Cross-coupling Reactions Of Aryl Research Articles

Simple thiazole-based ligands for palladium(II) Suzuki-Miyaura aryl cross-coupling catalysts

Two new palladium(II) catalysts, each containing a phenylthiazole ligand (2-methyl- (1a) and 2-amino-4-phenyl-1,3-thiazole (1b)) are prepared and characterized. The crystal structure of one, 2-methyl-4-phenyl)palladium(II) acetate (3a), is presented; it crystallizes as a dimer, with the ligand attached through the nitrogen on the thiazole and the ortho-carbon on the phenyl ring. The organometallic compounds can be used as catalysts in Suzuki-Miyaura aryl cross-coupling reactions. They are compatible with a wide range of functional groups, including carbonyls, amines, and phenols.

Nickel-Catalyzed Cross-Coupling Reaction of Aryl Bromides/Nitriles with Imidazolium Salts Involving Inert C-N Bond Cleavage.

We herein present a nickel-catalyzed cross-coupling reaction of aryl halides and nitriles with imidazolium salts. A series of 2-arylated imidazoles could be obtained in moderate to good yields through inert C-N bond cleavage. The imidazolium salt in this reaction acts as both a coupling partner and N-heterocyclic carbene (NHC) ligand precursor. Mechanistic studies reveal that consecutive steps of migratory insertion of the NHC into the aryl C-Ni bond and β-C elimination might be involved in the proposed reaction mechanism.

Photoinduced cross-coupling of aryl halides enabled by n-tetrabutylphosphonium phthalate

Phthalate acts as an electron shuttle bridge to realize aryl cross-coupling reactions by two-point non-covalent interaction.

Pyrazole-Mediated C-H Functionalization of Arene and Heteroarenes for Aryl-(Hetero)aryl Cross-Coupling Reactions.

Herein we introduce a transition-metal-free protocol that involves a commercially available, inexpensive pyrazole molecule to conduct C-C cross-coupling reactions at room temperature via a radical pathway. Using this method, an aryldiazonium salt has been coupled to a wide range of arenes and heteroarenes including benzene, mesitylene, thiophene, furan, benzoxazole to result the corresponding biaryl products. The full reaction mechanism is elucidated along with the crystallographic probation of an active initiator species. A potassium-stabilized deprotonated pyrazole steers single-electron transfer to the substrate and behaves as an initiator for the reaction.

Homogeneous Catalyzed Aryl–Aryl Cross-Couplings in Flow

AbstractAryl–aryl cross-coupling reactions are important reactions for the production of various biaryl compounds. This short review covers the various aryl–aryl cross-coupling reactions carried out in flow, focusing on the metal species of the aryl nucleophiles used in the cross-coupling reactions.1 Introduction2 Suzuki–Miyaura Coupling (B)3 Migita–Kosugi–Stille Coupling (Sn)4 Negishi Coupling (Zn)5 Kumada–Tamao–Corriu Coupling (Mg)6 Murahashi Coupling (Li)7 Conclusion

Synthesis of Enaminone‐Pd(II) Complexes and Their Application in Catalysing Aqueous Suzuki‐Miyaura Cross Coupling Reaction

Summary of main observation and conclusionA series of Pd(II)‐enaminone complexes, termed Pd(eao)2, have been synthesized and characterized. The investigation on the catalytic activities of these new Pd(II)‐reagents has proved that the Pd(eao)2‐1 possesses excellent catalytic activity for the Suzuki‐ Miyaura cross coupling reactions of aryl bromides/chlorides with aryl/vinyl boronic acids in the environmentally benign media of aqueous PEG400 at low loading (5 mol‰). The superiority of this Pd(II)‐reagent to those commercial Pd(II) and Pd(0) catalysts in catalyzing the reactions has been confirmed by parallel experiments. What's more, Pd(eao)2‐2 has been found as a practical catalyst for the homo‐coupling reactions of aryl boronic acids.

Pd(NHC)(cinnamyl)Cl-catalyzed Suzuki cross-coupling reaction of aryl sulfonates with arylboronic acids.

A series of N-heterocyclic carbene (NHC)-palladium catalysts have been synthesized and applied to catalyze the Suzuki coupling reaction efficiently between aryl sulfonates and arylboronic acids with the potassium phosphate heptahydrate as a base. The desired yields are obtained even with less reactive aryl tosylates or aryl mesylates as substrates. This method was applied successfully to the synthesis of the (R)-2-(t-butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol which is the key intermediate of sacubitril, a component of the newly approved antihypertensive drug "Entresto."

Hydroxyl-functionalized triazolylidene-based PEPPSI complexes: metallacycle formation effect on the Suzuki coupling reaction.

We report the preparation and full characterization of a series of hydroxyl functionalized 1,2,3-triazolylidene-based PEPPSI complexes 2a-c and their catalytic application in the Suzuki cross coupling reaction of aryl chlorides/amides with boronic acids. Under basic reaction conditions, complexes 2a-c show a notable increase in their catalytic efficiency compared with two ether-wingtip functionalized PEPPSI analogues (3 and 4) and a commercially available NHC-Pd complex (5). The catalytic results suggest that deprotonation of the hydroxyl group in complexes 2a-c plays an important role in the overall process. Deprotonation of the alcohol moiety of complexes 2a-b with sodium tert-butoxide allows for the isolation of metallacycles 6a-b, which are proposed as the active species of cross coupling reactions.

Recent Developments in C-H Activation for Materials Science in the Center for Selective C-H Activation.

Organic electronics is a rapidly growing field driven in large part by the synthesis of π-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of π-conjugated molecules and polymers, but the synthesis of intermediates necessary for traditional cross-couplings can include multiple steps with toxic and hazardous reagents. Direct arylation through C–H bond activation has the potential to reduce the number of steps and hazards while being more atom-economical. Within the Center for Selective C–H Functionalization (CCHF), we have been developing C–H activation methodology for the synthesis of π-conjugated materials of interest, including direct arylation of difficult-to-functionalize electron acceptor intermediates and living polymerization of π-conjugated polymers through C–H activation.

Electrochemical Preparation of Aryl Mom Ethers

In organic synthesis, methoxymethyl (MOM) ethers are frequently used as acid-labile protecting group [1] or leaving group in aryl cross-coupling reactions [2]. Their preparation commonly involves MOM chloride, a carcinogenic liquid with high vapour pressure which should be avoided as much as possible [3]. Therefore, we started to synthezise aryl MOM ethers without the use of MOM chloride by application of sustainable electrosynthetic methods [4]. Anodic decarboxylation of 2-aryloxy acetic acids under non-Kolbe conditions and trapping of the corresponding cation with methanol gives the desired MOM ethers (Figure 1). Indeed, this pathway is described for few aliphatic α-alkoxyacetic acids [5] and unsubstituted phenoxyacetic acid [6], but scope of this transformation to prepare substituted aryl MOM ethers has not been investigated so far. We now present our studies on the preparation of substituted aryl MOM ethers by anodic decarboxylation using an undivided cell setup. A wide range of substituents on the phenyl moiety is tolerated, giving access to valuable protected phenols [7].

N,N′-Bisaryl Substituted Chiral Linker-Bridged Bis(N-Heterocyclic Carbene) Palladium Complexes: Design, Synthesis, and Catalytic Properties

A series of novel N,N′-bisaryl bis(NHC) (NHC = N-heterocyclic carbene) precursors 5a–e, 12a–d, and 13a–c and their palladium complexes 14a–e, 15a–d, and 16a,b with (1R,2R)-cyclohexene and (1R,2R)-diphenylethylene linkers have been designed, synthesized in good yields, and fully characterized by NMR, HRMS, and elemental analysis. The X-ray single crystal analysis of 15a showed that these complexes adopted a slightly distorted square-planar geometry around the Pd(II) center. These N,N′-bisaryl-bis(NHC)-Pd complexes exhibit excellent catalytic activity in asymmetric aryl–aryl cross-coupling reactions of arylboronic acids and aryl halides. The axial chiral biaryl compounds could be achieved in high yields (up to 74%) and good enantioselectivities (up to 60% ee) within 24 h. The results show that for this kind of bis(NHC) palladium catalysts the structure characteristics of the chiral linkers have decisive effect on the enantioselectivities of cross-coupling reactions.

Neil K. Garg

Angewandte Chemie International EditionVolume 56, Issue 14 p. 3748-3748 Author ProfileFree Access Neil K. Garg First published: 31 January 2017 https://doi.org/10.1002/anie.201700568Citations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract „I can never resist jelly beans. I would have liked to have discovered the wheel. ...“ This and more about Neil K. Garg can be found on page 3748. Neil K. Garg The author presented on this page has recently published his 10th article in Angewandte Chemie in 10 years: “Nickel-Catalyzed Esterification of Aliphatic Amides”: L. Hie, E. L. Baker, S. M. Anthony, J.-N. Desrosiers, C. Senanayake, N. K. Garg, Angew. Chem. Int. Ed. 2016, 55, 15129; Angew. Chem. 2016, 128, 15353. Date of birth: December 18, 1978 Position: Professor, Department of Chemistry and Biochemistry, University of California, Los Angeles E-mail: neilgarg@chem.ucla.edu Homepage: http://garg.chem.ucla.edu/ ORCID: 0000-0002-7793-2629 Education: 2000 BS, New York University 2005 PhD supervised by Professor Brian M. Stoltz, California Institute of Technology 2005–2007 Postdoctoral studies with Professor Larry E. Overman, University of California, Irvine Awards: 2015 Arthur C. Cope Scholar Award; 2016 Mitsui Chemicals Catalysis Science Award of Encouragement; 2016 Merck Award, Royal Society of Chemistry; 2016 Guggenheim Fellowship; 2016 Thieme–IUPAC Prize; 2016 Tetrahedron Young Investigator Award; 2017 Elias J. Corey Award for Outstanding Original Contribution in Organic Synthesis, American Chemical Society Research: Methodology, catalysis, total synthesis Hobbies: Hiking, editing videos, watching basketball I can never resist jelly beans. I would have liked to have discovered the wheel. The most exciting thing about my research is my co-workers and their ideas. Guaranteed to make me laugh is the movie Forgetting Sarah Marshall. The most enjoyable chemistry adventure in my career was chasing the dragmacidin alkaloids in cahoots with Richmond Sarpong and Daniel Caspi, as a graduate student in the Stoltz Lab. My top three films of all time are Zoolander, Cinema Paradiso, and Star Wars. The downside of my job is that it is fun and perhaps too addictive. My favorite quote is “I feel like I am taking crazy pills” (Mugatu from Zoolander). I like refereeing because it is a great way to engage in the newest science and be an advocate for my field. The biggest problem that scientists face is being overly critical of each other. What I look for first in a publication is something unexpected. My favorite piece of research is the Woodward/Eschenmoser synthesis of vitamin B12. If I won the lottery, I would invest the cash. When I'm frustrated, I try to have a good laugh. My 5 top papers: References 1“The First Total Synthesis of Dragmacidin D”: N. K. Garg, R. Sarpong, B. M. Stoltz, J. Am. Chem. Soc. 2002, 124, 13179. (Led to my current interests in complex-molecule synthesis and cross-coupling methods.) 2“Total Synthesis of (−)-Sarain A”: N. K. Garg, S. Hiebert, L. E. Overman, Angew. Chem. Int. Ed. 2006, 45, 2912; Angew. Chem. 2006, 118, 2978. (My contributions as a postdoc to the total synthesis of sarain A, which had been an ongoing pursuit in the Overman laboratory). 3“Cross-Coupling Reactions of Aryl Pivalates with Boronic Acids”: K. W. Quasdorf, X. Tian, N. K. Garg, J. Am. Chem. Soc. 2008, 130, 14422. (This was the first paper from my independent career. Demonstrated that phenol-derived esters can undergo cross-coupling reactions by using nickel catalysis.) 4“Total Synthesis of (−)-N-Methylwelwitindolinone C Isothiocyanate”: A. D. Huters, K. W. Quasdorf, N. K. Garg, J. Am. Chem. Soc. 2011, 133, 15797. (The first total synthesis of a long-standing target.) 5“Conversion of amides to esters by the nickel-catalysed activation of amide C−N bonds”: L. Hie, N. F. F. Nathel, T. K. Shah, E. L. Baker, X. Hong, Y.-F. Yang, P. Liu, K. N. Houk, N. K. Garg, Nature 2015, 524, 79 (An exciting “post-tenure” direction for my laboratory, involving the activation of amide C−N bonds). Citing Literature Volume56, Issue14March 27, 2017Pages 3748-3748 ReferencesRelatedInformation

Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water.

N-(3-Chloro-2-quinoxalinyl)-N'-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N'-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.

Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents

A reusable silicon-based transfer agent (1) has been designed, synthesized, and validated for effective room-temperature palladium-catalyzed cross-coupling reactions (CCRs) of aryl and heteroaryl chlorides with readily accessible aryl lithium reagents. The crystalline, bench-stable siloxane transfer agent (1) is easily prepared via a one-step protocol. Importantly, this "green" CCR protocol circumvents prefunctionalization, isolation of organometallic cross-coupling partners, and/or stoichiometric waste aside from LiCl. DFT calculations support a σ-bond metathesis mechanism during transmetalation and lead to insights on the importance of the CF3 groups.

2-Aryl-indenylphosphine ligands: design, synthesis and application in Pd-catalyzed Suzuki-Miyaura coupling reactions.

A focused library of phosphine ligands was constructed for structural optimization. The catalyst can be used to perform the Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl chlorides.

ChemInform Abstract: Development of Chiral Bis‐hydrazone Ligands for the Enantioselective Cross‐Coupling Reactions of Aryldimethylsilanolates.

A palladium-catalyzed, enantioselective, aryl–aryl cross-coupling reaction using 1-naphthyldimethylsilanolates and chiral bis-hydrazone ligands has been developed. A family of glyoxal bis-hydrazone ligands containing various 2,5-diarylpyrrolidine groups was prepared to evaluate the influence of ligand structure on the rate and enantioselectivity of the cross-coupling. New synthetic routes to the 1-amino-2,5-diarylpyrrolidines were developed to enable the structure/reactivity–selectivity studies. Role reversal experiments of aryldimethylsilanolates and aryl bromides result in biaryl products with the same configuration and similar enantioselectivities implying that reductive elimination is the stereodetermining step. The origin of stereoselectivity is rationalized through computational modeling of diarylpalldium(II) complex which occurs through a conrotatory motion for the two aryl groups undergoing C–C bond formation.

Palladium-catalyzed cross-coupling reaction of aryl(trialkyl)silanes with aryl nitriles

Using highly stable, readily accessible, and recyclable 2-(2-hydroxyprop-2-yl)cyclohexyl-substituted arylsilanes activated by a mild phosphate base, palladium-catalyzed silicon-based aryl–aryl cross-coupling reaction proceeds for the first time with aryl nitriles in a highly chemoselective manner.

ChemInform Abstract: Unification of Anion Relay Chemistry with the Takeda and Hiyama Cross‐Coupling Reactions: Identification of an Effective Silicon‐Based Transfer Agent.

AbstractAn efficient method for the cross coupling reaction of aryl‐ and alkenyllithium reagents with aryl and alkenyl halides is presented.

A highly active catalytic system for Suzuki–Miyaura cross-coupling reactions of aryl and heteroaryl chlorides in water

An easily available Pd(OAc)(2)/(2-mesitylindenyl)dicyclohexylphosphine/Me(octyl)(3)N(+)Cl(-)/K(3)PO(4)·3H(2)O catalytic system was developed and it shows high catalytic activity in the Suzuki-Miyaura cross-coupling reaction of a diverse array of aryl and heteroaryl chlorides in water. Notably, this catalytic system also works with ultra-low loading of the catalyst with high turnover numbers.

Suzuki–Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines

Suzuki–Miyaura cross-coupling reaction with 2-heteroarylboronic acids is generally challenging due to these acids easy decomposition. To overcome this problem, we developed a coupling method that uses 2-heteroaryl pinacol boronates in the presence of 1.0mol% Pd(OAc)2 and 2.0mol% S-Phos with 4equiv amount of LiOH in dioxane and H2O at 80°C for 30min. This developed method allowed for the synthesis of a wide variety of 2-heteroaryl pyrimidines from 2-chloropyrimidyl derivatives in high yields, and is also useful in the preparation of various biaryl derivatives from heteroaryl chlorides.