Showing papers in "Journal of Organic Chemistry in 1994"

Acceleration of the Dess-Martin Oxidation by Water

Abstract: The Dess-Martin periodinane (DMP), l,l,l-triacetoxy-l,l-dihydro-l,2-benziodoxol-3(LH)-one (2),l is one of the mildest and most convenient reagents available for oxidation of alcohols (Figure 1). DMP enjoys increasing use despite suggestion that its behavior can be capricious.2 Recently, Ireland has addressed a problem of inconsistency in DMP batch quality by offering an improved procedure for synthesizing the reagenta2 Important as it is to have a reliable method of preparing pure DMP, we suspect that many D-M (Dess-Martin) oxidations in the literature have been effected not by DMP, but by an impurity commonly present in DMP samples. In our own laboratory, a crucial D-M oxidation in the total synthesis of rapamycin3 proceeded consistently only with a single 2-year old batch of the reagent, material that was largely insoluble in CDC13 and that exhibited a complex proton NMR spectrum. Several other samples of DMP, including relatively pure reagent prepared according to the Ireland method,2 failed to perform the desired transformation. Questions about the composition of the effective sample motivated the present Dess-Martin periodinane study. In attempts to obtain the impurities present in the effective DMP reagent, we explored Dess and Martin's preparation of the oxidant. However, pure, crystalline DMP was reproducibly obtained using their procedure by adhering to the following details: (1) In order to permit greater ease of stirring during oxidation of iodobenzoic acid, the initially viscous reaction mixture was more dilute than in the D-M preparation, which may ensure that oxidation proceeds to ~ompletion.~ (2) Iodinane oxide 1 was heated at 85 "C in Ac20 and AcOH at least 1 h beyond the time that dissolution was complete. (3) After acetylation, the mixture was allowed to stand for 1-2 days to permit crystallization of DMP.5 (4) During isolation of the product, exposure to atmosphere was strictly avoided. The resulting DMP was crystalline and completely soluble in CH2Clz and CDC13. The reagent contained a small amount of AcOH, but otherwise its NMR spectra showed no significant (>3%) extraneous peaks. When pure DMP prepared as above was used under inert conditions (flame-dried glassware, dry solvents,

Lanthanide triflates as water-tolerant Lewis acids. Activation of commercial formaldehyde solution and use in the aldol reaction of silyl enol ethers with aldehydes in aqueous media

Abstract: Lanthanide trifluoromethanesulfonates (triflates), especially ytterbium triflate (Yb(OTf) 3 ), were found to be stable Lewis acids in water. In the presence of a catalytic amount of lanthanide triflate, formaldehyde in water solution (commercial formaldehyde solution) was activated and the hydroxymethylation reaction of silyl enol ethers proceeded smoothly. Lanthanide triflates were also quite effective in the aldol reaction of silyl enol ethers with aldehydes in aqueous media; and watersoluble aldehydes such as acetaldehyde, acrolein, and chloroacetaldehyde could be employed for direct use. Moreover, in all these reactions, lanthanide triflates were quantitatively recovered after the reactions were completed and could be reused

Structure of Curacin A, a Novel Antimitotic, Antiproliferative and Brine Shrimp Toxic Natural Product from the Marine Cyanobacterium Lyngbya majuscula

Abstract: Bioassay-guided fractionation of the organic extract of a Curacao collection of Lyngbya majuscula led to the isolation of a new lipid, curacin A, with exceptional brine shrimp toxic and antiproliferative activities. Its unique thiazoline-containing structure has been deduced from spectroscopic information. Pure curacin A is an antimitotic agent (IC 50 values in three cell lines ranging from 7 to 200 nM) that inhibits microtubule assembly and the binding of colchicine to tubulin

Synthesis of Peptide Nucleic Acid Monomers Containing the Four Natural Nucleobases: Thymine, Cytosine, Adenine, and Guanine and Their Oligomerization

Abstract: The preparation of mixed-sequence PNAs (PNAs containing the four natural nucleobases; thymine, cytosine, adenine, and guanine) is described. The PNA monomers containing thymine, Cbz-protected cytosine, or adenine or benzyl-protected guanine were prepared via convergent syntheses. Subsequent to introduction of the carboxymethyl linker at N-1 of the pyrimidines or N-9 of the purines and suitable protection of exocyclic groups, the nucleobase derivatives were coupled to the Boc-protected backbone esters 10a or 10b and finally hydrolyzed affording the monomers 12a-d. The exocyclic amino groups of cytosine and adenine were protected with a benzyloxycarbonyl group. The exocyclic amino groups of guanine was left unprotected whereas O 6 was protected as the benzyl ether. Two mixed-sequence 10-mers, each with five purines incorporated, and a mixed-sequence 15-mer containing seven purines were assembled essentially following standard solid phase peptide synthesis protocols

Cationic BINAP-Ru(II) Halide Complexes: Highly Efficient Catalysts for Stereoselective Asymmetric Hydrogenation of .alpha.- and .beta.-Functionalized Ketones

Abstract: Cationic ruthenium-BINAP complexes 5, 7, and 10 of the formula [RuX((S)-BINAP)(arene)]Y, where X=Cl, Br, I; Y=Cl, Br, I, BF 4 , B(C 6 H 5 ) 4 ; arene=benzene, p-cymene, ethyl benzoate, and their enantiomers have been prepared by the reaction of arene-ruthenium halide complexes 4, 6, and 9 with (S)-BINAP or (R)-BINAP. Structures of the complexes were established by spectroscopy, conductivity, and a single-crystal X-ray analysis (5d: orthorhombic, P2 1 2 1 2; a=20.141(2) A, b=18.504(1) A, c=12.241(1) A, V=4562.0(7) A 3 , Z=4, R=0.078 for unique 4177 reflections). BINAP derivatives with various substituents at the para and meta positions of four phenyl rings on phosphorous atoms and their cationic Ru(II) complexes have also been synthesized. These BINAP-Ru (II) complexes have been used as catalysts for the asymmetric hydrogenation of various unsaturated organic compounds such as α- and β-keto esters, allylic alcohols, and α,β-unsaturated carboxylic acids in excellent diastereo- and/or enantioselectivities. Catalytic activities and stereoselectivities depend highly on reaction conditions such as solvent, temperature, and additives. Variation of halogen ligands bound to ruthenium atom and substituents on four phenyl rings of BINAP also have exerted remarkable effects on the efficiency of the catalysis. Asymmetric hydrogenation of methyl (∓)-2-(benzamidomethyl)-3-oxobutanoate catalyzed by the species derived from 9c and 3,5-(tBu) 2 -BINAP afforded the corresponding syn-(2S,3R)-17 in 98% de and 99% ee

Isolation and Structure of Spongistatin 1

Abstract: An Eastern Indian Ocean marine sponge in the genus onaia was located in the Republic of the Maldives and found to contain a structurally unprecedented macrocyclic lactone named spongistatin 1. The new perhydropyran-containing structure, as shown below, was found to be remarkably potent and specific, log molar TCI50 to < -10, against twenty human cancer cell lines in the U.S. National Cancer Institute s panel of sixty.

A General Method for Molecular Tagging of Encoded Combinatorial Chemistry Libraries

Abstract: Acylcarbenes can be used to attach chemically inert, vanillin-linked tagging molecules directly to an unfunctionalized Merrifield polystyrene solid support and thus to allow encoding of combinatorial libraries prepared by a wide range of chemistries

Efficient synthesis of polyhydroxylated fullerene derivatives via hydrolysis of polycyclosulfated precursors

Abstract: Cyclosulfated fullerene derivatives were hydrolyzed in the presence of water or in aqueous NaOH solution giving polyhydroxylated fullerenes. Both sulfated precursors and hydroxylated products were characterized. 7 figs.

Development and Application of a Continuous Microwave Reactor for Organic Synthesis

Abstract: A laboratory-scale continuous microwave reactor (CMR) he been developed and used to conduct organic syntheses routinely, rapidly, and safely in a range of solvents, under pressures up to 1400 kPa and at temperatures up to 200 o C. Advantages and applications of the CMR are discussed, along with the rationale for the design. Reactions carried out with the CMR included nucleophilic substitution, addition, esterification, transesterification, acetalization, amidation, base- and acid-catalyzed hydrolysis, isomerization, decarboxylation, and elimination. Name reactions included the Michael addition, Hofmann degradation, Williamson ether synthesis, and the Mannich, Finkelstein, Baylis-Hillman, and Knoevenagel reactions

Highly Efficient and Accelerated Suzuki Aryl Couplings Mediated by Phosphine-Free Palladium Sources

Abstract: Suzuki aryl cross-couplings employing aryl bromides and aryl iodides proceed under mild conditions (65 o C) with high efficiency (substrate-to-catalyst ratios in excess of 500) in the presence of phosphine-free palladium catalysts derived from palladium acetate, Pd 2 (dba) 3 .C 6 H 6 (dba=dibenzylideneacetone), and [(η 3 -C 3 H 5 )PdCl] 2 . Phosphine inhibition is shown to play a key role in limiting catalytic efficiency; qualitative comparison studies show that the phosphine-free systems are 1-2 orders of magnitude more active than phosphine-supported catalytic systems. Pd[P(Ph) 3 ] 4 proved to be the least active of the catalytic species screened. The phosphine-free methodology appears to be generally applicable; cross-couplings of aryl iodides yielding biaryls 6 and 7 proceed without noticeable steric or electronic effects. Cross-couplings employing aryl bromides are insensitive to electronic effects in the synthesis of 6 but are slowed by steric hindrance in the synthesis of 7. Acceleration of cross-coupling is observed in the presence of polar cosolvents and at high pH

Highly Enantioselective, Catalytic Epoxidation of Trisubstituted Olefins

Abstract: Chiral (salen)Mn(III) complexes have been found to be highly selective catalysts for the asymmetric epoxdation of several cyclic and acyclic trisubstituted olefins. These results are interpreted with a transition state model for epoxidation involving a skewed, side-on approach of olefin to a (salen)Mn(oxo) intermediate

A Novel Catalytic Effect of Lead on the Reduction of a Zinc Carbenoid with Zinc Metal Leading to a Geminal Dizinc Compound. Acceleration of the Wittig-Type Olefination with the RCHX2-TiCl4-Zn Systems by Addition of Lead

Abstract: A catalytic amount of lead promotes further reduction of zinc carbenoid (ICH 2 ZnI) with zinc in THF to give a geminal dizinc compound (CH 2 (ZnI) 2 ), which is a key intermediate for the methylenation of carbonyl compounds with a CH 2 I 2 , zinc, and TiCl 4 system

Synthesis of Diacetylene Macrocycles Derived from 1,2-Diethynyl Benzene Derivatives: Structure and Reactivity of the Strained Cyclic Dimer

Abstract: Diacetylene macrocycles (2-4) (n=1-3) (R=H, C 4 H 9 , C 6 H 13 , C 10 - H 21 , C 12 H 25 , OC 10 H 21 ) have been prepared from the oxidative coupling of 1,2-diethynylbenzene derivatives. These compounds can be produced in useful quantities and are of interest as precursors to novel conjugated organic polymers. The reported results indicate that when the R groups are large the dimeric macrocycle (n=1) can be prepared in as high as 74% yield from the corresponding 1,2-diethynylbenzene in a one-step procedure. An alternate multistep procedure was found to pro- duce the tetrameric macrocycle (n=3, R=C 6 H 13 ) in 45% yield. The hig- hly strained dimeric macrocycle was characterized by an X-ray structure and was found to be very reactive. The dimers undergo a rapid very exo- thermic polymerization at 100-125°C, indicative of a chain reaction. Reaction of the dimeric macrocycle with iodine results in intramolecu- lar cyclization and a new 20π electron tetraiodide fused ring system. Reaction of the tetraiodide with oxygen produces a related compound in which to of the iodides have been converted to ketones

Ab Initio Examination of Anomeric Effects in Tetrahydropyrans, 1,3-Dioxanes, and Glucose

Abstract: Axial and equatorial structures of 2-methyl-, 2-hydroxy-, 2-methoxy-, 2-amino-, 2-fluoro-, and 2-chlorotetrahydropyran, of the 2-tetrahydropyranylammonium cation, of 2-methyl-, 2-hydroxy, and 2-methoxy-1,3-dioxane, and of the corresponding cyclohexanes have been fully optimized at the HF9/6-31G * level. NBO analysis of the Hartree-Fock wave functions confirms that the anomeric effects of hydroxy-, methoxy-, fluoro-, and chloropyrans and of glucose and methyl glucoside are indeed due to hyperconjugation. In cyclohexane, tetrahydropyran, and glucose theoretical ΔE values involving the OH and OMe substituents are nearly identical

Synthesis of Chiral 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) via a Novel Nickel-Catalyzed Phosphine Insertion

Abstract: 2,2{prime}-Bis(diphenylphosphino)-1,1{prime}binaphthyl (BINAP), introduced in the early 1980`s, has become one of the most successful chiral ligands for catalytic asymmetric induction. Its wide application has been somewhat limited due to the scarce supply and expense of BINAP and up to now, there has been only one reported practical synthesis of chiral BINAP.

Copper(I)-Catalyzed Amination of Propargyl Esters. Selective Synthesis of Propargylamines, 1-Alken-3-ylamines, and (Z)-Allylamines

Abstract: Copper(I)-catalyzed aminations of propargyl phosphates and acetates proceed under mild reaction conditions to give the corresponding propargylamines which are precursors of 1-alken-3-ylamines and (Z)-allylamines

The Synthesis of Cyclic Enol Ethers via Molybdenum Alkylidene-Catalyzed Ring-Closing Metathesis

Abstract: An efficient method for the construction of five- and six-membered cyclic vinyl ethers from unsaturated esters using stoichiometric titanium reagents to convert the esters to acyclic olefinic enol ethers which are then transformed to the desired products by catalytic ring-closing olefin metathesis with a molybdenum alkylidene complex is described

Classical Organic Reactions in Pure Superheated Water

Abstract: At high temperatures and pressures, pure liquid water becomes a surprisingly effective medium for the reactions of organic compounds. It may function simultaneously as a convenient solvent, catalyst, and reagent for reactions which are typically acid- or base-catalyzed. Rapid and highly selective conversions are observed for the majority of the compounds in this study

Aromatic Nonpolar Nucleosides as Hydrophobic Isosteres of Pyrimidine and Purine Nucleosides.

Abstract: Described are the design, synthesis, and structures of three nonpolar nucleoside isosteres to be used as probes of noncovalent bonding in DNA and as isosteric replacements for the natural nucleosides in designed nucleic acid structures. Reaction of substituted aryl Grignards with 3',5'-bis-O-toluoyl-α-deoxyibofuranosyl chloride and subsequent deprotection with sodium methoxide in methanol afforded the two β-C-nucleoside pyrimidine analogs 1 and 2. The dimethylindolyl nucleoside 3, a purine isostere, was obtained by a nucleophilic displacement on α-chlorodeoxyribofuranose by the sodium salt of 4,6-dimethylindole, followed by deprotection. Regio- and stereochemistry of the products were established with NOE difference spectra and (1)H NMR splitting patterns. Analogs 1 and 2 are nonpolar isosteres of thymidine, and nucleoside 3 is an isostere of 2-aminodeoxyadenosine, the triply-bonded Watson-Crick partner of thymidine. Semiempirical AM1 calculations were carried out to provide bond length information to assess structural similarities between the isosteres and their natural counterparts.