SYNTHESIS OF XANTHENES, INDANES, AND TETRAHYDRONAPHTHALENES VIA INTRAMOLECULAR PHENYLCARBONYL COUPLING REACTIONS

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SYNTHESIS OF XANTHENES, INDANES, AND

TETRAHYDRONAPHTHALENES VIA INTRAMOLECULAR

PHENYL-CARBONYL COUPLING REACTIONS

Chih-Wei Kuo a; Jim-Min Fang a

a Department of Chemistry, National Taiwan University, Taipei, Taiwan, Republic of China Online Publication Date: 13 January 2001

To cite this Article Kuo, Chih-Wei and Fang, Jim-Min(2001)'SYNTHESIS OF XANTHENES, INDANES, AND

TETRAHYDRONAPHTHALENES VIA INTRAMOLECULAR PHENYL-CARBONYL COUPLING REACTIONS',Synthetic Communications,31:6,877 — 892

To link to this Article: DOI: 10.1081/SCC-100103323 URL: http://dx.doi.org/10.1081/SCC-100103323

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SYNTHESIS OF XANTHENES, INDANES,

AND TETRAHYDRONAPHTHALENES VIA

INTRAMOLECULAR PHENYL–CARBONYL

COUPLING REACTIONS

Chih-Wei Kuo and Jim-Min Fang*

Department of Chemistry, National Taiwan University, Taipei, Taiwan, 106, Republic of China

ABSTRACT

Benzaldehydes and acetophenones bearing tethered car-bonyl chains underwent the intramolecular phenyl–carcar-bonyl coupling reactions, by mediation of samarium diiodide and hexamethylphosphoramide, to afford the xanthenes and fused benzocarbocyclic compounds containing carbonyl and hydro-xyl substituents.

INTRODUCTION

SmI2is a one-electron-transfer reducing agent1–6that can be utilized in the reductive couplings of carbonyl compounds to form pinacols.7–9When a,b-unsaturated esters, ketones, and amides are treated with SmI2, reduc-tions by saturation of the double bonds10–14 or reductive couplings at b-carbons16–21may occur, depending on the reaction conditions. Besides the well-documented pinacolic couplings of aromatic carbonyl compounds,7–9

877

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* Corresponding author.

SYNTHETIC COMMUNICATIONS, 31(6), 877–892 (2001)

we found that various benzaldehydes and acetophenones can undergo the phenyl–carbonyl coupling reactions on treatment with SmI2 and HMPA.21,22 In such reactions, benzaldehydes and acetophenones may be considered as extended vinylogous conjugated carbonyls.23–25We have also demonstrated in four examples21,22that beazaldehydes and acetophenones bearing appropriate carbonyl tethers can proceed via the intramolecular phenyl–carbonyl coupling reactions to give some benzene-fused oxacyclic compounds. We thus studied further such SmI2/HMPA-promoted reactions as a route to construct xanthenes and benzene-fused carbocyclic com-pounds.

RESULTS AND DISCUSSION Preparation of Xanthenes

The diphenyl ethers 1a and 1b containing appropriate formyl and acetyl substituents were prepared according to Equation 1. By the mediation of (CuOTf )2 C6H6 and Cs2CO3, 3-(dimethoxymethyl)phenol underwent a coupling reaction26with 2-bromobenzaldehyde to give 1a in 72% yield, after hydrolysis of the moiety of dimethyl acetal. Coupling of 3-(dimethoxy-methyl)phenol with 2-bromoacetophenone, followed by hydrolysis, also afforded compound 1b in 83% yield.

The intramolecular phenyl–carbonyl coupling reaction was achieved by slow addition of a THF solution of 1a to the deep purple solution of SmI2/HMPA in THF at 0
C (Eq. 2). After stirring at room temperature for 2 h, the reaction mixture was treated with NH4Cl solution and exposed to the air to furnish the final oxidative step to regenerate the aromaticity, giving the xanthenecarbaldehyde 2a in 81% yield. Compound 2a decom-posed gradually on standing (even in the refrigerator); it was thus converted to the stable xanthones27–303a and 3b by oxidation with pyridinium dichro-mate (PDC) or KMnO4. The xanthonecarboxylic acid 3b is known to bind to human serum albumin and lower the level of oxygen in blood.27–30

(1)

Under similar reaction conditions, the cyclization of 1b was less effec-tive (Eq. 3), giving a 38% yield of xanthenecarbaldehyde 2b, along with 12% recovery of 1b. The presumed Sm(III)-enolate intermediate B was trapped by alkylation with benzyl bromide to give 4 in a stereoselective manner.21,22 The relative (3S*,9S*,9aS*) configuration of 4 was established by the NOESY analysis. Thus, the methyl group (at  1.23) showed an obvious NOE correlation with the aldehyde proton (at  9.45). H-9a (at  2.92) also showed a strong NOE correlation with the benzyl protons (at  3.00), but not with the methyl group. The intramolecular coupling reaction might proceed via transition state A, followed by alkylation of the intermediate B via the less hindered face, to give 4 with the (3S*,9S*,9aS*) configuration. (2)

(3)

Preparation of Benzene-Fused Carbocyclic Compounds

Coupling of 3-bromobenzaldehyde dimethyl acetal with 3-butenyl-magnesium bromide in the presence of PdCl2(pddf ),31 followed by acid-catalyzed hydrolysis, gave 3-(3-butenyl)benzaldehyde 5a in 83% yield (Eq. 4). Ozonolysis of 5a afforded the aldehyde 6a (91%), whereas Wacker oxidation32 yielded the methyl ketone 6d (64%). Oxidation of 5a with MnO2in MeOH by the mediation of NaCN produced methyl 3-(3-butenyl)benzoate 5b, which was subjected to ozonolysis to give 6b in 76% overall yield. Compound 6c was similarly prepared in a three-step sequence: (a) coupling of 3-bromoacetophenone dimethyl acetal with 3-butenylmagnesium bromide; (b) acid-catalyzed hydrolysis of the acetal; and (c) ozonolysis of the double bond. Starting with the coupling reactions of 4-pentenylmagnesium bromide with 3-bromobenzaldehyde dimethyl acetal or 3-bromoacetophenone dimethyl acetal, compounds 6e–h were obtained in 59–73% yields by similar methods.

The SmI2/HMPA promoted intramolecular cyclizations of 6a–h were carried out to produce the benzocyclic compounds 7a–h, including the indane and naphthalene derivatives (Eqs. 4 and 5). An aromatic carbonyl was generally more reactive than an aliphatic carbonyl on treatment with SmI2. The intramolecular coupling reaction was considered to proceed via a nucleophilic addition of the cyclohexadienyl Sm(III) intermediate to the aliphatic carbonyl, similar to that operated in the transition state A. The bulky HMPA molecules might coordinate with the samarium species21,22,33–36 to disfavor any coupling at the ketyl or ortho positions of the aromatic carbonyls.

SUMMARY

This study shows the limitation and scope of the SmI2/HMPA pro-moted cyclizations of aromatic carbonyl compounds. This method afforded some carbonyl- and hydroxyl-substituted derivatives of xanthenes, indanes, and naphthalenes, which were not readily accessible by other methods. Provided with suitably designed substrates and optimized reaction con-ditions, this method may also be useful in the synthesis of other heterocyclic aromatic compounds.37–39

EXPERIMENTAL

Melting points are uncorrected. Chemical shifts are reported relative to CHCl3 (H 7.26) and CDCl3 [C (central line of t) 77.0]. All reactions

requiring anhydrous conditions were conducted in a flame-dried apparatus under an atmosphere of nitrogen. Syringes and needles for the transfer of reagents were dried at 120
C and allowed to cool in a desiccator over P2O5 before use. Ethers were distilled from sodium benzophenone ketyl, and (chlorinated) hydrocarbons from CaH2. Column chromatography was carried out on Kieselgel 60 (40–63 mm). Merck silica gel 60F sheets were used for analytical thin-layer chromatography. The acronym dppf repre-sents 1,10-bis(diphenylphosphino)ferrocene.

Caution: HMPA should be handled with caution, as it is considered as a potential carcinogen.

2-(3-Formylphenoxy)benzaldehyde (1a)

Under an atmosphere of argon, a mixture of (CuOTf )2 C6H6 (90% purity, 70 mg, 0.25 mmol), Cs2CO3(3.26 g, 10 mmol) and toluene (30 mL) was placed in a two-necked flask. A solution of 3-(dimethoxymethyl)phenol (1.68 g, 10 mmol), 2-bromobenzaldehyde (925 mg, 5 mmol), and EtOAc (22 mg, 0.25 mmol) in toluene (15 mL) was added dropwise. After refluxing at 110
C for 12 h, the mixture was cooled, treated with Et2O (20 mL), and washed with aqueous NaOH (1 N solution). The organic phase was concen-trated by rotary evaporation to give a crude product (the dimethyl acetal of 1a), which was dissolved in THF (20 mL) and treated with a small amount of aqueous HCl (1 N solution) at room temperature for 3 h. The mixture was extracted with EtOAc, dried (Na2SO4), concentrated, and chromatographed on a silica gel column by elution with EtOAc/hexane (1:9) to give 1a (817 mg, 3.62 mmol, 72% overall yield).

1a: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.25; IR (neat) 1701 cm1; 1 H NMR (CDCl3, 200 MHz)  6.95 (1H, d, J ¼ 8.2 Hz), 7.27–7.39 (2H, m) 7.52–7.62 (3H, m), 7.67–7.72 (1H, m), 7.97 (1H, dd, J ¼ 7.7, 1.7 Hz), 9.99 (1H, s), 10.46 (1H, s); 13C NMR (CDCl3, 50 MHz)  118.3, 119.1, 124.3, 124.9, 125.9, 127.2, 128.9, 130.8, 135.9, 138.2, 157.5, 158.7, 188.8, 191.1; MS m/z (rel intensity) 226 (100, Mþ ); HRMS calcd. for C14H10O3 226.0630. Found 226.0625. 3-(2-Acetylphenoxy)benzaldehyde (1b)

According to the procedure similar to that for 1a, coupling of 3-(dimethoxymethyl)phenol (1.01 g, 6 mmol) with 2-bromoacetophenone (597 mg, 3 mmol) using (CuOTf )2C6H6 (42 mg, 0.15 mmol), Cs2CO3 (2.15 g, 6.6 mmol), and EtOAc (13 mg, 0.15 mmol) in toluene solution, followed by an acid-catalyzed hydrolysis, gave compound 1b (597 mg, 83%).

1b: Solid; m.p. 58
–59
C; TLC (EtOAc/hexane (1:19)) Rf¼0.09; IR (KBr) 1682, 1698 cm1; 1H NMR (CDCl3, 300 MHz)  2.61 (3H, s), 6.96 (1H, d, J ¼ 8.3 Hz), 7.22–7.32 (2H, m), 7.49 (1H, s), 7.46–7.53 (1H, m), 7.57 (1H, d, J ¼ 8.0 Hz), 7.66 (1H, d, J ¼ 7.4 Hz), 7.87 (1H, dd, J ¼ 7.7, 1.7 Hz), 9.98 (1H, s);13C NMR (CDCl3, 75 MHz)  31.2, 117.7, 119.9, 124.4, 125.4, 130.7, 130.9, 133.8, 138.2, 155.0, 157.5, 191.2, 198.3; MS m/z (rel intensity) 240 (98, Mþ), 197 (100); HRMS calcd. for C15H12O3 240.0786. Found 240.0784.

Representative Procedure for the SmI2/HMPA Promoted Reactions A deep blue SmI2solution (0.1 M, 1.5 mmol) was prepared by treat-ment of Sm (240 mg, 1.6 mmol) with 1,2-diiodoethane (423 mg, 1.5 mmol) in anhydrous THF (15 mL) for 1.5 h at room temperature. HMPA (1.05 mL, 6 mmol) was added, and the resulting deep purple solution was cooled to 0
C. A solution of 1a (113 mg, 0.5 mmol) in THF (7 mL) was added dropwise over a period of 45 m via a syringe pump. The mixture was stirred at 0
C for 30 m, warmed to room temperature, and stirred at room temperature for 2 h. The serum cap was removed, and saturated NH4Cl aqueous solution (0.5 mL) was added. After addition of Et2O (20 mL), the resulting precipitates were removed by passing them through a pad of silica gel, and the crude product was obtained by elution with EtOAc. Further purification by silica gel column (EtOAc/hexane (1:4)) afforded a sample of 2a (92 mg, 81%), which decomposed gradually on standing.

9-Hydroxy-9H-xanthene-3-carbaldehyde (2a) TLC (EtOAc/hexane (1:4)) Rf¼0.28; IR (KBr) 1698, 3209 cm1; 1 H NMR (CDCl3, 200 MHz)  3.10 (1H, br s, OH), 5.71 (1H, s), 7.08–7.l8 (2H, m), 7.277.36 (1H, m), 7.48–7.57 (3H, m), 7.64 (1H, d, J ¼ 7.8 Hz), 9.86 (1H, s);13C NMR (CDCl3, 50 MHz)  63.0, 116.6, 117.9, 121.9, 123.8, 123.9, 128.8, 129.4, 129.8, 130.4, 137.1, 150.2, 150.9, 191.5; MS (FAB) m/z (rel intensity) 225 (20, Mþ 1), 154 (100). 9-Hydroxy-9-methyl-9H-xanthene-3-carbaldehyde (2b)

Treatment of 1b (120 mg, 0.5 mmol) with SmI2 (2 mmol)/HMPA (1.4 mL) in THF solution (20 mL), according to the representative procedure, gave the title compound 2b (45 mg, 38% yield), along with a 12% recovery of 1b (15 mg).

2b: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.13; IR (neat) 1701, 3389 cm1; 1H NMR (CDCl3, 200 MHz)  1.69 (3H, s), 2.75 (1H, br, s), 7.11–7.37 (3H, m), 7.56 (1H, d, J ¼ 1.5 Hz), 7.64 (1H, dd, J ¼ 8.0, 1.5 Hz), 7.72 (1H, dd, J ¼ 7.6, 1.5 Hz), 7.88 (1H, d, J ¼ 8.0 Hz), 9.96 (1H, s); 13 C NMR (CDCl3, 50 MHz)  34.5, 66.6, 116.3, 117.6, 124.0, 124.1, 126.3, 127.5, 129.1, 134.6, 136.8, 149.1, 149.9, 153.6, 191.4; MS m/z (rel intensity) 240 (2, Mþ), 209 (100); HRMS calcd. for C14H8O3 (MþCH4) 224.0474. Found 224.0475.

9-Oxo-9H-xanthene-3-carbaldehyde (3a)30

Compound 2a (113 mg, 0.5 mmol) was treated with pyridinium dichro-mate (376 mg, 1 mmol) and Celite (200 mg) in CH2Cl2 (20 mL) for 2 h at room temperature. The reaction mixture was filtered through a pad of silica gel and rinsed with EtOAc. The filtrate was concentrated, and chromato-graphed on a silica gel column by elution with EtOAc/hexane (1:9) to give 3a (106 mg, 94%). 3a: Solid; m.p. 125
–127
C; 1H NMR (CDCl3, 200 MHz)  7.37 (1H, t, J ¼ 7.9 Hz), 7.47 (1H, d, J ¼ 8.5 Hz), 7.68–7.82 (2H, m), 7.92 (1H, d, J ¼ 1.0 Hz), 8.27 (1H, dd, J ¼ 8.0, 1.0 Hz), 8.41 (1H, d, J ¼ 8.0 Hz), 10.11 (1H, s). 9-Oxo-9H-xanthene-3-carboxylic Acid (3b)27

A mixture of 2a (23 mg, 0.1 mmol) and KMnO4(24 mg, 0.15 mmol) in water (10 mL) was heated at 60
C for 20 m. The mixture was cooled, and extracted with CH2Cl2. The organic phase was dried (Na2SO4), filtered, and concentrated to give 3b (21 mg, 91%). 3b: Solid; m.p. >300
C;1H NMR (CD3COCD3, 300 MHz)  7.49 (1H, t J ¼ 7.6 Hz), 7.64 (1H, d, J ¼ 8.5 Hz), 7.86–7.94. (2H, m), 8.10 (1H, d, J ¼1.4 Hz), 8.24 (1H, dd, J ¼ 8.1, 1.4 Hz), 8.39 (1H, d, J ¼ 8.1 Hz), 10.23 (1H, s). 3-Benzyl-9-hydroxy-9-methyl-9,9a-dihydro-3H-xanthene-3-carbaldehyde (4)

According to the representative procedure, the intermediate resulting from the intramolecular coupling reaction of 1b (120 mg, 0.5 mmol) was

trapped by alkylation with benzyl bromide (4 equiv) at room temperature for 2 days to give 4 (35 mg, 21%) after silica gel chromatography.

4: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.3; IR (neat) 1720, 3423 cm1; 1 H NMR (CDCl3, 200 MHz)  1.23 (3H, s), 1.94 (1H, br s), 2.91 (1H, m), 3.00 (2H, s), 5.22 (1H, t, J ¼ 1.8 Hz), 5.77 (1H, dt, J ¼ 10.1, 1.8 Hz), 6.11 (1H, dd, J ¼ 10.1, 3.0 Hz), 6.88 (1H, d, J ¼ 8.1 Hz), 6.98 (1H, t, J ¼ 7.4 Hz), 7.10–7.26 (6H, m), 7.46 (1H, dd, J ¼ 7.7, 1.5 Hz), 9.45 (1H, s); 13C NMR (CDCl3, 50 MHz)  25.8, 41.4, 43.7, 56.4, 70.4, 101.3, 115.9, 121.1, 124.5, 126.0, 126.4, 127.0, 127.9, 129.0, 130.4, 131.5, 136.0, 150.1, 151.0, 199.1; HRMS calcd. for (C22H20O3CH2O) 302.1306. Found 302.1310.

3-(3-Oxopropyl)benzaldehyde (6a)

Under an atmosphere of argon, 3-butenylmagnesium bromide (20 mmol, 20 mL of 1 M solution in Et2O) was added dropwise to a mixture of 3-bromobenzaldehyde dimethyl acetal (1.99 g, 10 mmol) and PdCl2(dppf ) (73 mg, 0.1 mmol) in anhydrous Et2O (10 mL) at 78
C. The mixture was stirred for 24 h at room temperature, and quenched by addition of aqueous NH4Cl (0.5 N solution). The aqueous layer was separated and extracted with Et2O. The organic phase was combined, dried (Na2SO4), filtered, and concentrated. The crude acetal product was dissolved in Me2CO (30 mL) and stirred with a small amount of p-TsOH at room temperature for 4 h. The mixture was partitioned with water and EtOAc. The aqueous layer was separated and extracted three times with EtOAc. The combined organic phase was dried (Na2SO4), filtered, concentrated, and chromatographed on a silica gel column by elution with EtOAc/hexane (1:99) to give 3-(3-butenyl)benzaldehyde (5a, 1.33 g, 83%).

Ozone was passed through a CH2Cl2solution (50 mL) of 5a (1.20 g, 7.5 mmol) at 78
C until the light blue color of ozone persisted. Me2S (5 mL) was added. The mixture was warmed to room temperature and stirred for 16 h. The mixture was concentrated, and chromatographed on a silica gel column by elution with EtOAc/hexane (l:19) to give 6a (1.11 g, 91%).

6a: Oil; TLC (EtOAc/hexane (1:9)) Rf¼ 0.12; IR (neat) 1698 cm1; 1

H NMR (CDCl3, 200 MHz)  2.71–2.80 (2H, m), 2.95 (2H, td, J ¼ 7.7, 1.4 Hz), 7.36–7.43 (2H, m), 7.58–7.65 (2H, m), 9.73 (1H, t, J ¼ 1.1 Hz), 9.89 (1H, s);13C NMR (CDCl3, 50 MHz)  27.4, 44.6, 127.9, 128.9, 129.0, 134.4, 136.5, 141.4, 192.1, 200.7; MS m/z (rel intensity) 162 (100, Mþ); HRMS calcd. for C10H10O2162.0681. Found 162.0696.

Methyl 3-(3-Oxopropyl)benzoate (6b)

A MeOH solution (20 mL) of 3-(3-butenyl)benzaldehyde (480 mg, 3 mmol) was treated with MnO2 (85% content, 1.84 g, 18 mmol), NaCN (232 mg, 4.5 mmol), and HOAc (0.26 mL, 4.5 mmol) at room temperature for 12 h. The mixture was filtered and rinsed with EtOAc. The filtrate was concentrated and chromatographed on a silica gel column by elution with EtOAc/hexane (1:99) to give methyl 3-(3-butenyl)benzoate (5b, 530 mg, 93%). According to the procedure similar to that for 6a, ester 5b (475 mg, 2.5 mmol) was subjected to ozonolysis to give 6b (395 mg, 82%).

6b: Solid; m.p. 71
–72
C; TLC (EtOAc/hexane (1:9)) Rf¼0.24; IR (KBr) 1720 cm1; 1H NMR (CDCl3, 200 MHz)  2.76 (2H, td, J ¼ 7.1, 1.1 Hz), 2.95 (2H, t, J ¼ 7.1 Hz), 3.86 (3H, s), 7.31–7.35 (2H, m), 7.82–7.85 (2H, m), 9.77 (1H, t, J ¼ 1.1 Hz);13C NMR (CDCl3, 50 MHz)  27.7, 44.9, 52.0, 127.5, 128.5, 129.2, 130.3, 132.9, 140.6, 166.9, 200.9; MS m/z (rel intensity) 192 (78, Mþ ), 160 (100); HRMS calcd. for C11H12O3 192.0787. Found 192.0789. 3-(3-Acetylphenyl)propanal (6c)

According to the procedure similar to that for 6a, coupling of 3-bromoacetophenone dimethyl acetal (1.17 g, 4.78 mmol) with 3-butenyl-magnesium bromide afforded 3-(3-butenyl)acetophenone dimethyl acetal, which was subjected to hydrolysis and ozonolysis to give 6c (589 mg, 70%). 6c: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.15; IR (neat) 1683, 1712 cm1; 1

H NMR (CDCl3, 200 MHz)  2.54 (3H, s), 2.77 (2H, td, J ¼ 7.3, 1.2 Hz), 2.96 (2H, t, J ¼ 7.3 Hz), 7.33–7.36 (2H, m), 7.73–7.75 (2H, m), 9.77 (1H, t, J ¼1.2 Hz); 13C NMR (CDCl3, 50 MHz)  26.5, 27.7, 44.9, 126.4, 127.8, 128.7, 133.1, 140.9, 198.1, 200.9; MS m/z (rel intensity) 176 (58, Mþ), 161 (100); HRMS calcd. for C11H12O2176.0837. Found 176.0831.

3-(3-Oxobutyl)benzaldehyde (6d)

Under an atmosphere of O2, a DMF solution (5 mL) of 3-(3-butenyl)-benzaldehyde (5a, 320 mg, 2 mmol) was added to a mixture of PdCl2(47 mg, 0.4 mmol), CuCl (218 mg, 2.2 mmol), and water (0.1 mL). The mixture was stirred for 24 h, and extracted with CH2Cl2after addition of aqueous NH4Cl solution (0.5 N solution). The organic phase was dried (Na2SO4), filtered, concentrated, and chromatographed on a silica gel column by elution with

EtOAc/hexane (1:9) to give 6d (225 mg, 64%), along with an 11% recovery of the starting material.

6d: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.13; IR (neat) 1716 cm1; 1 H NMR(CDCl3, 200 MHz)  2.09 (3H, s), 2.75 (2H, t, J ¼ 6.3 Hz), 2.91 (2H, t, J ¼ 6.3 Hz), 7.37–7.41 (2H, m), 7.62–7.66 (2H, m), 9.92 (1H, s); 13 C NMR (CDCl3, 50 MHz)  29.0, 29.9, 44.4, 127.8, 129.0 (2C), 134.6, 136.5, 142.0, 192.3, 207.3; MS m/z (rel intensity) 176 (70, Mþ), 133 (100); HRMS calcd. for C11H12O2176.0837. Found 176.0839.

3-(4-Oxobutyl)benzaldehyde (6e)

According to the procedure similar to that for 6a, 3-(4-pentenyl)-benzaldehyde (5e, 522 mg, 3 mmol) was subjected to ozonolysis to give 6e (311 mg, 59%).

6e: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.36; IR (neat) 1698 cm1; 1 H NMR (CDCl3, 200 MHz)  1.93 (2H, quin, J ¼ 7.2 Hz), 2.43 (2H, t, J ¼7.2 Hz), 2.68 (2H, t, J ¼ 7.2 Hz), 7.39–7.41 (2H, m), 7.64–7.67 (2H, m), 9.71 (1H, s), 9.93 (1H, s); 13C NMR (CDCl3, 50MHz)  23.2, 34.5, 42.8, 127.8, 129.0, 129.1, 134.5, 136.5, 142.3, 192.3, 201.7; MS m/z (rel intensity) 176 (24, Mþ

), 132 (100); HRMS calcd. for C11H12O2 176.0837. Found 176.0842.

4-(3-Acetylphenyl)butanal (6f)

According to the procedure similar to that for 6a, 3-(4-pentenyl)-acetophenone (5f, 552 mg, 3 mmol) was subjected to ozonolysis to give 6f (418 mg, 73%).

6f: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.14; IR (neat) 1683, 1709 cm1; 1 H NMR (CDCl3, 300 MHz)  1.98 (2H, quin, J ¼ 7.4 Hz), 2.48 (2H, t, J ¼7.4 Hz), 2.60 (3H, s), 2.72 (2H, t, J ¼7.4 Hz), 7.38–7.40 (2H, m),7.78–7.79 (2H, m), 9.76 (1H, s); 13C NMR (CDCl3, 75 MHz)  23.3, 26.5, 34.7, 42.8, 126.2, 127.9, 128.5, 133.1, 137.2, 141.7, 198.1, 201.8; MS m/z (rel intensity) 190 (11, Mþ ), 131 (100); HRMS calcd. for C12H14O2190.0994. Found 190.0994. 3-(4-Oxopentyl)benzaldehyde (6g)

Wacker oxidation of 3-(4-pentenyl)benzaldehyde (5e, 261 mg, 1.5 mmol), according to the procedure similar to that for 6d, gave 6g (203 mg, 71%), along with a 12% recovery of the starting material.

6g: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.17; IR (neat) 1713 cm 1 ; 1 H NMR(CDCl3, 200 MHz)  1.91 (2H, quin, J ¼ 7.4 Hz), 2.11 (3H, s), 2.44 (2H, t, J ¼ 7.4 Hz), 2.68 (2H, t, J ¼ 7.4 Hz), 7.42–7.44 (2H, m), 7.67–7.72 (2H, m), 9.97 (1H, s);13C NMR (CDCl3, 50 MHz)  24.9, 30.0, 34.7, 42.6, 127.9, 129.1, 129.3, 134.7, 136.6, 142.7, 192.5, 208.3; MS m/z (rel intensity) 190 (84, Mþ ), 133 (100), 119 (16); HRMS calcd. for C12H14O2190.0994. Found 190.0992. 5-(3-Acetylphenyl)-2-pentanone (6h)

According to the procedure similar to that for 6d, coupling of 3-bromoacetophenone dimethyl acetal with 4-pentenylmagnesium bromide, followed by hydrolysis, afforded 3-(4-pentenyl)acetophenone (5f ), which was subjected to Wacker oxidation to give 6h (427 mg, 70%).

6h: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.13; 1H NMR (CDCl3, 200 MHz)  1.92 (2H, quin, J ¼ 7.5 Hz), 2.13 (3H, s), 2.46 (2H, t, J ¼7.5 Hz), 2.60 (3H, s), 2.68 (2H, t, J ¼ 7.5 Hz), 7.38–7.40 (2H, m), 7.77–7.82 (2H, m); 13C NMR (CDCl3, 50 MHz)  24.9, 26.5, 29.8, 34.7, 42.5, 126.0, 127.9, 128.5, 133.1, 137.0, 142.0, 198.2, 208.4; MS m/z (rel intensity) 204 (23, Mþ

), 147 (100); HRMS calcd. for C13H16O2204.1150. Found 204.1152.

1-Hydroxyindane-5-carbaldehyde (7a)

By a procedure similar to that for 2a, treatment of 6a (81 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7a (59 mg, 72%).

7a: Solid; m.p. 58
–59
C; TLC (EtOAc/hexane (3:7)) Rf¼0.24; IR (KBr) 1686, 3378 cm1;1H NMR (CDCl3, 200 MHz)  1.85–2.04 (1H, m), 2.44–2.60 (1H, m), 2.78–2.90 (1H, m), 2.98–3.15 (1H, m), 5.24 (1H, t, J ¼6.6 Hz), 7.51 (1H, d, J ¼ 8.1 Hz), 7.69 (1H, s), 7.70 (1H, d, J ¼8.1 Hz), 9.93 (1H, s); 13C NMR (CDCl3, 50 MHz)  29.3, 35.9, 75.8, 124.6, 125.8, 129.2, 136.6, 144.1, 151.9, 192.3; MS m/z (rel intensity) 162 (95, Mþ

), 133 (100); HRMS calcd. for C10H10O2162.0681. Found 162.0680.

Methyl 1-Hydroxyindane-5-carboxylate (7b)

By a procedure similar to that for 2a, treatment of 6b (96 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7b (34 mg, 35%).

7b: Solid; m.p. 68
–69
C; TLC (EtOAc/hexane (1:4)) Rf¼0.17; IR (KBr) 1718, 3418 cm1; 1H NMR (CDCl3, 200 MHz)  1.67 (1H, br s), 1.86–2.04 (1H, m), 2.48–2.60 (1H, m), 2.78–2.90 (1H, m), 2.98–3.12 (1H, m), 3.88 (3H, s), 5.24 (1H, t, J ¼ 6.4 Hz), 7.44 (1H, d, J ¼ 8.4 Hz), 7.88 (1H, s), 7.90 (1H, d, J ¼ 8.4 Hz);13C NMR (CDCl3, 75 MHz)  29.5, 36.0, 52.1, 75.9, 124.0, 126.1, 128.4, 130.1, 143.4, 150.0, 167.2; MS m/z (rel intensity) 192 (47, Mþ), 133 (100); HRMS calcd. for C11H12O3 192.0787. Found 192.0791.

5-Acetyl-1-indanol (7c)

By a procedure similar to that for 2a, treatment of 6c (88 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7c (63 mg, 72%).

7c: Solid; m.p. 45
–46
C; TLC (EtOAc/hexane (1:4)) Rf¼0.13; IR (KBr) 1678, 3388 cm1;1H NMR (CDCl3, 200 MHz)  1.88–2.02 (1H, m), 2.44–2.57 (1H, m), 2.55 (3H, s), 2.72–2.88 (1H, m), 2.96–3.02 (1H, m), 5.22 (1H, t, J ¼ 6.5 Hz), 7.43 (1H, d, J ¼ 8.3 Hz), 7.77 (1H, s), 7.78 (1H, d, J ¼ 8.3 Hz); 13C NMR (CDCl3, 50 MHz)  26.8, 29.5, 35.9, 75.8, 124.1, 124.7, 127.3, 137.2, 143.6, 150.3, 198.4; MS m/z (rel intensity) 176 (43, Mþ

), 161 (100); HRMS calcd. for C11H12O2176.0838. Found 176.0847.

1-Hydroxy-1-methylindane-5-carbaldehyde (7d)

By a procedure similar to that for 2a, treatment of 6d (88 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7d (62 mg, 70%).

7d: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.17; IR (neat) 1686, 3396 cm1;1H NMR (CDCl3, 300 MHz)  1.55 (3H, s), 1.72–1.68 (1H, m), 2.10 (1H, br s), 2.14–2.30 (1H, m), 2.81–2.91 (1H, m), 2.99–3.09 (1H, m), 7.47 (1H, d, J ¼ 8.2 Hz), 7.70 (1H, s), 7.73 (1H, d, J ¼ 8.2 Hz), 9.95 (1H, s); 13 C NMR (CDCl3, 75 MHz)  27.3, 29.1, 42.4, 80.9, 122.9, 126.0, 129.0, 129.5, 136.6, 143.4, 192.2; MS m/z (rel intensity) 176 (58, Mþ ), 161 (100); HRMS calcd. for C11H12O2176.0837. Found 176.0843.

1-Hydroxy-1,2,3,4-tetrahydro-6-naphthaldehyde (7e)

By a procedure similar to that for 2a, treatment of 6e (88 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7e (51 mg, 58%), along with a 14% recovery of 6e.

7e: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.18; IR (neat) 1698, 3387 cm1; 1H NMR (CDCl3, 200 MHz)  l.77–2.07 (4H, m), 2.18 (1H, br s), 2.82 (2H, m), 4.77 (1H, t, J ¼ 5.1 Hz), 7.57–7.68 (3H, m), 9.91 (1H, s); 13 C NMR (CDCl3, 50 MHz)  18.9, 29.0, 32.1, 68.1, 127.2, 129.0, 130.4, 135.4, 137.9, 145.6, 192.3; MS m/z (rel intensity) 176 (59, Mþ ), 147 (100); HRMS calcd. for C11H12O2176.0837. Found 176.0840.

6-Acetyl-1,2,3,4-tetrahydro-1-naphthol (7f)

By a procedure similar to that for 2a, treatment of 6f (95 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7f (68 mg, 71%), along with an 8% recovery of 6f. 7f: Oil; TLC (EtOAc/hexane (1:9)) Rf¼0.05; 1H NMR (CDCl3, 300 MHz)  l.76–2.05 (4H, m), 2.40 (1H, br s), 2.53 (3H, s), 2.70–2.86 (2H, m), 4.75 (1H, br s), 7.50 (1H, d, J ¼ 8.0 Hz), 7.64 (1H, s), 7.71 (1H, d, J ¼8.0 Hz); 13C NMR (CDCl3, 75 MHz)  18.9, 26.6, 29.2, 32.1, 67.9, 125.9, 128.6, 128.9, 136.0, 137.4, 144.2, 198.3; MS m/z (rel intensity) 190 (75, Mþ

), 147 (100); HRMS calcd. for C12H14O2190.0994. Found 190.0999.

1-Hydroxy-1-methyl-1,2,3,4-tetrahydro-6-naphthaldehyde (7g) By a procedure similar to that for 2a, treatment of 6g (95 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7g (59 mg, 62%), along with a 17% recovery of 6g.

7g: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.23; IR (neat) 1698, 3424 cm1; 1H NMR (CDCl3, 300 MHz)  1.57 (3H, s), 1.86–2.04 (5H, m), 2.85–2.89 (2H, m), 7.58 (1H, s), 7.70 (1H, d, J ¼ 8.0 Hz), 7.77 (1H, d, J ¼8.0 Hz), 9.95 (1H, s); 13C NMR (CDCl3, 75 MHz)  20.3, 29.6, 30.8, 38.4, 70.8, 127.2, 127.4, 130.5, 135.2, 137.1, 149.7, 192.2; MS m/z (rel inten-sity) 190 (1, Mþ), 175 (100); HRMS calcd. for C12H14O2190.0994. Found 190.0995.

6-Acetyl-1-methyl-1,2,3,4-tetrahydro-1-naphthol (7h)

By a procedure similar to that for 2a, treatment of 6h (102 mg, 0.5 mmol) with SmI2/HMPA in THF gave 7h (48 mg, 47%), along with a 19% recovery of 6h.

7h: Oil; TLC (EtOAc/hexane (1:4)) Rf¼0.17; IR (neat) 1681, 3433 cm1;1H NMR (CDCl3, 200 MHz)  1.51 (3H, s), 1.88–1.93 (4H, m),

2.13 (1H, br s), 2.52 (3H, s), 2.79 (2H, t, J ¼ 5.6 Hz), 7.61–7.70 (3H, m); 13

C NMR (CDCl3, 50 MHz)  20.3, 26.6, 29.7, 30.7, 39.4, 70.5, 126.1, 126.6, 128.8, 135.6, 136.4, 148.2, 198.2; MS m/z (rel intensity) 204 (7, Mþ

), 189 (100); HRMS calcd. for C13H16O2204.1150. Found 204.1152.

ACKNOWLEDGMENTS

We thank the National Science Council for financial support.

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