Internationale Ausgabe: DOI: 10.1002/anie.201502666 Porphyrinoids Deutsche Ausgabe: DOI: 10.1002/ange.201502666 Regioselective Nucleophilic Functionalization of Antiaromatic Nickel(II) Norcorroles** Ryo Nozawa, Keitaro Yamamoto, Ji-Young Shin, Satoru Hiroto, and Hiroshi Shinokubo* Abstract: Treatment of antiaromatic nickel(II) norcorrole with potassium cyanide provided nickel(II) 3-cyanonorcorrole with perfect regioselectivity without the help of a catalyst. The reaction of the nickel(II) norcorrole with phenol or thiophenol in the presence of a base also yielded substitution products. The antiaromatic 16p conjugation system in the norcorrole core was preserved in the functionalized products. Introduction of phenylthio groups significantly decreased the HOMO–LUMO gap and enhanced the near IR absorption property. Electrophilic substitution is one of the most diagnostic reactions of aromatic compounds. In electrophilic substitu- tion, an electrophile directly replaces hydrogen on an sp 2 - carbon atom. In contrast, nucleophilic substitution (S N Ar) is only observed if an aromatic compound possesses both a strong electron-withdrawing group (to activate the sub- strate) and a halide (to act as a leaving group). [1] Nucleophilic substitution of hydrogen on some electrophilic arenes may also occur through oxidative hydride substitution. [2] The driving force in these processes is aromatic stabilization, which facilitates the formation of the original p-conjugation system in the initial unconjugated addition intermediate. Antiaromatic compounds are generally unstable and reactive. [3] We recently prepared the antiaromatic nickel(II) dimesitylnorcorrole 1 (see Scheme 1) and explored its proper- ties and functions. [4–6] Herein, we demonstrate that 1 is reactive enough with nucleophiles to furnish substitution products because of its low-lying LUMO. The reaction between 1 and a nucleophile directly afforded either the cyanation or thiolation product regioselectively without the antiaromatic property of the norcorrole core being lost. Although several antiaromatic porphyrinoids have been characterized, [7] this type of nucleophilic substitution reac- tivity has not been disclosed. The direct C  H cyanation and thiolation of arenes have recently been developed extensively. However, such reactions are only feasible with the help of transition-metal catalysts. [8, 9] Treating 1 with an excess of potassium cyanide (20 equiv) in acetonitrile/THF (1:1) at 80 8C in air afforded the nickel(II) 3-cyanonorcorrole 2 in 56 % yield (Scheme 1). Small amounts of the 3,7- and 3,12-dicyanation products (3 and 4, respec- tively) were also formed in 4 % total yield as a 1:1 regioiso- meric mixture. The yield of 1 was dramatically lower when the same reaction was performed under a nitrogen atmosphere, thus indicating that the functionalization reaction proceeds through oxidative hydride substitution. [10] The 1 H NMR spectrum of 2 revealed that it was unsymmetrical, with seven pyrrole protons in the upfield region from d = 2.4 to 3.2 ppm. The anomalous chemical shifts of the pyrrole protons clearly suggest the presence of a strong paratropic ring current in 2. The calculated nucleus-independent chem- ical shift (NICS) values were markedly positive (see Table S1 in the Supporting Information), thus confirming the magneti- cally antiaromatic nature of 2. [11] Note that the 16p antiar- omatic cyclic conjugation network was maintained after cyanation. This result is somewhat counterintuitive because nucleophiles may attack at either the meso- or a-positions to break the antiaromatic p-conjugation circuit. [12] Both dicya- nation products 3 and 4 also exhibited upfield-shifted pyrrole protons. The structures of 3 and 4 were assigned on the basis of the identities of the mesityl protons. We then found that thiophenol could also be regioselec- tively introduced to 1. The nickel(II) 3-phenylthionorcorrole 5 was obtained in 29 % yield along with an inseparable mixture of the disubstitution products 6, 7, and 8 (12 % yield; see Scheme 2 for structures), when 1.0 equivalent of thio- phenol was used in the presence of K 2 CO 3 (1.0 equiv) at room Scheme 1. Cyanation of the nickel(II) norcorrole 1 with potassium cyanide. Mes = mesityl, THF = tetrahydrofuran. [*] R. Nozawa, K. Yamamoto, Prof. Dr. J.-Y. Shin, Prof. Dr. S. Hiroto, Prof. Dr. H. Shinokubo Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Aichi, 464-8603 (Japan) E-mail: hshino@apchem.nagoya-u.ac.jp [**] This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “pi-System Figuration (26102003) and the Pro- gram for Leading Graduate Schools ”Integrative Graduate Educa- tion and Research in Green Natural Sciences“, MEXT (Japan). H.S. is grateful to The Asahi Glass Foundation for financial support. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201502666. . Angewandte Zuschriften 8574 # 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2015, 127, 8574 –8577