The synthesis of unsymmetrically N-substituted chiral 1,4,7-triazacyclononanes

A number of chiral unsymmetrically N-substituted 1,4,7-triazacyclononane ligands have been prepared by modular methods. The key step in the synthesis centres on the macrocyclisation of three tertiary amide precursors under standard Richman-Atkins conditions which allows for subsequent N-functionalisation.     

An efficient one-pot route to symmetrically and unsymmetrically substituted 1,4,7-triazacyclononanes also results in the isolation of a stable macrocyclic aminal

A one-pot methodology has been developed for the direct synthesis of symmetrically and unsymmetrically N-substituted derivatives of 1,4,7-triazacyclononane. In the course of these studies the unexpected eight-membered cyclic aminal 7 has been isolated via an acid-catalysed rearrangement of enamine 5.     

Synthesis and application of novel catalytically active polymers containing 1,4,7-triazacyclononanes

New polymers containing 1,4,7-triazacyclononanes have been synthesised by means of ring opening metathesis polymerisation (ROMP); their complexes with Mn(II) catalyse the oxidation of simple olefins by hydrogen peroxide.     

The synthesis of an isopropyl substituted 1,4,7-triazacyclononane via an in situ sequential macrocyclisation method

Using L-valine methyl ester hydrochloride as starting material, the synthesis of (2S)-2-isopropyl-1,4,7-trimethyl-1,4,7-triazacyclononane is described. Various standard Richman-Atkins cyclisation methods gave only poor yields in the key macrocyclisation step. Efficient macrocyclisation yields were, however, realised when an in situ sequential cyclisation method was developed.     

Simple and efficient synthetic routes to d-cycloserine

d-Cycloserine has been successfully synthesized in good yields through three new synthetic routes from a readily available d-serine. In each synthesis, cyclization served as the key step, and two of the routes employed one-pot operations for the preparation of the target product. These methods featured the use of mild reaction conditions and simple treatments.     

Highly efficient catalytic routes to spiroketal motifs

The versatile and efficient synthesis of a variety of spiroketal motifs via the double intramolecular hydroalkoxylation of aliphatic and aromatic alkyne diols was achieved using simple and readily accessible Ir(I) and Rh(I) cyclooctadiene complexes as catalysts.     

Two efficient four-step routes to marine toxin tanikolide

We have presented two facile four-step syntheses of (±)-tanikolide from ethyl 2-oxocyclopentanecarboxylate. The overall chemical yields of the two sequences reached as high as 76 and 85%, respectively. The first strategy involved alkylation, Baeyer-Villiger reaction, saponification, and reduction/lactonization. The second approach for synthesizing tanikolide took advantage of the same intermediate, the alkylated ketoester 2, which was converted to the target molecule in such three steps as deethoxycarbonylation, hydroxymethylation, and Baeyer-Villiger reaction. Our strategies are advantageous because of their high yields and suitability for the preparation of 1 in multigram or larger quantities.     

Potential routes to cyclobuta[1,2-C] cyclopropabenzene

The CpCo(CO)₂-catalyzed cyclization of 1-trimethylsilyl-1, 5-hexadiyne (4) with propargyltetrahy-dropyranylether (5 leads to the formation of both possible regioisomers of the benzocyclobutene product: 3-trimethylsilyl-4-tetrahydropyranyloxymethylbenzocyclobutene (6) and the corresponding 5-tetrahydropyranyloxymethyl-isomer 7. On the other hand, cyclization of the same diyne with 3-(trimethylsilyloxy) propyne (10) gave only the 3,4-disubstituted product as the free alcohol 11. Compound 6 was iododesilylated, the ether hydrolyzed, and the alcohol tosylated to give 4-iodo-5-tosyloxymethylbenzocyclobutene 13, also obtainable more directly from 11 by treatment with ICI and tosylation. Iodide 13 could be reacted with n-butyllithium to give a variety of products incorporating the n-butylgroup and derived from crosscoupling of the carbon skeleton of starting material. The title compound 1 may be an intermediate en route to the observed products, but was not detected. Several thermal elimination routes to 1 from appropriately 4,5-substituted benzocyclobutenes were unsuccessful. Flash vacuum thermolysis of 11 furnished the silyloxyderivative 21 through elimination of methane.     

Stereoselective diversity-oriented syntheses of functionalized saccharides from bicyclic carbohydrate 1,2-lactones

Bicyclic carbohydrate 1,2-lactones have been synthesized in only two steps and high yields by saponification and subsequent cyclization from known malonate addition products to glycals. The gluco-configured lactone serves as an important precursor for diversity-oriented syntheses. Thus, stereoselective opening of the lactone ring was realized with various nucleophiles in the presence of Sc(OTf)₃. This enabled the introduction of different substituents at the anomeric position, to afford a broad variety of 1-functionalized carbohydrates. On the other hand, stereoselective α-substitution of the gluco-configured lactone with different electrophiles and subsequent ring opening gives a collection of 2-functionalized saccharides. More than 30 products have been isolated in analytically pure form, and their configurations were unequivocally established by various NMR methods. Thus, carbohydrate 1,2-lactones are attractive precursors for the stereoselective synthesis of diverse saccharides.     

Convenient one-pot syntheses of 1,2-dithiole-3-thiones and 3-imino-1,2-dithioles from terminal alkynes

The reaction of acetylide anions with carbon disulfide or phenyl isothiocyanate followed by addition of sulfur in the presence of a protonating agent such as a primary amine or alcohol affords 1,2-dithiole-3-thiones or 3-imino-1,2-dithioles in good to excellent yields.     

Recent advances in indole syntheses: new routes for a classic target

Indoles are the most abundant heterocycles in biologically active natural products, pharmaceuticals, agrochemicals, and are relevant substructures in functional materials. As a result, the development of methodologies that enable the synthesis of these compounds is continuously demanded. This review summarizes most recent and relevant approaches towards the preparation of this prevalent structural motif.     

Facile routes to natural acyclic polyenes syntheses of spilanthol and trail pheromone for termite

The synthetic procedures for spilanthol and trail-following pheromone for a southern subterranean termite were described. The syntheses heavily depend on the new diene synthesis using titanium reagent.     

Ruthenium-catalyzed oxidation of a carbon-carbon triple bond: facile syntheses of alkenyl 1,2-diketones from alkynes

A new oxidation procedure of alkynes catalyzed by Tp(PPh(3))(CH(3)CN)Ru-Cl is presented, which provides an efficient way to obtain alkenyl 1,2-diketones via ruthenium alkenyl 1,2-diketone intermediates. In contrast, the analogous reactions with Tp(PPh(3))(PhCN)Ru-Cl gave rise to the ruthenium metallacycle complexes.     

Two routes to 1,2-cyclohexanediol catalyzed by zeolites under solvent-free condition

Two routes to 1,2-cyclohexanediol were studied. Specifically: (a) the hydrolysis of cyclohexene oxide and (b) the direct dihydroxylation of cyclohexene with aqueous hydrogen peroxide. Both reactions were carried out with zeolites as catalysts under solvent-free conditions, aiming to establish green routes for the synthesis of 1,2-cyclohexanediol. In the first route, H-Beta and H-ZSM-5 zeolites were used as catalysts, respectively. According to the results, H-ZSM-5 was a suitable catalyst for the hydrolysis of cyclohexene oxide. A 88.6 % yield of 1,2-cyclohexanediol could be obtained at a 96.2 % conversion of cyclohexene oxide under mild conditions, and the catalyst could be reused for three times. Compared with H-ZSM-5, H-Beta gave a much lower selectivity (63 %), although it was more active. In the second route, Ti-Beta zeolites with three different Ti loadings prepared via a simple two-step strategy were characterized and used. The results indicated that it was the framework Ti species which was responsible for the catalytic activity. The resultant Ti-Beta-3 % could give a 90.2 % cyclohexene conversion at a 66.2 % selectivity of 1,2-cyclohexanediol.     

Tmtacn, tacn, and triammine complexes of (eta 6-arene)OsII: syntheses, characterizations, and photosubstitution reactions (tmtacn = 1,4,7-trimethyl-1,4,7-triazacyclononane; tacn = 1,4,7-triazacyclononane)

A series of (eta 6-arene)OsII complexes containing the saturated nitrogen donor ligands tmtacn, tacn, and NH3 are prepared and characterized. The electrochemical properties and photochemical reactions of these complexes are studied, and the solid-state structures for [(eta 6-p-cymene)Os(tacn)](PF6)2 (1) and [(eta 6-p-cymene)Os(tmtacn)](PF6)2 (2) are determined. Single-crystal X-ray data: 1, orthorhombic, space group Pbca-D2h15 (No. 61), with a = 14.716(3) A, b = 17.844(3) A, c = 18.350(4) A, V = 4819(2) A3, and Z = 8; 2, monoclinic, space group C2-C2(3) (No. 5), with a = 17.322(4) A, b = 10.481(3) A, c = 15.049(4) A, beta = 98.72 degrees, V = 2701(1) A3, and Z = 4.     

Sulfilimines in organic syntheses: new entries into tetrahydro-1,2-benzothiazepine and 1,2-benzisothiazole systems

Novel ring transformations of thiochroman-4-ones and benzo[b]thiophen3(2H)-ones to tetrahydro-1,2-benzothiazepin-5-ones and 1,2-benzisothiazoles via sulfilimine intermediates are described.     

Highly efficient syntheses of hyaluronic acid oligosaccharides

Highly efficient syntheses of hyaluronic acid oligosaccharides have been accomplished through the pre-activation based iterative one-pot strategy. A series of oligosaccharides ranging from di- to hexasaccharides were rapidly assembled using only near stoichiometric amounts of the building blocks without aglycon adjustment or purifications of intermediate oligosaccharides. Deprotection and oxidation protocols were developed for protective group removal and oxidation-state adjustment. The availability of such structurally well defined synthetic hyaluronic acid oligosaccharides will greatly facilitate the establishment of detailed structure-function relationships.     

Practical and high-yield syntheses of dihydromorphine from tetrahydrothebaine and efficient syntheses of (8S)-8-bromomorphide

A practical method for the conversion of tetrahydrothebaine to dihydromorphine in 92% yield is described. The procedure should allow more efficient production of opium products and may be easily modified for large-scale synthesis. The conversion of codeine to (8S)-8-bromomorphide, a potentially valuable intermediate to 6-demethoxyoripavine and derivatives, is also described. The absolute configuration of (8S)-8-bromomorphide was determined by a single-crystal X-ray diffraction study of the hydrobromide salt.     

Chemoenzymatic syntheses of novel ligands derived from trans-cyclohexane-1,2-diamine: application in the enantioselective addition of diethylzinc to aromatic aldehydes

Enantiopure (1R,2R)-cyclohexane-1,2-diamine derivatives, easily prepared from the corresponding (±)-trans-2-dialkylaminocyclohexanols through a chemoenzymatic route, have been employed as ligands in the enantioselective addition of diethylzinc to aromatic aldehydes. Of all the ligands tested, C₂-symmetric bisaminoamides derived from pyridine-2,6-dicarboxylic acid proved to be the most efficient.