Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Single-Electron Oxidation/Alterable C3- and C10-Arylation of 9‑MeOphenanthrene Tao Wang,† Huijun Ma,† Shitong Zhang,† Zong-Jun Li,§ Minghao Zhang,† Feng Li,† Fuxing Sun,† Jinbao Xiang,† Mufang Ke,† and Qifeng Wang*,†,‡ †
International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), Department of Organic Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China ‡ Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Beijing 100190, P. R. China § State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China S Supporting Information *
ABSTRACT: A reactivity pattern for C3-arylation of 9-MeO-phenanthrene has been established for the first time by using 2-naphthyl amines as coupling partners. A series of phenanthrene- and naphthalene-based multifunctionalized polycyclic aromatic hydrocarbons have been obtained in good to excellent yields. Alternative C10-arylation of 9MeO-phenanthrene has also been accomplished, using 2-naphthalenol derivatives as coupling partners. Trifluoroacetic acid is found crucial for the regioselectivity. Density functional theory calculations and electrochemical analyses have been performed to rationalize the reaction mechanism.
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Scheme 1. Approaches for Regioselective Functionalization of 9-Phenanthrenol Derivatives
olycyclic aromatic hydrocarbons (PAHs) are of great interest to researchers in organic chemistry, supramolecular chemistry, and material science.1,2 With unique characteristics of a π-conjugated system, strong π−π interaction, and a rigid skeleton, PAHs and their derivatives have been widely used as optoelectronic materials,3−5 have served as model compounds of graphene,6−8 and have been applied in self-assembly of supramolecular structures9,10 and in the synthesis of chiral catalysts11−13 and functional polymers.14 Phenanthrene is one of the most representative PAHs, and the syntheses of functionalized-phenanthrene have been attractive for over half a century.15 Ever since the determination of 9,10-double bond character of phenanthrene in 1952,16,17 it has been widely established that regioselective C−H functionalization of 9phenanthrenol derivatives occurs on K-region, including lithiation,18 electrophilic substitution,17,19−21 and oxidative coupling22−24 (Scheme 1). This fundamental reactivity pattern supplied an irreplaceable route for introducing functional groups on 9-phenanthrenol and its derivatives in the past decades, and a strategy for achieving different regioselectivity has long-term been absent in the literature. A breakthrough of the present reactivity pattern will not only promote the development of phenanthrene-based functional materials but also supply a concept for exploring regioselectivity of other PAHs.25−34 In this Letter, we report the first example of C3-arylation of 9methoxyl phenanthrene, using 2-naphthyl amine derivatives as coupling partners. The regioselectivity of the reaction is conceptually innovative. The reaction process is concise and highly efficient. In addition, C10-arylation of 9-methoxyl © XXXX American Chemical Society
phenanthrene with 2-methoxyl naphthalene has also been achieved in moderate to good yields. A detailed mechanistic investigation based on density functional theory (DFT) calculations and electrochemical analyses have been performed, and C3-arylation versus C10-arylation is rationalized as a singleelectron oxidation/C3-nucleophilic attack process versus a radical coupling process, respectively. Received: May 1, 2018
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DOI: 10.1021/acs.orglett.8b01380 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
employed, the yield of 4a could reach to 38% (entry 6). The reaction relied greatly on our selected solvent system and replacing CH2Cl2 with other solvents led to dramatic decrease of the yields (entries 7−9). A further increase of the stoichiometry of K2S2O8 and 2a, as well as prolonging the reaction time, could slightly improve the yield of 4a to 46% (entries 10, 11 and 12). In the end, we used (NH4)2S2O8 as the oxidant, and the yield of 4a could be improved to 71% (based on 1H NMR). Under the optimized conditions, 4a was isolated in 65% yield. The regioselectivity of 4a was confirmed by X-ray diffraction analysis after demethylation. Interestingly, substrates 1 and 2a both showed excellent regioselectivity in this cross-dehydrogenative coupling (CDC) process, and the C10-site of 1 was coupled with the C1-site of 2a (Scheme 2). Introducing other functional
In recent years, with the development of transition metalcatalyzed C−H direct arylation, Shi,35 Glorius,36 and Itami37,38 independently accomplished K-region direct arylation of phenanthrene. Our initial attempts for exploring remote reactive sites of 9-phenanthrenol were based on our developed Pd(II)catalyzed ortho-metalation/meta-arylation strategy.39,40 This strategy, with O-acylated 9-phenanthrenol as substrates, was proved quite unsuccessful, indicating low reactivity of O-acylated 9-phenanthrenol compared to phenanthrene.35,36,38 Then, we realized that PAHs-based substrates tend to form radical ions instead of C−M bonds.34,41 Therefore, a coupling strategy based on single-electron oxidation was proposed. A key challenge in this strategy is the control of regioselectivity among nine types of C−H bonds in 9-phenanthrenol. In fact, without the aid of transition metal catalysts, intermolecular dehydrogenative coupling reactions between different aromatic structures were rarely achievable.34,41,42 To achieve this target, we first analyzed the oxidation potentials of 9-methoxyl phenanthrene 1, together with a series of coupling candidates, including 2-methoxyl naphthalene 2a and N,N-dimethyl-2-naphthalenamine 3a. The electrochemical analysis showed the oxidation potentials of 1, 2a, and 3a were 1.427, 1.482, and 0.797 V, respectively (see Supporting Information (SI)). Compound 2a has a nearly equal oxidation potential to 1, while 3a has a much lower oxidation potential and they both were selected as representative coupling partners. Then, we started our investigation under chemical oxidative conditions, using 2a as the coupling partner first. After a careful condition optimization, the results are summarized in Table 1. In entry 1, when Koser’s reagent was used as an oxidant,
Scheme 2. Regioselectivity Confirmation of Products 4
Table 1. Condition Optimization for Reaction Between Compounds 1 and 2a
entry
oxidant (equiv)
solvent
yield (%)a
1 2 3 4 5 6 7 8 9 10 11b 12b,c 13b,c
PhI(OTs)OH (3.0) FeCl3 (3.0) BQ (3.0) DDQ (3.0) PhI(OAc)2 (3.0) K2S2O8 (3.0) K2S2O8 (3.0) K2S2O8 (3.0) K2S2O8 (3.0) K2S2O8 (6.0) K2S2O8 (6.0) K2S2O8 (6.0) (NH4)2S2O8 (6.0)
CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 THF/TFA = 1:1 CHCl3/TFA = 1:1 toluene/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1 CH2Cl2/TFA = 1:1
