Porphyrinoids DOI: 10.1002/ange.201201853 Effective meso Fabrications of Subporphyrins** Masaaki Kitano, Shin-ya Hayashi, Takayuki Tanaka, Hideki Yorimitsu, Naoki Aratani, and Atsuhiro Osuka* Subporphyrins, which are legitimate ring-contracted porphyr- ins in terms of the regular arrangement of three pyrrolic units and methine carbons, have emerged as a novel functional pigment since their first synthesis in 2006. [1] Interest in these macrocycles initially lay on the influence of symmetry change from D 4h of metalloporphyrins to C 3v of boron(III) subpor- phyrins. In the meantime however, it has turned out that subporphyrins have attractive attributes, such as a 14p- electronic aromatic circuit, bowl-shaped bent structure, and variable electronic properties that are tunable by meso-aryl substituents. [2, 3] Despite these promises, the synthetic chemis- try of subporphyrins lags far behind the porphyrin counter- part, since only symmetric meso-aryl-substituted subporphyr- ins, such as triphenyl subporphyrin 1, can be prepared by the condensation of tri-N-pyrrolylborane or pyridine-tri-N-pyr- rolylborane with aryl aldehydes in a practical sense. As has been extensively demonstrated in the porphyrin chemistry, rational synthetic routes to nonsymmetrically substituted subporphyrins are highly desirable for exploration of sub- porphyrin-based functional molecular systems. [4] So far, how- ever, such a rational nonsymmetric fabrication method has been unknown for a subporphyrin except for low-yielding statistical cross-condensation reactions that entail tedious separation steps. [2c,d,f] Furthermore, there is no synthetic route to meso-alkenyl or meso-alkynyl subporphyrins despite their high promise as functional dyes, as suggested by the very rich chemistry of porphyrin counterparts that were pioneered by Therien [5] and Anderson. [6] Herein, we present the synthesis of meso-free and meso- bromo subporphyrins 2 and 3, which can be effective synthetic precursors for nonsymmetrically substituted subporphyrins, judging from the extensive and successful uses of meso-free [7] and meso-bromo porphyrins. [8] Tribenzosubporphines 4 were the first synthesized meso-free subporphyrins, but their meso- positions are entirely unreactive towards electrophiles such as bromine and N-bromosuccinimide (NBS), because they correspond to nodes in their HOMO as revealed by DFT calculations. [2a] On the other hand, meso-free subporphyrin 2 has been suggested to be a useful precursor for 3 by DFT calculations (see the Supporting Information), which predicts favorable HOMO characteristics for meso halogenation. We thought that meso-free subporphyrin 2 might be prepared by the condensation of pyridine tripyrromethene borane salt with trimethyl orthoformate. Along this synthetic line, we first attempted the condensation of tripyrrane 5 [9] with neat BH 3 ·NEt 3 at 100 8C for 1 h, and the resulting solution was evaporated to leave a residue, to which an equivalent amount of pyridine was added to form pyridine tripyrromethene borane precursor. This was condensed with 20 equivalents of trimethyl orthoformate in the presence of trifluoroacetic acid (TFA) to furnish 2 along with its reduced congener, meso-free subchlorins, [10] as by-products. To make the separation easier, the resultant mixture was oxidized with MnO 2 for the conversion of the meso-free subchlorins into 2. Subsequent separation over a simple silica gel column gave 2 in 4.4 % yield (method A; Supporting Information). The final oxidation step is beneficial for product separation but causes non-negligible oxidative damage to 2. On the basis of mechanistic consideration that the subchlorin was formed by the action of acid on subporphyrinogen intermediates, which was considered for the formation of chlorins in the Adler porphyrin synthesis, [11] we thus attempted acid-free, simple thermal reaction of 6 generated in situ from 5 with BH 3 ·NEt 3 and trimethyl orthoformate in 1,2-dichlorobenzene at various temperatures (method B; Scheme 1). Gratifyingly, the acid-free condensation reaction at 100 8C furnished 2 in 9.7% yield without contamination of subchlorin by-products. The 1 H NMR spectrum of 2 in CDCl 3 exhibits a singlet at 8.89 ppm owing to the free meso proton. As expected, the bromination of 2 proceeded with NBS in CHCl 3 at 0 8C to provide 3 quantitatively. The structures of 2 and 3-OCOCF 3 were revealed by a single-crystal X-ray diffraction analysis [*] M. Kitano, S. Hayashi, Dr. T. Tanaka, Prof.Dr. H. Yorimitsu, Dr. N. Aratani, Prof. Dr. A. Osuka Department of Chemistry, Graduate School of Science Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan) E-mail: osuka@kuchem.kyoto-u.ac.jp Dr. N. Aratani PRESTO, Japan Science and Technology Agency (Japan) [**] This work was supported by Grants-in-Aid (Nos. 22245006 (A) and 20108001 “pi-Space”) for Scientific Research from MEXT. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201201853. A ngewandte Chemi e 1 Angew. Chem. 2012, 124,1–6  2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! Ü Ü