Syntheses of aporphine and homoaporphine alkaloids by intramolecular ortho-arylation of phenols with aryl halides via SRN1 reactions in liquid ammonia

The photostimulated intramolecular ortho-arylation reactions of bromoarenes linked with pendant phenoxy containing N-substituted tetrahydroisoquinolines in liquid ammonia afforded aporphine (54-82% yield) alkaloid derivatives via SRN1 reactions. This strategy was extended for the first time to the synthesis of a homoaporphine derivative (40% yield). Tetrahydroisoquinoline precursors that contained electron-withdrawing groups on nitrogen (i.e., amides, sulfonamides, and carbamates) gave cyclized products, whereas precursors with basic nitrogens (i.e., NH or NMe) either failed to yield cyclized products or gave aporphines in only low yield.     

DESs: Green solvents for transition metal catalyzed organic reactions

The recent development about using DESs as green solvents in transition metal catalyzed organic reactions was highlighted, and Au, Metal impregnated on magnetite, Pd, Ru catalyzed organic reactions proceeded smoothly in DESs and gave corresponding products in reasonable yields. And in some cases, the catalytic systems could be recycled up to several times.     

DESs: Green solvents for transition metal catalyzed organic reactions

In this review, the recent development about using DESs as green solvents in transition metal catalyzed organic reactions was highlighted. Firstly, the development of DESs was simply introduced. After presenting the advantages of DESs, transition metals catalyzed organic reactions using DESs as green solvents were classified and introduced in detail. Different transition metals such as Au, metal impregnated on magnetite, Pd and Ru catalyzed organic reactions proceeded smoothly in DESs and gave corresponding products in good yields. And in some cases, the catalytic systems could be recycled up to several times without any decrease in activity.     

Dynamic path bifurcation in the Beckmann reaction: support from kinetic analyses

The reactions of oximes to amides, known as the Beckmann rearrangement, may undergo fragmentation to form carbocations + nitriles when the migrating groups have reasonable stability as cations. The reactions of oxime sulfonates of 1-substituted-phenyl-2-propanone derivatives (7-X) and related substrates (8-X, 9a-X) in aqueous CH(3)CN gave both rearrangement products (amides) and fragmentation products (alcohols), the ratio of which depends on the system; the reactions of 7-X gave amides predominantly, whereas 9a-X yielded alcohols as the major product. The logk-logk plots between the systems gave excellent linear correlations with slopes of near unity. The results support the occurrence of path bifurcation after the rate-determining TS of the Beckmann rearrangement/fragmentation reaction, which has previously been proposed on the basis of molecular dynamics simulations. It was concluded that path-bifurcation phenomenon could be more common than thought and that a reactivity-selectivity argument based on the traditional TS theory may not always be applicable even to a well-known textbook organic reaction.     

The reactions of beta- and alpha-pyranose peracetates with PCl5, and utilization of the products to construct sarsasapogenin glycosides.

The reactions of beta- and alpha-pyranose peracetates with PCl5 gave products regioselectively chlorinated. The reactions of 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose (5) and -beta-D-galactopyranose (6) with PCl5 in CCl4 and that of methyl 2,3,4-tri-O-acetyl-beta-D-glucuronatopyranose (7) with PCl5 in toluene gave 2-O-trichloroacetyl-beta-D-pyranosyl chlorides 4, 12 and 14, respectively, as major products, and alpha-D-pyranosyl chlorides 11, 13 and 15, respectively, as minor products. On the other hand, the reactions of compounds 8 and 9 which were alpha-anomers of 5 and 6, respectively, with PCl5 gave as major products transformed acetyl groups at C-6 to -C(Cl) = CCl2 or -C(Cl)2-CCl3 group (16 and 17 from 8 and 18 from 9). The same reaction of 10, which was alpha-anomer of 7, gave alpha-chloride 15 as a major product. The glycosidation of sugar derivative 4 with sarsasapogenin 23 gave beta-glycoside 24 (29.1%) and alpha-glycoside 25 (46.9%), and that of 12 with 23 gave beta-glycoside 26 (24.0%) and alpha-glycoside 27 (40.8%). The improvement of the yields of beta-glycosides 24 and 26 (66.9 and 62.1% for 24 and 26, respectively) in the glycosidations were accomplished by the employment of alpha-bromides 28 and 29 obtained from 4 and 6, respectively. The glycosidations of monoglycosides 30 and 31 obtained by the treatment 24 and 26, respectively, with ammonia-saturated ether with sugar acetate bromides 32 and 34 gave diglycoside derivatives 35 and 33, respectively.     

Palladacycle mediated synthesis of cyano-functionalized chiral 1,2-diphosphine and subsequent functional group transformations

Cyano-functionalized allylic phosphine substrates containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary were synthesized from bromoacetaldehyde dimethylacetal via a one-pot process. The diastereoselective hydrophosphination reactions of the cis- and trans-allylic phosphine substrates gave the cyano-functionalized chiral 1,2-bis(diphenylphosphino)ethane products with high yield and stereoselectivity. The subsequent organic transformation reactions of the cyano-substituted products chemoselectively afforded the formyl- and hydroxyl-functionalized chiral 1,2-diphosphine complexes with retention of stereochemistry. The coordination properties and absolute configurations of the novel 1,2-diphosphine complexes were established by single crystal X-ray crystallography. The optically pure 1,2-bis(diphenylphosphino)ethane ligands with cyano-, formyl- and hydroxyl-functionalities could be liberated in high yields from the corresponding dihalo palladium complexes by treatment with aqueous potassium cyanide.     

Highly Reactive Intermediates from the Cocondensation Reactions of Iron,Cobalt and Nickel Vapor with Arenes

In 1969, P. L. Timms reported the first preparative cocondensation reactions of metal vapors with organic and inorganic substrates. The use of this technique in preparative chemistry soon spread rapidly, but in recent years there has been less activity in this sector. If metal atom reactions are not utilized primarily for the formation of new products, but for the synthesis of highly reactive intermediates, a new synthetic strategy may be developed. Our aims are reaction sequences which, based on an effective cocondensation reaction, lead gradually and selectively to new substance classes. This principle can be illustrated by the example of the cocondensation products of arenes and iron, cobalt, or nickel vapor, which decompose between ?70 and ?50°C. The classes of products accessible by this method extend from clusters, through π-complexes, organophosphorus and organoboron cage compounds to pure organic cycloaddition products.     

Pd(0)‐Catalyzed Cu(I)‐Thiophene‐2‐carboxylate‐mediated Cross‐Coupling of Heteroaromatic Thioethers and Boronic Acids—First Liebeskind–Srogl Reaction in Water

The first example of a Liebeskind–Srogl cross‐coupling reaction in water as sole reaction solvent is reported. 2‐(Methylthio)pyridine and 2‐(methylthio)benzothiazole were reacted in the presence of a Pd(0) catalyst and copper(I) thiophene‐2‐carboxylate with a series of arylboronic acids. These cross coupling reactions in water proceeded well with electron‐rich boronic acids and gave comparable yields to literature examples using organic solvents. Electron‐poor boronic acids gave somewhat lower yields in aqueous medium.     

Synthesis,Structure, and Antimicrobial Activity of the Reaction Products of Chloronitro-Substituted Benzofurazanes and Benzofuroxanes with Morpholine

New amination reactions of morpholine with a series of chloronitro-substituted benzofurazanes and -furoxanes were studied. The reactions of morpholine with 5,7-dichloro-4,6-dinitrobenzofuroxane and 4-chloro-5-nitro- and 5-chloro-4-nitrobenzofurazanes gave products of the aromatic nucleophilic substitution of the chlorine substituents in the nitrogenous heterocycles. The composition and structure of the products were established by chemical, physical, and physicochemical methods. The reaction of morpholine with 4,6-dinitrobenzofuroxane gave a stable Meisenheimer σ-complex, the structure of which was assessed by X-ray diffraction analysis. The synthesized compounds showed high antibacterial and antimycotic activities toward pathogenic human and animal microflora.     

Synthesis of 2-(3-tropolonyl)-1-benzopyrylium perchlorates and related compounds

3-Acetyltropolone ( 1 ) reacted with 2-hydroxybenzaldehyde ( 3a ) in the presence of perchloric acid in ethyl orthoformate to afford 2-(3-tropolonyl)-1-benzopyrylium perchlorate ( 4a ). The reactions with 2-hydroxy-5-methylbenzaldehyde ( 3b ), 5-chloro-2-hydroxybenzaldehyde ( 3c ), and 2-hydroxy-1-naphthalde-hyde ( 3d ) gave respectively the corresponding products 4b-d . The reactions of 2-acetyl-7-methylamino-tropone ( 2 ) with 3a-d also gave the corresponding products 5a-d , respectively.     

Enantioselective Friedel–Crafts reactions of ethenetricarboxylates and substituted pyrroles and furans and intramolecular reaction of benzene derivatives

Compared to enantioselective Friedel–Crafts reactions of indoles, reactions of alkylidene malonates with monocyclic aromatic compounds generally proceed with low enantioselectivity. The Friedel–Crafts reactions of ethenetricarboxylates 1 and monocyclic heteroaromatic compounds, such as substituted pyrroles and furans were investigated. The reaction of 1 with 2,4-dimethylpyrrole in the presence of a chiral bisoxazoline–copper(II) complex (10 mol %) in tetrahydrofuran at room temperature gave alkylated products in up to 72% ee. The reaction of 1 with 2-substituted furans gave alkylated products in 46–62% ee. The absolute stereochemistry of the furan Friedel–Crafts product 7e was determined by transformation to the known 2,3-dimethylbutyric acid. The intramolecular reaction of benzene derivatives gave cyclized products up to 56% ee.     

Highly atom efficient catalytic reactions utilizing water and alcohols as reagents

In this accounts, we describe our recent studies on hydrolysis, alcoholysis, and addition of alcohols to organic molecules. The reactions utilizing water and alcohols as a reagent are one of the most basic and simple reactions. The palladium-catalyzed asymmetric hydrolysis and alcoholysis of vinyl ethers gave valuable axially chiral 1,1′-bi-2-naphthol and 1,1′-bi-2-phenol derivatives and chiral P-chirogenic compounds in optically active form. The reaction is applied for hydrolytic deallylation of N-allyl amide and allyl esters. The later one was achieved by palladium/ruthenium dual catalysts which is the first example of catalytic irreversible ester hydrolysis. Gold complexes also catalyzed vinyl ether alcoholysis and hydroalkoxylation of olefins. In the later reaction, simple unactivated olefins can be used as substrates and gave the product in 92% yield. The copper-DTBM-SEGPHOS complex catalyzed alcoholysis of azlactones which is the first example showing zero-order kinetic resolution.     

Highly stereoselective anti-aldol reactions catalyzed by simple chiral diamines and their unique application in configuration switch of aldol products

Chiral derivatives of trans-1,2-diaminocyclohexane with different N,N-dialkyl groups in well-defined orientations have been synthesized, and applied as catalysts for the asymmetric aldol reaction between a variety of aldehydes and ketones. Enantiomeric catalyst 1j catalyzed the reaction in ethanol and provided excellent diastereoselectivity and enantioselectivity. Significantly, simple replacement of organic solvents with water switched the products of the aldol reactions from anti to syn configuration. Such catalytic reactions led to the products with anti to syn diastereoselectivity up to 99:1 in ethanol, while in water gave the products with syn to anti diastereoselectivity up to 99:1.     

有机合成的新世纪――－有机合成近年进展鉴赏

本文简要介绍了2005年至今有机合成领域的进展,第一部份有机合成方法学的一些新进展中突出介绍了金属参与的有机合成反应、自由基介导的合成反应、"一个反应瓶"内的多步反应以及不对称反应四个方面;第二部份复杂天然产物全合成则以10个分子的为例介绍这方面的进展。     

Solution-phase parallel synthesis of an N-alkylated dihydropteridinone library from fluorous amino acids

Parallel synthesis of an N-alkylated dihydropteridinone library has been accomplished in five steps starting from two displacement reactions of 4,6-dichloro-5-nitropyrimidine, first with fluorous amino acids, then with secondary amines. The hydrogenation of the nitro group followed by microwave-assisted cyclization gave the dihydropteridinones. Further diversification was achieved by the reaction of dihydropteridinones with benzyl halides to afford mono-N-alkylated products. All the reaction intermediates and final products were purified by SPE or precipitation without the need to perform chromatography.     

Three types of reactions with intramolecular five-membered ring compounds in organic synthesis

There are three types of reactions with intramolecular five-membered ring compounds in organic syntheses: The first type is reactions involving intramolecular five-membered ring compounds which are utilized for the ease of synthesis of these compounds and the stability of the products. The second is reactions performed via intramolecular five-membered ring intermediates, because such intermediates are very reactive and labile compounds. The third is the metal-catalyzed reactions with the intramolecular five-membered ring compounds because these metal compounds have catalytic activities. The third type reactions involving intramolecular five-membered ring pincer compounds are also provided.The first type reactions include carbonylations, alkenylations, alkynylations, acylations, isocyanations, Diels-Alder reactions, etc. The second type reactions include carbonylations, cross-coupling reactions, hydroacylations, ring expansion reactions, carbocyclizations, etc. The third type reactions include cross-coupling reactions, rearrangements, metatheses, reductions, Michael reactions, dehydrogenations, Diels-Alder reactions, etc.     

Reactions of novel mono- and difluoroacetyltrialkylsilanes with sulfur and phosphorus ylides

The reactions of difluoroacetyltrialkylsilanes with methylidene triphenylphosphorane and benzylidene triphenylphosphorane are affected by the nature of the silyl substituents giving either the enol silyl ether or normal Wittig product exclusively, or mixture of both. Reactions with Horner-Emmons type ylide gave only the alkene products. Reactions of mono- and difluoroacetyltrialkylsilanes with dimethylsulfoxonium methylide gave the enol silyl ether products exclusively. Conversion of an enol silyl ether to an epoxide was effected with m-CPBA.     

Synthesis and photophysical properties of EuS nanoparticles from the thermal reduction of novel Eu(III) complex

EuS nanoparticles were synthesized by the thermal reduction of single source precursor (SSP), (PPh4)[Eu(S2CNEt2)4].2H2O, under microwave irradiation. The average size of the EuS nanoparticles was found to be 8 nm (3-16 nm in size). The organic products on the EuS surface were observed by using FT-IR, NMR, and MS analyses. We have found that these are resulted from the chemical reactions of SSP and cover the nanocrystal surface. A thermal reaction of SSP gave EuS nanoparticles and the organic product (*SCN(Et)2). The organic product would make a dimmer, (Et)2NC(S)-(S)CN(Et)2, by the couping of the radicals formed in the thermal reaction and/or thiopolymer in the solution through the polymerization of the radicals. The effective surface modification by the organic products led to protection of the EuS surface, resulting in the formation of the strongly luminescent EuS nanoparticles at room temperature (emission peak = 350 nm, fwhm = 58 nm, emission quantum yield = 27 +/- 5%).     

Enzymatic C-terminal amidation of amino acids and peptides

Herein, we describe two versatile and high yielding enzymatic approaches for the conversion of semi-protected amino acid and peptidyl C-terminal α-carboxylic acids into their corresponding amides. In the first approach, the lipase Candida antarctica lipase-B (Cal-B), and in the second approach, the protease Subtilisin A, are used, respectively. We found that by using the ammonium salt of the α-carboxylic acid instead of separate ammonia sources, the enzymatic amidation reactions proceeded much faster without side reactions and gave near to quantitative yields of products.     

Regioselective Diels-Alder reactions of 3-indolylquinones

6-(3-Indolyl)quinolinequinone derivatives gave regioselective Diels-Alder reactions with a variety of dienophiles, yielding polycyclic carbazole derivatives. One-pot reactions, proceeding through a cascade of reactions including regioselective Michael and Diels-Alder steps, gave heptacyclic derivatives starting from indoles and 2,5,8(1H)-quinolinetriones. Double Diels-Alder reactions of 6-(3-indolyl)quinolinequinones and dihalobenzoquinones gave eleven-cycle products in one step.