Synthesis of xanthenes, Indanes, and tetrahydronaphthalenes via intramolecular phenyl-carbonyl coupling reactions

Article abstract of DOI:10.1081/SCC-100103323

Benzaldehydes and acetophenones bearing tethered carbonyl chains underwent the intramolecular phenyl-carbonyl coupling reactions, by mediation of samarium diiodide and hexamethylphosphoramide, to afford the xanthenes and fused benzocarbocyclic compounds c

Full text of DOI:10.1081/SCC-100103323

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SYNTHESIS OF XANTHENES,
INDANES, AND
TETRAHYDRONAPHTHALENES
VIA INTRAMOLECULAR
PHENYL–CARBONYL COUPLING
REACTIONS
Chih-Wei Kuo a & Jim-Min Fang b
a Department of Chemistry , National Taiwan
University , Taipei, Taiwan, 106, Republic of China
b Department of Chemistry , National Taiwan
University , Taipei, Taiwan, 106, Republic of China
Published online: 09 Nov 2006.
To cite this article: Chih-Wei Kuo & Jim-Min Fang (2001) SYNTHESIS OF
XANTHENES, INDANES, AND TETRAHYDRONAPHTHALENES VIA INTRAMOLECULAR
PHENYL–CARBONYL COUPLING REACTIONS, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:6, 877-892, DOI: 10.1081/SCC-100103323
To link to this article: http://dx.doi.org/10.1081/SCC-100103323
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SYNTHETIC COMMUNICATIONS, 31(6), 877–892 (2001)
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–carbonyl
coupling reactions, by mediation of samarium diiodide and
hexamethylphosphoramide, to afford the xanthenes and fused
benzocarbocyclic compounds containing carbonyl and hydro-
xyl substituents.
INTRODUCTION
SmI2 is a one-electron-transfer reducing agent1–6 that can be utilized in
the reductive couplings of carbonyl compounds to form pinacols.7–9 When
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-
carbons16–21 may occur, depending on the reaction conditions. Besides the
well-documented pinacolic couplings of aromatic carbonyl compounds,7–9
* Corresponding author.
877
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

878
KUO AND FANG
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.23–25 We have also
demonstrated in four examples21,22 that 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 reaction26 with 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.
(1)
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 0ꢀC (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 xanthones27–30 3a 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

PHENYL–CARBONYL COUPLING REACTIONS
879
(2)
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.
(3)

880
KUO AND FANG
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 MnO2 in 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

PHENYL–CARBONYL COUPLING REACTIONS
881

882
KUO AND FANG
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 120ꢀC 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 110ꢀC 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)) Rf ¼ 0.25; IR (neat) 1701 cmÀ1
;
1H 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%).

PHENYL–CARBONYL COUPLING REACTIONS
883
1b: Solid; m.p. 58ꢀ–59ꢀC; TLC (EtOAc/hexane (1:19)) Rf ¼ 0.09; IR
1
(KBr) 1682, 1698 cmÀ1; H 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 SmI2 solution (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 0ꢀC. 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 0ꢀC 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)) Rf ¼ 0.28; IR (KBr) 1698, 3209 cmÀ1
;
1H NMR (CDCl3, 200 MHz) ꢀ 3.10 (1H, br s, OH), 5.71 (1H, s), 7.08–7.l8
(2H, m), 7.27À7.36 (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 À1), 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).

884
KUO AND FANG
2b: Oil; TLC (EtOAc/hexane (1:9)) Rf ¼ 0.13; IR (neat) 1701,
1
3389 cmÀ1; H 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);
13C 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 (MþÀCH4) 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. 125ꢀ–127ꢀC; 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 60ꢀC 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. >300ꢀC; 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 ¼ 1.4 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

PHENYL–CARBONYL COUPLING REACTIONS
885
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)) Rf ¼ 0.3; IR (neat) 1720, 3423 cmÀ1
;
1H 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 (C22H20O3ÀCH2O) 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 À78ꢀC.
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 CH2Cl2 solution (50 mL) of 5a (1.20 g,
7.5 mmol) at À78ꢀC 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)) Rf ¼ 0.12; IR (neat) 1698 cmÀ1
;
1H 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 C10H10O2 162.0681. Found 162.0696.

886
KUO AND FANG
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. 71ꢀ–72ꢀC; TLC (EtOAc/hexane (1:9)) Rf ¼ 0.24; IR
1
(KBr) 1720 cmÀ1; H 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)) Rf ¼ 0.15; IR (neat) 1683, 1712 cmÀ1
;
1H 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 ¼ 1.2 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 C11H12O2 176.0837. 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 CH2Cl2 after 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

PHENYL–CARBONYL COUPLING REACTIONS
887
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)) Rf ¼ 0.13; IR (neat) 1716 cmÀ1
;
1H 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);
13C 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 C11H12O2 176.0837. 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)) Rf ¼ 0.36; IR (neat) 1698 cmÀ1
;
1H NMR (CDCl3, 200 MHz) ꢀ 1.93 (2H, quin, J ¼ 7.2 Hz), 2.43 (2H, t,
J ¼ 7.2 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)) Rf ¼ 0.14; IR (neat) 1683, 1709 cmÀ1
;
1H NMR (CDCl3, 300 MHz) ꢀ 1.98 (2H, quin, J ¼ 7.4 Hz), 2.48 (2H, t,
J ¼ 7.4 Hz), 2.60 (3H, s), 2.72 (2H, t, J ¼ 7.4 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
C12H14O2 190.0994. 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.

888
KUO AND FANG
6g: Oil; TLC (EtOAc/hexane (1:9)) Rf ¼ 0.17; IR (neat) 1713 cmÀ1
;
1H 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
C12H14O2 190.0994. 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)) Rf ¼ 0.13; 1H NMR (CDCl3,
200 MHz) ꢀ 1.92 (2H, quin, J ¼ 7.5 Hz), 2.13 (3H, s), 2.46 (2H, t,
J ¼ 7.5 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 C13H16O2 204.1150.
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. 58ꢀ–59ꢀC; TLC (EtOAc/hexane (3:7)) Rf ¼ 0.24; IR
1
(KBr) 1686, 3378 cmÀ1; H 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 ¼ 6.6 Hz), 7.51 (1H, d, J ¼ 8.1 Hz), 7.69 (1H, s), 7.70 (1H, d,
J ¼ 8.1 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 C10H10O2 162.0681. 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%).

PHENYL–CARBONYL COUPLING REACTIONS
889
7b: Solid; m.p. 68ꢀ–69ꢀC; TLC (EtOAc/hexane (1:4)) Rf ¼ 0.17; IR
1
(KBr) 1718, 3418 cmÀ1; H 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. 45ꢀ–46ꢀC; TLC (EtOAc/hexane (1:4)) Rf ¼ 0.13; IR
1
(KBr) 1678, 3388 cmÀ1; H 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 C11H12O2 176.0838. 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)) Rf ¼ 0.17; IR (neat) 1686,
1
3396 cmÀ1; H 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);
13C 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 C11H12O2 176.0837. 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.

890
KUO AND FANG
7e: Oil; TLC (EtOAc/hexane (1:4)) Rf ¼ 0.18; IR (neat) 1698,
1
3387 cmÀ1; H 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);
13C 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 C11H12O2 176.0837. 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)) Rf ¼ 0.05; 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 ¼ 8.0 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 C12H14O2 190.0994. 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)) Rf ¼ 0.23; IR (neat) 1698,
1
3424 cmÀ1; H 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 ¼ 8.0 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 C12H14O2 190.0994. 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)) Rf ¼ 0.17; IR (neat) 1681,
1
3433 cmÀ1; H NMR (CDCl3, 200 MHz) ꢀ 1.51 (3H, s), 1.88–1.93 (4H, m),

PHENYL–CARBONYL COUPLING REACTIONS
891
2.13 (1H, br s), 2.52 (3H, s), 2.79 (2H, t, J ¼ 5.6 Hz), 7.61–7.70 (3H, m);
13C 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 C13H16O2 204.1150. Found 204.1152.
ACKNOWLEDGMENTS
We thank the National Science Council for financial support.
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Received in Japan April 13, 2000