to give tetrahydrocarbazoles

Tetrahydrocarbazoles have been prepared in one-flask syntheses from indoles, ketones or aldehydes, and maleimides, with acid catalysis. The reactions involve a condensation of the indole with the ketone or aldehyde, followed by an in situ trapping of the vinylindole in a Diels-Alder addition with a maleimide. Isomerization of the double bond into the indole nucleus gave the tetrahydrocarbazoles which were isolated ( 6, 9 , and 10 ). Variation of the indole, carbonyl compound, and maleimide has been explored. The predominant stereochemistry of the tetrahydro ring in the products is all-cis, although a second stereoisomer has been isolated. Two regioisomers were generated from all unsymmetrical 2-alkanones, except 2-butanone, which gave the single isomer 9a . Aromatization of tetrahydrocarbazoles 6 to carbazoles 7 was accomplished with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.     

Aryl aldehydes as traceless dielectrophiles in bifunctional titanocene-catalyzed propargylic C-X activations

The titanocene-catalyzed construction of all-carbon substituted tertiary centers directly from aromatic aldehydes is described. The starting aldehyde behaves as a traceless functionality in the formation of multiple carbon-carbon bonds through consecutive carbon-heteroatom bond activations. The sequential addition of a metal acetylide and a second carbon nucleophile to the dielectrophilic aldehyde enables the construction of symmetrical and unsymmetrical 1,4-diynes in good yields.     

Vanadium(V)‐Induced Oxidative Cross‐Coupling of Various Boron and Silyl Enolates

Intermolecular oxidative cross‐coupling of two different enolates is one of the most useful reactions to synthesize unsymmetrical 1,4‐dicarbonyl compounds. In this study, the oxovanadium(V)‐induced intermolecular oxidative cross‐coupling of enolates afforded unsymmetrical 1,4‐dicarbonyl compounds. Various boron and silyl enolates underwent the formation of ketone–ester, ester–ketone, ester–ester, amide–ketone and amide–ester coupling products . These results clearly show the versatility of the present oxidative cross‐coupling protocol.     

Multi-component regio- and diastereoselective cobalt-catalyzed hydrovinylation/allylboration reaction sequence

The combination of a regioselective cobalt-catalyzed 1,4-hydrovinylation and the diastereoselective allylboronation reaction leads to a wide scope of functionalized hydroxydienyl esters in a one-pot reaction in excellent yields. With catalytic amounts of base, these products are easily converted either into α,β,γ,δ-unsaturated hydroxyl esters or complex tetrasubstituted tetrahydropyrans in chemo- and diastereoselective fashions. In addition, a high-yielding four-component one-pot reaction involving an acrylate, two different and unsymmetrical 1,3-dienes, and an unsaturated aldehyde is presented.     

The mannich reaction-II : Derivatization of aldehydes and ketones using dimethyl(methylene)ammonium salts

Aldehydes and ketones have been converted efficiently to their corresponding Mannich products by various dimethyl(methylene)ammonium salts under a range of reaction conditions. The several methods used to form these derivatives are compared. Excellent approaches to aldehyde derivatives involve treating the enol silyl ether of the carbonyl compound with methyllithium and then an iminium salt, or directly adding the iminium salt to the enol silyl ether. Ketones may be derivatized effectively by treatment with potassium hydride, followed by an iminium salt, or from the enol silyl ether by addition of the iminium reagent. Use of iminium reagents in the Mannich reaction is recommended because the yields are often good and the site of attachment on an unsymmetrical ketone is both predictable and controllable.     

Synthesis of substituted quinolines using the dianion addition of N-Boc-anilines and alpha-tolylsulfonyl-alpha,beta-unsaturated ketones

A short and versatile synthesis of substituted quinolines is provided. Alkylation of sodium tolylsulfinate with bromomethyl- or chloromethyl ketones generates beta-keto sulfones. Knoevenagel condensation of the beta-keto sulfones with an aldehyde provides alpha-tolylsulfonyl-alpha,beta-unsaturated ketones. Michael addition of the dianion of N-Boc-anilines in the presence of CuCN and LiCl with the unsaturated ketone generates a 1,4-adduct, which after deprotection of the Boc group and thermal elimination of the tolyl sulfone provides the quinoline.     

Synthesis of α-allenic aldehydes and allenyl trimethylsilyl ketones via (trimethylsilyloxy)butatrienes

α-Lithiated (trimethylsilyloxy)butatrienes, generated by 1,4-elimination of methanol from 1-trimethylsilyloxy-4-methoxy-2-alkynes with tert-butyllithium, give mixtures of α-allenic aldehydes and allenyl trimethylsilyl ketones which can be separated by distillation. The ratio aldehyde/ketone is solvent dependent.     

磷钨酸铜绿色催化合成缩醛(酮)及其催化活性测定

合成了绿色杂多酸盐催化剂磷钨酸铜;将环己酮、苯甲醛同乙二醇、1,2-丙二醇的缩合反应作为探针反应,测定了催化剂的催化活性,比较系统地考察了催化剂用量、物料配比、反应时间、带水剂用量等因素对反应产率的影响.结果表明:在底物醛(酮)用量0.2 mol、醛(酮)/乙二醇(1,2-丙二醇)摩尔比1.0/1.5、催化剂用量0.5 g、带水剂环己烷用量18 mL、一定温度下回流反应2.0 h,1,4-二氧螺[4,5]癸烷产率为83.3%,3-甲基-1,4-二氧螺[4,5]癸烷产率为89.7%,2-苯基-1,3-二氧环戊烷产率为66.7%,4-甲基-2-苯基-1,3-二氧环戊烷产率为78.5%.     

A Method for Preparing Phosphinic Acids from Hypophosphites: III. Synthesis of α-Hydroxy Phosphinic Acids

A one-pot method is proposed for preparing unsymmetrical -hydroxy phosphinic acids from ammonium hypophosphite. Bis(trimethylsilyl) phosphonites formed in situ on addition of bis(trimethylsilyl) hypophosphite to activated unsaturated compounds are brought without isolation into the Abramov reaction with an aldehyde or ketone. A series of new -hydroxy phosphinic acids are obtained.     

Organomanganese (II) reagents XII: An efficient one-pot preparation of unsymmetrical secondary or tertiary alcohols

Various unsymmetrical secondary or tertiary alcohols have been prepared in high yields by an efficient one-pot procedure involving the acylation of an organomanganese reagent by an acyl chloride and addition to the ketone formed of various organometallic compounds (RLi, RmgX, LiAlH₄, NaBH₄. The complexation of the intermediate ketone by the metallic salts present in the reaction mixture allows to perform the 1–2 addition step under exceptionally mild conditions (0 to 20°C).     

Direct observation of aldehyde insertion into rhodium-aryl and -alkoxide complexes

Several organorhodium(I) complexes of the general formula (PPh(3))(2)(CO)RhR (R = p-tolyl, o-tolyl, Me) were isolated and were shown to insert aryl aldehydes into the aryl-rhodium(I) bond. Under nonaqueous conditions, these reactions provided ketones in good yield. The stability of the arylrhodium(I) complexes allowed these reactions to be run also in mixtures of THF and water. In this solvent system, diarylmethanols were generated exclusively. Mechanistic studies support the formation of ketone and diarylmethanol by insertion of aldehyde into the rhodium-aryl bond and subsequent beta-hydride elimination or hydrolysis to form diaryl ketone or diarylmethanol products. Kinetic isotope effects and the formation of diarylmethanols in THF/water mixtures are inconsistent with oxidative addition of the acyl carbon-hydrogen bond and reductive elimination to form ketone. Moreover, the intermediate rhodium diarylmethoxide formed from insertion of aldehyde was observed directly during the reaction. Its structure was confirmed by independent synthesis. This complex undergoes beta-hydrogen elimination to form a ketone. This alkoxide also reacts with a second aldehyde to form esters by insertion and subsequent beta-hydrogen elimination. Thus, reactions of arylrhodium complexes with an excess of aldehyde formed esters by a double insertion and beta-hydrogen elimination sequence.     

Synthesis of silylallene glycosides and diene diglycosides by C-glycosidation of D-glucal with 1,4-bis(trimethylsilyl)-2-butyne

[reaction: see text] Silylmethylallenyl glycosides, symmetrical and unsymmetrical diene glycosides, were synthesized by C-glycosidation with 1,4-bis(trimethylsilyl)-2-butyne in good yield. The nature of the product is controlled by the choice of Lewis acid, BF(3).OEt(2), or SnCl(4). The efficient construction of unsymmetrical diene glycosides was achieved in one pot on the basis of the order of addition of sugar starting materials.     

Easy α-alkylation of ketones with alcohols through a hydrogen autotransfer process catalyzed by RuCl2(DMSO)4

The electrophilic α-alkylation of ketones with alcohols is accomplished by a hydrogen autotransfer process catalyzed by RuCl₂(DMSO)₄. The reaction can produce either simple alkylated ketones or α,β-unsaturated ketones just by choosing the appropriate starting ketones (methyl ketones or bicyclic methylenic ketones, respectively), as well as quinolines (by using 2-aminobenzyl alcohol derivatives) or the corresponding alcohol derivatives by the addition of an extra equivalent of the initial alcohol. In the last case, after the above alkylation process reduction of the carbonyl compound takes place. A mechanistic study seems to indicate that the process goes through the oxidation of the alcohols with ruthenium (after a previous deprotonation) to yield the corresponding aldehyde and a ruthenium hydride intermediate. In turn, the aldehyde suffers a classical aldol reaction with the starting ketone to form the corresponding α,β-unsaturated ketone, which finally is reduced through a Michael-type addition by the aforementioned ruthenium hydride intermediate.     

Catalytic cycloaddition of diazoalkanes to fullerene C60

Cycloaddition to fullerene C₆₀ of monosubstituted diazomethanes generated in situ by oxidation of aldehyde hydrazones in the presence of Pd(acac)₂-2 PPh₃-4 Et₃Al as catalytic system resulted in selective formation of homofullerenes in which the alkyl substituent is located above the plane of the five-membered ring in C₆₀. Under analogous conditions, unsymmetrical disubstituted diazomethanes generated from the corresponding ketone hydrazones gave rise to mixtures of stereoisomeric 5,6-open adducts.     

Synthesis of key fragments of amphidinolide Q--a cytotoxic 12-membered macrolide

β-hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.     

缩醛/缩酮的合成研究进展

醛/酮与醇或原甲酸酯进行亲核加成反应生成的产物缩醛/缩酮,是一类重要的有机化合物。在有机合成中,该反应也广泛用于醛/酮羰基的保护或者乙二醇的保护,因此,缩醛/缩酮的合成研究引起广泛的关注。本文根据反应体系的不同,从酸催化、电催化和光催化三个方面对近年来缩醛/缩酮的合成研究进展进行详细综述。期望该综述作为学生基础有机化学课程的课后拓展阅读内容,能加深学生对基础反应的理解,培养学生的科研创新思维。     

New liquid crystalline compounds based on 2-arylthiophenes and 2-(biphenyl-4-yl)thiophenes

A general and versatile route to the 2-alkyl-5-(4'-cyanophenyl)thiophenes was established, involving the condensation of an aryl vinyl ketone with an aldehyde in the presence of a thiazolium catalyst (Stetter procedure) to give a 1,4-diketone which with Lawesson's reagent undergoes ring-closure to give the corresponding arylthiophene. In the final step the exchange of a bromo substituent on the phenyl ring for a cyano group is accomplished by copper(I) cyanide in N,N-dimethylforamamide at reflux. The same sequence afforded 2-alkyl-5-(4'-cyanobiphenylyl)thiophenes. Several of the 1,4-diketones were obtained by conjugate addition of nitroalkanes to aryl vinyl ketones, and treatment of the γ-nitroketones with silica gel-supported potassium permanganate. Three alkyl 5-(4-cyanophenyl)thiophene-2-carboxylates were prepared by condensing β-chlorovinylaldehydes with thioglycolates. The cyanophenylthiophenes exhibited only monotropic phases, but incorporation of an additional phenyl ring provided cyanobiphenylylthiophenes of wide nematic ranges. Transition temperatures of binary mixtures of the cyanophenylthiophenes with 4-n-pentyl-4'-cyanobiphenyl were measured, and extrapolated virtual nematic-isotropic transition temperatures were determined.     

Synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin: a formal total synthesis

The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.     

Comparaison de la reactivite du bromure d'ethylmagnesium et du diethylmagnesium vis-a-vis des cetones α,β-ethyleniques dans divers solvants

The reactivity of diethylmagnesium and ethylmagnesium bromide towards 2-cyclohexenone in various solvents is studied. The 1,2 addition is always predominant, but diethylmagnesium adds almost exclusively in 1,2 manner to this ketone while ethylmagnesium bromide gives both 1,2 and 1,4 addition products with a ratio dependent of the solvent basicity. Thus, in hydrocarbons (hexane, benzene), the magnesium reagents behave similary; and with more basic solvents, for EtMgBr the yield of the 1,4 addition product increases and that of the 1,2 addition product decreases.With another α,β-ethylenic ketone, trans-3-penten-2-one, 1,4 addition occurs predominantly with both magnesium reagents, diethylmagnesium and ethylmagnesium bromide, but diethylmagnesium gives again much more 1,2 addition product than ethylmagnesium bromide.     

Synthesis of 3-benzoyl-3,4-dihydro-2H- and 3,4-dihydro-2,2-disubstituted-benzopyrans via alkynyl grignard reagents

The versatility of the new route to a substituted chromane via a lithiated allene recently described by us [1] is reported. The relatively more stable alkynols 2–4 were readily identified and thus provide evidence for the formation of vinyl acetylene carbinol as an intermediate in the new route. Accordingly, phenylacetylene magnesium bromide [2] reacted with suitable aldehyde or ketone to give the alkynols 2–4 which condensed further with the same or different aldehyde or ketone to give 3-benzoyl heteroring-substituted chromanes 5–17.