CuI-catalyzed intramolecular O-vinylation of carbonyl compounds

The first copper-catalyzed intramolecular O-vinylation of carbonyl compounds with vinyl bromides was reported, among which the efficient formation of 5-, 6- and even 7-membered cyclic alkenyl ethers was achieved with beta-ketoesters as nucleophiles.     

Synthesis of multisubstituted furans via copper-catalyzed intramolecular O-vinylation of ketones with vinyl bromides

With the catalysis of CuI/3,4,7,8-tetramethyl-1,10-phenanthroline, various ketones smoothly underwent the intramolecular O-vinylation with vinyl bromides leading to the efficient synthesis of the corresponding multisubstituted furans.     

Palladium-catalyzed intermolecular alpha-arylation of zinc amide enolates under mild conditions

The intermolecular alpha-arylation and vinylation of amides by palladium-catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of amides is reported. Reactions of three different types of zinc enolates have been developed. The reactions of aryl halides occur in high yields with isolated Reformatsky reagents generated from alpha-bromo amides, with Reformatsky reagents generated in situ from alpha-bromo amides, and with zinc enolates generated by quenching lithium enolates of amides with zinc chloride. This use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of amide arylation. The reactions occur at room temperature or 70 degrees C with bromoarenes containing cyano, nitro, ester, keto, fluoro, hydroxyl, or amino functionality and with bromopyridines. Moreover, the reaction has been developed with morpholine amides, the products of which are precursors to ketones and aldehydes. The arylation of zinc enolates of amides was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive, dimeric, Pd(I) complex [[P(t-Bu)3]PdBr]2.     

Mild and efficient copper-catalyzed cyanation of aryl iodides and bromides

An efficient copper-catalyzed cyanation of aryl iodides and bromides is reported. Our system combines catalytic amounts of both copper salts and chelating ligands. The latter, which have potential nitrogen- and/or oxygen-binding sites, have never previously been used in this type of reaction. A protocol has been developed that enables the cyanation of aryl bromides through the copper-catalyzed in situ production of the corresponding aryl iodides using catalytic amounts of potassium iodide. Aryl nitriles are obtained in good yields and excellent selectivities in relatively mild conditions (110 degrees C) compared with the Rosenmund-von Braun cyanation reaction. Furthermore, the reaction is compatible with a wide range of functional groups including nitro and amino substituents. The protocol reported herein involves two main innovations: the use of catalytic amounts of ligands and the use of acetone cyanohydrin as the cyanating agent in copper-mediated cyanation reactions.     

Enantioselective total synthesis of tricyclic myrmicarin alkaloids

[reaction: see text] An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium-catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper-catalyzed enantioselective conjugate reduction of a beta-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented.     

Copper-catalyzed oxidative amination of benzoxazoles via C-H and C-N bond activation: a new strategy for using tertiary amines as nitrogen group sources

An efficient and conceptually new method for oxidative amination of azoles with tertiary amines via copper-catalyzed C-H and C-N bond activation has been developed. This protocol can be performed in the absence of external base and only requires atmospheric oxygen as oxidant. The catalyst system is very simple and efficient, which opens a new way for using tertiary amines as nitrogen group sources for C-N bond formation reactions.     

1,3-Dipolar cycloaddition of N-substituted dipolarophiles and nitrones: highly efficient solvent-free reaction

New isoxazolidines were synthesized in good to excellent yields by 1,3-dipolar cycloaddition of N-vinylamide dipolarophiles and nitrones. Strikingly, solvent-free conditions gave high conversion and yields, shortened reaction time, and minimized degradation products. N-Vinyloxazolidin-2-one and its analogues used in these cycloaddition reactions were conveniently prepared in excellent yields by a modified version of Buchwald's one-step copper-catalyzed vinylation using vinyl bromide. From the adducts, a two-step access to various unsymmetric aspartate derivatives was also described.     

Highly efficient synthesis of phenols by copper-catalyzed hydroxylation of aryl iodides, bromides, and chlorides

8-Hydroxyquinolin-N-oxide was found to be a very efficient ligand for the copper-catalyzed hydroxylation of aryl iodides, aryl bromides, or aryl chlorides under mild reaction conditions. This methodology provides a direct transformation of aryl halides to phenols and to alkyl aryl ethers. The inexpensive catalytic system showed great functional group tolerance and excellent selectivity.     

Copper-catalyzed coupling of amides and carbamates with vinyl halides

[reaction: see text] A general and efficient copper-catalyzed method for the amidation of vinyl bromides and iodides has been developed. This protocol uses a combination of 5 mol % copper iodide and 20 mol % N,N'-dimethyl ethylenediamine. Substrates bearing ester, silyl ether, and amino groups were successfully coupled under the reaction conditions. The double bond geometry of the vinyl halides was retained under the reaction conditions.     

Nickel-catalyzed enantioselective vinylation of aryl 2-azaallyl anions

A unique enantioselective nickel-catalyzed vinylation of 2-azaallyl anions is advanced for the first time. This method affords diverse vinyl aryl methyl amines with high enantioselectivities, which are frequently occurring scaffolds in natural products and medications. This C–H functionalization method can also be extended to the synthesis of enantioenriched 1,3-diamine derivatives by employing suitably elaborated vinyl bromides. Key to the success of this process is the identification of a Ni/chiraphos catalyst system and a less reducing 2-azaallyl anion, all of which favor an anionic vinylation route over a background radical reaction. A telescoped gram scale synthesis and a product derivatization study confirmed the scalability and synthetic potential of this method.

A unique enantioselective Ni-catalyzed vinylation of 2-azaallyl anions is advanced. This method affords vinyl aryl methyl amine or 1,3-diamine derivatives with high enantioselectivities, which are frequently occurring scaffolds in medications.     

Efficient heterogeneous vinylation of aryl halides using potassium vinyltrifluoroborate

An efficient heterogeneously palladium catalysed procedure for the vinylation of aryl iodides and bromides is reported. Using common reaction conditions (Pd/C 2 mol %, AcONa·3H₂O, NMP or NMP/H₂O), good to complete conversions (40-100%) with high selectivities (79-100%) towards the expected vinylaromatic were achieved.     

Recent advances in the synthesis of N-alkenyl carbazoles

N-Alkenyl carbazoles are important building blocks of poly(vinylcarbazole), which is used in photosensitive materials, semiconductors, electroluminescent devices, and non-linear optical materials. Recently, a CN bond formation reaction using transition-metal-catalyzed amination and transition-metal-catalyzed vinylation was successfully extended to the synthesis of N-alkenyl carbazoles. In this paper, I discuss recent examples of the synthesis of N-alkenyl carbazoles, including palladium and copper-catalyzed cross-coupling reactions of carbazoles with alkenes/alkenyl halides, and iridium-catalyzed vinylation of carbazole using vinyl acetate.     

Mild and efficient copper-catalyzed amination of aryl bromides with primary alkylamines

[reaction: see text] An efficient copper-catalyzed amination of aryl bromides with primary alkylamines was developed that uses commercially available diethylsalicylamide as the ligand. This amination reaction can be performed at 90 degrees C in good yield. A variety of functional groups are compatible with these reaction conditions. Preliminary results show that this reaction can be carried out under solvent-free conditions with comparable yields.     

Practical procedures for the preparation of N-tert-butyldimethylsilylhydrazones and their use in modified Wolff-Kishner reductions and in the synthesis of vinyl halides and gem-dihalides

In this work we develop practical chemistry for the preparation of N-tert-butyldimethylsilylhydrazone (TBSH) derivatives from carbonyl-containing compounds and show that these products serve as superior alternatives to simple hydrazones in Wolff-Kishner-type reduction reactions, in the Barton vinyl iodide preparation, in the synthesis of vinyl bromides, and in the synthesis of gem-diiodides, gem-dibromides, and gem-dichlorides. In our new procedure for silyl hydrazone synthesis, aliphatic and aromatic ketones and aldehydes are shown to undergo highly efficient coupling (typically >95% yield) to form the corresponding TBSH derivatives when combined with equimolar amounts of 1,2-bis(tert-butyldimethylsilyl)hydrazine (BTBSH) and a catalytic quantity of scandium trifluoromethanesulfonate (typically, 0.01 mol %), neat, or in solvent. Optimized procedures are provided for the use of TBSH derivatives in a Wolff-Kishner-type reduction protocol that proceeds at low temperature (23-100 degrees C) and in a single reaction flask. Similarly, protocols for the use of TBSH derivatives as precursors to vinyl halides and gem-dihalides are described in detail.     

Facile and convenient synthesis of aryl hydrazines via copper-catalyzed C–N cross-coupling of aryl halides and hydrazine hydrate

An efficient and convenient method for the synthesis of aryl hydrazines has been developed via copper-catalyzed cross-coupling of aryl bromides and hydrazine with a readily accessible ligand and water as a solvent. The multigram scale procedure is applicable to aryl bromides bearing both moderately electron-donating and electron-withdrawing substituents in the aromatic nucleus. No column chromatography is required to obtain aryl hydrazine hydrochlorides in good yields.     

Palladium-catalyzed sonogashira and hiyama reactions using phosphine-free hydrazone ligands

Palladium/copper-catalyzed Sonogashira cross-coupling reaction of aryl halides with a variety of terminal alkynes under amine-free conditions in dimethylformamide (DMF) at 80 degrees C gave internal arylated alkynes using PdCl2(MeCN)2 with phosphine-free hydrazone 2a as a ligand and CuI as the cocatalyst in good yields. We also found PdCl2/hydrazone ligand 1d in PhMe at 80 degrees C was a phosphine-free efficient catalyst system for a Hiyama cross-coupling reaction of aryl bromides with aryl(trialkoxy)silanes in good yields.     

Highly efficient and practical phosphoramidite-copper catalysts for amination of aryl iodides and heteroaryl bromides with alkylamines and N(H)-heterocycles

A highly efficient copper-catalyzed system using phosphoramidite as ligands was applied to N-arylation of alkylamines and N(H)-heterocycles with aryl iodides and heteroaryl bromides. The reactions were carried out in relative mild conditions and good to excellent yields were obtained.     

Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.     

Copper-promoted/catalyzed CN and CO bond cross-coupling with vinylboronic acid and its utilities

The mildest method of N-vinylation has been discovered. The synthetic utilities of the N- and O-vinylated products include protecting group, cyclopropanation and Grubbs’ ring closure metathesis reactions.     

The first Cu(I)-mediated nucleophilic trifluoromethylation reactions using (trifluoromethyl)trimethylsilane in ionic liquids

The new ionic liquids (5a-8a) were used as reaction media for nucleophilic trifluoromethylation reactions of trifluoromethyl(trimethyl)silane with (1) aryl, allyl, benzyl, and alkyl halides in Cu(I)-mediated C-C bond formation reactions, and (2) carbonyl functionalities catalyzed with Ph3P or CsF. In addition, conversion of benzyl bromide as a model compound to benzyl fluoride was examined in using 6a CsF as the fluorinating reagent. The morpholinium-based ionic liquid (6a) stood out as an efficient solvent system comparable to organic solvents and superior to the other new ionic liquids prepared in this work as well as to [bmim]+[PF6]-. Neat reactions of N-methyloxazolidine (1), N-methylmorpholine (2), N-methylimidazole (3) or N-methyltriazole (4) with 2-(2-ethoxyethoxy)ethyl bromide (BrCH2CH2OCH2CH2OCH2CH3, ) or 2-bromoethyl methyl ether (BrCH2CH2OCH3, 10) at 75 or 105 degrees C gave the N-(2-ethoxyethoxy)ethyl- or N-methoxyethyl-substituted oxazolidinium, morpholinium, imidazolium and triazolium quaternary bromides (1a-4a, 1b-4b) which were metathesized with LiN(SO2CF3)2 to form the respective room-temperature liquid bis(trifluoromethanesulfonyl)amides 5a-8a and 5b-8b in high yields with transition or melting points < -78 degrees C as determined by DSC. All of the ionic liquids are thermally stable to > 310 degrees C as determined by thermogravimetric analyses (TGA). Densities range between 1.29 and 1.53 g cm(-3) at 25 degrees C.