Pd-catalyzed cross-coupling reactions of arenediazonium salts with arylsilanes and aryltrifluoroborates in water

Pd-catalyzed cross-coupling reactions of various arenediazonium salts with ArSi(OR)₃ and KArBF₃ have been achieved in good to excellent yields under simple aerobic conditions in water at room temperature. The functional group tolerance makes these transformations as attractive alternatives to the traditional cross-coupling approaches. Furthermore, the sequence can also be performed in a one-pot domino process, omitting the isolation of the intermediate arenediazonium salt.     

Palladium-catalyzed cross-coupling of five-membered heterocyclic silanolates

The preparation of pi-rich 2-aryl heterocycles by palladium-catalyzed cross-coupling of sodium heteroarylsilanolates with aryl iodides, bromides, and chlorides is described. The cross-coupling process was developed through extensive optimization of the following key variables: (1) identification of stable, isolable alkali metal silanolates, (2) identification of conditions for preformation and isolation of silanolate salts, (3) judicious choice in the palladium catalyst/ligand combination, and (4) selection of the protecting group on the nitrogen of indole. It was found that the alkali metal silanolates, either isolated or formed in situ, offered a significant rate enhancement and broader substrate scope over the use of silanols activated by Br?nsted bases such as NaOt-Bu. In addition, the optimized conditions for the cross-coupling of 2-indolylsilanolates were readily applied to the cross-coupling of 2-pyrrolyl-, 2-furyl-, and 2-thienylsilanolates.     

Analysis of key steps in the catalytic cross-coupling of alkyl electrophiles under Negishi-like conditions

The use of tpy'(tpy'= 4,4',4'-tri-tert-butyl-terpyridine) as a ligand for nickel allows for the isolation of a Ni(I)-alkyl complex and a Ni(II)-alkyl halide complex, both of which can be used as mechanistic probes of key steps in alkyl cross-coupling reactions.     

A sequential highly stereoselective hydroboration and Suzuki-Miyaura cross-coupling reaction of fluoroalkylated internal acetylenes: a practical one-pot synthesis of fluoroalkylated trisubstituted alkenes

The one-pot synthesis of trisubstituted alkenes starting from fluoroalkylated internal alkynes was investigated. Hydroboration of the alkynes proceeded in a highly regio- and stereoselective manner to give the corresponding vinylboranes in excellent yields. Without isolation, treatment of the vinylboranes with various aryl halides under the Suzuki-Miyaura cross-coupling conditions gave the fluoroalkylated trisubstituted alkenes in high yields with complete retention of the olefinic geometry.     

Palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organometallics

The palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organozinc, organotin and organoaluminum reagents in the presence of lithium chloride takes place to afford alkylbenzenes in good yields. However, the coupling reaction with organolithium and Grignard reagents proceeds unsatisfactorily with poor regioselectivity. On the basis of the isolation of an oxidative addition product of phenyl fluoroalkanesulfonate to palladium, a catalytic cycle in the reaction is suggested.     

Successive Replacement of Halogen Atoms in 4,6-Dihaloquinolines in Cross-coupling Reactions with Arylboronic Acids Catalyzed by Palladium and Nickel Complexes

Conditions were found where in 6-halo-4-quinolines (halogen = iodine, bromine, or chlorine) the halogen atoms were replaced in succession by similar or different aryl groups in cross-coupling reactions with arylboric acids catalyzed by palladium and nickel complexes. Basing on successive Suzuki reaction a convenient procedure was developed for preparation of diarylquinolines that did not require isolation of the intermediate monoarylation product and afforded almost quantitative yields of diarylquinolines.     

Aryl trihydroxyborates: easily isolated discrete species convenient for direct application in coupling reactions

A conceptually and practically simple alternative approach to the use of arylboron species as the organometallic component in cross-coupling processes is described whereby trihydroxyborate salts are isolated and directly employed. The protocol derives practical benefit from the ease and convenience of the isolation and subsequent use of the discrete borate salts, eliminates the need for additional base, and aids the use of correct reaction stoichiometry.     

Photoreaction between benzoylthiophenes and N-BOC-tryptophan methyl ester

Drug-induced photoallergy requires as the first step formation of covalent drug-protein photoadducts. One of the key amino acids involved in this process is tryptophan (Trp). In this context, several diaryl ketones, including 2-benzoylthiophene (BT), [2-(5-benzoyl-5-thienyl)]-2-methylpropanoic methyl ester (TPA methyl ester) and 4-(2-thienylcarbonyl)phenyl]-2-methylpropanoic methyl ester (SUP methyl ester) have been irradiated in the presence of N-BOC-(L)-tryptophan methyl ester. Laser flash photolysis has allowed to detect three neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal hydrogen-atom abstraction. This correlates well with the isolation of homodimers, as well as with cross-coupling products, in the preparative irradiation. The main cross-coupling products were in all cases lactones arising from the reaction of the Trp-derived skatolyl radicals with the corresponding ketyl radicals. These lactones were obtained as the (4R) stereoisomers with remarkable diasteroselectivity. No coupling products through the phenyl p-position of BT or TPA methyl ester were found. By contrast, ketone homodimers and cross-coupling products arising from reaction through the thienyl 5-position were obtained when using BT and SUP methyl ester; this is very interesting, because stable LAT-derived products are difficult to isolate.     

Efficient Stille cross-coupling reaction using aryl chlorides or bromides in water

An efficient Stille cross-coupling reaction using a variety of aryl halides in neat water has been developed. Employing palladium-phosphinous acid catalyst [(t-Bu)(2)P(OH)](2)PdCl(2) allows formation of biaryls from aryl chlorides and bromides in good to high yields. Functional groups such as ketones and nitriles are tolerated, and organic cosolvents are not required. The air stability and solubility in water of the palladium complexes used in this study facilitate operation of the coupling reaction and product isolation. The feasibility of catalyst recycling has also been demonstrated.     

Traceless liquid-phase synthesis of biphenyls and terphenyls using pentaerythritol as a tetrapodal soluble support

Application of a novel sulfonate-based traceless multifunctional linker system using pentaerythritol as a tetrapodal soluble support was demonstrated using liquid-phase parallel and combinatorial preparation of biphenyl and terphenyl compounds. Nickel-catalyzed reactions of pentaerythritol tetrakis(arenesulfonate)s with arylmagnesium bromides generated the desired products in sufficient yields through reductive cleavage/cross-coupling of the C-S bond. Homogeneous pentaerythritol-supported reactions could be accomplished using less nucleophile with shorter reaction periods than could the corresponding heterogeneous polymer-supported reactions. This liquid-phase approach using a small polyfunctionalized support combines advantages of solution-phase and solid-phase syntheses by allowing high reactivity, high atom economy, simple isolation, and real-time monitoring of the reaction progress.     

Silicon-based cross-coupling reaction: an environmentally benign version

Much attention has been paid to the cross-coupling reaction of organosilicon compounds due to their stability, non-toxicity, and natural abundance of silicon. In addition, the silicon-based cross-coupling has many advantages over other cross-coupling protocols. Successful examples of the silicon-based cross-coupling reaction are reviewed, focusing especially on the advances made in the last decade. Having had a number of highly effective palladium catalysts developed mainly for other cross-coupling reactions, the development of the silicon-based protocol owes heavily to the design of organosilicon reagents which effectively undergo transmetalation, a key elemental step of the silicon-based cross-coupling reaction. This tutorial review thus classifies various organosilicon reagents depending on substituents on silicon and surveys their cross-coupling reactions with various electrophiles.     

Carbon networks based on 1,5-naphthalene units. Synthesis of 1,5-naphthalene nanostructures with extended pi-conjugation

The synthesis and spectroscopic characterization of nanometer-sized conjugated molecules of 5-X-naphthylethynyl (X= NO(2), NMe(2)) units with precise length and constitution have been carried out. A new extended pi-conjugated 5-nitronaphthyl family was synthesized by palladium-catalyzed cross-coupling reaction between the protected 5-iodonaphthylethynyl 5a and 1-ethynyl-5-nitronaphthalene 9, or the resulting ethynyl compound 11 and the 1-iodo-5-nitronaphthalene 3. Catalytic oxidative dimerization of the terminal acetylene compounds permits the isolation of the corresponding 1,3-butadiyne derivatives 16-18, with the nitro groups at the ends of the conjugation, in excellent yields. A new family of conjugated 5-nitro-(naphthylethynyl)-[5-(N,N-dimethylamino)]naphthalene (20-22), was also synthesized by palladium-catalyzed cross-coupling reaction between 5-iodo-N,N-dimethylnaphthalene-1-amine (19) with the appropriate terminal acetylene (9, 11, and13 respectively). Compounds 20-22 show a fluorescence emission and also exhibit a charge-transfer absorption in the visible spectrum. X-ray structure of 20 confirms a centrosymmetric dimer association with an interplanar distance of 3.43 A, and the naphthalene rings adopt an anti conformation around the Ctbd1;C triple bond.     

Synthesis of Benzo[a]carbazoles through Visible Light-Induced Cycloaromatization

We report herein a synthesis of 5,6-diarylbenzo[a]carbazoles by a sequence of 6π-electrocyclization followed by β-elimination. The highly functionalized 2,3-disubstituted indoles used for this cycloaromatization process are prepared by Pd-catalyzed cyclizative cross-coupling of ortho-alkynylanilines with ortho-alkynylbenzamides. The combination of these two reactions allows us to develop a facile synthesis of benzo[a]carbazoles directly from two easily accessible internal alkynes without isolation of the indole intermediates.     

Total syntheses of the thiopeptides amythiamicin C and D

The thiopeptides amythiamicin C and D were synthesized by employing amide bond formation, a Stille cross-coupling reaction, and two Negishi cross-coupling reactions as key transformations. The central 2,3,6-trisubstituted pyridine ring of the target compounds was introduced as a 2,6-dibromo-3-iodopyridine, which was selectively metalated at the 3-position and connected to the complete Southern fragment of the amythiamicins by a Negishi cross-coupling. For the synthesis of amythiamicin C, this step was followed by a Negishi cross-coupling at C-6 of the pyridine core. Subsequent attachment of the Eastern fragment was achieved by amide bond formation and macrolactam ring closure by a Stille cross-coupling at C-2. The Eastern bithiazole fragment of the amythiamins was constructed also by regioselective metalation and cross-coupling reactions. The pivotal step involved the diastereoselective addition of 4-bromothiazole-2-magnesium bromide to a chiral sulfinyl imine. For the synthesis of amythiamicin D, the order of cross-coupling at C-6, amide bond formation, and cross-coupling at C-2 was changed. The amide bond formation to the Eastern fragment was performed first and it was subsequently attempted to close the macrolactam by an intramolecular regioselective Stille cross-coupling at C-2. Despite the low regioselectivity of this reaction it paved the way to the immediate completion of the amythiamicin D synthesis when followed by a Negishi cross-coupling at C-6 with 2-zincated methyl thiazole-5-carboxylate.     

Iron(I) in Negishi cross-coupling reactions

Herein we demonstrate both the importance of Fe(I) in Negishi cross-coupling reactions with arylzinc reagents and the isolation of catalytically competent Fe(I) intermediates. These complexes, [FeX(dpbz)(2)] [X = 4-tolyl (7), Cl (8a), Br (8b); dpbz = 1,2-bis(diphenylphosphino)benzene], were characterized by crystallography and tested for activity in representative reactions. The complexes are low-spin with no significant spin density on the ligands. While complex 8b shows performance consistent with an on-cycle intermediate, it seems that 7 is an off-cycle species.     

2-Ethoxy-3-pyridylboronic acid: a versatile reagent for the synthesis of highly-functionalised 3-aryl/heteroaryl-pyridines via Suzuki cross-coupling reactions

This paper describes the commercially-viable synthesis and isolation of 2-ethoxy-3-pyridylboronic acid on a ca. 70 g scale via a directed ortho-metalation reaction on readily-available 2-ethoxypyridine. A range of efficient cross-coupling reactions of 2-ethoxy-3-pyridylboronic acid with selected aryl/heteroaryl halides under palladium-catalysed Suzuki-Miyaura conditions yield novel 2-ethoxy-3-aryl/heteroaryl-pyridines in high yield (heteroaryl=pyridyl, pyrimidyl, pyrazyl). The X-ray crystal structure of 2-ethoxy-3-pyridylboronic acid reveals that the boronic acid group takes part in an intramolecular O-H?O bond with the adjacent ethoxy substituent, and an intermolecular O-H?N bond.     

Pd(PPh3)2Cl2-CuCl体系催化有机高价碘杂环化合物与末端炔烃的化学选择性交叉偶联反应

以有机高价碘杂环化合物1,2为底物,在Pd(PPh3)2Cl2-CuCl催化剂存在下与末端炔烃进行交叉偶联反应,实验发现该反应为--化学选择性反应,控制反应体系的物料比、温度及反应时间可以分别得到单偶联或双偶联产物,从而证实了有机高价碘杂环化合物的碘盐在进行交叉偶联反应时的反应活性比sp2的碘化物高.     

Palladium-catalyzed cross-coupling reactions in one-pot multicatalytic processes

Palladium-catalyzed cross-coupling reactions have been investigated in multicatalytic processes to synthesize disubstituted alkenes and alkanes from carbonyl derivatives. The use of copper-catalyzed methylenation reactions is the key starting reaction to produce terminal alkenes which are not isolated, but submitted to further structure elongation. Not only is the isolation of the alkene intermediate unnecessary, but also the copper catalyst is a beneficial cocatalyst in the palladium-catalyzed cross-coupling reactions. The desired products are thus typically obtained in higher yields using this one-pot approach. We have used these processes to synthesize hydroxylated (E)-stilbenoids, which are known chemopreventive and chemotherapeutic agents, odorant-substituted indanes, and non-natural amino acids, such as homophenylalanine.     

可见光参与的氧化偶联反应研究进展

实现资源和能源利用高效化、操作简单化、条件温和化、环境友好化以及产物高效选择性是有机合成的重要研究方向,而探索绿色温和条件下构建化学键的有效方法是有机合成领域的基本挑战之一。伴随着金属有机化学的发展,过渡金属催化的偶联反应已经成为构建碳-碳和碳-杂键的有效手段,而传统的交叉偶联一般是基于亲核试剂与亲电试剂之间的反应,需要进行预官能团化和再官能团化的步骤。近年来,在此基础上发展起来的氧化偶联反应利用合适的氧化剂实现两个亲核试剂直接构建化学键也得到了国内外有机化学家的广泛关注。氧化偶联反应的发展极大地提高了构建碳-碳键及碳-杂键的效率,尤其是利用交叉脱氢偶联实现直接的碳-氢键或杂-氢键的活化直接构建化学键,避免了传统偶联过程中的预官能团化步骤,为直接利用简单的原料实现高效、复杂的有机合成开辟了一条新的道路。越来越多的第一过渡金属催化的氧化偶联反应涉及到单电子转移的过程,这种自由基氧化偶联模式在绿色化学的发展中具有光明的前景。可见光是一种可再生的资源,可见光催化符合绿色合成、环境友好和可持续发展的理念,在有机合成领域中引起了广泛的关注。建立在光诱导的单电子转移过程的基础上,可见光催化为实现温和条件下构建化学键提供了一种新的思路。虽然很多的有机分子不能有效吸收可见光,但是利用可见光催化剂(光敏剂)在电子和能量转移过程中的独特优势,能够有效实现在可见光作用下的一系列光化学反应。光催化是有机合成构建新物质的一种有效的手段,随着光催化在有机合成领域中的发展,一系列新型温和而有效的可见光催化的氧化偶联反应也逐渐被报道。虽然过渡金属催化的氧化偶联反应已经取得了重大的进展,但是利用可见光催化的策略以实现两个亲核试剂之间化学键的构建作为一个新的领域,近年来才刚刚发展起来。尤其是结合可见光催化条件温和、环境友好的特点和氧化偶联反应的原子经济性特点,将可见光诱导的单电子转移过程运用到交叉脱氢偶联反应,引起了广泛的关注。光催化氧化偶联反应不仅解决了传统偶联中的步骤经济性和原子经济性的问题,同时也具备了可见光反应温和环保的特点。近几年来已经发展了多种类型的光催化氧化偶联反应,包括光催化氧化含氮化合物的偶联反应、光催化氧化脱羧偶联反应、以及光催化交叉偶联放氢反应等。但是在光催化氧化偶联领域的相关报道大多局限于含氮化合物和易氧化的底物的活化氧化,因此任然存在着很多的挑战。本文总结了最近几年来的不同反应类型的可见光催化的氧化偶联的研究和进展。而对这些反应的理解和认识,可以为人们发展更多的高效率和高选择性的可见光催化氧化偶联反应提供帮助。     

N-tosylhydrazones: versatile reagents for metal-catalyzed and metal-free cross-coupling reactions

Transition metal-catalyzed cross-coupling reactions have been established as one of the most powerful tools for the construction of C-C and C-X bonds. In this context, the development of novel metal-catalyzed cross-coupling processes that do not require stoichiometric organometallic reagents is particularly attractive. Recently, N-tosylhydrazones have emerged as a new type of versatile coupling partners for transition metal-catalyzed cross-coupling reactions as well as metal-free cross-coupling reactions, and have attracted increasing attention. This tutorial review summarizes recent important developments in this area with N-tosylhydrazones as versatile coupling partners.