Synthesis of Substituted 1,6-Diarylnaphthalenes via a Tandem

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Synthesis of Substituted 1,6-Diarylnaphthalenes via a Tandem Claisen Rearrangement and Ene Reaction Protocol Chieh-Kai Chan, Yu-Hsin Chen, Yu-Lin Tsai, and Meng-Yang Chang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00108 • Publication Date (Web): 01 Mar 2017 Downloaded from http://pubs.acs.org on March 3, 2017

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The Journal of Organic Chemistry

Synthesis of Substituted 1,6-Diarylnaphthalenes via a Tandem Claisen Rearrangement and Ene Reaction Protocol Chieh-Kai Chan, Yu-Hsin Chen, Yu-Lin Tsai and Meng-Yang Chang* Department of Medicinal and Applied Chemistry, General Research Centers of R&D office, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

ABSTRACT: In this article, we developed a concise synthetic route for the synthesis of polysubstituted naphthalenes starting from commercially available isovanillin and its derivatives. Reaction with styryl bromide via O-styrylation, Claisen rearrangement, ene reaction, and O-alkylation occurred in high yields. The key structures were confirmed by single-crystal X-ray diffraction.

Tandem reactions provide a concise route to prepare architecturally complex polycyclic molecules in very few steps. Domino reactions involve two consecutive reactions operating in the same reaction vessel. Nevertheless, reactions occurring in one-pot and via a cascade procedure are regarded as powerful tools for the formation of multiple carbon-carbon bonds. Therefore, the development of new synthetic routes involving tandem and one-pot protocols is of significant interest.1 However, study of the Claisen rearrangement reaction over a hundred years ago resulted in a potentially useful synthetic tool for chemists.2 Over the years, this effective reaction has attracted considerable attention from many research groups and has been utilized for the synthesis of numerous complex products.3 The Claisen rearrangement is cataloged as a new [3,3] reorganization of allyl aryl or vinyl ethers by the synthetic community. Other Claisen-type [3,3] rearrangements have been explored and have shown great application in synthetic methods.4-10 Among them, applications of the domino Claisen/ene strategy in synthesis has also been well developed.11 Polysubstituted naphthalenes are regarded as a crucial structural motif with widespread applications in biological, chemical, and physical purposes.12 Among them, arylnaphthalenes and related compounds play important roles in electronic materials, nanotechnology, bioactivity, and polymer fields.13 Consequently, many synthetic strategies for the preparation of the prominent naphthalene skeleton have been developed.14 Even if the different reported methodologies are well developed to date, the use of no extra additive agents and metal-free conditions for the synthesis of substituted naphthalenes is of great interest.

Previously, Youn’s group described that a cyclization reaction for the multi-step synthesis of polysubstituted naphthalenes in the presence of gold catalysts.14i de Koning and coworkers developed the tBuOK-assisted condensation reaction under irradiation condition system for the synthesis functionalized naphthalenes14j and phenanthrenes.14k Compared with these closely synthetic works for the formation of naphthalene skeleton by the use of transition-metal catalyst or base/irradiation, we provided a one-pot and metal free synthetic protocol within short reaction time (1 h) under refluxing decalin condition (Scheme 1). Scheme 1. Synthesis of naphthalene derivatives.

As part of our ongoing interest in the synthetic application of commercially available isovanillin 1a, reaction of 1a with allyl bromide 2a was studied to prepare versatile substituted 2-allylbenzaldehyde in a three-step procedure, including O-allylation, Claisen rearrangement and O-methylation.15 Accordingly, changing 2a to styryl bromides 2b-c for the Ostyrylation of 1a gave 3b-c in high yields. Intriguingly, when 3b-c were reacted under the same conditions, the expected 2styrylbenzaldehyde was not observed, but instead naphtha-

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lenes 4a-b were obtained in high yields. The structure of 3c was confirmed by single-crystal X-ray crystallography.16 In a comparison of reported literature, it was revealed that the synthesis of substituted naphthalenes from isovanillin derivatives via the Claisen-ene reaction has not been developed. To the best of our knowledge, we primary innovation appears to be the discovery that ary-substitution of allyl moiety accelerates ene-type cyclo-condensation under milder condition by a onepot synthetic route. Herein, a tandem Claisen rearrangement and ene reaction protocol in a for the one-pot synthesis of substituted 1,6-diarylnaphthalenes starting from isovanillin 1a and styryl bromide 2b-c is reported (Scheme 2). Scheme 2. Synthesis of isovanillin (1a) with bromides (2)

a

Conditions: 5 (1.0 mmol), RB(OH)2 (1.1 mmol), Pd(OAc)2 (5.6 mg, 2.5 mol%), PPh3 (13 mg, 5.0 mol%), Na2CO3 (159 mg, 1.5 mmol), DME/EtOH (9/1, 10 mL), reflux, 18 h. bIsolated yields. As shown in Scheme 3, the O-styrylation of 1 with 2 proceeded well in a K2CO3/MeCN system for the synthesis of Ostyrylbenzaldehydes 3d-x, which were isolated in 84% to 95% yields. Notably, according to the reported literature, 2b-c were prepared from commercially available substituted αmethylstyrene with NBS (1.05 equiv.) catalyzed by p-TsOH (0.1 equiv.) in DCM (10 mL) with a modest yield.19 The structure of 3v was also determined by single-crystal X-ray crystallography.16 Scheme 3. Synthesis of 3

During our studies concerning the aryl group substituent on the starting material, the preparation of 2-bromo-5-hydroxy-4methoxybenzaldehyde 5 starting from veratraldehyde in threesteps including (i) NBS-mediated bromination, (ii) H2SO4promoted selective demethylation, and (iii) Suzuki-Miyaura coupling, proceeded well with an overall 90% yield.17 Based on the Suzuki-Miyaura cross coupling reaction rule,18 a series of aryl substituted isovanillin synthons 1b-s were obtained. The reactions of 5 with various aryl boronic acids gave the desired 1b-s in high yields. The corresponding yields are shown in Table 1, and the structure of 1k was unambiguously confirmed using single-crystal X-ray crystallography.16

Table 2. Synthesis of 3 and 4a,b

Table 1. Scope of aryl substituted isovanillinsa,b

entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

RB(OH)2, R = Ph 2-MeC6H4 3-MeC6H4 4-MeC6H4 2-OMeC6H4 3-OMeC6H4 4-OMeC6H4 2-FC6H4 3-FC6H4 4-FC6H4 4-CF3C6H4 3,4-(OMe)2C6H3 3,4,5-(OMe)3C6H2 4-PhC6H4 3-PhC6H4 1-naphthyl 2-naphthyl 2-thienyl

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Yield (%) 1b, 93 1c, 88 1d, 86 1e, 87 1f, 90 1g, 94 1h, 88 1i, 95 1j, 91 1k, 94 1l, 91 1m, 94 1n, 90 1o, 95 1p, 92 1q, 87 1r, 95 1s, 75


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The Journal of Organic Chemistry rangement. Based on the results, a mechanism for the tandem Claisen/ene reaction was proposed, as shown in Scheme 4. A rearrangement of 3a-b occurred to form intermediate I. Based on the keto-enol tautomer rule, intermediate II was converted to III.3 Through a single bond rotation, dehydrogenative cyclization occurred to give III with the migration of HA in III. Finally, HB dehydrative aromatization occurred to give 1naphthols 6a (Ar = Ph) and 6b (Ar = 4-PhC6H4), and both were isolated in a yield of 95%. Scheme 4. Possible mechanism

a

For the Claisen/ene/O-alkylation reactions: (i) 3 (1.0 mmol), decalin (5 mL), 200℃, 1 h. (ii) K2CO3 (207 mg, 1.5 mmol), R2X (1.2 mmol), acetone (10 mL), reflux, 6 h. bIsolated yields. Based on our previous experience with the one-pot consecutive Claisen rearrangement and O-alkylation for the synthesis of 2-allylbenzaldehyde,15 we believe that a concise mechanism including a Claisen rearrangement, ene reaction and aromatization reaction occurred when allyl bromide 2a was converted to styryl bromide 2b or 2c (Scheme 2). Therefore, the substrate scope of O-styrylated 3d-x was examined using the tandem reaction conditions. As shown in Table 2, phenyl substituted 4d was reacted under the optimized conditions, resulting in an 88% yield. Substrates with electrondonating substituents such as methyl and methoxy groups at the ortho-, meta- or para- position gave the corresponding products 4e-j in modest to good yields. No obvious yield changes were observed when the substituents were changed to electron-withdrawing groups such as fluoro or trifluoro groups for the synthesis of 4k-n. Nevertheless, the strong electrondonating substituents, veratrole and 1,2,3-trimethoxybenzene, were also appropriate for the transformation of polyoxygenated 1,6-phenylnaphthalenes 4o-p. In addition to those with substituted phenyl groups, the meta- and para- phenyl substituted compounds also reacted well under these conditions to afford the desired 1,6-phenylnaphthalenes 4q-r. The fully aromatic substrates reacted smoothly with 1- and 2-naphthyl to form the corresponding products 4s-t. In particular, the heterocycle substituted 4u was also prepared in this transformation. The reaction was extended to O-4-phenylstyrylated 3v-x (Ar = 4-PhC6H4) to give the desired 4v-x. Further Oalkylation of the R2 group was also screened using various substituents, including i-propyl, n-butyl, cyclopentyl, and benzyl groups, and the desired 4y-ab were successfully prepared in high yields. The structures of 4h, 4m, 4v, 4w and 4aa were also determined by single-crystal X-ray crystallography.16 To further investigate the Claisen-ene reaction, 3a and 3b were selected as model substrates to conduct the tandem rear-

In summary, a convenient protocol for the synthesis of functionalized 1,6-diarylnaphthalenes in good to excellent yields was described. This concise strategy provides an efficient, non-metal, irradiation free and well-operated method. Various aryl substituted isovanillins were also prepared and reported as a sustainable development in the synthetic field. The structures of some products were confirmed by X-ray single-crystal diffraction analysis. EXPERIMENT SECTION General All reagents and solvents were obtained from commercial sources and used without further purification. Reactions were routinely carried out under an atmosphere of dry nitrogen with magnetic stirring. Products in organic solvents were dried with anhydrous magnesium sulfate before concentration in vacuo. Purity was determined by NMR and melting point. Melting points were determined with a SMP3 melting apparatus. 1H and 13C NMR spectra were recorded on a Varian spectrometer operating at 400 and at 100 MHz, respectively. Chemical shifts (δ) are reported in parts per million (ppm) and the coupling constants (J) are given in Hertz. High resolution mass spectra (HRMS) were measured with a mass spectrometer microTOF-Q by ESI using a hybrid ion-trap. X-ray crystal structures were obtained with a diffractometer (CAD4, Kappa CCD). General synthetic route for the synthesis of 1b-1s. Pd(OAc)2 (5.6 mg, 2.5 mol%) and PPh3 (13 mg, 5.0 mol%) were added to a solution of 2-bromo-5-hydroxy-4-methoxybenzaldehyde 5 (1.0 mmol) in DME/EtOH (9/1, 10 mL) at reflux. Then, Na2CO3 (159 mg, 1.5 mmol) and arylboronic acid (1.1 mmol) were added to the solution directly. The reaction mixture was stirred at reflux for 18 h, cooled to rt, and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1~6/1) afforded compounds 1b-1s. 4-hydroxy-5-methoxy-[1,1'-biphenyl]-2-carbaldehyde (1b). Yield



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= 93% (212 mg); Colorless solid; mp = 94-95 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C14H12O3Na 251.0679, found 251.0681; 1H NMR (400 MHz, CDCl3): δ 9.77 (s, 1H), 7.59 (s, 1H), 7.41-7.31 (m, 5H), 6.84 (br s, 1H), 6.83 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.3, 151.3, 145.3, 140.5, 137.4, 129.9 (2x), 128.0 (2x), 127.6, 127.0, 112.5, 112.1, 55.9. 4-hydroxy-5-methoxy-2'-methyl-[1,1'-biphenyl]-2-carbaldehyde (1c). Yield = 88% (213 mg); Colorless solid; mp = 118-119 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C15H14O3Na 265.0835, found 265.0837; 1H NMR (400 MHz, CDCl3): δ 9.79 (s, 1H), 7.59 (s, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.21 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 6.84 (s, 1H), 6.23 (br s ,1H), 3.94 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.4, 151.2, 145.3, 140.7, 137.8, 137.4, 130.6, 128.4, 128.0, 127.2, 127.1, 112.5, 112.1, 56.0, 21.1. 4-hydroxy-5-methoxy-3'-methyl-[1,1'-biphenyl]-2-carbaldehyde (1d). Yield = 86% (208 mg); Colorless solid; mp = 112-113 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C15H14O3Na 265.0835, found 265.0834; 1H NMR (400 MHz, CDCl3): δ 9.80 (s, 1H), 7.58 (s, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.17-7.14 (m, 2H), 6.84 (s, 1H), 6.00 (br s, 1H), 3.97 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.4, 151.1, 145.3, 140.8, 138.0, 137.6, 130.8, 128.6, 128.1, 127.5, 127.3, 112.5, 112.1, 56.1, 21.3. 4-hydroxy-5-methoxy-4'-methyl-[1,1'-biphenyl]-2-carbaldehyde (1e). Yield = 87% (211 mg); Colorless solid; mp = 98-99 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C15H14O3Na 265.0835, found 265.0835; 1H NMR (400 MHz, CDCl3): δ 9.79 (s, 1H), 7.58 (s, 1H), 7.23 (br s ,4H), 6.82 (s, 1H), 6.21 (br s, 1H), 3.93 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.5, 151.3, 145.2, 140.6, 137.5, 134.5, 129.8 (2x), 128.8 (2x), 127.1, 112.5, 112.1, 55.9, 20.9. 4-hydroxy-2',5-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde (1f). Yield = 90% (232 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C15H14O4Na 281.0784, found 281.0784; 1H NMR (400 MHz, CDCl3): δ 9.63 (s, 1H), 7.57 (s, 1H), 7.44-7.37 (m, 1H), 7.25 (dd, J = 2.0, 7.6 Hz, 1H), 7.07-7.03 (m, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 6.50 (br s, 1H), 3.90 (s, 3H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl ): δ 191.6, 156.5, 151.3, 145.2, 136.1, 3 131.4, 129.6, 127.5, 126.4, 120.6, 112.7, 112.0, 110.6, 55.9, 55.2. 4-hydroxy-3',5-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde (1g). Yield = 94% (243 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C15H14O4Na 281.0784, found 281.0787; 1H NMR (400 MHz, CDCl3): δ 9.82 (s, 1H), 7.57 (s, 1H), 7.35 (t, J = 8.0 Hz, 1H), 6.97-6.89 (m, 3H), 6.85 (s, 1H), 5.90 (br s, 1H), 3.98 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.2, 159.4, 150.9, 145.4, 140.4, 139.1, 129.3, 127.7, 122.8, 115.9, 113.3, 112.5, 112.0, 56.2, 55.3. 4-hydroxy-4',5-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde (1h). Yield = 88% (227 mg); Colorless solid; mp = 161-162 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C15H14O4Na 281.0784, found 281.0786; 1H NMR (400 MHz, CDCl3): δ 9.77 (s, 1H), 7.54 (s, 1H), 7.24 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.80 (s, 1H), 3.92 (s, 3H), 6.60 (br s, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.4, 159.3, 151.3, 145.1, 140.3, 131.1 (2x), 129.8, 127.2, 113.6 (2x), 112.5, 112.1, 56.0, 55.2. 2'-fluoro-4-hydroxy-5-methoxy-[1,1'-biphenyl]-2-carbaldehyde

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(1i). Yield = 95% (234 mg); Colorless solid; mp = 120-121 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C14H11FO3Na 269.0584, found 269.0586; 1H NMR (400 MHz, CDCl3): δ 9.65 (s, 1H), 7.54 (s, 1H), 7.36-7.23 (m, 2H), 7.18-7.14 (m, 1H), 7.10-7.05 (m, 1H), 6.77 (s, 1H), 6.00 (br s, 1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.7, 159.5 (d, J = 244.1 Hz), 151.4, 145.8, 133.1, 132.04, 132.02, 130.0 (d, J = 8.4 Hz), 127.5, 125.1 (d, J = 15.9 Hz), 124.1 (d, J = 3.8 Hz), 115.5 (d, J = 22.0 Hz), 112.7, 56.0. 3'-fluoro-4-hydroxy-5-methoxy-[1,1'-biphenyl]-2-carbaldehyde (1j). Yield = 91% (224 mg); Colorless solid; mp = 104-105 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C14H11FO3Na 269.0584, found 269.0586; 1H NMR (400 MHz, CDCl3): δ 9.77 (s, 1H), 7.55 (s, 1H), 7.41-7.36 (m, 1H), 7.12-7.05 (m, 3H), 6.82 (s, 1H), 6.01 (br s, 1H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.8, 162.3 (d, J = 246.4 Hz), 151.2, 145.7, 139.8 (d, J = 7.6 Hz), 139.0 (d, J = 2.3 Hz), 129.7 (d, J = 8.4 Hz), 127.3, 126.0 (d, J = 3.0 Hz), 116.9 (d, J = 22.0 Hz), 114.7 (d, J = 21.2 Hz), 112.8, 112.0, 56.1. 4'-fluoro-4-hydroxy-5-methoxy-[1,1'-biphenyl]-2-carbaldehyde (1k). Yield = 94% (231 mg); Colorless solid; mp = 129-130 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C14H11FO3Na 269.0584, found 269.0587; 1H NMR (400 MHz, CDCl3): δ 9.70 (s, 1H), 7.50 (s, 1H), 7.30-7.27 (m, 2H), 7.09-7.04 (m, 2H), 6.79 (s, 1H), 6.73 (br s, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 162.3 (d, J = 246.4 Hz), 151.4, 145.4, 139.3, 133.5 (d, J = 3.7 Hz), 131.5 (d, J = 8.4 Hz, 2x), 127.1, 115.0 (d, J = 21.3 Hz, 2x), 112.6, 112.2, 56.0. Singlecrystal X-ray diagram: crystal of 1k was grown by slow diffusion of EtOAc into a solution of 1k in CH2Cl2 to yield colorless prisms. The compound crystallizes in the Orthorhombic crystal system, space group P b c a, a = 5.5903(2) Å , b = 11.7704(4) Å , c = 34.3826(13) Å , V = 2262.38(14) Å 3, Z = 8, dcalcd = 1.446 g/cm3, F(000) = 1024, 2 range 1.18-26.39o, R indices (all data) R1 = 0.0409, wR2 = 0.1019. 4-hydroxy-5-methoxy-4'-(trifluoromethyl)-[1,1'-biphenyl]-2carbaldehyde (1l). Yield = 91% (270 mg); Colorless solid; mp = 119-120 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C15H11F3O3Na 319.0553, found 319.0550; 1H NMR (400 MHz, CDCl ): δ 9.73 (s, 1H), 7.68 (d, J = 8.0 Hz, 3 2H), 7.55 (s, 1H), 7.48 (d, J = 8.0 Hz, 2H), 6.84 (s, 1H), 6.45 (br s, 1H), 3.97 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.6, 151.4, 145.9, 141.4, 138.7, 130.4, 129.6 (q, J = 32.6 Hz), 127.3 (2x), 125.1 (q, J = 3.8 Hz, 2x), 124.0 (d, J = 270.6 Hz), 113.1, 112.1, 56.1. 4-hydroxy-3',4',5-trimethoxy-[1,1'-biphenyl]-2-carbaldehyde (1m). Yield = 94% (271 mg); Colorless solid; mp = 185-186 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C16H16O5Na 311.0890, found 311.0891; 1H NMR (400 MHz, CDCl3): δ 9.80 (s, 1H), 7.53 (s, 1H), 6.93-6.87 (m, 2H), 6.86 (s, 1H), 6.82 (s, 1H), 6.03 (br s, 1H), 3.96 (s, 3H), 3.91 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.3, 151.0, 148.9, 148.6, 145.2, 140.4, 130.3, 127.6, 122.7, 113.3, 112.5, 112.0, 110.9, 56.1, 56.0, 55.9. 4-hydroxy-3',4',5,5'-tetramethoxy-[1,1'-biphenyl]-2-carbaldehyde (1n). Yield = 90% (286 mg); Colorless solid; mp = 201-202 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C17H18O6Na 341.0996, found 341.0994; 1H NMR (400 MHz, CDCl3): δ 9.82 (s, 1H), 7.54 (s, 1H), 6.84 (s, 1H), 6.54 (s, 2H), 5.91 (br s, 1H), 3.99 (s, 3H), 3.90 (s, 3H), 3.87 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 191.1, 152.9 (2x), 150.8, 145.4, 140.5, 137.9, 133.4, 127.8, 112.4, 111.9, 107.6 (2x), 60.9, 56.25 (2x),


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56.21.

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4-hydroxy-5-methoxy-[1,1':4',1''-terphenyl]-2-carbaldehyde (1o). Yield = 95% (289 mg); Colorless solid; mp = 176-177 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C20H16O3Na 327.0992, found 327.0989; 1H NMR (400 MHz, CDCl3): δ 9.90 (s, 1H), 7.70-7.64 (m, 4H), 7.63 (s, 1H), 7.50-7.37 (m, 5H), 6.90 (s, 1H), 6.08 (br s, 1H), 4.00 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.2, 151.1, 145.5, 140.8, 140.2, 140.1, 136.6, 130.6 (2x), 128.8 (2x), 127.63, 127.57, 127.0 (2x), 126.9 (2x), 112.7, 112.1, 56.2. 4-hydroxy-5-methoxy-[1,1':3',1''-terphenyl]-2-carbaldehyde (1p). Yield = 92% (280 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C20H16O3Na 327.0992, found 327.0992; 1H NMR (400 MHz, CDCl3): δ 9.90 (s, 1H), 7.68-7.59 (m, 4H), 7.63 (s, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.49-7.44 (m, 2H), 7.40-7.34 (m, 2H), 6.91 (s, 1H), 6.01 (br s, 1H), 3.99 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.1, 151.0, 145.5, 141.4, 140.4, 138.2, 129.0, 128.9 (2x), 128.8 (2x), 128.7, 127.7, 127.6, 127.2 (2x), 126.6, 112.7, 112.1, 56.2. 5-hydroxy-4-methoxy-2-(naphthalen-1-yl)benzaldehyde (1q). Yield = 87% (242 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C18H14O3Na 301.0835, found 301.0836; 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.77 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.56-7.40 (m, 4H), 6.90 (s, 1H), 6.89 (br s, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.1, 151.4, 145.6, 138.5, 135.1, 133.1, 132.8, 128.4, 128.3, 128.1 (2x), 126.5, 125.9, 125.6, 124.7, 113.0, 112.2, 55.9. 5-hydroxy-4-methoxy-2-(naphthalen-2-yl)benzaldehyde (1r). Yield = 95% (264 mg); Colorless solid; mp = 150-151 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C18H14O3Na 301.0835, found 301.0838; 1H NMR (400 MHz, CDCl3): δ 9.87 (s, 1H), 7.93-7.86 (m, 3H), 7.81 (s, 1H), 7.65 (s, 1H), 7.56-7.50 (m, 3H), 6.94 (s, 1H), 6.11 (br s, 1H), 3.99 (s, 3H); 13C NMR (100 MHz, CDCl ): δ 191.2, 151.0, 145.5, 140.4, 135.1, 3 132.9, 132.6, 129.3, 128.0, 127.95, 127.89, 127.77, 127.68, 126.7, 126.5, 112.7, 112.3, 56.2. 5-hydroxy-4-methoxy-2-(thiophen-2-yl)benzaldehyde (1s). Yield = 75% (176 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C12H10O3SNa 257.0248, found 257.0245; 1H NMR (400 MHz, CDCl3): δ 9.92 (s, 1H), 7.49 (s, 1H), 7.34 (dd, J = 0.8, 5.2 Hz, 1H), 7.04-7.02 (m, 1H), 6.96-6.95 (m, 1H), 6.85 (s, 1H), 6.51 (br s, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 151.2, 145.8, 138.4, 132.4, 129.0, 127.9, 127.3, 126.7, 112.8, 112.7, 56.1. General synthetic route for the synthesis of 3b-3x. K2CO3 (207 mg, 1.5 mmol) and styryl bromides 2b-c (1.2 mmol) were added to a solution of 1 (1.0 mmol) in MeCN (10 mL) at rt. The reaction mixture was stirred at reflux for 12 h, cooled to rt, and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1~6/1) afforded compounds 3b-3x. 4-methoxy-3-((2-phenylallyl)oxy)benzaldehyde (3b). Yield = 94% (252 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C17H16O3Na 291.0992, found 291.0991; 1H NMR (400 MHz, CDCl3): δ 9.92 (s, 1H), 7.50-7.45 (m, 4H), 7.38-7.28 (m, 3H), 6.97 (d, J = 8.4 Hz, 1H), 5.61 (d, J = 0.8 Hz, 1H), 5.50 (d, J = 0.8 Hz, 1H), 5.00 (s, 2H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.7, 155.0, 148.4, 142.3, 138.1, 129.9, 128.4 (2x), 128.0, 126.8, 126.0 (2x), 114.8, 111.7, 110.8, 70.6, 56.0.

3-((2-([1,1'-biphenyl]-4-yl)allyl)oxy)-4-methoxybenzaldehyde (3c). Yield = 95% (327 mg); Colorless solid; mp = 104-105 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C23H20O3Na 367.1305, found 367.1303; 1H NMR (400 MHz, CDCl3): δ 9.85 (s, 1H), 7.63-7.57 (m, 6H), 7.53 (d, J = 2.0 Hz, 1H), 7.49-7.43 (m, 3H), 7.38-7.34 (m, 1H), 6.97 (d, J = 8.4 Hz, 1H), 5.71 (d, J = 0.8 Hz, 1H), 5.56 (d, J = 0.8 Hz, 1H), 5.05 (s, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.6, 155.0, 148.4, 141.7, 140.6, 140.3, 136.8, 129.8, 128.6 (2x), 127.2, 126.9 (2x), 126.8 (2x), 126.3 (3x), 114.9, 111.7, 110.7, 70.5, 55.9. Single-crystal X-ray diagram: crystal of 3c was grown by slow diffusion of EtOAc into a solution of 3c in CH2Cl2 to yield colorless prisms. The compound crystallizes in the Monoclinic crystal system, space group P 21/c, a = 5.7601(3) Å , b = 29.9866(16) Å , c = 10.0387(5) Å , V = 1731.79(16) Å 3, Z = 4, dcalcd = 1.321 g/cm3, F(000) = 728, 2 range 1.36-26.39o, R indices (all data) R1 = 0.0569, wR2 = 0.1041. 5-methoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2-carbaldehyde (3d). Yield = 92% (317 mg); Colorless solid; mp = 82-83 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C23H20O3Na 367.1305, found 367.1304; 1H NMR (400 MHz, CDCl3): δ 9.83 (s, 1H), 7.64 (s, 1H), 7.54-7.52 (m, 2H), 7.49-7.32 (m, 8H), 6.88 (s, 1H), 5.65 (d, J = 0.8 Hz, 1H), 5.56 (d, J = 0.8 Hz, 1H), 5.06 (s, 2H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.9, 153.9, 147.7, 142.4, 141.6, 138.2, 137.5, 130.1 (2x), 128.4 (2x), 128.2 (2x), 127.93, 127.90, 126.8, 126.0 (2x), 114.9, 113.0, 110.9, 70.6, 56.1. 5-methoxy-2'-methyl-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3e). Yield = 91% (326 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H22O3Na 381.1461, found 381.1459; 1H NMR (400 MHz, CDCl ): δ 9.82 (s, 1H), 7.62 (s, 1H), 7.513 7.48 (m, 2H), 7.36-7.28 (m, 4H), 7.28-7.15 (m, 3H), 6.84 (s, 1H), 5.62 (d, J = 0.8 Hz, 1H), 5.53 (d, J = 0.8 Hz, 1H), 5.02 (s, 2H), 3.88 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.8, 153.8, 147.5, 142.3, 141.7, 138.1, 137.8, 137.3, 130.7, 128.5, 128.3 (2x), 128.0, 127.8, 127.2, 126.6, 125.9 (2x), 114.8, 112.8, 110.7, 70.4, 55.9, 21.2. 5-methoxy-3'-methyl-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3f). Yield = 87% (312 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H22O3Na 381.1461, found 381.1460; 1H NMR (400 MHz, CDCl ): δ 9.85 (s, 1H), 7.64 (s, 1H), 7.543 7.52 (m, 2H), 7.40-7.32 (m, 4H), 7.24-7.19 (m, 3H), 6.88 (s, 1H), 5.65 (d, J = 0.4 Hz, 1H), 5.56 (d, J = 0.4 Hz, 1H), 5.06 (s, 2H), 3.93 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 153.9, 147.6, 142.4, 141.8, 138.2, 137.9, 137.4, 130.8, 128.6, 128.4 (2x), 128.1, 127.9, 127.2, 126.7, 126.0 (2x), 114.9, 112.9, 110.8, 70.6, 56.0, 21.3. 5-methoxy-4'-methyl-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3g). Yield = 92% (330 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H22O3Na 381.1461, found 381.1459; 1H NMR (400 MHz, CDCl ): δ 9.87 (s, 1H), 7.65 (s, 1H), 7.563 7.53 (m, 2H), 7.41-7.28 (m, 7H), 6.88 (s, 1H), 5.66 (d, J = 0.8 Hz, 1H), 5.58 (d, J = 0.8 Hz, 1H), 5.07 (s, 2H), 3.94 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 153.9, 147.6, 142.4, 141.7, 138.2, 137.8, 134.6, 130.0 (2x), 128.9 (2x), 128.4 (2x), 127.9, 126.8, 126.0 (2x), 114.9, 112.9, 110.9, 70.6, 56.0, 21.0. 2',5-dimethoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3h). Yield = 89% (333 mg); Colorless solid; mp = 84-85 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C24H22O4Na 397.1410, found 397.1412; 1H NMR (400 MHz, CDCl3): δ 9.67 (s, 1H), 7.64 (s, 1H), 7.55-7.52 (m, 2H), 7.44-7.28 (m, 5H), 7.10-7.06 (m, 1H), 6.99 (d, J = 8.4



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Hz, 1H), 6.83 (s, 1H), 5.66 (d, J = 0.8 Hz, 1H), 5.57 (d, J = 0.8 Hz, 1H), 5.06 (s, 2H), 3.91 (s, 3H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.1, 156.6, 154.0, 147.6, 142.4, 138.2, 137.2, 131.5, 129.7, 128.3 (2x), 127.8, 127.0, 126.4, 126.0 (2x), 120.7, 114.9, 113.5, 110.6, 110.3, 70.5, 56.0, 55.3. 3',5-dimethoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3i). Yield = 91% (341 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H22O4Na 397.1410, found 397.1409; 1H NMR (400 MHz, CDCl ): δ 9.86 (s, 1H), 7.63 (s, 1H), 7.533 7.50 (m, 2H), 7.38-7.30 (m, 4H), 6.98-6.94 (m, 3H), 6.88 (s, 1H), 5.64 (d, J = 0.8 Hz, 1H), 5.55 (d, J = 0.8 Hz, 1H), 5.04 (s, 2H), 3.89 (s, 3H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.6, 159.2, 153.7, 147.6, 142.3, 141.3, 138.8, 138.0, 129.1, 128.2 (2x), 127.8, 126.6, 125.8 (2x), 122.5, 115.7, 114.8, 113.1, 112.7, 110.6, 70.4, 55.9, 55.0. 4',5-dimethoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3j). Yield = 92% (344 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H22O4Na 397.1410, found 397.1409; 1H NMR (400 MHz, CDCl ): δ 9.84 (s, 1H), 7.61 (s, 1H), 7.533 7.50 (m, 2H), 7.39-7.29 (m, 5H), 6.99 (d, J = 8.8 Hz, 2H), 6.85 (s, 1H), 5.64 (d, J = 0.8 Hz, 1H), 5.55 (d, J = 0.8 Hz, 1H), 5.04 (s, 2H), 3.91 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 159.5, 153.9, 147.4, 142.4, 141.4, 138.1, 131.2 (2x), 129.7, 128.3 (2x), 127.9, 126.7, 126.0 (2x), 114.8, 113.7 (2x), 112.9, 110.8, 70.5, 56.0, 55.2. 2'-fluoro-5-methoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3k). Yield = 90% (326 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C23H19FO3Na 385.1210, found 385.1209; 1H NMR (400 MHz, CDCl ): δ 9.76 (d, J = 2.8 Hz, 1H), 7.65 (s, 3 1H), 7.53-7.51 (m, 2H), 7.44-7.29 (m, 5H), 7.263-7.15 (m, 2H), 6.86 (s, 1H), 5.65 (d, J = 0.8 Hz, 1H), 5.56 (d, J = 0.8 Hz, 1H), 5.06 (s, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.1, 159.6 (d, J = 244.9 Hz), 154.0, 148.1, 142.3, 138.1, 134.2, 132.1 (d, J = 2.3 Hz), 130.1 (d, J = 8.3 Hz), 128.3 (2x), 127.9, 127.0, 126.0 (2x), 125.1 (d, J = 15.9 Hz), 124.1 (d, J = 3.8 Hz), 115.6 (d, J = 22.0 Hz), 115.0, 113.4, 110.8, 70.5, 56.0. 3'-fluoro-5-methoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3l). Yield = 90% (326 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C23H19FO3Na 385.1210, found 385.1208; 1H NMR (400 MHz, CDCl ): δ 9.82 (s, 1H), 7.63 (s, 1H), 7.523 7.50 (m, 2H), 7.43-7.30 (m, 4H), 7.16-7.10 (m, 3H), 6.84 (s, 1H), 5.64 (d, J = 0.8 Hz, 1H), 5.55 (d, J = 0.8 Hz, 1H), 5.04 (s, 2H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.2, 162.3 (d, J = 246.4 Hz), 153.9, 147.9, 142.3, 139.9 (d, J = 2.2 Hz), 139.6 (d, J = 7.6 Hz), 138.0, 129.6 (d, J = 8.4 Hz), 128.3 (2x), 127.9, 126.6, 126.0 (d, J = 3.0 Hz), 125.9 (2x), 116.8 (d, J = 2.0 Hz), 114.9, 114.7 (d, J = 21.2 Hz), 112.7, 110.9, 70.5, 56.0. 4'-fluoro-5-methoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3m). Yield = 88% (319 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C23H19FO3Na 385.1210, found 385.1208; 1H NMR (400 MHz, CDCl3): δ 9.79 (s, 1H), 7.61 (s, 1H), 7.52-7.50 (m, 2H), 7.39-7.32 (m, 5H), 7.18-7.13 (m, 2H), 6.82 (s, 1H), 5.64 (d, J = 1.2 Hz, 1H), 5.54 (d, J = 1.2 Hz, 1H), 5.05 (s, 2H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.7, 162.7 (d, J = 246.3 Hz), 154.0, 147.9, 142.4, 140.5, 138.2, 133.6 (d, J = 3.0 Hz), 131.7 (d, J = 7.6 Hz, 2x), 128.4 (2x), 128.0, 126.9, 126.1 (2x), 115.4, 115.1 (d, J = 19.0 Hz, 2x), 113.0, 111.1, 70.7, 56.2. 5-methoxy-4-((2-phenylallyl)oxy)-4'-(trifluoromethyl)-[1,1'biphenyl]-2-carbaldehyde (3n). Yield = 95% (392 mg); Colorless solid; mp = 111-112 oC (recrystallized from hexanes and EtOAc);

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HRMS (ESI, M++Na) calcd for C24H19F3O3Na 435.1179, found 435.1179; 1H NMR (400 MHz, CDCl3): δ 9.78 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.53-7.50 (m, 4H), 7.40-7.32 (m, 3H), 6.84 (s, 1H), 5.65 (d, J = 0.8 Hz, 1H), 5.54 (d, J = 0.8 Hz, 1H), 5.07 (s, 2H), 3.94 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.1, 154.1, 148.3, 142.4, 141.4, 139.8, 138.2, 130.7, 130.5 (2x), 130.2 (d, J = 31.5 Hz, 2x), 128.5 (2x), 128.1, 126.9, 125.3 (q, J = 3.8 Hz, 2x), 124.0 (d, J = 270.6 Hz), 115.1, 112.9, 111.2, 70.7, 56.2. 3',4',5-trimethoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3o). Yield = 85% (344 mg); Colorless solid; mp = 122-123 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H24O5Na 427.1516, found 427.1515; 1H NMR (400 MHz, CDCl ): δ 9.79 (s, 1H), 7.54 (s, 1H), 7.453 7.43 (m, 2H), 7.30-7.22 (m, 3H), 6.89-6.86 (m, 3H), 6.82 (s, 1H), 5.57 (d, J = 0.8 Hz, 1H), 5.48 (d, J = 0.8 Hz, 1H), 4.96 (s, 2H), 3.85 (s, 3H), 3.84 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 190.6, 153.6, 148.7, 148.4, 147.2, 142.2, 141.2, 137.8, 129.8, 128.1 (2x), 127.6, 126.5, 125.7 (2x), 122.5, 114.6, 113.1, 112.6, 110.7, 110.5, 70.2, 55.7, 55.63, 55.57. 3',4',5,5'-tetramethoxy-4-((2-phenylallyl)oxy)-[1,1'-biphenyl]-2carbaldehyde (3p). Yield = 89% (387 mg); Colorless solid; mp = 113-114 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C26H26O6Na 457.1622, found 457.1624; 1H NMR (400 MHz, CDCl ): δ 9.81 (s, 1H), 7.54 (s, 1H), 7.463 7.43 (m, 2H), 7.31-7.23 (m, 3H), 6.85 (s, 1H), 6.56 (s, 2H), 5.58 (d, J = 0.8 Hz, 1H), 5.48 (d, J = 0.8 Hz, 1H), 4.98 (s, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 3.83 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 190.5, 153.6, 152.7 (2x), 147.4, 142.2, 141.4, 137.8, 137.7, 132.9, 128.1 (2x), 127.7, 126.6, 125.7 (2x), 124.4, 114.7, 112.5, 110.5, 107.3, 70.3, 60.6, 55.93 (2x), 55.87. 5-methoxy-4-((2-phenylallyl)oxy)-[1,1':4',1''-terphenyl]-2carbaldehyde (3q). Yield = 86% (362 mg); Colorless solid; mp = 122-123 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C29H24O3Na 443.1618, found 443.1617; 1H NMR (400 MHz, CDCl ): δ 9.93 (s, 1H), 7.71 (d, J = 8.0 Hz, 3 2H), 7.69-7.66 (m, 3H), 7.56-7.47 (m, 6H), 7.43-7.34 (m, 4H), 6.94 (s, 1H), 5.67 (d, J = 0.4 Hz, 1H), 5.58 (d, J = 0.8 Hz, 1H), 5.09 (s, 2H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.9, 154.0, 147.8, 142.4, 141.2, 140.8, 140.2, 138.2, 136.4, 130.6 (2x), 130.5, 128.8 (2x), 128.4 (2x), 128.0, 127.6, 127.0 (2x), 126.9 (2x), 126.0 (2x), 115.0, 112.9, 111.0, 70.6, 56.1. 5-methoxy-4-((2-phenylallyl)oxy)-[1,1':3',1''-terphenyl]-2carbaldehyde (3r). Yield = 90% (378 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C29H24O3Na 443.1618, found 443.1619; 1H NMR (400 MHz, CDCl ): δ 9.92 (s, 1H), 7.71-7.62 (m, 5H), 3 7.57-7.46 (m, 5H), 7.41-7.34 (m, 5H), 6.94 (s, 1H), 5.66 (d, J = 0.8 Hz, 1H), 5.57 (d, J = 0.8 Hz, 1H), 5.08 (s, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl ): δ 190.9, 154.0, 147.8, 142.4, 141.6, 3 141.4, 140.4, 138.2, 138.1, 129.0, 128.87, 128.85 (4x), 128.4 (2x), 128.0, 127.6, 127.2 (2x), 126.7, 126.1 (2x), 115.0, 113.0, 111.0, 70.7, 56.2. 4-methoxy-2-(naphthalen-1-yl)-5-((2phenylallyl)oxy)benzaldehyde (3s). Yield = 84% (331 mg); Colorless solid; mp = 177-178 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C27H22O3Na 417.1461, found 417.1459; 1H NMR (400 MHz, CDCl3): δ 9.50 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.73 (s, 1H), 7.60-7.33 (m, 10H), 6.91 (s, 1H), 5.69 (d, J = 0.8 Hz, 1H), 5.61 (d, J = 0.8 Hz, 1H), 5.12 (s, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.8, 154.1, 148.0, 142.5, 139.8, 138.2, 135.2, 133.4, 132.9, 128.5, 128.4 (2x), 128.3, 128.2, 128.03, 127.99, 126.7, 126.14, 126.11 (2x), 125.8, 124.9, 115.1, 113.8, 110.5, 70.7, 56.2.


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4-methoxy-2-(naphthalen-2-yl)-5-((2phenylallyl)oxy)benzaldehyde (3t). Yield = 86% (339 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C27H22O3Na 417.1461, found 417.1460; 1H NMR (400 MHz, CDCl3): δ 9.91 (s, 1H), 7.95-7.89 (m, 3H), 7.85 (s, 1H), 7.70 (s, 1H), 7.58-7.54 (m, 5H), 7.42-7.34 (m, 3H), 6.98 (s, 1H), 5.68 (d, J = 0.8 Hz, 1H), 5.59 (d, J = 0.8 Hz, 1H), 5.10 (s, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.9, 153.9, 147.7, 142.4, 141.5, 138.1, 134.9, 132.8, 132.6, 129.3, 128.41, 128.38 (2x), 127.95 (2x), 127.93, 127.8, 127.6, 126.9, 126.7, 126.5, 126.0, 114.9, 113.1, 110.9, 70.6, 56.1. 4-methoxy-5-((2-phenylallyl)oxy)-2-(thiophen-2-yl)benzaldehyde (3u). Yield = 88% (308 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C21H18O3SNa 373.0874, found 373.0871; 1H NMR (400 MHz, CDCl3): δ 10.04 (s, 1H), 7.61 (s, 1H), 7.52-7.49 (m, 2H), 7.43 (dd, J = 1.2, 9.2 Hz, 1H), 7.39-7.30 (m, 3H), 7.13-7.11 (m, 1H), 7.07-7.06 (m, 1H), 6.95 (s, 1H), 5.64 (d, J = 0.8 Hz, 1H), 5.54 (d, J = 0.8 Hz, 1H), 5.05 (s, 2H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.5, 153.8, 148.1, 142.2, 138.5, 138.1, 133.4, 129.2, 128.4 (2x), 128.0, 127.4, 126.9, 126.0 (2x), 115.0 (2x), 113.5, 110.9, 70.5, 56.1. 4-((2-([1,1'-biphenyl]-4-yl)allyl)oxy)-5-methoxy-[1,1'-biphenyl]2-carbaldehyde (3v). Yield = 91% (383 mg); Colorless solid; mp = 151-152 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C29H24O3Na 443.1618, found 443.1619; 1H NMR (400 MHz, CDCl ): δ 9.85 (s, 1H), 7.68 (s, 1H), 7.62 (br 3 s, 6H), 7.50-7.35 (m, 8H), 7.89 (s, 1H), 5.73 (d, J = 0.4 Hz, 1H), 5.59 (d, J = 0.4 Hz, 1H), 5.11 (s, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 154.0, 147.8, 142.0, 141.7, 140.8, 140.5, 137.6, 137.1, 130.1 (2x), 128.7 (2x), 128.3 (2x), 128.0, 127.3, 127.1 (2x), 126.9 (2x), 126.8, 126.5 (2x), 115.1, 113.0, 111.0, 70.7, 56.1. Single-crystal X-ray diagram: crystal of 3v was grown by slow diffusion of EtOAc into a solution of 3v in CH2Cl2 to yield colorless prisms. The compound crystallizes in the Monoclinic crystal system, space group C c, a = 17.9825(12) Å , b = 7.8621(5) Å , c = 31.386(2) Å , V = 4375.1(5) Å 3, Z = 4, dcalcd = 1.277 g/cm3, F(000) = 1776, 2 range 1.32-26.45o, R indices (all data) R1 = 0.0581, wR2 = 0.1038. 4-((2-([1,1'-biphenyl]-4-yl)allyl)oxy)-5-methoxy-4'-methyl-[1,1'biphenyl]-2-carbaldehyde (3w). Yield = 88% (382 mg); Colorless solid; mp = 139-140 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H26O3Na 457.1774, found 457.1776; 1H NMR (400 MHz, CDCl3): δ 9.87 (s, 1H), 7.68 (s, 1H), 7.63 (br s, 6H), 7.48-7.44 (m, 2H), 7.39-7.28 (m, 5H), 6.88 (s, 1H), 5.73 (s, 1H), 5.60 (s, 1H), 5.11 (s, 2H), 3.94 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.0, 154.0, 147.6, 142.0, 141.8, 140.7, 140.5, 137.8, 137.0, 134.6, 130.0 (2x), 129.0 (2x), 128.7 (2x), 127.3, 127.1 (2x), 126.9 (2x), 126.8, 126.4 (2x), 115.0, 113.0, 111.0, 70.7, 56.1, 21.1. 4-((2-([1,1'-biphenyl]-4-yl)allyl)oxy)-4'-fluoro-5-methoxy-[1,1'biphenyl]-2-carbaldehyde (3x). Yield = 89% (390 mg); Colorless solid; mp = 150-151 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C29H23FO3Na 461.1523, found 461.1525; 1H NMR (400 MHz, CDCl3): δ 9.81 (s, 1H), 7.65 (s, 1H), 7.61 (br s, 6H), 7.47-7.43 (m, 2H), 7.38-7.34 (m, 3H), 7.197.14 (m, 2H), 6.83 (s, 1H), 5.72 (s, 1H), 5.58 (s, 1H), 5.10 (s, 2H), 3.94 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.6, 162.7 (d, J = 246.3 Hz), 154.1, 147.9, 141.9, 140.8, 140.54, 140.52, 137.0, 133.6 (d, J = 3.0 Hz), 131.7 (d, J = 8.3 Hz, 2x), 128.7 (2x), 127.3, 127.1 (2x), 126.93 (2x), 126.91, 126.5 (2x), 115.3 (d, J = 21.3 Hz, 2x), 115.1, 113.0, 111.1, 70.7, 56.2. General synthetic route for the synthesis of 4b-4ab. Decalin (8 mL) was added to a solution of 3 (1.0 mmol) at rt. The reaction

mixture was stirred at 200oC for 1 h. The reaction mixture was cooled to rt. Decalin was evaporated to afford crude product under reduced pressure. Then, K2CO3 (207 mg, 1.5 mmol) and R2X (R2 = Me, i-Pr, n-butyl, cyclopentyl or benzyl, 1.2 mmol) were added to the solution of crude product in acetone (10 mL) at rt. The reaction mixture was stirred at reflux for 6 h. cooled to rt, and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1~6/1) afforded compounds 4b-4ab. 1,2-dimethoxy-7-phenylnaphthalene (4b). Yield = 92% (243 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C18H16O2Na 287.1043, found 287.1041; 1H NMR (400 MHz, CDCl3): δ 8.358.34 (m, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.79-7.76 (m, 2H), 7.65 (dd, J = 1.6, 8.4 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.53-7.49 (m, 2H), 7.42-7.38 (m, 1H), 7.31 (d, J = 8.8 Hz, 1H), 4.04 (s, 3H), 4.03 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.7, 143.2, 141.4, 138.8, 129.2, 128.82, 128.77 (2x), 128.2, 127.5 (2x), 127.3, 123.92, 123.86, 119.2, 115.2, 61.1, 56.9. 7-([1,1'-biphenyl]-4-yl)-1,2-dimethoxynaphthalene (4c). Yield = 94% (320 mg); Colorless solid; mp = 147-148 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C24H20O2Na 363.1356, found 363.1355; 1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 2.0, 1H), 7.89 (s, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.8 Hz, 2H), 7.70-7.68 (m, 3H), 7.64 (d, J = 8.8 Hz, 1H), 7.51-7.47 (m, 2H), 7.41-7.37 (m, 1H), 7.32 (d, J = 8.8 Hz, 1H), 4.06 (s, 3H), 4.03 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.7, 143.3, 140.7, 140.3, 140.2, 138.3, 129.3, 128.9, 128.8 (2x), 128.3, 127.8 (2x), 127.5 (2x), 127.3, 127.1 (2x), 123.9, 123.7, 119.1, 115.3, 61.2, 56.9. 1,2-dimethoxy-4,7-diphenylnaphthalene (4d). Yield = 88% (300 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C24H20O2Na 363.1356, found 363.1355; 1H NMR (400 MHz, CDCl3): δ 8.43 (dd, J = 0.4, 2.0 Hz, 1H), 7.89 (dd, J = 0.4, 8.8 Hz, 1H), 7.79-7.76 (m, 2H), 7.59 (dd, J = 2.0, 8.8 Hz, 2H), 7.55-7.53 (m, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.48-7.44 (m, 1H), 7.42-7.38 (m, 2H), 7.264 (s, 1H), 4.09 (s, 3H), 4.04 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.6, 141.3, 140.4, 138.7, 136.8, 130.1 (2x), 129.6, 128.8 (2x), 128.3 (2x), 127.5 (2x), 127.38, 127.36, 126.9, 126.7, 123.9, 119.4, 116.3, 61.2, 56.9. 1,2-dimethoxy-7-phenyl-4-(o-tolyl)naphthalene (4e). Yield = 89% (315 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C25H22O2Na 377.1512, found 377.1514; 1H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 1.6 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.797.77 (m, 2H), 7.59 (dd, J = 2.0, 8.8 Hz, 1H), 7.53-7.49 (m, 2H), 7.44-7.28 (m, 6H), 4.09 (s, 3H), 4.04 (s, 3H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.5, 141.3, 140.4, 138.7, 138.0, 136.9, 130.8, 129.6, 128.8 (2x), 128.2, 128.1, 127.5 (2x), 127.3, 127.2, 126.9, 126.8, 123.8, 119.4, 116.2, 61.2, 56.9, 21.5. 1,2-dimethoxy-7-phenyl-4-(m-tolyl)naphthalene (4f). Yield = 87% (308 mg); Colorless solid; mp = > 250 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H22O2Na 377.1512, found 377.1514; 1H NMR (400 MHz, CDCl3): δ 8.41 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.79-7.76 (m, 2H), 7.59 (dd, J = 1.6, 8.8 Hz, 1H), 7.52-7.48 (m, 2H), 7.43-7.27 (m, 5H), 7.25 (s, 1H), 4.08 (s, 3H), 4.04 (s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.5, 141.3, 140.4, 138.7, 138.0, 136.9, 130.8, 129.6, 128.8 (2x), 128.2, 128.1, 127.5 (2x), 127.4, 127.2, 126.9, 126.8, 123.8, 119.4, 116.2, 61.2, 56.9, 21.5. 1,2-dimethoxy-7-phenyl-4-(p-tolyl)naphthalene (4g). Yield = 83%



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(294 mg); Colorless solid; mp = 88-89 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H22O2Na 377.1512, found 377.1514; 1H NMR (400 MHz, CDCl3): δ 8.39 (d, J = 2.0 Hz, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.77-7.75 (m, 2H), 7.57 (dd, J = 2.0, 9.2 Hz, 2H), 7.51-7.47 (m, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.41-7.37 (m, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 4.07 (s, 3H), 4.02 (s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.5, 141.3, 138.7, 137.5, 137.1, 136.8, 129.9 (2x), 129.6, 129.0 (2x), 128.8 (2x), 127.5 (2x), 127.4, 127.0, 126.8, 123.8, 119.4, 116.3, 61.2, 56.9, 21.2. 1,2-dimethoxy-4-(2-methoxyphenyl)-7-phenylnaphthalene (4h). Yield = 90% (333 mg); Colorless solid; mp = 115-116 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H22O3Na 393.1461, found 393.1466; 1H NMR (400 MHz, CDCl3): δ 8.41 (d, J = 1.2 Hz, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.607.45 (m, 5H), 7.41-7.38 (m, 1H), 7.7.34 (dd, J = 1.6, 7.2 Hz, 1H), 7.263 (s, 1H), 7.13 (dd, J = 0.8, 7.6 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 4.10 (s, 3H), 4.03 (s, 3H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 157.2, 148.0, 142.5, 141.4, 138.5, 133.3, 132.0, 129.2, 129.1, 128.7 (2x), 127.5 (2x), 127.39, 127.38, 127.2, 127.1, 123.5, 120.6, 119.3, 116.7, 111.1, 61.2, 56.8, 55.6. 1,2-dimethoxy-4-(3-methoxyphenyl)-7-phenylnaphthalene (4i). Yield = 91% (337 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C25H22O3Na 393.1461, found 393.1462; 1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.78-7.75 (m, 2H), 7.58 (dd, J = 1.6, 8.8 Hz, 1H), 7.52-7.47 (m, 2H), 7.45-7.37 (m, 2H), 7.258 (s, 1H), 7.12-7.06 (m, 2H), 7.026.99 (m, 1H), 4.08 (s, 3H), 4.03 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.5, 147.9, 142.7, 141.9, 141.3, 138.8, 136.6, 129.6, 129.3, 128.8 (2x), 127.5 (2x), 127.4, 126.9, 126.8, 123.9, 122.6, 119.4, 116.2, 115.8, 112.9, 61.2, 56.9, 55.3. 1,2-dimethoxy-4-(4-methoxyphenyl)-7-phenylnaphthalene (4j). Yield = 90% (333 mg); Colorless solid; mp = 105-106 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H22O3Na 393.1461, found 393.1458; 1H NMR (400 MHz, CDCl3): δ 8.39 (d, J = 2.0 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.777.74 (m, 2H), 7.57 (dd, J = 2.0, 8.8 Hz, 1H), 7.51-7.47 (m, 2H), 7.44 (d, J = 8.8 Hz, 2H), 7.41-7.36 (m, 1H), 7.22 (s, 1H), 7.05 (d, J = 8.8 Hz, 2H), 4.06 (s, 3H), 4.02 (s, 3H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.1, 148.0, 142.4, 141.3, 138.7, 136.5, 132.8, 131.1 (2x), 129.6, 128.8 (2x), 127.5 (2x), 127.4, 127.1, 126.8, 123.8, 119.4, 116.3, 113.8 (2x), 61.2, 56.9, 55.4. 4-(2-fluorophenyl)-1,2-dimethoxy-7-phenylnaphthalene (4k). Yield = 88% (315 mg); Colorless solid; mp = 109-110 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C24H19FO2Na 381.1261, found 381.1261; 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 1.6 Hz, 1H), 7.78-7.75 (m, 2H), 7.66 (dd, J = 2.0, 8.8 Hz, 1H), 7.59 (dd, J = 2.0, 8.8 Hz, 1H), 7.52-7.37 (m, 5H), 7.31 (dd, J = 0.8, 7.2 Hz, 1H), 7.28 (s, 1H), 7.24 (d, J = 8.4 Hz, 1H), 4.10 (s, 3H), 4.03 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.1 (d, J = 244.8 Hz), 147.9, 143.2, 141.3, 138.8, 132.4 (d, J = 3.8 Hz), 130.1, 129.6 (d, J = 7.6 Hz), 129.4, 128.8 (2x), 127.7, 127.5 (2x), 127.4 (d, J = 13.6 Hz), 127.2, 126.5, 124.1, 119.5, 117.2, 115.9, 115.7, 61.2, 57.0. 4-(3-fluorophenyl)-1,2-dimethoxy-7-phenylnaphthalene (4l). Yield = 86% (308 mg); Colorless solid; mp = 80-81 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C24H19FO2Na 381.1261, found 381.1263; 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.787.75 (m, 2H), 7.61 (dd, J = 1.6, 8.8 Hz, 1H), 7.53-7.45 (m, 3H), 7.42-7.38 (m, 1H), 7.32-7.29 (m, 1H), 7.25-7.23 (m, 1H), 7.24 (s, 1H), 7.19-7.14 (m, 1H), 4.09 (s, 3H), 4.04 (s, 3H); 13C NMR (100

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MHz, CDCl3): δ 162.7 (d, J = 244.8 Hz), 143.0, 142.6 (d, J = 7.6 Hz), 141.1, 138.9, 135.3, 129.8 (d, J = 8.3 Hz), 129.6, 128.8 (2x), 127.49 (2x), 127.46, 126.6, 126.4, 125.8 (d, J = 3.0 Hz), 124.2, 123.5, 119.5, 117.0 (d, J = 21.2 Hz), 116.3, 114.3 (d, J = 20.4 Hz), 61.2, 56.9. 4-(4-fluorophenyl)-1,2-dimethoxy-7-phenylnaphthalene (4m). Yield = 90% (322 mg); Colorless solid; mp = 96-97 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C24H19FO2Na 381.1261, found 381.1261; 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 2.0 Hz, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.787.75 (m, 2H), 7.59 (dd, J = 2.0, 8.8 Hz, 1H), 7.52-7.45 (m, 4H), 7.42-7.38 (m, 1H), 7.23-7.18 (m, 2H), 7.22 (s, 1H), 4.08 (s, 3H), 4.04 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 162.3 (d, J = 244.9 Hz), 147.9, 142.8, 141.2, 138.8, 136.4 (d, J = 3.0 Hz), 135.6, 131.6 (d, J = 22.47.6 Hz, 2x), 129.6, 128.8 (2x), 127.5 (2x), 127.4, 127.0, 126.5, 124.0, 119.5, 116.5, 115.3 (d, J = 21.3 Hz, 2x), 61.2, 57.0. Single-crystal X-ray diagram: crystal of 4m was grown by slow diffusion of EtOAc into a solution of 4m in CH2Cl2 to yield colorless prisms. The compound crystallizes in the Monoclinic crystal system, space group C 2/c, a = 53.153(6) Å , b = 5.7648(6) Å , c = 26.264(3) Å , V = 7203.2(14) Å 3, Z = 16, dcalcd = 1.322 g/cm3, F(000) = 3008, 2 range 0.86-26.45o, R indices (all data) R1 = 0.0659, wR2 = 0.0996. 1,2-dimethoxy-7-phenyl-4-(4-(trifluoromethyl)phenyl)naphthalene (4n). Yield = 94% (384 mg); Colorless solid; mp = 83-84 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C25H19F3O2Na 431.1229, found 431.1232; 1H NMR (400 MHz, CDCl3): δ 8.45 (d, J = 1.6 Hz, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.80-7.76 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.61 (dd, J = 2.0, 8.8 Hz, 1H), 7.53-7.50 (m, 2H), 7.43-7.39 (m, 1H), 7.25 (s, 1H), 4.11 (s, 3H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 144.1, 143.3, 141.0, 139.0, 135.1, 130.4 (2x), 129.7, 129.6 (d, J = 32.6 Hz), 128.8 (2x), 127.51, 127.48 (2x), 126.6, 126.2, 125.3 (q, J = 3.8 Hz, 2x), 124.3, 124.2 (d, J = 243.3 Hz), 119.6, 116.5, 61.2, 57.0. 4-(3,4-dimethoxyphenyl)-1,2-dimethoxy-7-phenylnaphthalene (4o). Yield = 91% (364 mg); Colorless solid; mp = 121-122 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C26H24O4Na 423.1567, found 423.1565; 1H NMR (400 MHz, CDCl3): δ 8.41 (d, J = 1.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.787.76 (m, 2H), 7.60 (dd, J = 2.0, 8.8 Hz, 1H), 7.52-7.48 (m, 2H), 7.41-7.37 (m, 1H), 7.256 (s, 1H), 7.09-7.01 (m, 3H), 4.08 (s, 3H), 4.04 (s, 3H), 3.99 (s, 3H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.7, 148.5, 147.9, 142.5, 141.2, 138.7, 136.6, 133.1, 129.6, 128.8 (2x), 127.45 (2x), 127.36, 127.1, 126.8, 123.8, 122.2, 119.4, 116.3, 113.4, 111.1, 61.2, 56.9, 56.0 (2x). 1,2-dimethoxy-7-phenyl-4-(3,4,5-trimethoxyphenyl)naphthalene (4p). Yield = 72% (310 mg); Colorless solid; mp = 116-117 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C27H26O5Na 453.1673, found 453.1673; 1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.76-7.75 (m, 2H), 7.60 (dd, J = 2.0, 8.8 Hz, 1H), 7.52-7.48 (m, 1H), 7.41-7.37 (m, 1H), 7.256 (s, 1H), 4.07 (s, 3H), 4.04 (s, 3H), 3.96 (s, 6H), 3.90 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 153.1 (2x), 147.9, 142.7, 141.2, 138.8, 137.5, 136.7, 136.0, 129.6, 128.8 (2x), 127.5 (2x), 127.4, 127.0, 126.7, 124.0, 119.4, 116.1, 107.3 (2x), 61.2, 61.0, 57.0, 56.2 (2x). 4-([1,1'-biphenyl]-4-yl)-1,2-dimethoxy-7-phenylnaphthalene (4q). Yield = 83% (346 mg); Colorless solid; mp = 144-145 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H24O2Na 439.1669, found 439.1668; 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 2.0 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.78-


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7.74 (m, 4H), 7.72-7.69 (m, 2H), 7.62-7.59 (m, 2H), 7.61 (s, 1H), 7.52-7.48 (m, 4H), 7.42-7.38 (m, 2H), 7.30 (s, 1H), 4.09 (s, 3H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.7, 141.3, 140.8, 140.3, 139.4, 138.8, 136.3, 130.5 (2x), 129.7, 128.9 (2x), 128.8 (2x), 127.5 (2x), 127.43, 127.41, 127.14 (2x), 127.08 (2x), 126.9, 126.7, 124.0, 119.5, 116.3, 61.3, 56.9. 4-([1,1'-biphenyl]-3-yl)-1,2-dimethoxy-7-phenylnaphthalene (4r). Yield = 77% (321 mg); Colorless solid; mp = 69-70 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H24O2Na 439.1669, found 439.1671; 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 2.0 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.787.76 (m, 2H), 7.71-7.67 (m, 3H), 7.61-7.58 (m, 2H), 7.52-7.45 (m, 6H), 7.41-7.36 (m, 2H), 7.31 (s, 1H), 4.09 (s, 3H), 4.04 (s, 3H); 13C NMR (100 MHz, CDCl ): δ 148.0, 142.7, 141.3, 141.2, 3 140.94, 140.89, 138.8, 136.6, 129.6, 129.0, 128.9, 128.84 (2x), 128.81 (2x), 128.79, 127.51 (2x), 127.47, 127.40, 127.2 (2x), 126.9, 126.7, 126.1, 124.0, 119.5, 116.3, 61.3, 56.9. 3,4-dimethoxy-6-phenyl-1,1'-binaphthalene (4s). Yield = 87% (340 mg); Colorless solid; mp = 162-163 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C28H22O2Na 413.1512, found 413.1512; 1H NMR (400 MHz, CDCl3): δ 8.45 (d, J = 2.0 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.76-7.73 (m, 2H), 7.64-7.60 (m, 1H), 7.54-7.33 (m, 10H), 4.14 (s, 3H), 4.01 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.8, 141.3, 138.8, 138.1, 134.8, 133.5, 132.9, 129.3, 128.8 (2x), 128.2, 128.1, 128.0, 127.9, 127.5 (2x), 127.4, 127.2, 126.5, 126.1, 125.9, 125.3, 123.9, 119.3, 117.1, 61.3, 56.9. 3,4-dimethoxy-6-phenyl-1,2'-binaphthalene (4t). Yield = 89% (348 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C28H22O2Na 413.1512, found 413.1511; 1H NMR (400 MHz, CDCl3): δ 8.45 (d, J = 2.0 Hz, 1H), 7.99-7.92 (m, 5H), 7.78 (d, J = 7.6 Hz, 2H), 7.67 (dd, J = 1.2, 8.4 Hz, 1H), 7.60-7.56 (m, 3H), 7.53-7.49 (m, 2H), 7.42-7.38 (m, 1H), 7.36 (s, 1H), 4.12 (s, 3H), 4.06 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.7, 141.2, 138.8, 138.0, 136.7, 133.4, 132.6, 129.6, 128.8 (2x), 128.7, 128.4, 128.0, 127.8 (2x), 127.5 (2x), 127.4, 127.0, 126.8, 126.4, 126.1, 124.0, 119.5, 116.6, 61.3, 56.9. 2-(3,4-dimethoxy-6-phenylnaphthalen-1-yl)thiophene (4u). Yield = 90% (311 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C22H18O2SNa 369.0925, found 369.0923; 1H NMR (400 MHz, CDCl3): δ 8.50 (d, J = 2.0 Hz, 1H), 8.27 (d, J = 8.8 Hz, 1H), 7.857.82 (m, 2H), 7.71 (dd, J = 2.0, 8.8 Hz, 1H), 7.57-7.53 (m, 2H), 7.49 (dd, J = 1.6, 4.8 Hz, 1H),7.47-7.43 (m, 1H), 7.46 (s, 1H), 7.32 (dd, J = 1.2, 3.6 Hz, 1H), 7.25-7.24 (m, 1H), 4.15 (s, 3H), 4.08 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 147.7, 143.2, 141.3, 141.0, 138.9, 129.6, 128.8 (2x), 128.7, 127.41 (2x), 127.39, 127.38, 127.36, 127.25, 126.4, 125.6, 124.2, 119.4, 117.4, 61.1, 56.8. 7-([1,1'-biphenyl]-4-yl)-1,2-dimethoxy-4-phenylnaphthalene (4v). Yield = 93% (387 mg); Colorless solid; mp = 138-139 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H24O2Na 439.1669, found 439.1669; 1H NMR (400 MHz, CDCl3): δ 8.49 (d, J = 1.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.70-7.67 (m, 2H), 7.64 (dd, J = 1.6, 8.8 Hz, 1H), 7.55 (s, 1H), 7.54-7.46 (m, 6H), 7.41-7.37 (m, 1H), 7.28 (s, 1H), 4.11 (s, 3H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.6, 140.7, 140.4, 140.3, 140.1, 138.2, 136.8, 130.1 (2x), 129.6, 128.8 (2x), 128.3 (2x), 127.8 (2x), 127.5 (2x), 127.4, 127.3, 127.0 (2x), 126.9, 126.8, 123.7, 119.3, 116.4, 61.2, 56.9. Single-crystal X-ray diagram: crystal of 4v was grown by slow diffusion of EtOAc into a solution of 4v in CH2Cl2 to yield colorless prisms. The compound

crystallizes in the Orthorhombic crystal system, space group P 21 21 21, a = 7.7664(8) Å , b = 8.1366(9) Å , c = 34.746(4) Å , V = 2195.7(4) Å 3, Z = 4, dcalcd = 1.260 g/cm3, F(000) = 880, 2 range 2.35-26.38o, R indices (all data) R1 = 0.0827, wR2 = 0.1015. 7-([1,1'-biphenyl]-4-yl)-1,2-dimethoxy-4-(p-tolyl)naphthalene (4w). Yield = 92% (396 mg); Colorless solid; mp = 191-192 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C31H26O2Na 453.1825, found 453.1824; 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 2.0 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.70-7.67 (m, 2H), 7.63 (dd, J = 2.0, 8.8 Hz, 1H), 7.47 (t, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.41-7.37 (m, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.255 (s, 1H), 4.10 (s, 3H), 4.04 (s, 3H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.5, 140.7, 140.24, 140.17, 138.1, 137.5, 137.1, 136.8, 129.9 (2x), 129.6, 129.1 (2x), 128.8 (2x), 127.8 (2x), 127.5 (2x), 127.3, 127.1 (2x), 127.0, 126.9, 123.6, 119.3, 116.3, 61.2, 56.9, 21.2. Single-crystal X-ray diagram: crystal of 4w was grown by slow diffusion of EtOAc into a solution of 4w in CH2Cl2 to yield colorless prisms. The compound crystallizes in the Monoclinic crystal system, space group C 2/c, a = 16.4015(13) Å , b = 10.9309(10) Å , c = 254.431(2) Å , V = 4463.0(7) Å 3, Z = 8, dcalcd = 1.281 g/cm3, F(000) = 1824, 2 range 1.64-26.36o, R indices (all data) R1 = 0.0045, wR2 = 0.1048. 7-([1,1'-biphenyl]-4-yl)-4-(4-fluorophenyl)-1,2dimethoxynaphthalene (4x). Yield = 91% (395 mg); Colorless solid; mp = 167-168 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H23FO2Na 457.1574, found 457.1575; 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 2.0 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.8 Hz, 2H), 7.69-7.67 (m, 2H), 7.64 (dd, J = 2.0, 8.8 Hz, 1H), 7.517.46 (m, 4H), 7.41-7.36 (m, 1H), 7.22 (t, J = 8.8 Hz, 2H), 7.23 (s, 1H), 4.10 (s, 3H), 4.04 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 162.3 (d, J = 244.8 Hz), 148.0, 142.8, 140.7, 140.3, 140.0, 138.3, 136.3 (d, J = 3.8 Hz), 135.6, 131.6 (d, J = 8.3 Hz, 2x), 129.7, 128.8 (2x), 127.8 (2x), 127.6 (2x), 127.4, 127.1 (2x), 127.0, 126.6, 123.9, 119.4, 116.5, 115.3 (d, J = 21.2 Hz, 2x), 61.3, 57.0. 1-isopropoxy-2-methoxy-4,7-diphenylnaphthalene (4y). Yield = 93% (343 mg); Colorless solid; mp = 115-116 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C26H24O2Na 391.1674, found 391.1674; 1H NMR (400 MHz, CDCl3): δ 8.65 (d, J = 2.0 Hz, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.897.87 (m, 2H), 7.70-7.46 (m, 9H), 7.37 (s, 1H), 4.92-4.86 (m, 1H), 4.09 (s, 3H), 1.59 (d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 148.1, 141.3, 140.6, 140.5, 138.2, 136.1, 130.9, 130.0 (2x), 128.7 (2x), 128.2 (2x), 127.3 (2x), 127.2 (2x), 126.8, 126.5, 123.7, 120.3, 116.4, 75.6, 56.7, 22.8 (2x). 1-butoxy-2-methoxy-4,7-diphenylnaphthalene (4z). Yield = 91% (348 mg); Colorless gum; HRMS (ESI, M++Na) calcd for C27H26O2Na 405.1825, found 405.1823; 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 7.6 Hz, 2H), 7.65 (dd, J = 2.0, 8.8 Hz, 1H), 7.62-7.49 (m, 7H), 7.47-7.43 (m, 1H), 7.33 (s, 1H), 4.31 (t, J = 5.6 Hz, 2H), 4.07 (s, 3H), 2.06-1.99 (m, 2H), 1.77-1.72 (m, 2H), 1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.0, 141.3, 140.4, 138.4, 136.4, 130.03 (2x), 129.97, 128.8 (2x), 128.3 (2x), 127.3 (2x), 127.27, 127.25, 126.9, 126.6, 123.8, 119.6, 116.5, 73.5, 56.9, 32.5, 19.4, 13.9. 1-(cyclopentyloxy)-2-methoxy-4,7-diphenylnaphthalene (4aa). Yield = 90% (355 mg); Colorless solid; mp = 144-145 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C28H26O2Na 417.1831, found 417.1830; 1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.80-



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7.77 (m, 2H), 7.62-7.46 (m, 8H), 7.43-7.39 (m, 1H), 7.28 (s, 1H), 5.22-5.18 (m, 1H), 4.03 (s, 3H), 2.16-2.04 (m, 4H), 1.91-1.82 (m, 2H), 1.75-1.71 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 148.0, 141.4, 140.8, 140.5, 138.2, 136.0, 130.9, 130.1 (2x), 128.8 (2x), 128.3 (2x), 127.3 (2x), 127.2 (2x), 126.9, 126.5, 123.7, 120.1, 116.7, 85.0, 56.9, 33.0 (2x), 23.8 (2x). 1-(benzyloxy)-2-methoxy-4,7-diphenylnaphthalene (4ab). Yield = 87% (362 mg); Colorless solid; mp = 88-89 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C30H24O2Na 439.1674, found 439.1675; 1H NMR (400 MHz, CDCl3): δ 8.63 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 7.857.82 (m, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.74-7.46 (m, 12H), 7.44 (s, 1H), 5.43 (s, 2H), 4.14 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 141.6, 141.0, 140.3, 138.4, 137.9, 136.7, 130.0 (2x), 129.9, 128.9, 128.7 (2x), 128.4 (2x), 128.3 (2x), 128.2 (2x), 127.9, 127.3 (2x), 127.2, 126.8, 126.6, 123.7, 119.7, 116.2, 75.5, 56.7. General synthetic route for the synthesis of 6a-6b. Decalin (8 mL) was added to a solution of 3a-3b (1.0 mmol) at rt. The reaction mixture was stirred at 200oC for 1 h. The reaction mixture was cooled to rt. Decalin was evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/EtOAc = 10/1~6/1) afforded compounds 6a-6b. 2-methoxy-7-phenylnaphthalen-1-ol (6a). Yield = 95% (238 mg); Colorless solid; mp = 124-125 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C17H14O2Na 273.0886, found 273.0888; 1H NMR (400 MHz, CDCl3): δ 8.44 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.67 (dd, J = 2.0, 8.8 Hz, 1H), 7.53-7.49 (m, 2H), 7.45 (d, J = 8.8 Hz, 1H), 7.42-7.38 (m, 1H), 7.27 (d, J = 8.8 Hz, 1H), 6.16 (s, 1H), 4.01 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 141.6, 141.3, 140.0, 137.9, 128.73 (2x), 128.65, 128.1, 127.4 (2x), 127.2, 124.2, 124.0, 119.3, 119.1, 113.2, 57.0. 7-([1,1'-biphenyl]-4-yl)-2-methoxynaphthalen-1-ol (6b). Yield = 95% (310 mg); Colorless solid; mp = 172-173 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for C23H18O2Na 349.1199, found 349.1198; 1H NMR (400 MHz, CDCl3): δ 8.46 (d, J = 1.6 Hz, 1H), 7.89-7.84 (m, 3H), 7.75-7.67 (m, 5H), 7.51-7.47 (m, 2H), 7.45 (d, J = 8.8 Hz, 1H), 7.41-7.37 (m, 1H), 7.28 (d, J = 8.8 Hz, 1H), 6.13 (s, 1H), 4.02 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 141.6, 140.7, 140.2, 140.04, 140.00, 137.4, 128.8 (2x), 128.7, 128.1, 127.7 (2x), 127.5 (2x), 127.3, 127.0 (2x), 124.2, 123.8, 119.3, 119.0, 113.2, 57.1.

ASSOCIATED CONTENT Supporting Information Scanned spectroscopic data for all compounds and X-ray analysis data of 1k, 3c, 3v, 4h, 4m, 4v, 4w and 4aa. This information is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *Email: [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENT The authors would like to thank the Ministry of Science and Technology of the Republic of China for financial support (MOST 105-2113-M-037-001). This study is supported partially by Kaohsiung Medical University “Aim for the Top

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Synthesis of Substituted 1,6-Diarylnaphthalenes via a Tandem

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