Benzimidazolyl Palladium Complexes as Highly ... - ACS Publications

Letter Cite This: ACS Catal. 2019, 9, 6993−6998

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Benzimidazolyl Palladium Complexes as Highly Active and General Bifunctional Catalysts in Sustainable Cross-Coupling Reactions Jiancheng Zhu and Vincent N. G. Lindsay* Department of Chemistry, North Carolina State University, 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States

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ABSTRACT: A family of air- and moisture-stable dinuclear palladium complexes bearing 2-benzimidazolyl ligands is reported and shown to be a highly effective and general catalytic platform in diverse cross-coupling reactions. The rigidity and conformation of the ligand scaffold was readily modified via tethering of the 2-benzimidazolyl moiety to diamine ligands, resulting in significant changes in catalytic activity. Under optimal conditions, Suzuki, Heck, and Sonogashira-type couplings of aryl bromides can all be performed efficiently with good functional group compatibility using only 0.1 mol % of catalyst, in aqueous or alcohol solvents. Experimental evidence highlights the importance of the bifunctional character of the ligand for catalytic activity, where the basic N-functionality in the ligand framework is proposed to accelerate (trans)metalation steps via intramolecular assistance. KEYWORDS: protic NHC, N-Heterocyclic Carbene, ambidentate ligand, cross-coupling, green chemistry

T

Scheme 1. Reactivity of Protic NHC- and Imidazolyl-Metal Complexes as Bifunctional Catalysts

ransition-metal-catalyzed cross-coupling reactions constitute some of the most valuable and synthetically productive steps in the formation of organic compounds and materials relevant to an array of chemical industries.1,2 While tremendous advances have been achieved in terms of functional group compatibility, variability, and ease of access to the substrates and metal catalyst, sustainability challenges still exist regarding the applicability of these reactions to the large-scale production of fine chemicals and pharmaceuticals. To this end, the design of novel and readily accessible catalytic systems aimed at performing these reactions under environmentally benign conditions, using minute amounts of transition-metal catalyst in nontoxic solvents, are deemed critical.3 The energy invested by pharmaceutical and fine chemical industries to solve these issues and minimize the toxic waste generated from these processes is known to be enormous,4 highlighting the tremendous synthetic value of these reactions. N-heterocyclic carbenes (NHCs) have emerged as a prominent class of σ-donating ligands in transition-metal catalysis, because of their electronic and steric tunability and the robust nature of the resulting complexes.5 The Nsubstituents of azole-based NHCs are known to have important influence on the coordination sphere of the metal center, and the traditional N,N′-disubstituted NHC-metal complexes have been widely employed in an array of catalytic reactions. However, the use of protic NHC-metal complexes (pNHCs) or their deprotonated 2-imidazolyl-metal analogues as catalysts, with one or both nitrogen atoms left unsubstituted (Scheme 1),6 remains scarce, possibly because of their known © XXXX American Chemical Society

metal-dependent tautomerization to their N-bound metal-azole isomers.7 In their protonated form (Scheme 1a), these complexes have been found to act as bifunctional catalysts via their H-bond donating abilities with carbonyl-containing substrates (Scheme 1b).6c,8 When deprotonated, the resulting 2-imidazolyl-metal complexes are known to be effective Received: June 11, 2019 Revised: July 2, 2019 Published: July 5, 2019 6993

DOI: 10.1021/acscatal.9b02420 ACS Catal. 2019, 9, 6993−6998

Letter

ACS Catalysis nucleophilic species and Lewis bases at the free N-position.9 We envisioned that such bifunctional character could be valuable in the quest for more active catalysts in cross-coupling reactions.10 Indeed, the unsubstituted nitrogen atom of the 2benzimidazolyl ligand could directly participate in the catalysis by accelerating the (trans)metalation step of the mechanisms (Scheme 1c). Herein, we report the expedient synthesis and characterization of three novel dinuclear 2-benzimidazolylpalladium complexes bearing either monodentate or tridentate ligands, and their application as highly active bifunctional precatalysts in Suzuki, Sonogashira, and Heck cross-coupling reactions under environmentally benign conditions. The denticity of the ligand and the level of flexibility of the benzimidazolyl moiety was found to have a profound influence on catalytic activity, and experimental evidence using an analogous N-methyl substituted metal-NHC complex highlights the importance of the ligand’s Lewis basic nitrogen, conferring a bifunctional character to the complexes and significantly improving their catalytic performance. To the best of our knowledge, this is the first example of protic NHC- or 2-imidazolyl metal-based complexes used as catalysts for cross-coupling reactions. The present studies thus provide the foundation for their use as simple yet powerful bifunctional catalysts, where the concept of intramolecular Lewis base assistance should find widespread use in the future development of metal-catalyzed transformations beyond cross-coupling reactions. Mainly due to the work of Hahn, Ikariya, and Crabtree, several efficient methods are available for the preparation of protic NHC-metal complexes with a wide array of transition metals.6 In the case of late transition metals such as palladium, Hahn and co-workers have shown that oxidative addition of a 2-halobenzimidazole to a Pd(0) species, followed by kinetic Nprotonation of the resulting 2-benzimidazolyl-metal complex constitutes an efficient and straightforward approach for the formation of monodentate derivatives.9a−c In view of using them in bifunctional and sustainable catalysis, we sought to avoid hindered phosphines as ancillary ligands and thus elected diamines such as bipyridine derivatives, which are ubiquitous in palladium catalysis because of their robust character and ability to stabilize the metal center in transient intermediates.11 Thus, reaction of Pd2(dba)3 in the presence of 2-iodo-Nmethylbenzimidazole and 2,2′-bipyridine at 80 °C, followed by treatment with NH4PF6, provided dinuclear complex 1a (Scheme 2a).12 While formation of this dinuclear species from the 2-benzimidazolyl-metal adduct instead of kinetic protonation to the pNHC complex was unexpected,9h it provided evidence for the intermediacy of such a monomeric species in solution following oxidative addition.13 X-ray crystallographic analysis of this dicationic complex revealed a unique boat-type C2-symmetrical bimetallacyclic structure. Importantly for our catalyst design, which relies on the presence of a free Lewis basic N-functionality in the ligand, reaction of this stable dinuclear species with benzoyl chloride at room temperature afforded the corresponding N-benzoyl NHC complex 1b, which strongly suggests equilibration of 1a to its monomeric form in solution (Scheme 2b). In agreement with previous observations in other pNHC complexes,9 this experiment supports the hypothesis that the benzimidazolyl nitrogen is in fact a competent nucleophile, which is key to its subsequent use as bifunctional catalyst. A distinct feature of pNHC and 2-imidazolyl-metal complexes compared to N,N′-disubstituted NHC species is

Scheme 2. (a) Synthesis of Dinuclear Pd Complex 1a and (b) Evidence for Its Equilibration to Monomers in Solutiona

a

PF6 counteranions were omitted in the X-ray structures for clarity.

their possible tautomerization to the N-bound metal-azole complexes,7 which in our case could lead to decomposition during catalysis. In order to lock the metal complex in its desired C-bound form for a more robust catalyst, we prepared two tridentate (pincer) versions of the ligand framework found in 1a, where metalation to afford complexes 2 and 3 was readily achieved from the corresponding nonhalogenated benzimidazoles and Pd(OAc)2 via carboxylate-assisted C−H activation (Scheme 3). In contrast with complex 1a where the Pd−C(1) bond is free to rotate in its monomeric form, this framework also significantly restricts the orientation of the benzimidazolyl group as pseudo-coplanar with the bipyridine moiety, which is a factor that could affect the catalytic behavior of the complexes. X-ray crystallographic analysis of dinuclear complex 3 indeed showed a flatter bimetallacyclic structure Scheme 3. Synthesis of 2-Benzimidazolylpalladium Pincer Complexes 2 and 3 by Carboxylate-Assisted C−H Activationa

a

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PF6 counteranions were omitted in the X-ray structures for clarity. DOI: 10.1021/acscatal.9b02420 ACS Catal. 2019, 9, 6993−6998

Letter

ACS Catalysis

tridentate yet somewhat flexible benzimidazolyl ligand, suggest (1) the relevance of the polydenticity of the ligand to protect the C-bound form of the key benzimidazolyl moiety, and (2) the importance of having some flexibility of the benzimidazolyl moiety in the ligand to potentially help stabilize intermediates of the mechanism. With these Suzuki cross-coupling conditions in hand, a variety of substrates were tested in the reaction to evaluate the generality of the process, where the free N-functionality in 3 is proposed to assist the transmetalation via Lewis acid/base interaction with the boronic acid partner (Scheme 4). The

compared to 1a (Scheme 3b), with a significantly smaller C(1)−Pd−N(2)−C(1)′ dihedral angle (40° for 3, 57° for 1a) and a longer distance between the two Pd centers (3.74 Å for 3, 3.41 Å for 1a). Importantly, all three dinuclear complexes reported here were found to be stable to storage in air and moisture for extended periods of time, and were used in catalysis without the need for dry solvents or inert atmosphere (vide infra). In order to evaluate the catalytic activity of these new benzimidazolyl-Pd complexes, we elected the Suzuki crosscoupling of 4-bromoanisole 4a and phenylboronic acid as a model reaction (Table 1).14 In absence of any phosphine or

Scheme 4. Selected Scope of Accessible Products in the Suzuki Cross-Coupling Catalyzed by 3a

Table 1. Evaluation of the Bifunctional Catalysts 1a−3 Prepared Using a Suzuki Cross-Coupling as a Model Reaction

entry

catalyst (mol %)

base

solvent

yielda (%)

1 2 3 4 5 6 7 8

Pd(OAc)2:bipy (1:1) 1a (1) 2 (1) 3 (1) 3 (0.25) 3 (0.25) 3 (0.10) −

KOH KOH KOH KOH KOH K2CO3 K2CO3 K2CO3

H2O H2O H2O H2O H2O EtOH EtOH EtOH

99 65 95 89b 3 > 2. Indeed, because of the rigid nature of its tether, it is expected that 2 exists in an even more flat conformation than 3, where the benzimidazolyl moiety is rigidified as coplanar with the rest of the pincer ligand. On the other hand, the benzimidazolyl group in 1a is technically free to rotate to sterically accommodate intermediates of the catalytic cycle, although its monodentate nature could lead to decomposition following tautomerization from its C-bound form to its N-bound form under the protic conditions used.7 These results, electing 3 as a superior catalyst, possessing a 6995

DOI: 10.1021/acscatal.9b02420 ACS Catal. 2019, 9, 6993−6998

Letter

ACS Catalysis Scheme 5. Selected Scope of Accessible Products in the Copper-Free Sonogashira Cross-Coupling Catalyzed by 3a

Scheme 7. Insight into the Importance of the Bifunctional Character of Catalyst 3a

a a

b

See Schemes 4−6 for Suzuki, Sonogashira, and Heck conditions.

Isolated yields. 1 mol % of catalyst 3 was used.

ing stilbene derivatives (Scheme 6). In this process, Na2CO3 was identified as an ideal base with n-BuOH as solvent in the

3 is a far superior catalyst in all three cases, suggesting that the free nitrogen in the monomer of 3 plays an important role to accelerate these reactions.17 Further mechanistic studies will be needed in the future to elucidate the exact nature of this effect for specific transformations. In summary, we report the synthesis and application of a new family of air- and moisture-stable benzimidazolylpalladium complexes as highly active bifunctional catalysts in Suzuki, Sonogashira, and Heck cross-coupling reactions under sustainable conditions, using only 0.1 mol % of catalyst. The denticity of the ligand and the level of flexibility of the benzimidazolyl moiety were found to be critical factors for their catalytic performance, where a flexible tridentate analogue (3) was identified as a superior candidate for catalysis. In this design, the basic N-functionality of the ligand is proposed to assist in the catalysis to accelerate key (trans)metalation steps of the mechanism. Notably, experimental evidence using a Nmethylated derivative (8) as a monofunctional analogue provided further insight into the importance of the bifunctionality of the complexes. Mechanistic studies and extension of the present concept of their use as bifunctional catalysts in other reactions with different transition metals and ligand analogues are currently underway in our laboratories and will be reported in due course.

Scheme 6. Selected Scope of Accessible Products in the Heck Cross-Coupling Catalyzed by 3a

a

Isolated yields. b1 mol % of catalyst 3 was used.

presence of TBAI.14 Notably, the use of biomass-derived protic solvents such as alcohols in Heck reactions is relatively rare.1f,g Again, both electron-rich (7a, 7b, 7h) and electron-poor (7c− 7g) aryl bromides, as well as a heterocyclic derivative (7i) provided good yields using only 0.1 mol % catalyst. Methyl vinyl ketone is also shown to be a competent acceptor in the reaction when 1 mol % 3 was used, albeit in lower yield (7j). A notable feature of these three types of reactions is their compatibility with aryl chlorides and unprotected aniline functional groups, which were both found to be unreactive under our conditions (see 5c, 6b, 7b, 7d, 7h). Synthetically, this can be an advantage, where sequential orthogonal couplings could potentially be achieved using our conditions in conjunction with known aryl chloride coupling or Buchwald−Hartwig amination conditions, respectively. In order to gain further insight into the importance of the bifunctional character of our benzimidazolyl palladium catalysts, we prepared Pd(II) complex 8, an analogue of 3 where the basic N-functionality is blocked by a methyl group (Scheme 7). Evaluation of 8 as a catalyst under our optimal Suzuki, Sonogashira, and Heck conditions indeed revealed that

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.9b02420. Crystallographic data for compound 1a C36H30N8Pd2(F6P)2(C3H6O)3 (CIF) Crystallographic data for compound 1b C25H20ClF6N4OPPd (CIF) Crystallographic data for compound 3 C36H26N8Pd2(F6P)2(C2H3N)3 (CIF) Experimental details and spectroscopic data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. 6996

DOI: 10.1021/acscatal.9b02420 ACS Catal. 2019, 9, 6993−6998

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ACS Catalysis ORCID

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Vincent N. G. Lindsay: 0000-0002-7126-325X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by North Carolina State University startup funds. REFERENCES

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Letter

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(12) The yield of formation of 1a was found to be variable (18%− 50%) and highly dependent on the quality and age of Pd2(dba)3 as received from commercial sources. See: (a) Zalesskiy, S. S.; Ananikov, V. P. Pd2(dba)3 as a Precursor of Soluble Metal Complexes and Nanoparticles: Determination of Palladium Active Species for Catalysis and Synthesis. Organometallics 2012, 31, 2302−2309. (b) Pentsak, E. O.; Kashin, A. S.; Polynski, M. V.; Kvashnina, K. O.; Glatzel, P.; Ananikov, V. P. Spatial imaging of carbon reactivity centers in Pd/C catalytic systems. Chem. Sci. 2015, 6, 3302−3313. (13) Similar formations of dinuclear species from imidazolyl-metal complexes have been observed previously. See: (a) Jin, H.; Kluth, P.; Hahn, F. E. Synthesis of Complexes with Protic NH,NR-NHC Ligands by Oxidative Addition of N-Alkyl-2-iodoimidazoles to [M(PPh3)4] (M = Pd, Pt) Complexes. Eur. J. Inorg. Chem. 2017, 2774−2781. (b) He, F.; Danopoulos, A. A.; Braunstein, P. Trifunctional pNHC, Imine, Pyridine Pincer-Type Iridium(III) Complexes: Synthetic, Structural, and Reactivity Studies. Organometallics 2016, 35, 198−206. (c) Bertani, R.; Mozzon, M.; Michelin, R. A.; Benetollo, F.; Bombieri, G.; Castilho, T. J.; Pombeiro, A. J. L. Synthesis, chemical and electrochemical deprotonation reactions of aminocarbene complexes of palladium(II) and platinum(II). X-ray structure of {(PPh3)ClPt[μ-COCH2CH2N-C,N]}2. Inorg. Chim. Acta 1991, 189, 175−187. (14) See the Supporting Information for details. (15) (a) Gao, Y.; Ou, Y.; Gooßen, L. J. Pd-Catalyzed Synthesis of Vinyl Arenes from Aryl Halides and Acrylic Acid. Chem. - Eur. J. 2019, 25, 8709−8712. (b) Molloy, J. J.; Seath, C. P.; West, M. J.; McLaughlin, C.; Fazakerley, N. J.; Kennedy, A. R.; Nelson, D. J.; Watson, A. J. B. Interrogating Pd(II) Anion Metathesis Using a Bifunctional Chemical Probe: A Transmetalation Switch. J. Am. Chem. Soc. 2018, 140, 126−130. (c) Molander, G. A.; Brown, A. R. Suzuki− Miyaura Cross-Coupling Reactions of Potassium Vinyltrifluoroborate with Aryl and Heteroaryl Electrophiles. J. Org. Chem. 2006, 71, 9681− 9686. (d) Darses, S.; Michaud, G.; Genêt, J.-P. Potassium Organotrifluoroborates: New Partners in Palladium-Catalysed Cross-Coupling Reactions. Eur. J. Org. Chem. 1999, 1875−1883. (e) Kerins, F.; O’Shea, D. F. Generation of Substituted Styrenes via Suzuki CrossCoupling of Aryl Halides with 2,4,6-Trivinylcyclotriboroxane. J. Org. Chem. 2002, 67, 4968−4971. (f) Molander, G. A.; Rivero, M. R. Suzuki Cross-Coupling Reactions of Potassium Alkenyltrifluoroborates. Org. Lett. 2002, 4, 107−109. (16) (a) Cassar, L. Synthesis of aryl- and vinyl-substituted acetylene derivatives by the use of nickel and palladium complexes. J. Organomet. Chem. 1975, 93, 253−257. (b) Dieck, H. A.; Heck, F. R. Palladium catalyzed synthesis of aryl, heterocyclic and vinylic acetylene derivatives. J. Organomet. Chem. 1975, 93, 259−263. (c) Ljungdahl, T.; Bennur, T.; Dallas, A.; Emtenä s , H.; MÅrtensson, J. Two Competing Mechanisms for the Copper-Free Sonogashira Cross-Coupling Reaction. Organometallics 2008, 27, 2490−2498. (d) Gazvoda, M.; Virant, M.; Pinter, B.; Košmrlj, J. Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation. Nat. Commun. 2018, 9, 4814. (e) Wagner, R. W.; Johnson, T. E.; Li, F.; Lindsey, J. S. Synthesis of Ethyne-Linked or Butadiyne-Linked Porphyrin Arrays Using Mild, Copper-Free, Pd-Mediated Coupling Reactions. J. Org. Chem. 1995, 60, 5266−5273. (17) During the review of this manuscript, an analogous N-blocking experiment was reported with a Fe-based protic NHC catalyst used for ketone hydrogenation: Mühlen, C.; Linde, J.; Rakers, L.; Tan, T. T. Y.; Kampert, F.; Glorius, F.; Hahn, F. E. Synthesis of Iron(0) Complexes Bearing Protic NHC Ligands: Synthesis and Catalytic Activity. Organometallics 2019, 38, 2417−2421.

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DOI: 10.1021/acscatal.9b02420 ACS Catal. 2019, 9, 6993−6998