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This procedure can be used as an alternative method to the Reissert-type reduction of azaaromatics.

We described herein the optimization of the synthetic methodology exploited to obtain the pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine sedative prototype 1a and novel analogues designed by successive molecular simplifications. By applying microwave irradiation during the hetero Diels-Alder key-step to obtain the heterotricyclic scaffold, under solvent-free conditions, we were able to obtain the desired compounds in drastically shorter times and better yields. Additionally, in vivo evaluation of the sedative effects of these heterocyclic derivatives showed that 1a and the novel structurally-related analogue 1e were the most efficient compounds to impair the locomotor activity in mice at the dose of 10micromol/kg.

In the presence of ClCO2Et, the use of CuI in MeNO2 efficiently catalyzed the Reissert-type acylation of isoquinoline derivatives with acylzirconocene chlorides. In the reaction of quinolines with acylzirconocene chlorides, the choice of catalyst and solvent was crucial to the regioselective formation of adducts. The cationic RhI-catalyzed reaction in MeNO2 preferentially afforded 1,2 adducts. On the other hand, the CuI-catalyzed reaction in CH2Cl2 preferentially afforded 1,4 adducts.

The Reissert-like alkenylation of 3,4-dihydroisoquinoline (I) with alkenylzirconocenes (II) in the presence of ethyl chloroformate gives alkenylated tetrahydroisoquinoline (IV) regioselectively.

Phthalimide is also applicable to the Cu-catalyzed N-cyclopropylation with cyclopropylboronic acid.

The formation of the 2- or 5-substituted pyrroles is determined by a nature of the electrophiles used and in some cases the temperature.

A new heterocycle, furo[4,3,2-de][1]benzopyran (2), was synthesized. A key step in the sequence was the allylic bromination of 3,4-dihydrofuro[4,3,2-de][1]benzopyran (8) to give 3-bromo-3,4-dihydrofuro[4,3,2-de][1]-benzopyran (10) using N-bromosuccinimide under irradiation and high dilution conditions. Bromide 10 was dealt with 1,8-diazabicyclo[5.4.0]undec-7-ene to afford compound 2. Several reactions of 2 were examined. Protonation of 2 in trifluoroacetic acid occurred at the 2-position to form a pyrylium ion 12. Catalytic hydrogenation of 2 with palladium on charcoal proceeded smoothly to give 8. Reduction of 2 by sodium and ethanol afforded 3-ethyl-4-hydroxybenzofuran (14). Electrophilic substitutions of 2 such as formylation, acetylation, and bromination, occurred easily at the 2-position. The above results show that compound 2 has both properties of benzofuran and 4-methylenepyran.

Various metal oxides have been examined as catalysts for the hydrodechlorination of CFC-113 to form 1-chloro-1,2,2-trifluoroethylene (CFC-1113). NiO was most effective and over silica gel- or Y zeolite-supported Ni catalyst, 100% conversion of CFC-113 and 96% selectivity to CFC-1113 were attained.

In the presence of titanium(IV) bromide, N-tosyl aldimines smoothly reacted with ketene bis(trimethylsilyl) acetals at low temperature, and upon esterification anti-β-amino esters were obtained selectively.

Slightly oxidized cadmium, zinc-bearing and cadmium-bearing ferrites have been prepared by air oxidation of iron(II) hydroxide suspensions at initial (Cd + Zn):Fetot mol ratios (rCd + Zn) of 0.10:2.90–1.00:2.00 at pH 10.0 and 65 °C. The upper limit of Cd: Fetot mol ratio in the ferrites was found to be about 0.1:1, and for each Zn:(Cd + Zn + Fetot) mol ratio in the suspensions upper limits were also found, respectively. The lattice constant a0 and Mossbauer spectra at room temperature of the cadmium, zinc-bearing ferrites suggested that at Cd2+:Zn2+ mol ratios of ⩽0.12:0.43 at the tetrahedral sites the crystal structure of the ferrites prepared at rCd + Zn= 1.00:2.00 is that of zinc-bearing ferrites and approaches that of cadmium-bearing ferrites with increasing Cd2+ :Zn2+ mol ratio. Also that at rCd + Zn= 0.10:2.90–0.80:2.20, homogenous mixtures of CdFe2O4–Fe3O4 and ZnFe2O4–Fe3O4 solid solutions are formed.

The chiral amino alcohol, cis -2-amino-1-acenaphthenol, was synthesized, and resolved by a simple procedure. This new chiral amino alcohol was converted into an oxazoline derivative and applied as a chiral auxiliary to the diastereoselective [2,3]-Wittig rearrangement.

The chiral imines prepared from an artificial chiral auxiliary, erythro-2-amino-1,2-diphenylethanol, and various aldehydes, reacted with organolithium reagents to give the corresponding chiral amines with excellent diastereofacial selectivity.

The chiral amino alcohol, cis -2-amino-3,3-dimethyl-1-indanol was synthesized and resolved. Its oxazolidinone derivative was found to be a highly efficient chiral auxiliary in an asymmetric alkylation reaction.

The chiral amino alcohol, cis -2-amino-1-acenaphethenol, was resolved via its ( R )-2-phenylpropionic acid salt. This amino alcohol was used as the precursor of a chiral oxazaborolidine, which was an efficient chiral catalyst in the asymmetric reduction of prochiral ketones.

The chiral oxazolidinone, derived from cis-2-amino-3,3-dimethyl-1-indanol, was found to be an efficient chiral auxiliary in the asymmetric Diels-Alder reaction.

The chiral amino alcohol, cis -2-amino-3,3-dimethyl-1-indanol was synthesized and resolved. Its oxazolidinone derivative was found to be a highly efficient chiral auxiliary in diastereoselective alkylation, acylation, bromination, and hydroxylation reactions.

The review describes the mechanism of chiral discrimination of racemic amines upon crystallization and the induction of chirality in organic reactions by using them as chiral auxiliaries. In order to form conglomerates, which can be resolved into the two enantiomers upon alternative seeding, both formation and packing of 21-columns are essentially very important. On the other hand, in order to achieve high efficiency in resolution through diastereomeric salt formation, which is the most practical method, one of a pair of diastereomeric salts derived from a racemic amine and an enantiomerically pure resolving agent should at least have two 21-columns and planar boundary surfaces in its crystal structure. On the basis of this knowledge, we developed several artificial chiral auxiliaries such as erythro-2-amino-1,2-diphenylethanol,cis-2-amino-1-acenaphthenol, andcis-2-amino-3,3-dimethyl-1-indanol. These were found to be very efficient chiral auxiliaries in asymmetric inductions: alkylation of chiral imines, catalytic borane-reduction, and alkylation of chiral N-acylated oxazolidinone.

Enantiopure 2-[2-(diphenylphosphino)phenyl]oxazoline, derived from a non-natural amino alcohol, cis-2-amino-3,3-dimethyl-1-indanol, was found to be an efficient ligand for the rhodium-catalyzed enantioselective hydrosilylation of ketones.

The conjugate addition of lithium amides 2 to tert-butyl 4-(OR)-substituted-2-pentenoates 1 produced a mixture of the syn- and anti-amino esters (3 and 4) in high yields. Sterically bulky OR groups, such as trityloxy and tert-butyldiphenylsilyloxy, gave the syn diastereomer 3 either exclusively or predominantly. The syn-selectivity may be explained by a modified Felkin−Anh model. The use of tert-butyldimethylsilyloxy as an OR group afforded a nearly 1:1 mixture of diastereoisomers, and the use of the smallest MeO group produced a 63:37 mixture of the syn 3 and anti isomer 4. The presence of Me group at the α-position (C-2 position) of the enoate enhanced the syn diastereoselectivity up to 100%; the conjugate addition to tert-butyl 4-methoxy-2-methyl-2-pentenoate (17) gave the syn-isomer 18 exclusively. This enhancement may be explained by the combination of chelation and allylic strain model 19 in which the smallest H orients inside to avoid an allylic strain. A phenyl group at the γ-position enhanced the...

A chiral amino alcohol, cis-2-amino-3,3-dimethyl-1-indanol (2), was converted into the corresponding enantiomerically pure phosphorus-containing oxazoline 4. Oxazoline 4 was found to be an efficient ligand for palladium-catalyzed enantioselective allylic amination reactions: In the amination reaction of (E)-1,3-diphenyl-2-propen-1-yl acetate (7a), 4 was found to be more efficient than the similar ligands 1a−c, derived from valinol, tert-leucinol, etc. Other 1,3-bis(p-substituted aryl)-2-propen-1-yl acetates were also converted to the corresponding amines in a similar manner and with excellent enantioselectivity. In the amination reaction of 1-alkyl-3,3-diphenyl-2-propen-1-yl acetates 11, the correponding amines 12 were obtained with excellent enantioselectivity when acetic acid was added to the reaction system.

A series of dapsone-related 4-aminophenyl and 2-aminothiazolyl derivatives was prepared, and their antinephritic activity and blood toxicity were evaluated. 5-(2-Pyridylsulfonyl)-2-thiazolamine (FR115092, 26 ) was effective against two nephritis models, namely graft- versus -host disease (GVHD) and autoimmune W/BF 1 mice, and showed none of the blood toxicity observed with dapsone.

5-(2-Pyridylsulfonyl)-2-thiazolamine (2) was effective both in mitomycin C (MMC)-induced thrombocytopenia and in an animal model of idiopathic thrombocytopenic purpura (ITP). It also suppressed the increase of autoantibodies against platelets in the ITP model and showed no blood toxicity. Chemical modification of 2 led to the discovery of more potent compounds against MMC-induced thrombocytopenia.

4-Chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was converted into alkyl 1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl telluride, which was lithiated using alkyllithium followed by the reaction with electrophiles.

Lewis acids such as AlCl3 or EtAlCl2 dramatically catalyzed the hydrosilylation of alkynes 1 with trialkylsilanes to produce the corresponding cis-vinylsilanes 2 in a regio- and trans-stereoselective manner. For example, the hydrosilylation of 1-dodecyne 1a with triethylsilane in the presence of 0.2 equiv of AlCl3 gave cis-1-(triethylsilyl)-1-dodecene in 93% yield. Other alkyl- and phenyl-substituted terminal and internal acetylenes also underwent trans-hydrosilylation very smoothly. In the case of alkoxy- or silyloxy-substituted acetylenes, the use of 1.2 equiv of AlCl3 or EtAlCl2 was essential to obtain the corresponding trans-hydrosilylation products in high yields. Moreover, AlCl3 catalyzed the hydrosilylation of aromatic allenes 11, producing the alkenylsilanes 12 with high regio- and stereoselectivities in moderate to high chemical yields. Not only the simple monosubstituted, but also the disubstituted and trisubstituted allenes, underwent the hydrosilylation reaction smoothly, serving as a useful t...

Two new metabolites, citreo-γ-pyrone and citreothiopyrane A, with interesting biological activity have been isolated from the mycelia of hybrid strains KO 0201 and 0211 derived from Penicillium citreo-viride B. IFO 6200 and 4692. Their structures have been elucidated based on their spectral data. In addition, their biological properties are also described. The structure of citreothiolactone previously reported has been revised.

As a part of the search for biologically active plant products, M cells, which form a collagen fiber network in vitro after a prolonged culture period, were used. The n-BuOH-soluble fraction of a methanol extract of leaves of Premna subscandens exhibited promotion of collagen network formation by M cells. Extensive isolation work guided by a bioassay afforded a phenylethanoid, acteoside, as an active compound.

From leaves of P. subscandens, harvested in Ishigaki Island, three iridoid glucoside diesters of 3,7-dimethyloctan-1,8-diol, named premnaodorosides D, E and F, and an iridoid glucoside diester of 3,7-dimethyloctan-2,6-dien-1,8-diol (premnaodoroside G) were isolated together with known congeners, premnaodorosides A, B and C. Their structures were determined by spectroscopic methods.

Electron-deficient heteroaromatic tellurides, which was obtained from the corresponding haloheteroaromatics, reacted selectively with n -butyllithium to give the lithio derivatives.

The EtAlCl2-mediated intramolecular addition of silyl enol ethers to both terminal and internal unactivated alkynes, bearing alkyl and phenyl susbstituents at the alkyne moiety, gave mono- and bicy...

A novel, efficient synthesis of cyclic carbonates from the reaction of epoxides and gaseous CO2 under mild conditions (1 atm, rt to 45 °C) was achieved in reasonable yields (65–83%) by using N-methyltetrahydropyrimidine (MTHP) that facilitated efficient delivery of CO2 from the gas phase to the reaction system.

1-Methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky’s diene) is recognized as a synthetically useful diene due to its high reactivity in the Diels−Alder reaction with electron-deficient alkenes to give oxygen-functionalyzed cyclohexenes and substituted cyclohexenones, which are important building blocks for the total synthesis of natural products. However, the development of catalytic enantioselective versions of Diels−Alder reactions using Danishefsky type dienes with electron-deficient alkenes has been difficult because of the instability of the dienes under Lewis acidic conditions. Only highly reactive C═O and C═N double bonds are employed in a hetero-Diels−Alder reaction which proceeds under catalysis of chiral Lewis acids. We have developed a new chiral ligand, BINAMIDE, which is easily prepared from 1,1′-binaphtyl-2,2′-diamine by acylation. The highly diastereo- and enantioselective Diels−Alder reaction of Danishefsky type dienes with electron-deficient alkenes in the presence of an Yb(III)-BINAM...

A new copper-mediated cross-coupling of arenes and arylboronic acids is described. Under the influence of Cu(OCOCF3)2, the C−H bond arylation of electron-rich arenes with arylboronic acids takes place to afford a range of biaryls in good yields. The reaction is selective for cross-coupling; no homocoupling product arising from arenes or arylboronic acids is detected. Multiple C−H bond arylation is possible with indoles and pyrroles furnishing interesting extended π-systems.

A new rhodium-based catalytic system for the direct C–H coupling of arenes and iodoarenes that shows high activity with reasonably broad scope was developed. Under the catalytic influence of RhCl(CO){P[OCH(CF3)2]3}2 and Ag2CO3, the direct C–H arylation of heteroarenes and arenes took place with iodoarenes to afford a range of biaryls in good to excellent yields with high regioselectivity. Thiophenes, furans, pyrroles, indoles, and alkoxybenzenes are applicable to this arylation protocol.

A simple and facile method for the cleavage of carbon–oxygen bonds promoted by niobium pentachloride(V) is described. Excellent yields and regioselectivities were observed with various alkyl aryl ethers to give the phenols. NMR studies revealed the formation of monoaryloxy niobium salt(V), and a neighboring-group effect may play a significant role in the regioselectivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Two new monoterpene glucosides, demethylsecologanol and 3'''-O-glucosylsenburiside II, were isolated from Ophiorrhiza liukiuensis (Rubiaceae) together with 23 known compounds, including camptothecins and beta-carboline-type alkaloids. Their structures were determined by spectroscopic analysis.

Friedel–Crafts acylation catalyzed by niobium pentachloride with silver salt is described. Aromatic compounds with Ac 2 O or Bz 2 O were smoothly converted into the corresponding ketones in good to excellent yields. This system was also applied to the Sakurai–Hosomi reaction using acetals. The reaction proceeded quite rapidly to give the desired products in excellent yields.

A simple and convenient method for the differentiation of alkoxy groups on aromatic rings is described. Niobium(V) is found to possess a strong Lewis acid property to transform alkyl arylethers smoothly to the corresponding phenols in high yields. The excellent regioselectivity was also observed in dialkoxy benzene derivatives under mild conditions.

Various silacycles with vinylsilane framework are synthesized via the Lewis acid-catalyzed intramolecular hydrosilylation of alkynes. The cyclization proceeds in an endo-trans or/and in an exo-trans manner, depending on the substrate structure. This methodology is applicable to the synthesis of five-, six-, seven-, and eight-membered medium-sized silacycles. Furthermore, it is possible to obtain a silole derivative via the intramolecular hydrosilylation of the ortho-alkynyl-substituted phenylsilane 10.

Extensive isolation work on the n-BuOH-soluble fraction obtained from the leaves of Premna subscandens, collected on Ishigaki island, Okinawa, afforded six compounds. Two were identified as megastigmane glucosides, 7-(3,5-dihydroxy-1,1,5-trimethylcyclohexylidene)-9-methylprop++ +-8-enyl 9-O-beta-D-glucopyranoside and 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside. The structures of the remaining four new compounds were elucidated to be a 2'-O-beta-D-apiofuranosyl derivative of 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside, named premnaionoside, benzyl alcohol beta-D-(2'-O-beta-D-xylopyranosyl)glucopyranoside, phenethyl alcohol beta-D-(2'-O-beta-D-glucopyranosyl)glucopyranoside, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester by spectroscopic analyses.