Brønsted Acid-catalyzed Tandem Cycloaromatization of Naphthalene-based Bisacetals: Selective Synthesis of ortho-Fused Six-hexagon Benzenoids Ikko Takahashi, Masaki Hayashi, Takeshi Fujita, and Junji Ichikawa* Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571 (E-mail: junji@chem.tsukuba.ac.jp) Naphthalenes bearing two acetal moieties connected by a methylene-2,1-phenylene group underwent regioselective tandem cycloaromatization using a catalytic amount of trifluoromethane- sulfonic acid in 1,1,1,3,3-hexafluoropropan-2-ol to afford ortho- fused six-hexagon benzenoids with high selectivities and in excellent yields. REPRINTED FROM Vol.46 No.3  2017 p.392–394 CMLTAG March 5, 2017 The Chemical Society of Japan
Ikko Takahashi, Masaki Hayashi, Takeshi Fujita, and Junji Ichikawa* Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571 (E-mail: junji@chem.tsukuba.ac.jp) Naphthalenes bearing two acetal moieties connected by a methylene-2,1-phenylene group underwent regioselective tan- dem cycloaromatization using a catalytic amount of trifluoro- methanesulfonic acid in 1,1,3,3-hexafluoropropan-2-ol. Five substrates were successfully employed in this protocol to afford ortho-fused six-hexagon benzenoids with high selectivities and in excellent yields. Keywords:  Polycyclic aromatic hydrocarbon (PAH)  | Cycloaromatization | Fluorinated alcohol Polycyclic aromatic hydrocarbons (PAHs) have polyform structures comprising benzene rings, and are considered to be promising candidates for functional materials such as electronic devices and liquid crystals. 1 As the number of benzene rings in PAHs increases, the number of structural isomers exponen- tially increases. Although PAHs of substantial sizes have numerous isomers, research has typically focused on isomers of specific families such as acenes, 1b–1d,2 phenacenes, 1d,1c,3 and helicenes, 1f,4 and not on other ortho -fused isomers despite their great potential. 5 We recently developed a Brønsted acid-catalyzed cyclo- aromatization of carbonyl compounds, resulting in the synthesis of phenanthrene and anthracene derivatives. 6 As the method served as a powerful tool for benzene-ring construction, we embarked on the synthesis of PAHs in a variety of shapes via double cycloaromatization of substrates bearing two reactive sites. 7 This protocol would enable rapid access to higher-order PAHs by simultaneous construction of multiple fused benzene rings. We selected naphthalenes 1 and 2 bearing two phenylacet- aldehyde-related moieties as cyclization precursors (Scheme 1). Their tandem cycloaromatization afforded ortho-fused benze- noids, with the structure depending on the substitution pattern on the naphthalene ring. As a result, five predicted isomers of the ortho-fused benzenoids bearing six benzene rings were selectively synthesized in excellent yields from readily available cyclization precursors. The cyclization precursors 1a and 2a bearing two phenyl- acetaldehyde-related moieties on the 2- and 7-positions of the naphthalene ring were readily available starting from naph- Scheme 1.  Synthesis of ortho-fused six-hexagon benzenoids via TfOH-catalyzed tandem cycloaromatization. Scheme 2. Preparation of bis(vinyl ether) 1a and bisacetal 2a . thalene-2,7-diyl bis(trifluoromethanesulfonate) (4a) , which was obtained via double O -sulfonylation of naphthalene-2,7-diol (5a) (Scheme 2). Bis(vinyl ether) 1a was prepared via the Suzuki–Miyaura cross-coupling of 4a with (2-formylphenyl)- boronic acid, followed by a Wittig reaction with (methoxy- methyl)triphenylphosphonium chloride. However, although hy- drolysis of 1a afforded the corresponding dial, it was unstable for use in the subsequent cycloaromatization. In contrast, bisacetal 2a was directly prepared via the Suzuki–Miyaura cross-coupling of 4a with 2-[(1,3-dioxolan-2-yl)methyl]phenyl- boronic acid pinacolate. Other bisacetal precursors 2b–2e were also prepared similarly (see Supporting Information). We sought suitable conditions for tandem cycloaromatiza- tion of bis(vinyl ether) 1 a 7k,8 and bisacetal 2 a 9 as model substrates (Table 1). First, the reaction of 1a was investigated using a catalytic amount of trifluoromethansulfonic acid (TfOH) and 1,1,1,3,3-hexafluoropropan-2-ol (HFIP) as the solvent. 10 On treatment with 15 mol % of TfOH, bis(vinyl ether) 1a at 0.05 M in HFIP underwent tandem cycloaromatization to afford dibenzo[ c,m ]tetraphene (3a) 11 and naphtho[1,2-c ]chrysene (3a') in 79% total yield and in a 75:25 ratio (Entry 1). 12 Neither more concentrated nor more dilute conditions improved the total yield of 3a and 3a' (Entries 2 and 3). In contrast, when bisacetal 2a at 0.1 or 0.3 M in HFIP was treated with 15 mol % of TfOH, the product yield and ratio significantly improved to afford 3a exclusively in almost quantitative yields (Entries 4 and 5). As a result, the efficiency and selectivity remained excellent even when the amount of TfOH was reduced to 10mol % (Entry 7). The selective formation of 3a is attributed to the following factors: (i) the first cycloaromatization would proceed at the α- position of the naphthalene core in accordance with the regio- selectivity observed in normal electrophilic aromatic substitution Table 1. Screening of conditions for tandem cycloaromatiza- tion of 1a and 2a
²Yield was determined by 1HNMR spectroscopy using CH 2 Br 2 as an internal standard. Isolated yield was shown in parentheses. bIsomer ratio was determined by 1HNMR spectroscopy. cEE/EZ/ZZ = 37:55:8. reactions and (ii) the second cycloaromatization might proceed avoiding steric hindrance, which explains the better selectivity of bisacetal 2a. Not only bisacetal 2a but also bisacetals 2b–2e participated in the tandem cycloaromatization under the above-mentioned optimal conditions (Table 2). Naphthalenes 2b and 2c , bearing two phenylacetaldehyde acetal moieties on the 1,4- and 1,5- positions, respectively, successfully underwent tandem cyclo- aromatization to afford benzo[s]picene (3b) 13 and dibenzo[ c,l ]- chrysene (3c) 14 as the only products in 84% and 99% yields, respectively (Entries 2 and 3). Although the reactions of 2b and 2c required cycloaromatization on the less-reactive β-positions of the naphthalene core in the first cyclization, benzenoids 3b and 3c were obtained in high to excellent yields. Tandem cycloaromatization of 1,6- and 1,7-disubstituted naphthalenes 2d and 2e also proceeded to afford benzo[ a ]picene (3d) 11 and naphtho[2,1-c]chrysene (3e), 15 respectively, as major products (Entries 4 and 5). In each case, one of two possible products was selectively formed, presumably because regioselective cyclo- aromatization proceeded preferably on the α-position of the naphthalene core. In summary, we achieved systematic synthesis of a series of rarely offered ortho -fused six-hexagon benzenoids via TfOH- catalyzed tandem cycloaromatization of naphthalene-based bisacetals. The use of benzenoids larger than naphthalene as platforms will enable the synthesis of more extensive ortho- fused benzenoids. This work was financially supported by JSPS KAKENHI Grant Number JP16H04105 and JSPS KAKENHI Grant Number JP16H01002 in Precisely Designed Catalysts with Customized Scaffolding (J.I.). We acknowledge generous gifts of (CF 3 ) 2 CHOH (HFIP) and TfOH from Central Glass Co., Ltd. Supporting Information is available on http://dx.doi.org/ 10.1246/cl.161122.
References and Notes
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