Showing papers in "Journal of Organic Chemistry in 1996"

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures1

Abstract: Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C−C multi...

Scandium Trifluoromethanesulfonate as an Extremely Active Lewis Acid Catalyst in Acylation of Alcohols with Acid Anhydrides and Mixed Anhydrides.

Abstract: Scandium trifluoromethanesulfonate (triflate), which is commercially available, is a practical and useful Lewis acid catalyst for acylation of alcohols with acid anhydrides or the esterification of alcohols by carboxylic acids in the presence of p-nitrobenzoic anhydrides. The remarkably high catalytic activity of scandium triflate can be used for assisting the acylation by acid anhydrides of not only primary alcohols but also sterically-hindered secondary or tertiary alcohols. The method presented is especially effective for selective macrolactonization of ω-hydroxy carboxylic acids.

Palladium-Catalyzed Suzuki-Type Self-Coupling of Arylboronic Acids. A Mechanistic Study

Abstract: Symmetrical biaryls are formed from arylboronic acids both under tetrakis(triphenylphosphine)palladium and under palladium(II) acetate catalysis. The principal mechanistic features of these self-couplings have been determined.

A Novel Oxidizing Reagent Based on Potassium Ferrate(VI)(1).

Abstract: A new, efficient preparation has been devised for potassium ferrate(VI) (K(2)FeO(4)). The ability of this high-valent iron salt for oxidizing organic substrates in nonaqueous media was studied. Using benzyl alcohol as a model, the catalytic activity of a wide range of microporous adsorbents was ascertained. Among numerous solid supports of the aluminosilicate type, the K10 montmorillonite clay was found to be best at achieving quantitative formation of benzaldehyde, without any overoxidation to benzoic acid. The roles of the various parameters (reaction time and temperature, nature of the solvent, method of preparation of the solid reagent) were investigated. The evidence points to a polar reaction mechanism. The ensuing procedure was applied successfully, at room temperature, to oxidation of a series of alcohols to aldehydes and ketones, to oxidative coupling of thiols to disulfides, and to oxidation of nitrogen derivatives. At 75 degrees C, the reagent has the capability of oxidizing both activated and nonactivated hydrocarbons. Toluene is turned into benzyl alcohol (and benzaldehyde). Cycloalkanes are also oxidized, in significant (30-40%) yields, to the respective cycloalkanols (and cycloalkanones). Thus, potassium ferrate, used in conjunction with an appropriate heterogeneous catalyst, is a strong and environmentally friendly oxidant.

Alkane Oxidation with Molecular Oxygen Using a New Efficient Catalytic System: N-Hydroxyphthalimide (NHPI) Combined with Co(acac)(n)() (n = 2 or 3).

Abstract: A novel class of catalysts for alkane oxidation with molecular oxygen was examined. N-Hydroxyphthalimide (NHPI) combined with Co(acac)n (n = 2 or 3) was found to be an efficient catalytic system for the aerobic oxidation of cycloalkanes and alkylbenzenes under mild conditions. Cycloalkanes were successfully oxidized with molecular oxygen in the presence of a catalytic amount of NHPI and Co(acac)2 in acetic acid at 100 °C to give the corresponding cycloalkanones and dicarboxylic acids. Alkylbenzenes were also oxidized with dioxygen using this catalytic system. For example, toluene was converted into benzoic acid in excellent yield under these conditions. Ethyl- and butylbenzenes were selectively oxidized at their α-positions to form the corresponding ketones, acetophenone, and 1-phenyl-1-butanone, respectively, in good yields. A key intermediate in this oxidation is believed to be the phthalimide N-oxyl radical generated from NHPI and molecular oxygen using a Co(II) species. The isotope effect (kH/kD) in t...

Amino Acid Derivatives of β-Cyclodextrin

Abstract: The syntheses of the heptaamino acid-substituted β-cyclodextrins per-6-[(phenylalanyl)amino]-β-cyclodextrin (6), per-6-cysteinyl-β-cyclodextrin (7), as well as the per-2,3-dimethyl-per-6-cysteinyl-β-cyclodextrin (12) are described. The amino acids were coupled to the primary face of the β-cyclodextrin torus using the backbone carboxylic acid functionality of phenylalanine and the side chain thiol group of cysteine. In the case of the heptacysteinyl derivatives, polyzwitterionic compounds were obtained and shown to be highly water soluble.

Convergent Synthetic Routes to Orthogonally Fused Conjugated Oligomers Directed toward Molecular Scale Electronic Device Applications

Abstract: This paper describes the synthetic organic phase of a project directed toward the construction of molecular scale electronic devices. Outlined is a convergent synthetic route to orthogonally fused conjugated organic oligomers. The final systems are to have a potentially conducting chain fused perpendicularly to a second potentially conducting chain via a σ bonded network. One of the core segments synthesized is based on a spirobithiophene moiety with a central silicon atom. It is formed by a zirconium-promoted bis(bicyclization) of a tetrapropargylsilane. The second core is a 9,9‘-spirobifluorene system. Terminal halide groups provide the linkage points for further extension of the chains via Pd-catalyzed or Pd/Cu-catalyzed cross coupling methods. All four branching arms are affixed to the core in a single operation, thus making the syntheses highly convergent. In the cases of the larger functionalized systems, alkyl substituents on the thiophenes afford soluble materials. In order to prepare the molecule...

Bond Dissociation Energies of O−H Bonds in Substituted Phenols from Equilibration Studies

Abstract: Bond dissociation energies (BDE) of several phenolic compounds have been determined by studying the equilibration of couples of phenols and of the corresponding phenoxyl radicals by means of EPR spectroscopy. Measurements were carried out in highly concentrated solutions submitted to continuous photolysis in the presence of di-tert-butyl peroxide. Since under this experimental condition the decay of the phenoxyl radicals was slower than the hydrogen transfer reaction from phenols to phenoxyls, equilibrium concentrations of the two radicals were actually measured. Due to the fact that the radical species are continuously generated in solution, phenols giving short-lived phenoxyl radicals could also be investigated by this method. All of the examined phenols are characterized by O−H bonds weaker than that of the parent compound, PhOH, and their BDE values can be calculated to a good approximation by an additive rule using fixed contributions for the various substituents. Only in the case of the sterically c...

Conformationally Unbiased Macrocyclization Reactions by Ring Closing Metathesis

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Approaches to combinatorial synthesis of heterocycles : a solid-phase synthesis of 1,4-dihydropyridines

Abstract: N-Immobilized enamino esters 2 derived from amine-functionalized PAL or Rink polystyrene resins react with preformed 2-arylidene β-keto esters or directly with β-keto esters and aldehydes to afford, upon trifluoroacetic acid cleavage, 1,4-dihydropyridine (DHP) derivatives in good yields. The mechanism of this transformation on solid support has been studied using 13C NMR and IR spectroscopies. This new solid-phase synthesis has been applied to the preparation of several bioactive DHPs and is designed to be amenable to the “split and pool” protocol for combinatorial library synthesis.

Palladium-Catalyzed Reaction of o-Ethynylphenols, o-((Trimethylsilyl)ethynyl)phenyl Acetates, and o-Alkynylphenols with Unsaturated Triflates or Halides: A Route to 2-Substituted-, 2,3-Disubstituted-, and 2-Substituted-3-acylbenzo[b]furans

Abstract: The reaction of o-ethynylphenols 3 with a wide variety of unsaturated halides or triflates 6 in the presence of Pd(OAc)2(PPh3)2, CuI, and Et3N (procedure A) gives 2-vinyl- and 2-arylbenzo[b]furans 7, in good to high yield, through a palladium-catalyzed coupling followed by an in situ cyclization step. Small amounts of 2,3-disubstituted-benzo[b]furans 8 are usually isolated as side products. In some cases, however, compounds 8 are generated in significant yield or even as the main products. The formation of 8 can be prevented by employing alternative procedures (B and C) that use o-((trimethylsilyl)ethynyl)phenyl acetates 5 as starting building blocks. Procedure B is based on the palladium-catalyzed reaction of 5 with 6 in the presence of Pd(PPh3)4, Et3N, and n-Bu4NF, followed by the hydrolysis of the resultant coupling derivative 12 under basic conditions. Procedure C affords 7 through an in situ coupling/cyclization of 5 with 6 in the presence of Pd(PPh3)4 and KOBut. The utilization of o-alkynylphenols 9...

Kahalalides: Bioactive Peptides from a Marine Mollusk Elysia rufescens and Its Algal Diet Bryopsis sp.(1).

Abstract: In addition to the previously reported bioactive kahalalide F six new peptides are described. Six of these, including kahalalide F, are cyclic depsipeptides, ranging from a C(31) tripeptide to a C(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens. The mollusk feeds on a green alga, Bryopsis sp., which has also been shown to elaborate some of these peptides in smaller yields, in addition to an acyclic analog of F, kahalalide G. The bioassay results of antitumor, antiviral, antimalarial, and OI (activity against AIDS opportunistic infections) tests are reported.

Hydrogen-Bonded Complexes of Diaminopyridines and Diaminotriazines: Opposite Effect of Acylation on Complex Stabilities.

Abstract: The association behavior of several 2,4-diamino-s-triazines, 2,6-diaminopyridines, and their acylated derivatives with uracil derivatives was studied. In solution (1)H-NMR and IR spectroscopy were used, and in the solid state as (co)crystals X-ray diffraction was used. Acylation of 2,6-diaminopyridine leads to an increase of the association constant in CDCl(3) of the complexes with N-propylthymine from 84 to 440-920 M(-)(1), whereas acylation of diamino-s-triazines leads to a dramatic fall in the association constant of the complexes with N-propylthymine from 890 to ca. 6 M(-)(1). This phenomenon is related to different conformational preferences of these compounds. The amide groups in bis(acylamino)pyridines prefer a trans conformation, with the carbonyl group anti with respect to the ring nitrogen and coplanar with the aromatic ring. The amides of bis(acylamino)triazines, however, reside predominantly in a cis conformation. Repulsive secondary electrostatic interactions between the cis-amide and uracil carbonyl groups are thought to be responsible for the low association constant of complexes of bis(acylamino)triazines with uracils. The relatively high dimerization constants of bis(acylamino)triazines have been rationalized by the strong tendency to dimerize via quadruple hydrogen bonding.

Asymmetric michael addition of malonate anions to prochiral acceptors catalyzed by l-proline rubidium salt

Abstract: l-Proline rubidium salt catalyzes the asymmetric Michael addition of malonate anions to prochiral enones and enals. This method can be applied to a wide range of substrates to give adducts with a p...

Practical Route to a New Class of LTD4 Receptor Antagonists

Abstract: A general approach to the synthesis of a new class of LTD4 antagonists is presented. The key diarylpropane framework was prepared by Claisen−Schmidt condensation and selective reduction of the enone. Depending on the bridge to the 7-chloroquinaldine moiety, alkylation or Heck coupling methodology was developed. The chiral sulfides were introduced by asymmetric reduction of the diarylpropanone intermediates and subsequent inversion of the chiral center.

Efficient and Highly Selective Oxidation of Primary Alcohols to Aldehydes by N-Chlorosuccinimide Mediated by Oxoammonium Salts.

Abstract: 2,2,6,6-Tetramethyl-1-piperidinyloxy catalyzes efficient oxidation of primary alcohols to aldehydes by N-chlorosuccinimide, in a biphasic dichloromethane-aqueous pH 8.6 buffer system in the presence of tetrabutylammonium chloride. Aliphatic, benzylic, and allylic alcohols are readily oxidized with no overoxidation to carboxylic acids. Secondary alcohols are oxidized to ketones with a much lower efficiency. Very high chemoselectivities are observed when primary alcohols are oxidized in the presence of secondary ones. Primary-secondary diols are selectively transformed into hydroxy aldehydes, with, in some cases, no detectable formation of the isomeric keto alcohols.

Efficient Reagents for the Synthesis of 5-, 7-, and 5,7-Substituted Indoles Starting from Aromatic Amines: Scope and Limitations

Abstract: Upon reaction with IPy2BF4, 4-substituted anilines give regioselectively the corresponding o-iodoanilines in nearly quantitative yield, in a process that can be carried out on a multigram scale. Palladium-catalyzed coupling of the resulting 2-iodoanilines with (trimethylsilyl)acetylene (TMSA), followed by efficient CuI-mediated nitrogen cyclization onto alkynes with concurrent elimination of the TMS substituent, allows a straightforward elaboration of 5-mono- and 5,7-disubstituted indoles from aromatic amines. This new approach to the aforementioned indoles does not requires protective groups on nitrogen at any step and can be adapted for preparing related 7-monosubstituted indoles. Moreover, examples iterating the process are given, allowing bisannulation and sequential double annulation and resulting in synthesis of benzodipyrroles. Additionally, suitable conditions for iodination of some of the target indoles with IPy2BF4 are discussed.

Exploratory Investigations Probing a Preparatively Versatile, Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening Sequence.

Abstract: A novel pyridinium salt photoelectrocyclization−nucleophilic bicyclic aziridine ring opening reaction sequence has been investigated in order to determine its preparative potential. N-Alkylpyridinium perchlorates were found to undergo photoinduced electrocyclization upon irradiation in nucleophilic solvents, such as H2O and MeOH, to efficiently produce 6-alkyl-6-azabicyclo[3.1.0]hex-2-en-4-yl alcohols and ethers. The bicyclic aziridine photoproducts react with a number of different nucleophiles (e.g., H2O, MeOH, AcOH, AcSH) under acid-catalyzed conditions to produce 5-(nucleophile-substituted)-4-(alkylamino)cyclopenten-3-yl alcohols and ethers. The aziridine ring opening processes are both regioselective and stereoselective, yielding trans,trans-trisubstituted cyclopentenes exclusively, apparently as a consequence of the operation of an SN2 mechanism. The effects of C-alkyl substitution on the regiochemistry of the pyridinium cation photocyclization reaction were briefly probed, and a method was developed...

Easy Access to Water-Soluble Fullerene Derivatives via 1,3-Dipolar Cycloadditions of Azomethine Ylides to C60

Abstract: Fullerenes show promise as biological agents against microorganisms provided the proper selectivity and solubility can be enhanced through functionalization. The authors present a method to increase the water solubility of fullerenes and they evaluate the effectiveness of these compounds for effectiveness in killing bacteria and fungus.