Copper-catalyzed electrophilic amination of functionalized diarylzinc reagents

The copper-catalyzed electrophilic amination of functionalized diarylzinc reagents with O-acyl hydroxylamines allows for the preparation of functionalized tertiary arylamines in high yields, and is noteworthy for the mild reaction conditions employed. The functionalized diarylzinc reagents were prepared via an iodine/magnesium exchange of the corresponding aryl iodide followed by transmetalation of the resultant Grignard species with ZnCl(2).     

Synthesis of stereodefined fused δ-hydroxy-γ-lactones from dealkylative cyclization of epoxy-diesters

A dealkylative lactonization of stereodefined aryl-substituted epoxides allows the preparation of densely functionalized fused δ-hydroxy-γ-lactones having three consecutive stereochemically defined stereocenters.     

Preparation of Functionalized α-Chloromethyl Ketones Using Rieke Zinc

The cross-coupling reaction of highly functionalized organozinc reagents with chloroacetyl chloride mediated by copper allows for the easy preparation of functonalized α-chloromethyl ketones in excellent yields.     

1-Hydroxycyclopropanecarboxaldehyde tetrahydropyranyl ether. Preparation and rearrangement of functionalized 1-vinylcyclopropanols.

The tetrahydropyranyl ether of 1-hydroxycyclopropanecarboxaldehyde, readily available from 1-hydroxycyclopropanecarboxylic acid, allows the preparation of functionalized 1-vinylcyclopropanols which undergo specific four- or five-membered ring annulations.     

Thiol‐functionalized 1,3‐benzoxazine: Preparation and its use as a precursor for highly polymerizable benzoxazine monomers bearing sulfide moiety

We describe a new strategy for preparation of benzoxazine monomers based on in situ preparation of a thiol‐functionalized benzoxazine and successive chemical modification of the thiol moiety. The thiol‐functionalized benzoxazine can be prepared from its precursor bearing two benzoxazine moieties linked by disulfide bond. Reductive cleavage of the disulfide bond of the precursor with using triphenylphosphine as a reducing agent allows successful preparation of the thiol‐functionalized benzoxazine. By performing this reduction process in the presence of epoxides and acrylates, the formation of the thiol moiety and its successive reaction with those electrophiles proceed efficiently to give the corresponding benzoxazines with sulfide moieties. The benzoxazine monomers thus prepared exhibit much higher polymerization ability than those without sulfide moiety. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1448–1457     

Highly functionalized benzene syntheses by directed mono or multiple magnesiations with TMPMgCl.LiCl

The direct magnesiation of highly functionalized aromatics bearing an ester, a nitrile, or a ketone can be readily performed by using an OBoc as a directing group and TMPMgCl.LiCl as a base. It allows, for example, the preparation of a meta-magnesiated benzophenone in >95%. After quenching, highly functionalized and substituted benzenes are obtained. [reaction: see text].     

New allene synthesis via carbocupration-zinc carbenoid homologation and beta-elimination sequence

[reaction: see text] Polysubstituted propadienes are obtained in good to excellent yields by the consecutive carbocupration-homologation-beta-elimination reactions on the easily accessible alkynyl sulfoxides or sulfones. This one-pot reaction also allows the preparation of functionalized allenes.     

Stereoselective preparation of functionalized acyclic alkenylmagnesium reagents using i-PrMgCl.LiCl

Acyclic functionalized alkenyl iodides are converted with high stereoselectivity to the corresponding functionalized alkenylmagnesium derivatives by the reaction with i-PrMgCl.LiCl between -40 and -20 degrees C. Functional groups such as a nitrile, chloride, iodide, and ester are readily tolerated. The conversion of an alkenyl iodide bearing a keto group to the corresponding silylated cyanohydrin allows preparation of the corresponding Grignard reagent affording, after acylation and deprotection, unsaturated 1,4-diketones.     

Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization

The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or aryllithium compound that undergoes a subsequent intramolecular anionic cyclization. Reaction of the organolithium intermediates with selected electrophiles allows the preparation of a wide variety of indole, tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran derivatives. Finally, the application of this strategy to the appropriate starting materials allows the preparation of some tryptamine and serotonin analogues.     

Synthesis of polysubstituted 5-azaindoles via palladium-catalyzed heteroannulation of diarylalkynes

A general and efficient procedure for the synthesis of functionalized 5-azaindoles through the catalyzed heteroannulation of 4-acetamido-3-iodopyridines and diarylalkynes is described. The reaction allows the preparation of a variety of substituted 2,3-diaryl-5-azaindoles in good to excellent yields.     

Approaches to the synthesis of 2,3-dihaloanilines. Useful precursors of 4-functionalized-1H-indoles

2,3-Dihaloanilines have been proved as useful starting materials for synthesizing 4-halo-1H-indoles. Subsequent or in situ functionalization of the prepared haloindoles allows the access to a wide variety of 2,4- or 2,3,4-regioselectively functionalized indoles in good overall yields. As no efficient synthetic routes to 2,3-dihaloanilines have been described in the literature, different approaches to the preparation of these 1,2,3-functionalized aromatic precursors are now presented. The most general one involves a Smiles rearrangement from the corresponding 2,3-dihalophenols and allows the preparation of 2,3-dihaloanilides in a straightforward and synthetically useful manner.     

Palladium-catalyzed domino C-S coupling/carbonylation reactions: an efficient synthesis of 2-carbonylbenzo[b]thiophene derivatives

A facile and selective palladium-catalyzed domino procedure has been developed for the preparation of 2-carbonylbenzo[b]thiophene derivatives from 2-gem-dihalovinylthiophenols. This protocol involves intramolecular C-S coupling/intermolecular carbonylation cascade sequences and allows access to various highly functionalized benzo[b]thiophenes in moderate yields.     

Metalation of 2-chloromethyl-2-oxazolines: synthesis of 1,2,3-tris(oxazolinyl)cyclopropanes and derivatives

2-Chloromethyl-2-oxazoline converts cleanly into trans-1,2,3-tris(oxazolinyl)cyclopropane upon treatment with strong bases such as LDA or KN(SiMe(3))(2). Deprotonation of the above cyclopropane followed by the addition of electrophiles allows the preparation of more functionalized tris(oxazolinyl)cyclopropanes.     

New In Situ Trapping Metalations of Functionalized Arenes and Heteroarenes with TMPLi in the Presence of ZnCl2 and Other Metal Salts

The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl₂, ZnCl₂, or CuCN at ?78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (?78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl?LiCl or TMPZnCl?LiCl.     

Synthesis of unsymmetrically substituted bipyridines by palladium-catalyzed direct C-H arylation of pyridine N-oxides

Substituted bipyridines were efficiently prepared by direct coupling between pyridine N-oxides and halopyridines using a palladium catalyst. Pyridine N-oxides with electron-withdrawing substituents gave the best yields. This method allows the convenient preparation of 2,2'-, 2,3'-, and 2,4'-bipyridines which are useful as functionalized ligands for metal complexes or as building blocks for supramolecular architectures.     

Synthesis of a Gln-Phe hydroxy-ethylene dipeptide isostere

[structure: see text] The protected Gln-Phe hydroxyethylene dipeptide isostere 1 was synthesized as a precursor for preparation of potential inhibitors of Botulinum neurotoxin B metalloprotease. The method allows for the synthesis of additional hydroxyethylene dipeptide isosteres such as 2 with functionalized P1 side chains. The isosteres prepared were coupled with a dipeptide to produce protected pseudotetrapeptide derivatives.     

Highly Hydrophobic Conducting Nanocomposites Based on a Fluoropolymer with Carbon Nanotubes

A procedure was suggested for preparing highly hydrophobic conducting coatings based on fluoropolymers with carbon nanotubes of two types: Taunit-MD and carbon nanotubes functionalized with alkyl groups. The surface resistance, contact angle, sliding angle, and surface roughness were measured; structural features of the nanocomposites were studied. The properties of the coatings obtained depend on the concentration and type of the carbon nanotubes used. Introduction of functionalized carbon nanotubes into a fluoropolymer matrix allows preparation of coatings with higher values of the sliding angle and electrical resistance. The contact angle and sliding angle depend on the surface roughness and structure in different fashions.     

Synthesis of functionalized pyrrole and indole derivatives through carbometallation of lithiated double bonds

Bis(2-lithioallyl)amines derived from bis(2-bromoallyl)amines undergo intramolecular carbometallation of a lithiated double bond, giving dilithiated dihydropyrroles. The cyclizations are promoted by N,N,N',N'-tetramethylethylenediamine (TMEDA). Reaction of these intermediates with electrophiles allows the preparation of some new fused and nonfused five-membered functionalized heterocycles. Although 2-lithioallylamines do not suffer intermolecular carbometallation, dimerization products are obtained with their copper or zirconium derivatives. Finally, the application of this new reaction to 2-lithio-N-(2-lithioallyl)anilines leads to 3-lithiomethylindole derivatives, which are transformed to functionalized indole derivatives by reaction with electrophiles.     

An efficient and convenient synthesis of unsymmetrical disulfides from thioacetates

We have developed convenient methods for the synthesis of functionalized unsymmetrical dialkyl disulfides under mild conditions in very good yields. The designed method is based on the reaction of (5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)-disulfanyl derivatives 1 with functionalized alkyl thiolate anions, generated in situ from thioacetates 2 and sodium methoxide or butylamine. The developed method allows the preparation of unsymmetrical disulfides bearing additional hydroxy, carboxy, amino, azido, biotin, or maleimide functionalities.     

A highly efficient and direct approach for synthesis of enantiopure beta-amino alcohols by reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes

A highly efficient and practical approach for the synthesis of optically pure beta-amino alcohols by the SmI2-induced reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes was developed. This method allows the preparation of a broad range of chiral beta-amino alcohols, including functionalized ones under mild conditions. It provides a straightforward access to enantiopure beta-amino alcohols that are widely applicable in asymmetric synthesis.