Palladium-catalysed cross-coupling reactions in the synthesis of some high polarizability materials

Liquid crystal materials of high optical anisotropy consist of moieties of high electron density in conjugation with each other along the molecular length. Such structures are conducive to convergent synthesis methods. Here we report the synthesis of a range of novel materials by the strategic use of palladium-catalysed cross-coupling methods. In addition to the traditional use of bromide and iodide leaving groups, invaluable use of the triflate leaving group and the importance of selective cross-coupling methods using both arylboronic acids and alkynylzinc chloride derivatives is illustrated. This systematic methodology allows the separate synthesis of the appropriate sub-units that can be efficiently coupled together to provide high overall product yields.     

Convenient Syntheses of Methyl 2-Bromo- and 2-Iodo-2,3-butadienoates

Syntheses of methyl 2-bromo- and 2-iodo-2,3-butadienoates 3 and 6 from readily available starting materials are described. 3 and 6 will be valuable building blocks for the synthesis of 2-aryl and 2-alkenyl substituted alka-2,3-dienoates via Palladium-catalyzed cross-coupling reactions.     

Nickel-Catalysed Cross-Electrophile Coupling of Benzyl Bromides and Sulfonium Salts towards the Synthesis of Dihydrostilbenes

A nickel-catalysed reductive cross-coupling reaction between benzyl sulfonium salts and benzyl bromides is reported. Simple, stable and readily available sulfonium salts have shown their ability as leaving groups in cross-electrophile coupling, allowing the formation of challenging sp³–sp³ carbon-carbon bonds, towards the synthesis of interesting dihydrostilbene derivatives. In addition, benzyl tosyl derivatives have been demonstrated to be suitable substrates for reductive cross-coupling by in-situ formation of the corresponding sulfonium salt.     

Synthesis and characterization of 1-phenyl-3-alkylbenzimidazol-2-ylidene salts and their catalytic activities in the Heck and Suzuki cross-coupling reactions

The synthesis and characterization of 1-phenyl-3-alkyl-substituted carbene precursors that were prepared from 1-phenyl substituted benzimidazole and various alkyl halides are reported. The new benzimidazolium salts (1a–e) were characterized by ¹H NMR, ¹³C NMR, FT-IR spectroscopic methods and elemental analyses. New in situ generated palladium-benzimidazolium complexes were tested for catalytic activity in the Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions.     

New synthetic strategies and disconnections in the synthesis of liquid crystals enabled by photoredox cross-coupling reactions

In this letter we describe the application of metallaphotoredox cross-electrophile couplings to the synthesis of liquid crystals using dual nickel and iridium catalysis. Given the proliferation of aryl and alkyl bromides in liquid crystal research we consider that the silyl-radical mediated cross-coupling of alkyl bromide with an aryl bromide (to afford a direct alkyl–aryl bond) will become an extremely powerful tool in the synthesis of liquid crystalline materials, and we use this to synthesise several well-known materials (PCH32, 5CB, CB7CB and CB15) in a single synthetic step from inexpensive and commercially available building blocks. The metallaphotoredox decarboxylative sp³–sp² cross-coupling of an aryl bromide with an alkyl carboxylic acid provides a complimentary method to form alkyl–aryl bonds, and we use this to successfully prepare trans PCH5 in a single synthetic step from commercially available building blocks. We also prepare novel methylene-linked materials in a single synthetic step, one of which exhibit the topical TB phase.     

Metal-free synthesis of (E)-vinyl sulfones via denitrative coupling reactions of β-nitrostyrenes with sodium sulfinates

Abstract

A practical metal-free procedure for the synthesis of (E)-vinyl sulfones has been developed through the coupling of β-nitrostyrenes with sodium sulfinates under microwave irradiation. This methodology provides a convenient and efficient approach to various (E)-vinyl sulfones from readily available starting materials with excellent regioselectivity. The present oxidative reaction involves an efficient denitrative radical cross-coupling of β-nitrostyrenes with sodium sulfinates via using AcOH as an additive.     

Copper promoted desulfurization and C-N cross coupling reactions: Simple approach to the synthesis of substituted 2-aminobenzoxazoles and 2,5-disubstituted tetrazole amines

Copper-supported novel, facile and efficient methods for the synthesis of various 2-amino-benzoxazoles and 2,5-diphenyltetrazoleamines have been demonstrated. The reaction procedures are simple, with excellent substrate tolerance in good to high yields thus paving an excellent and useful way to establish a library of potentially active drug molecules. This methodology represents the first concept of copper-catalyst promoted domino C-N cross-coupling reaction towards the construction of 2-aminobenzoxazoles. In addition, we described report for the synthesis of 2,5-diaryltetrazoleamines using copper via inter molecular C-N cross-coupling reaction with aryl iodides. The proposed reaction mechanism involves copper based desulphurization/nucleophilic substitution and subsequent C-N cross-coupling reactions. We established numerous applications of this methodology for synthesizing diverse heterocyclic derivatives i.e. both electron rich and electron deficient systems.     

Efficient anodic and direct phenol-arene C,C cross-coupling: the benign role of water or methanol

C,C cross-coupling reactions for the synthesis of nonsymmetrical biaryls represent one of the most significant transformations in contemporary organic chemistry. A variety of useful synthetic methods have been developed in recent decades, since nonsymmetrical biaryls play an evident role in natural product synthesis, as ligand systems in homogeneous catalysis and materials science. Transformation of simple arenes by direct C,H activation belongs to the cutting-edge strategies for creating biaryls; in particular the 2-fold C,H activation is of significant interest. However, in most examples very costly noble metal catalysts, ligand systems, and significant amount of waste-producing oxidants are required. Electrochemical procedures are considered as inherently "green" methods, because only electrons are required and therefore, no reagent waste is produced. Here, we report a metal-free electrochemical method for cross-coupling between phenols and arenes using boron-doped diamond (BDD) anodes in fluorinated media. Our sustainable approach requires no leaving functionalities. Employing water or methanol as mediator represents the key improvement for achieving nonsymmetrical biaryls with superb selectivity and synthetic attractive yields.     

Vinyl nosylates as partner in copper and silver co-catalyzed Sonogashira cross-coupling reactions

Vinyl nosylates, readily obtained from β-dicarbonyl derivatives, could be efficiently engaged in Sonogashira cross-coupling reactions, either cocatalyzed by copper or silver salts. The para-nitrobenzenesulfonate (nosylate) group allows this coupling to be performed under very mild conditions (room temperature). These new leaving group and mild conditions could be applied to the synthesis of acetylenic coumarinyl derivatives and to the total synthesis of an acetylenic monoterpene natural product, named cleviolide.     

A convenient hydroiodination of alkynes using I2/PPh3/H2O and its application to the one-pot synthesis of trisubstituted alkenes via iodoalkenes using Pd-catalyzed cross-coupling reactions

A facile hydroiodination of alkynes using readily-available reagents such as I₂, PPh₃, and H₂O has been developed. This is extended to the one-pot synthesis of trisubstituted alkenes from alkynes via iodoalkenes using Pd-catalyzed cross-coupling and related methods such as the Suzuki–Miyaura cross-coupling, Sonogashira cross-coupling reaction, and Mizoroki–Heck reaction.     

Synthetic Applications of Stereodefined 2-Substituted 1-Silyl-1-stannylethenes: A New Synthesis of 5-Ethenyl-5′-(1-propynyl)-2,2′-bithiophene,a Naturally-Occurring Phototoxin)

(E)-2-(5-Trimenthylstannyl-2-thienyl)ethenyldimethylphenylsilane. (E)-8, which can be stereospecifically prepared from (Z)-1-dimethylphenylsilyl-2-(2-thienyl)-1-trimethylstannyl-ethene, (Z)-6, or from (E)-2-(2-thienyl)ethenyldimethylphenylsilane, (E)-9, serves as an equivalent to the 2-ethenylthiophene d ¹', d ⁵-synthon, 20, in an efficient two-step synthesis of 5-ethenyl-5′-(1-propynyl)-2,2′-bithiophene, 10, a naturally-occurring phototoxin. In the first step of this synthesis compound (E)-8 undergoes a palladium-catalyzed cross-coupling reaction with 2-iodo-5-(1-propynyl)thiophene, 16, and in th second step the so obtained cross-coupling product, (E)-17, undergoes a protodesilylation reaction.     

Concise Synthesis of 6-Cyanobenzo[b]furan,a Useful Building Block

A new three-step synthesis of 6-cyanobenzo[b]furan (6) was developed, starting from commercially available 6-hydroxybenzo[b]furan-3-one (18). Key steps in this process were the first step, which was the reductive dehydration of 18 to produce 6-hydroxybenzo[b]furan (19), and the last step, which converted the aryl triflate 20 to the aryl cyanide 6 in a palladium-catalyzed cross-coupling protocol. Overall yield for this new synthesis was 49%.     

Enzymatic Resolution of α-Amino Phosphonous Acids -A Kinetic Comparison with Other α-Amino Acids Using 19F and 31P NMR Analysis

Abstract

We have previously reported (1,) the synthesis of a range of α-aminophosphonous acids and found them to be mimics of the naturally occurring amino acids. They inhibit the protein synthesis of E.Coli B (2) and other synthetases (3). We have now found that such compounds can be conveniently resolved via their N-acyl derivatives by enzymatic methods. Using penicillin-G-amidase from E.Coli (EC 3.5.1.11) the R-enantiomer is cleanly hydrolysed leaving the S-enantiomer intact.     

Sequential Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp²)–C(sp³) cross-coupling with alkyl Grignard reagents that are prone to dimerization and β-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C–N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis.     

Copper-catalyzed synthesis of N-aryl acridones from 2-amino benzophenones and aryl boronic acids via sequential double oxidative C–N coupling

Pot-economic synthesis of N-aryl acridones was performed with 2-aminobenzophenones and aryl boronic acids as starting materials. Cu-catalyzed chelation-assisted oxidative C–N cross-coupling reactions were well merged with the following intra-molecular oxidative dehydrogenative C–H amination reactions under an air atmosphere. The use of reagent capsules can further resolve the compatibility problem of reagents and simplify the operational process, providing a more straightforward access to the target products.     

Practical Synthesis of 1-(7-Fluoro-naphthalen-1-yl)piperazine Hydrochloride

A practical and scalable preparation of 1-(7-fluoronaphthalen-1-yl)-piperazine hydrochloride (1) is reported. The original route for the synthesis of this compound involved the use of 1-amino-7-fluoronaphthalene and bis(2-chloroethyl)amine hydrochloride, two highly toxic compounds. A new protocol has been developed that employs a palladium-catalyzed Buchwald–Hartwig cross-coupling reaction between 1-Boc-piperazine and 1-bromo-7-fluoronaphthalene followed by piperazine deprotection with HCl gas. In addition, an efficient palladium removal protocol allowed for the preparation of the target molecule with less than 20 ppm of this metal. This methodology has been successfully implemented to produce multigram quantities of 1 with excellent purity and low palladium content.     

Phosphine-Free Suzuki Cross-Coupling Reaction Using an Efficient and Reusable Pd Catalyst in an Aqueous Medium Under Microwave Irradiation

Abstract

We report here an improved, highly efficient, and general method for the ligand-free Suzuki cross-coupling reaction to the synthesis of biaryls, bipyridyls, thienylpyridine, and allylphenols. Microwave irradiation of (het)aryl halides and (hetaryl, allyl)arylboronic acid N-methyl-iminodiacetic acid (MIDA) ester, using polyurea microencapsulated palladium catalyst (Pd EnCat 30), gave the coupling adducts 1a–x in excellent yields in just 10–18 min.     

A comparative study of the synthetic paths from 1-butyne to 2E,4Z-heptadien-1-ol

2E,4Z-Heptadien-1-ol (1), the key intermediate in the synthesis of the grapevine moth sex pheromone, was obtained from 1-butyne by a number of alternative procedures, including various variants of the stereocontrolled building of the conjugatedE,Z-diene system (Cadiot—Chodkiewicz cross-coupling, alkyne—vinyl halide cross-coupling catalyzed by palladium complexes, anionotropic allylic rearrangement, partialcis- andtrans-reduction of the triple bond). None of them could provide for configurational uniformity of1. The most acceptable path to obtain1 in multigram amounts appears to be that which proceeds via the conjugated diynol and enynol intermediates with subsequent catalyticcis-hydrogenation.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 769–772, April, 1993.     

新型四硫富瓦烯硫杂冠醚衍生物的合成

在高度稀释条件下, 经4,5-二溴甲基-1,3-二硫杂环戊烯-2-硫酮(7)和多缩乙二醇的1,ω-二巯基衍生物的缩合反应, 方便地合成了4,5-位带二硫杂冠醚残基的2-硫代-1,3-二硫杂环戊烯的衍生物8a～8d, 中间体硫杂冠醚8c～8d的合成中有明显的“模板效应”. 在亚磷酸三乙酯存在下, 8a～8d经自偶联生成新型的对称双臂四硫富瓦烯(TTF)硫杂冠醚衍生物10a～10d, 而与4,5-二甲硫基-1,3-二硫杂环戊烯-2-酮(9)经交叉偶联生成新型的非对称单臂四硫富瓦烯硫杂冠醚衍生物11a～11d. 用循环伏安法研究了上述目标化合物的电化学性质和离子传感性质.     

A palladium catalyzed atom-efficient cross-coupling reactivity of triarylbismuths with α,β-unsaturated acyl chlorides

An atom-efficient cross-coupling reactivity of triarylbismuths (1 equiv) was demonstrated by cross-coupling reaction with 3 equiv of α,β-unsaturated acyl chlorides under palladium catalysis in the synthesis of a series of functionalized α, β-unsaturated ketones in high isolated yields.