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A new amino-protecting group is analyzed wherein a Michael acceptor is added to the protectant in order that treatment with a nucleophile will cause deblocking. The analysis involves basic structure-activity relationships and applications to peptide synthesis in solution through a beta-unsubstituted analogue of the 1,1-dioxobenzo(b)thiophene-2-ylmethyloxycarbonyl residue. The results show that, like Michael acceptors, urethanes obtained from allylic alcohols bearing 2-(alkyl- or arylsulfonyl) residues are sensitive to the incorporation of secondary amines at the alpha-beta-unsaturated site.

The application of catalytic amounts of the proazaphosphatranes P(meNCH2CH2)3N, P(i-PrNCH2CH2)3N and P(HNCH2CH2)(i-PrNCH2)2N as nonionic bases in the reaction of nitroalkanes with carbonyl compounds is described. The reaction occurs at room temperature with 2.2 equiv of magnesium sulfate to obtain the corresponding beta-nitroalkanols in excellent yields. Aldehydes react quantitatively in 5-60 min, while ketones need up to 3 h to react with nitromehane and up to 7 h for the reaction of ketones with higher nitroalkanes.

The allylation of imines with allyltrimethysilane triggered by a catalytic amount of fluoride ion and the evidences for its mechanism are analyzed. Although studies on the reaction of an allylsilane with a carbonyl compound under Lewis acid states or in the Sakurai-Hosomi reaction have been extensive, little research has been done on its aza analogue or the reaction between allylsilane and aldimine. An approach to represent the first example of a catalytic allylation of imines by allylsilane, which is non-Lewis acid mediated allylation of aldimines and can be used for homoallylamine synthesis, is presented.

A study relating to the synthesis of enantiomerically pure compounds demonstrates the development and application of an enzymatic reduction system. The system can be used to reduce both aromatic and aliphatic ketones with excellent stereoselectivity which, in turn, results in the synthesis of substantial yields of secondary alcohols with greater than 99% ee. The reagent used in the process is a biocatalysts which is easy to prepare and handle, the reaction proceeds under mild conditions and the production isolation is simple.

An experiment was conducted relating to carbonyl coupling reactions passing through a ketyl intermediate. The study reports that using a 250 W floodlamp to illuminate keto nitriles in the presence of Samarium(II) iodide enhances the yields of ketone-nitrile reductive coupling reactions. The sequencing of multiple reductive coupling reactions is also briefly investigated. The method developed is complementary to other procedures including the Samarium(II) iodide-promoted cyclization of keto carboxylic acid chlorides.

An experiment was conducted which related to research on the development of molecule-assembling, solid-phase organic synthesis techniques including the use of photolabile linkers in combinatorial chemistry. The study reports the development of a new photolabile linker with a pivaloyglycol moiety which is based on radical-induced beta-C,O bond cleavage. The new linker represents an excellent alternative for the cleavage of carboxylic acids.

A study relating to research on alkene hydroamination was conducted to alleviate the requirement of the use of internal alkynes or monosubstituted alkenes in cyclization pertaining to intra- and inter-molecular reactions for the production of heterocyclic and bicyclic products. Organolanthanide complexes were used to perform the intramolecular hydroamination of a hindered alkene. Results indicate that reduced substitution about the ligand and a larger metal ionic radius contribute to accelerated reaction with hindered olefins.

A study relating to research on Friedel-Crafts acylation reports on mechanistic observations relating to and the scope of this chemical process. The mechanistic study found that the trifluroacetic anhydride/H3PO4-mediated acylation system is indisputably a practical, atom-efficient alternative to Friedel-Crafts acylation suitable for the production of different fine chemical intermediates and for the bulk production of some simple acylated aromatics.

A study relating to alkynyl arenes and alkynylation reports the discovery of a unique catalyst (PdCl2(alaphos), where alaphos represents (2-dimethylamino)propyldiphenylphosphine) which efficiently catalyzes the cross-coupling of aryl triflates with alkynyl Grignard reagents to form substantial yields of alkanylarenes. This selective alkynylation procedure provides an efficient route to different types of conjugated aromatic compounds substituted with alkynyl groups.

A two-step methodology that can be used to create a general route to enynyl ketones and alkynyl ketones is presented. First, cross-coupling reactions between vinyl triflates or vinyl bromides against 1-(benzotriazol-1-yl)propargyl ethyl ether. is made. The resulting compound is reacted with primary halides to create intermediates hydrolyzed by dilute acid. Alkynyl ketones are formed through coupling reactions involving a variety of aryl iodides.

A general approach for the synthesis of substituted oligopyridines containing a single alkyne chain comprising one, two or three ethynyl groups, is described. The procedure was used for the synthesis of a large series of alkyne-substituted oligopyridines based on 2,2-bipyridine, 1,10-phennathroline, 2,2':6',2'-terpyridine or 1,8-naphthyridine substrates. Stepwise extension of the acetylene function by Cadiot-Chodkiewicz coupling and alkali-methanolic deprotectio results in the isolation of a family of novel dibutadinyl- and hexadiynyl-oligopyridine compounds.

The tandem Williamson synthesis/ether cleavage reaction is a novel and effective method for the resolution of all the enantiomers of 1,1'-binaphthalene-2,2'-diol and 2,2'-bis(bromomethyl)-1,1'-binaphthyl. Treatment of 2,2'-bis(bromomethyl)-1,1'-binaphthyl with 1,1'-binaphthalene-2,2'-diol and cesium or potassium carbonate in refluxing acetone afforded the formation of diastereoisomeric dioxacyclophanes in high yield and the cyclic tetraether as an isolated side product.

Highly reactive copper reagents were prepared by reduction of CuI.PBu3, CuI.PPh3, and CuCN.nLiX copper (I) complexes in a 3-step process. This involved reduction of the complex using lithium naphthalenide; oxidation at -78 to -35 degrees Celsius for alkyl bromides and -35 to 0 degrees Celsius for aryl bromides; and finally, reaction with an electrophile to form the product. Control of reduction temperature was an important factor in the process. The advantages and disadvantages of each copper complex are discussed.

Friedel-Crafts substitution reaction between 3,4-dimethoxytoluene and 2-(methoxymethylene)-3-methoxypropanenitrile followed by condensation with guanidine yields 75-85% ormetoprim, a dihydrofolate reductase inhibitor and potentiator of sulfadimethoxine. This synthetic route towards 2, 4-diamino-5-benzylpyrimidines is restricted by the benzyl substituent. However, an equally efficient technique is the base-catalyzed isomerization of cinnamonitrile. The second method is used in the synthesis of trimethoprim, a potentiator of sulfamethoxazole and a potent antibacterial drug itself.

The synthesis of alpha-acetoxy-3,3,3-trifluoropropyl sulfides provides the material for a study of their nucleophilic substitution reactions at the beta position. Acetoxylation is achieved by electrochemical means under very high substrate and electrolyte strengths. The subsequent study shows that nucleophilic attack on the beta position, otherwise difficult because of sulfur's stabilization of the nearby carbocation, proceeds efficiently with the use of electrogenerated acids rather than ordinary Lewis acids.

The stereocontrolled 1, 4-addition of the lithium amide of 3,5-dihydro-4H-dinaphth(2,1-c:1', 2'-e)azepine to alpha,beta-unsaturated esters, followed by cleavage of the benzylic C-N bonds of the chiral auxiliary, yields an asymmetric ammonia for Michael addition reactions. At optimized conditions (tert-butyl esters in DME with 1.5 equiv of the amide), the reactions at -63 degrees C produce very high chemical and diastereomeric yields. The beta-substituent may be varied over a wide range, with the S-amide adding to the E-ester to give chiral products in 95-99% enantiomeric excess.

In situ transmetalation of samarium(II) to copper(I) salts allows the conjugate 1,2- and 1,4-additions of aryl and alkyl halides to unsaturated ketones. The organosamarium reagents are preformed by reduction of the halides with SmI2. The copper salt CuI-P(OEt)3 in combination with 2 equivalents of the reagent provides the optimum conditions for the formation of carbon-to-carbon bonds through a series of radical and ionic reactions. The reactions produce 3-alkylated ketones in 30-82% yields.

The use of the silyl function allows three ways to start Michael reactions. Selective inter- and intramolecular additions are done through fluoride- or m-chlorobenzoate-catalyzed reaction of unsaturated diesters with silyl ketene acetals. Mild Lewis acids like ZnI2 catalyze less selective additions but still allow enough stereocontrol and a wider choice of silyl ketene acetals. Stronger Lewis acids like SnCl2/TiCl4 are useful in both silyl ketene acetal and silyl enol-initiated reactions with bis enones, the products of which can be further regiospecifically cyclized. All of these reactions take place with very high stereoselectivity.

Dimethyl(methylthio)sulfonium fluoroborate (DMTSF) and triethylamine trishydrofluoride (Et3N.3HF) in methylene chloride react with different olefins to produce beta-fluoroalkyl methyl thioethers. The introduction of the fluorine group into the alkene reagent follows an electrophilic anti-1,2-addition of methanesulfenyl fluoride. Stereospecific reactions from cis-cycloalkenes and trans-cyclodecenes give trans-1,2-substituted and cis-1,2-substituted cycloproducts, respectively. Unsymmetrical alkenes undergo regioselective Markovnikov-additions with DMTSF and Et3N.3HF.

The addition of dialkylzinc to o-phthalaldehyde in the presence of enantiomeric catalysts is a simplified method of preparing 3-ethyl- and 3-n-butylphthalides. The process involves enantioselective addition reaction and oxidation of the derived lactols utilizing chiral 1,2-disubstituted ferrocenyl amino alcohols as catalysts. The obtained 3-alkylphthalides have 80% to 81% yields without formation of unwanted products.

An enantioselective 1,2-aziridinomitosene synthesis by way of a chemoselective carbon-hydrogen insertion reaction of a metal carbene is described. This synthetic approach shows that metal carbene 5 may be subjected to an intramolecular carbon-hydrogen insertion reaction by one of two pathways. Cyclization via path a leads to azido ether 3 whereas path b results to 4. Subsequent closure of the azido alcohols obtained from 3 would lead to 1,2-aziridinomitosene 2 and azido ether 4 would lead to ent-2.

A highly practical procedure in epoxidation of terminal olefins maintains the environmental and economic advantages of H2O2 as the oxidant, while obtaining high yield and high selectivity. Other procedures have proven to be unsatisfactory for failing to meet the requirements of high yield and selectivity, sufficient productivity, low cost, safety. operational simplicity and environment-friendliness. The new system is comprised of Na2WO4 dihydrate, (aminomethyl)phosphonic acid and methyltri-n-octylammonium hydrogensulfate in a 2:1:1 molar ratio. It is also free from organic or inorganic chlorides. However, the method poses difficulty in the epoxidation of styrene and its simple derivatives.

Higher-order (6pi + 4pi) and (6pi + 2pi) cycloadditions can be done thermally to yield products identical to those in a photochemical process. Heating (eta-cycloheptatriene)tricarbonyl chromium(0), cHp-3-ene-Co(CO)3, with excess alkene or diene results in a bicyclo(4.2.1)nonadiene (BND) or a bicyclo(4.4.1)undecatriene. Uncomplexed cHp-3-ene thermally reacts with excess ethyl acrylate to form tricyclo(3.2.2.0)nonene (TN). Adding a catalytic amount of cHp-3-ene-Co(CO)3 completely reverses the chemoselectivity, yielding a 10:1 mix of BND and TN. The analogous (6 + 4) addition is slower but may be enhanced by replacing one CO ligand with triphenylphosphine.

A study relating to research on the role of dienes and polyenes in biologically active compounds and the synthesis of these dienes and polyenes describes details of the mild, highly stereoselective hydrogenolysis of 1,1-dibromo-1-alkenes including its mechanism, scope and limitations. The usefulness of the method for the preparation of conjugated polyenes and enediynes by Pd-catalyzed cross-coupling is also discussed.