Article pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
Catalytic Azoarene Synthesis from Aryl Azides Enabled by a Dinuclear Ni Complex Ian G. Powers, John M. Andjaba, Xuyi Luo, Jianguo Mei, and Christopher Uyeda* Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States S Supporting Information *
ABSTRACT: Azoarenes are valuable chromophores that have been extensively incorporated as photoswitchable elements in molecular machines and biologically active compounds. Here, we report a catalytic nitrene dimerization reaction that provides access to structurally and electronically diverse azoarenes. The reaction utilizes aryl azides as nitrene precursors and generates only gaseous N2 as a byproduct. By circumventing the use of a stoichiometric redox reagent, a broad range of organic functional groups are tolerated, and common byproducts of current methods are avoided. A catalyst featuring a NiNi bond is found to be uniquely effective relative to those containing only a single Ni center. The mechanistic origins of this nuclearity effect are described.
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INTRODUCTION
In principle, many of these challenges may be addressed by considering an alternative redox-neutral dimerization of a nitrene precursor. Free aryl nitrenes can be liberated from the photolysis or pyrolysis of aryl azides.8 Singlet aryl nitrenes predominantly decompose by ring-expansion to form unstable dehydroazepines, which then undergo poorly defined polymerization reactions. In competition with this process, intersystem crossing generates triplet nitrenes, which can dimerize by N N coupling but are often sufficiently reactive to abstract H atoms from the reaction medium to form anilines. Transition metal catalysis provides an avenue to achieve selective NN coupling through the intermediacy of metalstabilized nitrenes (Figure 1). Though MNR complexes have been extensively studied over the past few decades,9 systems that catalytically generate azoarenes are rare, and methods that achieve broad scope and high efficiency have yet to emerge.10,11 Many transition metal imides react with aryl azides to form tetrazene complexes that are resistant to N2 loss.12 Cenini first noted that azoarenes were generated as minor byproducts of benzylic CH amination reactions catalyzed by Co(porphyrin) complexes. Peters subsequently demonstrated that an Fe catalyst bearing a trisphosphinesilyl (SiP3) ligand could achieve improved selectivities for NN coupling (up to 57% yield) over CH abstraction for electronically neutral or electron-rich aryl azides.10b Additionally, Groysman reported a Fe(OCt-Bu2Ph)2 complex, which promotes the dimerization of ortho-disubstituted aryl azides (e.g., mesityl azide or 2,6diethylphenyl azide).10d Less hindered substrates form dimeric M2(μ-NAr)2 complexes that do not undergo NN coupling.
Azoarenes represent an important class of organic chromophores distinguished for their ability to function as photoswitches.1 At equilibrium in the dark, azoarenes reside predominantly in their thermodynamically preferred trans geometry; however, upon excitation at their π−π* or n−π* absorption bands, a substantial fraction of the less stable cis form can be generated.2 This isomerization has been utilized in molecular machines, probes, and therapeutics as a mechanism to trigger conformational changes using incident visible or UV light.3 Though early physical studies of azoarene photoswitching behavior were conducted on simple model compounds, including azobenzene itself,2a the motivation to incorporate these functionalities into more complex systems necessitates the development of new synthetic methods that ideally achieve NN coupling under mild conditions, in high yield, and with broad substrate scope. Certain classes of azoarenes are accessible by substitution reactions between nucleophilic arenes and electrophilic diazonium ions; however, symmetrical azoarenes are more commonly prepared by homodimerization methods that involve an oxidation state adjustment of a nitrogen-containing precursor, which then induces NN bond formation.4 For example, anilines can be oxidized with reagents such as KMnO4, MnO2, Ag2O, or O2/KOt-Bu to form azoarenes.5 Alternatively, nitroarenes can be reductively coupled using Zn or a hydride source.6 Despite this diversity of redox-based approaches, N N coupling is commonly a low-yielding step in the preparation of highly functionalized photoswitches. Furthermore, the limitations of current methods can necessitate that additional synthetic manipulations be performed following installation of the NN bond to reach a given target molecule.7 © XXXX American Chemical Society
Received: January 14, 2018 Published: February 28, 2018 A
DOI: 10.1021/jacs.8b00503 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
Article
Journal of the American Chemical Society
reactivity studies reported by Hillhouse. The (dtbpe)Ni NMes complex (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane) was shown to react with mesityl azide at room temperature to form azomesitylene.13 Despite the high yield of this stoichiometric process, the strong binding of the Ar2N2 product to Ni(0) precluded catalytic turnover. Here, we report that a dinuclear Ni complex (1)14 is capable of overcoming this challenge associated with product inhibition, leading to the development of a general method for the catalytic dimerization of aryl nitrenes.
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RESULTS AND DISCUSSION Comparison of Mononuclear and Dinuclear Ni Catalysts for Aryl Nitrene Dimerization. We initiated our studies by surveying Ni catalysts (Table 1) for the dimerization of a model aryl azide substrate (2). Zero-valent Ni complexes bearing monodentate phosphine or NHC ligands (entries 3 and 4) were found to be unsuitable as catalysts due to competing nitrene transfer to the ligand. For example, Ph3P/Ni(COD)2 promoted significant conversion of aryl azide 2 but yielded none of the desired azoarene. NMR analysis of the resulting reaction mixture revealed the formation of a new organic species, which was assigned as the Ph3PNAr product (Ar = 4trifluoromethylphenyl; 31P = 3.29 ppm)15 by comparison to an authentic sample prepared from Ph3P and 2 in the absence of Ni. Similar observations were made using the IPr ligand. Measurable yields of azoarene 3 were obtained using Ni complexes of bidentate N-donor ligands (Table 1, entries 5 and 6). For example, the [i‑PrIP]Ni(COD) catalyst (4) provided 3 in 13% yield after 1 h at room temperature (76% recovery of
Figure 1. (a) Design challenges associated with transition metalcatalyzed nitrene dimerization reactions. (b) Identification of a dinuclear Ni catalyst for the conversion of aryl azides to azoarenes.
We postulated that Ni complexes might be capable of promoting the catalytic coupling of aryl azides based on Table 1. Catalyst Comparison Studiesa
entry
catalyst
conversion
yield
1 2 3b 4c 5 6 7 8 9d
none Ni(COD)2 Ni(COD)2 + PPh3 Ni(COD)2 + IPr [i‑PrIP]Ni(COD) (4) [BPY]Ni(COD) (5) [i‑PrDAD]Ni(COD) (6) [i‑PrNDI]Ni2(C6H6) (1) [i‑PrNDI]Ni2(C6H6) (1)
98%
