Tetralones as precursors for the synthesis of 2,2′-disubstituted 1,1′-binaphthyls and related compounds

Article abstract of DOI:10.1016/j.tet.2008.08.079

Using tetralones as starting materials, the synthesis of biaryl compounds is described in this paper. The tetralones were initially converted into 1-bromo-3,4-dihydro-2-naphthalenecarbaldehydes before effecting aromatization into the corresponding naphthalenes. These products were then subjected to Suzuki-Miyaura cross-coupling reactions, with a variety of aromatic boronic acids containing substituents in the ortho position, to afford biaryl compounds. The biaryl compounds possess heteroatom containing substituents ortho to the newly formed biaryl axis.

Full text of DOI:10.1016/j.tet.2008.08.079

Tetrahedron 64 (2008) 10573–10580
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Tetralones as precursors for the synthesis of 2,20-disubstituted 1,
10-binaphthyls and related compounds
*
Simon S. Moleele, Joseph P. Michael, Charles B. de Koning
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 June 2008
Received in revised form 11 August 2008
Accepted 27 August 2008
Available online 3 September 2008
Using tetralones as starting materials, the synthesis of biaryl compounds is described in this paper. The
tetralones were initially converted into 1-bromo-3,4-dihydro-2-naphthalenecarbaldehydes before ef-
fecting aromatization into the corresponding naphthalenes. These products were then subjected to
Suzuki–Miyaura cross-coupling reactions, with a variety of aromatic boronic acids containing sub-
stituents in the ortho position, to afford biaryl compounds. The biaryl compounds possess heteroatom
containing substituents ortho to the newly formed biaryl axis.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
excess are obtained.12 Biaryl 5 can then be transformed into 8 in
a number of steps.
The synthesis of aromatic compounds containing biaryl axes is
important as a result of the biological activities associated with
biaryl natural products,1 as well as their use as ligands in transition
metal catalyzed reactions.2 Amongst this class of compounds are
biaryl compounds that possess two-heteroatom containing methy-
lene substituents ortho to the biaryl axis.
For example, the axially chiral secondary amine catalyst 1, which
finds application in the asymmetric hydroxyamination reaction,
has two methylene substituents attached to a shared nitrogen atom
(Fig. 1).3 In addition, the equivalent naphthyl basic skeleton, 1,10-
bis(hydroxymethyl)-2,20-binaphthyl 2, is found as a motif in Crams
host–guest complexation work.4 The naturally occurring com-
pound tellimagrandin II 3 contains two carbonyl functions flanking
the biaryl axis that could be derived from the corresponding biaryl
methyl alcohols.5
Another class of related biaryl compounds of interest to chem-
ists is the binaphthyl diol 4.6 These compounds have been
investigated as potential chiral photochromic optical triggers for
liquid crystals.7
General methods for the synthesis of biaryl compounds include
the use of oxidative coupling methods.8 Otherwise, traditional
methods for the assembly of the biaryl axis such as the Suzuki–
Miyaura, Stille and related reactions are generally used.9–11
For example, as shown in Figure 2 the synthesis of 5 proceeds by
means of a nickel-catalyzed coupling between arylbromide 6 and
Grignard 7. When this is mediated in the presence of a chiral fer-
rocene as shown in Figure 2, products with good enantiomeric
Recently, we have published the synthesis of aryl naphthalenes
using a different approach, where one of the rings of the naphtha-
lene was derived from commercially available a
-tetralones 9.13 The
tetralones are easily converted into halovinylaldehydes 10 before
being coupled with a variety of aromatic boronic acids 11 to provide
the aryldihydronaphthalenes 12. These were then converted into
1,2-disubstituted aryl naphthalenes such as 13 (Scheme 1).14
On completion of this work, we realized that if the aryl boronic
acid partner in this reaction contained a suitable substituent ortho
to the boronic acid moiety we would be able to assemble racemic
biarylnaphthalenes, such as 2, in a novel manner by using a com-
mercial tetralone as the starting material. Work toward this goal, as
well as related chemistry, is described in this paper.
HO
OH
HO
HO
CPh2OH
NH
O
O
O
HO
O
O
OR
RO
HO
RO
CPh2OH
R= 3,4,5-(HO)3C6H2CO, 3
(S)-1
OH
OH
OH
OH
(S)-2
4
* Corresponding author. Tel.: þ27 11 7176724; fax: þ27 11 7176749.
E-mail address: charles.dekoning@wits.ac.za (C.B. de Koning).
Figure 1.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.079

10574
S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
Table 1
Yields for Scheme 2
Entry
%
Entry
%
7
Br
14/15
16/18
17/19
76
70
80
15/20
18/21
19/22
98
77
94
PhPh2
catalytic Ni
6
MgBr
Fe
OEt
5
Steps
as shown in Scheme 3 and Table 2 afforded biarylnaphthalenes
26a–c, 27a–b, and 28a–c in good yields.
The next step entailed the removal of the isopropyl or benzyl
protecting group of either the phenol or naphthol and this proved to
NCOPh
8
B(OH)2
OiPr
Figure 2.
R1
23
R
R
R
R
i
ii
i
B(OH)2
OR
R
CHO
CHO
B(OH)2
Br
Br
O
R = R1= H 14
R = H; R1=OMe 16
R = R1=OMe 17
R=H or OMe; 10
R=H or OMe 9
R2= Bn, 24
R2=iPr, 25
R
R
R
R
11
OAc
Steps
R1
R1
CHO
R
Ar
Ar
ii
R
CHO
OR2
R=H or OMe; 12
R=H or OMe; 13
R
for R2=Bn
OH
Scheme 1. Reagents and conditions: (i) DMF, PBr3, CH2Cl2, reflux; (ii) cat. Pd(PPh3)4, aq
Na2CO3, boronic acid 11, DME/EtOH, reflux.
R = R1= H; R2 = Bn or iPr (see Table 2) 26a-c
R = H; R1=OMe; R2 = iPr 27a-b
R = R1= H 29
R1
R1
R = R1=OMe 30
Steps
i
R = R1=OMe; R2 = Bn or iPr (see Table 2) 28a-c
R
CHO
R
B(OH)2
CHO
Scheme 3. Reagents and conditions: (i) cat. Pd(PPh3)4, aq Na2CO3, boronic acid, DME/
EtOH, reflux; (ii) H2, Pd/C, EtOAc.
Br
O
R = R1= H 10a
R = R1= H 14
R = H; R1=OMe 16
R = R1=OMe 17
R = H; R1=OMe 10b
R = R1=OMe 10c
be problematic. For both 26c and 28c the protecting group was
a benzyl and we wished to remove it using standard hydrogenation
conditions with catalytic Pd/C. However, on performing the reaction
this not only resulted in the removal of the benzyl substituent but
also in the reduction of the aldehyde to the corresponding methyl
substituent to afford 29 and 30, respectively (Scheme 3 and Table 2).
As a next step the removal of the isopropyl protecting group of
26a, 27a, and 28a was attempted. Exposure of both substrates to
AlCl3 in dichloromethane resulted in a mixture of products 31a–c,
presumably as a mixture of both the hydroxyaldehydes and lactol as
shown in Scheme 4.15 However, the uncharacterized mixture of each
product was reduced with lithium aluminum hydride to afford
32a–c, unfortunatelyonly in mediocre yield over two steps (Table 3).
Removal of the isopropyl protecting groups of the related
naphthyl equivalents 26b–b did not meet with the same compli-
cations and 33a–c were isolated in good yields (Scheme 5).
Presumably this is as a result of more steric hindrance in the
naphthyl series and, therefore, cyclization is not taking place. All
three of these products were reduced separately into the desired
alcohols 34a–c in good yields.
11
R1
R1
ii
OH
OH
R
CHO
CHO
R
R = R1= H 15
R = R1= H 20
R = H; R1=OMe 18
R = R1=OMe 19
R = H; R1=OMe 21
R = R1=OMe 22
Scheme 2. Reagents and conditions: (i) cat. Pd(PPh3)4, aq Na2CO3, boronic acid 11,
DME/EtOH, reflux; (ii) NaBH4, EtOH reflux.
2. Results and discussion
Starting from 14 (prepared from a-tetralone 10a as previously
described13) using the well-developed Suzuki–Miyaura reaction
conditions, in the presence of commercially available for-
mylboronic acid 11, resulted in the formation of the desired
product 15 in excellent yields. Treatment of naphthylaldehydes 16
and 17, prepared from tetralones 10b and 10c under the same
reaction conditions (details described in Section 3) also afforded
the desired compounds 18 and 19 in excellent yield. All three
naphthylaldehydes were then reduced with sodium borohydride
to afford the desired products 20, 21, and 22 each containing two
methyl alcohol substituents ortho to the newly formed biaryl axis
(Table 1).
Table 2
Yields for Scheme 3
Entry
ArOR2
%
Entry
%
14/26a
14/26b
14/26c
16/27a
16/27b
17/28a
17/28b
17/28c
Phenyl, R2¼iPr
Naphthyl, R2¼iPr
Phenyl, R2¼Bn
Phenyl, R2¼iPr
Naphthyl, R2¼iPr
Phenyl, R2¼iPr
Naphthyl, R2¼iPr
Phenyl, R2¼Bn
97
79
94
74
87
80
60
97
26c/29
68
Alternatively, the three naphthalene derivatives 14, 16, and 17
were subjected to the same Suzuki–Miyaura reaction conditions in
the presence of 2-isopropoxynaphthylboronic acid 23, 2-benzyl
oxyphenyl boronic acid 24, and isopropoxyphenylboronic acid 25
28c/30
73

S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
10575
R1
R2
R1
R1
R2
R1
R2
i
CHO
OiPr
R2
CHO
OiPr
i
CHO
OH
CHO
OH
R1=R2= H, 26a
R1=OMe R2=H, 27a
R1=R2=OMe, 28a
R1=R2= H, 31a
R1=OMe R2=H, 31b
R1=R2=OMe, 31c
R1=R2= H, 26b
R1=OMe R2=H, 27b
R1=R2=OMe, 28b
R1=R2= H, 33a
R1=OMe R2=H, 33b
R1=R2=OMe, 33c
R1
R2
R1
R2
OH
O
OH
OH
R1
ii
ii
OH
OH
R2
R1=R2= H, 32a
R1=OMe R2=H, 32b
R1=R2=OMe, 32c
R1=R2= H, 34a
R1=OMe R2=H, 34b
R1=R2=OMe, 34c
Scheme 4. Reagents and conditions: (i) AlCl3, CH2Cl2; (ii) NaBH4, EtOH.
Scheme 5. Reagents and conditions: (i) AlCl3, CH2Cl2; (ii) NaBH4, EtOH.
In summary, by using tetralones as starting materials, biaryl
compounds containing substituents ortho to the biaryl axes can
easily be synthesized. These ortho disubstituted products can po-
tentially be utilized as ligands in metal catalyzed reactions.
allowed to cool to room temperature before being filtered and
washed with excess dichloromethane. The excess solvent was re-
moved on a rotary evaporator to obtain a black oil that was purified
by column chromatography using 5% ethyl acetate/hexane as eluent
to give the desired product 14 as a bright yellow solid (0.31 g, 69%
3. Experimental
3.1. General
yield). Mp¼106–108 ꢁC;13 1H NMR
d/ppm 10.67 (1H, s, CHO), 8.53–
8.50 (1H, m, ArH), 7.95–7.84 (3H, m, 3ꢂArH), 7.72–7.67 (2H, m,
2ꢂArH).
All reagents used were analytical grade reagents from Fluka and
Aldrich. n-BuLi was obtained from Aldrich and used as supplied.
THF was dried by distillation from sodium wire/benzophenone,
DMF by distillation from CaH2. All other solvents were BDH/HP high
purity grade and distilled before use. Thin layer chromatography
was carried out on Macherey-Nagel Alugram Sil G/UV254 Plates,
pre-coated with 0.25 mm silica gel 60. Detection was done under
ultra violet light at 254 nm. For column chromatography,
Macherey-Nagel silica gel (32–63 microns) was used, with gel mass
30 times that of sample, eluting with the stated solvent mixtures.
Melting points were determined on a Reichert hot-stage micro-
scope. Infrared spectra were run on the Bruker Vector 22 Fourier
Transform spectrometer. Absorption maxima are reported in
wavenumbers (cmꢀ1), with s¼strong, m¼medium, and w¼weak.
NMR spectroscopic analysis was done on an Ultrashield 300 MHz/
54 Bohr magnet. The frequency at which 1H NMR spectra were
reported was 300.131 MHz (rounded to 300 MHz) using tetrame-
thylsilane at 0.000 ppm as a standard. These spectra are reported as
parts per million (ppm), with s¼singlet, d¼doublet, dd¼doublet of
a doublet, t¼triplet, m¼multiplet. The 13C NMR spectra were
reported at a frequency of 75.475 MHz (rounded to 75 MHz) using
CDCl3 at 77.00 ppm as a standard.
3.3. 1-Bromo-6-methoxy-2-naphthaldehyde 16
Using the same procedure as described above, 6-methoxy-1-
bromo-3,4-dihydro-2-naphthaldehyde (3.98 g, 14.9 mmol) was
converted to 6-methoxy-1-bromo-2-naphthaldehyde 16 in the
presence of selenium powder (2.30 g, 29.8 mmol) and dimethyl
sulfoxide (2 ml). The product was obtained as a light brown solid
(2.85 g, 72% yield). Mp¼123–126 ꢁC;13 1H NMR
d/ppm 10.58 (1H, s,
CHO), 8.36 (1H, d, J¼9.4 Hz, ArH), 7.87 (1H, d, J¼8.6 Hz, ArH), 7.68
(1H, d, J¼8.8 Hz, ArH), 7.28 (1H, dd, J¼2.5, 9.4 Hz, ArH), 7.11 (1H, d,
J¼2.5 Hz, ArH), 3.96 (3H, s, OMe).
3.4. 1-Bromo-6,7-dimethoxy-2-naphthaldehyde 17
Using the same procedure as described above, 6,7-dimethoxy-1-
bromo-3,4-dihydro-2-naphthaldehyde (2.56 g, 8.65 mmol) was
converted to 6,7-dimethoxy-1-bromo-2-naphthaldehyde in the
presence of selenium powder (1.37 g, 17.3 mmol) and dimethyl
sulfoxide (2 ml). Product 17 was obtained as a light brown oil
(1.62 g, 64% yield). IR nmax (cmꢀ1) 1684 (s, C]O stretch), 1610 (s,
C]C stretch); 1H NMR
J¼8.4 Hz, 4-H), 7.76 (1H, s, 8-H), 7.61 (1H, d, J¼8.4 Hz, 3-H), 7.07
(1H, s, 5-H), 4.06 (3H, s, OMe), 4.03 (3H, s, OMe); 13C NMR
/ppm
d/ppm 10.56 (1H, s, CHO), 7.77 (1H, d,
d
3.2. 1-Bromo-2-naphthaldehyde 14
191.8 (CHO), 151.2 (C), 150.1 (C), 132.6, 128.8 (C), 127.9 (C), 126.7 (C),
125.3 (CH), 121.8 (CH), 105.6 (2ꢂCH), 55.4 (2ꢂOMe); MS (EI) m/z (%)
296 (Mþ81Br, 100), 295 (56), 294 (98), 293 (43), 206 (31), 178 (13),
150 (23), 144 (19), 116 (19), 115 (15); HRMS calculated for
1-Bromo-3,4-dihydro-2-naphthaldehyde (0.45 g, 1.89 mmol),
selenium powder (0.30 g, 5.69 mmol) and dimethyl sulfoxide
(0.5 ml) were slowly heated to 180 ꢁC. The reaction mixture was
heated at the same temperature for 5 min. The mixture was then
C
13H11O739Br Mþ 293.9892, found 293.9907.
3.5. 1-(2-Formylphenyl)-2-naphthaldehyde 15
Table 3
Comparison of yields over two steps for Schemes 4 and 5
To [Pd(PPh3)4] (0.52 g, 0.440 mmol) was added deoxygenated
solutions of 1-bromo-2-naphthaldehyde 14 (1.00 g, 4.42 mmol) in
DME (15 ml) and 2-formylphenylboronic acid (1.00 g, 6.64 mmol)
in ethanol (10 ml). This was followed by a deoxygenated solution of
aqueous sodium carbonate (4.06 g, 37.6 mmol in 19 ml water). The
Entry
%
Entry
%
26a/32a
27a/32b
28a/32c
45
41
52
26b/34a
27b/34b
28b/34c
97
75
84

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S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
resultant mixture was heated at reflux under nitrogen for 46 h over
which time it turned deep red. After allowing to cool to room
temperature, the mixture was quenched with water (50 ml) and
the organic material extracted with dichloromethane (3ꢂ100 ml).
The resultant organic extracts were combined, dried (MgSO4), fil-
tered through a Celite plug and the excess solvent removed using
a rotary evaporator. The resultant oil was purified by column
chromatography using 30% ethyl acetate/hexane as eluent to afford
dial 15 as a thick light brown oil (0.87 g, 76%).16 IR nmax (cmꢀ1) 1694
and dried (MgSO4) before being filtered through a Celite plug. The
excess dichloromethane was removed using a rotary evaporator.
The resultant oil purified by column chromatography using 30–50%
ethyl acetate/hexane as an eluent to obtain diol 20 as a thick yel-
lowish oil (0.82 g, 98%). IR nmax (cmꢀ1) 3406 (br s, O–H stretch),
1605, 1567 (s, C]C stretch); 1H NMR
d/ppm 7.89 (1H, d, J¼8.4 Hz,
ArH), 7.87 (1H, d, J¼7.8 Hz, ArH), 7.63 (1H, d, J¼8.4 Hz, ArH), 7.56
(1H, dd, J¼1.5, 7.2 Hz, ArH), 7.50–7.39 (3H, m, 3ꢂArH), 7.36–7.30
(1H, m, ArH), 7.18 (2H, br d, J¼8.4 Hz, 2ꢂArH), 4.46 (1H, d,
J¼11.7 Hz, ArCHaHbOH), 4.42 (1H, d, J¼11.7 Hz, ArCHaHbOH), 4.26
(1H, d, J¼11.6 Hz, PhCHcHdOH), 4.04 (1H, d, J¼11.6 Hz, PhCHcHdOH),
(vs, C]O), 1595 (m, C]C stretch); 1H NMR
d/ppm 9.84 (1H, s, CHO),
9.56 (1H, s, CHO), 8.17 (1H, dd, J¼1.5, 7.6 Hz, ArH), 8.10 (1H, d,
J¼8.6 Hz, ArH), 8.00 (1H, d, J¼8.6 Hz, ArH), 7.95 (1H, d, J¼8.1 Hz,
ArH), 7.78–7.60 (3H, m, 3ꢂArH), 7.48–7.36 (3H, m, 3ꢂArH); 13C
2.96 (2H, br s, 2ꢂOH); 13C NMR
d/ppm 139.5 (C), 137.6 (C), 136.6 (C),
136.2 (C), 132.9 (C), 132.6 (C), 130.6 (CH), 129.9 (CH), 128.4 (CH),
128.4 (CH),128.2 (CH),127.9 (CH), 127.3 (CH),126.3 (CH),126.2 (CH),
125.9 (CH), 63.1 (CH2OH), 63.0 (CH2OH); MS (EI) m/z (%) 264 (Mþ,
26), 246 (100), 231 (58), 215 (76), 202 (55); HRMS calculated for
NMR d/ppm 191.2 (CHO), 190.5 (CHO), 141.9 (C), 138.6 (C), 135.7 (C),
135.6 (C), 133.7 (CH), 132.8 (C), 132.2 (CH), 131.9 (C), 129.1 (CH),
129.1 (CH), 129.1 (CH), 128.4 (CH), 128.3 (CH), 127.5 (CH), 127.1 (CH),
122.2 (CH); MS (EI) m/z (%) 260 (Mþ, 25), 232 (28), 231 (100), 200
(11), 101 (9), 43 (3); HRMS calculated for C18H12O2 Mþ 260.0837,
found 260.0844.
C
18H16O2 Mþ 264.1150, found 264.1132.
3.9. [1-(2-Hydroxymethyl-phenyl)-6-methoxynaphthalen-2-
yl]-methanol 21
3.6. 1-(2-Formylphenyl)-6-methoxy-2-naphthaldehyde 18
Using the same methodology as outlined above, dial 18 (1.35 g,
4.65 mmol) in ethanol (10 ml) was converted into the diol 21 using
sodium borohydride (0.44 g, 11.6 mmol). The product was obtained
as sticky white flakes, which were further crystallized from
dichloromethane and hexane to give a white crystalline solid
(1.06 g, 77% yield). Mp¼147–148 ꢁC; IR nmax (cmꢀ1) 3385 (br s, O–H
In a similar way as described above 1-bromo-6-methoxy-2-
naphthaldehyde 16 (2.06 g, 7.77 mmol) in DME (20 ml) was stirred
together with 2-formylphenylboronic (1.75 g, 11.6 mmol), ethanol
(10 ml) and [Pd(PPh3)4] (0.90 g, 0.777 mmol) to give naph-
thaldehyde 18 as a brown oil (1.58 g, 70%). IR nmax (cmꢀ1) 1693,1677
(s, C]O stretch), 1617 and 1595 (s, C]C stretch); 1H NMR
d
/ppm
stretch), 1625, 1605 (s, C]C stretch); 1H NMR
d/ppm 7.76 (1H, d,
9.76 (1H, s, CHO), 9.56 (1H, s, CHO), 8.15 (1H, d, J¼7.5 Hz, ArH), 8.07
(1H, d, J¼8.7 Hz, ArH), 7.88 (1H, d, J¼8.7 Hz, ArH), 7.75–7.68 (2H, m,
2ꢂArH), 7.42 (1H, d, J¼6.9 Hz, ArH), 7.26–7.24 (2H, m, 2ꢂArH), 7.09
J¼8.4 Hz, ArH), 7.56–7.51 (2H, m, 2ꢂArH), 7.47–7.37 (2H, m,
2ꢂArH), 7.16–7.12 (2H, m, 2ꢂArH), 7.07 (1H, d, J¼9.2 Hz, ArH), 6.98
(1H, dd, J¼2.5, 9.2 Hz, ArH), 4.39 (1H, d, J¼11.6 Hz, ArCHaHbOH),
4.35 (1H, d, J¼11.6 Hz, ArCHaHbOH), 4.22 (1H, d, J¼11.6 Hz,
PhCHcHdOH), 4.02 (1H, d, J¼11.6 Hz, PhCHcHdOH), 3.91 (3H, s,
(1H, dd, J¼2.6, 9.2 Hz, ArH), 3.95 (3H, s, OCH3); 13C NMR
d/ppm
190.9 (CHO), 190.5 (CHO), 160.1 (C-6), 141.8 (C), 138.9 (C), 137.7 (C),
135.6 (C), 133.6 (CH), 132.1 (CH), 130.4 (C), 129.2 (CH), 128.7 (CH),
128.1 (CH), 128.0 (C), 127.9 (CH), 123.0 (CH), 120.2 (CH), 106.6 (CH),
55.5 (OCH3); MS (EI) m/z (%) 290 (Mþ, 45), 262 (22), 261 (100), 218
(19), 189 (25), 85 (15), 82 (22), 71 (20), 57 (43), 43 (38); HRMS
calculated for C19H14O3 Mþ 290.0943, found 290.0940.
OCH3), 3.23 (2H, br s, 2ꢂOH); 13C NMR
d/ppm 157.6 (6-C), 139.5 (C),
137.7 (C), 136.7 (C), 134.2 (C), 133.9 (C), 130.5 (CH), 129.9 (CH), 129.3
(C), 128.3 (CH), 128.0 (2ꢂCH), 127.9 (CH), 127.1 (CH), 118.8 (CH),
105.9 (CH), 62.9 (CH2OH), 62.8 (CH2OH), 55.3 (OCH3); MS (EI) m/z
(%) 294 (Mþ, 28), 276 (27), 264 (23), 188 (100), 171 (28), 159 (27),
144 (19), 128 (15), 115 (24), 91 (14); HRMS calculated for C19H18O3
Mþ 294.1256, found 294.1256.
3.7. 6,7-Dimethoxy-1-(2-formylphenyl)-2-naphthaldehyde 19
Using a similar method as described above, 1-bromo-6,7-
dimethoxy-2-naphthaldehyde 17 (1.00 g, 3.39 mmol) in DME
(10 ml) was mixed with 2-formylphenylboronic acid (0.76 g,
5.08 mmol) in ethanol (5 ml) using [Pd(PPh3)4] as the catalyst
(0.39 g, 0.339 mmol) gave dial 19 as a thick brown oil (0.86 g, 80%
yield). IR nmax (cmꢀ1) 1682 (s, C]O), 1619, 1595 (s, C]C stretch); 1H
3.10. [1-(2-Hydroxymethyl-phenyl)-6,7-dimethoxy-
naphthalen-2-yl]-methanol 22
Binaphthaldehyde 19 (0.80 g, 2.49 mmol) in ethanol (6 ml) was
similarly converted to diol 22 (0.75 g, 94% yield) using sodium
borohydride (0.24 g, 6.24 mmol). The product was obtained as
a thick yellow oil. IR nmax (cmꢀ1) 3337 (br s, O–H stretch), 1508 (s,
NMR d/ppm 9.77 (1H, s, CHO), 9.57 (1H, s, CHO), 8.18 (1H, d,
J¼7.6 Hz, ArH), 7.99 (1H, d, J¼8.6 Hz, ArH), 7.86 (1H, d, J¼8.6 Hz,
ArH), 7.81–7.68 (2H, m, 2ꢂArH), 7.45 (1H, d, J¼7.4 Hz, ArH), 7.24
(1H, s, 5-H), 6.56 (1H, s, 8-H), 4.05 (3H, s, OCH3), 3.67 (3H, s, OCH3);
C]C stretch); 1H NMR
d
/ppm 7.72 (1H, d, J¼8.3 Hz, ArH), 7.57–7.54
(1H, m, ArH), 7.48–7.39 (3H, m, 3ꢂArH), 7.17 (1H, d, J¼8.7 Hz, ArH),
7.15 (1H, s, 5-H), 6.40 (1H, s, 8-H), 4.41 (1H, d, J¼11.5 Hz, ArCH-
aHbOH), 4.36 (1H, d, J¼11.4 Hz, ArCHaHbOH), 4.25 (1H, d, J¼11.6 Hz,
PhCHcHdOH), 4.06 (1H, d, J¼11.6 Hz, PhCHcHdOH), 4.00 (3H, s,
13C NMR
d/ppm 191.2 (CHO), 190.8 (CHO), 151.9 (C), 150.6 (C), 139.8
(C), 139.4 (C), 135.5 (C), 133.8 (CH), 132.5 (C), 132.1 (CH), 130.9 (C),
129.2 (CH), 128.4 (C), 127.9 (CH), 127.4 (CH), 121.3 (CH), 106.7 (CH),
105.3 (CH), 56.1 (OCH3), 55.6 (OCH3); MS (EI) m/z (%) 320 (Mþ, 33),
291 (54), 216 (53), 206 (30), 178 (10), 150 (19), 86 (10), 84 (65), 82
(100); HRMS calculated for C20H16O4 Mþ 320.1049, found 320.1043.
OCH3), 3.63 (3H, s, OCH3), 3.04 (2H, br s, 2ꢂOH); 13C NMR
d/ppm
149.6 (C), 149.5 (C), 139.5 (C), 137.8 (C), 135.4 (C), 134.5 (C), 130.4
(CH), 129.9 (CH), 128.8 (C), 128.3 (CH), 128.2 (C), 128.1 (CH), 126.6
(CH), 125.7 (CH), 106.4 (CH), 105.0 (CH), 63.1 (CH2OH), 62.7
(CH2OH), 55.8 (OCH3), 55.5 (OCH3); MS (EI) m/z (%) 325 (Mþ1, 16),
324 (Mþ, 81), 306 (100), 291 (20), 278 (17), 275 (23), 261 (19), 245
(17), 215 (15), 203 (16), 189 (17); HRMS calculated for C20H20O4 Mþ
324.1362, found 324.1364.
3.8. 1-(2-Hydroxymethyl-phenyl)-2-naphthyl]-methanol 20
To a solution of dial 15 (0.83 g, 3.19 mmol) in ethanol (5 ml) was
added sodium borohydride (0.30 g, 7.97 mmol) portion-wise. The
reaction mixture warmed up and stirring was continued at room
temperature for 5 min before being poured into a separating funnel
containing water (50 ml). The organic material was extracted with
dichloromethane (3ꢂ100 ml) and the organic extracts combined
3.11. 1-(2-Isopropoxyphenyl)-2-naphthaldehyde 26a
Bromonaphthaldehyde 14 (1.00 g, 4.25 mmol) in DME (10 ml)
was stirred together with 2-isopropoxyphenylboronic acid 25

S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
10577
(1.15 g, 6.38 mmol) in ethanol (8 ml) using [Pd(PPh3)4] (0.49 g,
0.425 mmol) in a similar way as described above to give product
(1.42 g, 74% yield). IR nmax (cmꢀ1) 1677 (vs, C]O), 1618, 1596 (s,
C]C stretch); 1H NMR
/ppm 9.81 (1H, s, CHO), 8.03 (1H, d,
d
26a as a thick light brown oil (1.21 g, 97% yield). IR nmax (cmꢀ1
)
J¼8.6 Hz, ArH), 7.78 (1H, d, J¼8.6 Hz, ArH), 7.52 (1H, d, J¼9.2 Hz,
ArH), 7.47–7.42 (1H, m, ArH), 7.24–7.18 (2H, m, 2ꢂArH), 7.09–7.04
(3H, m, 3ꢂArH), 4.45–4.37 (1H, m, OCH(CH3)2), 3.97 (3H, s, OCH3),
1.06 (3H, d, J¼6.0 Hz, [OCH(CH3)2]), 0.99 (3H, d, J¼6.0 Hz,
1676 (s, C]O), 1618 (s, C]C stretch); 1H NMR
d/ppm 9.88 (1H, s,
CHO), 8.06 (1H, d, J¼8.6 Hz, ArH), 7.90 (2H, d, J¼8.9 Hz, 2ꢂArH),
7.64–7.56 (2H, m, 2ꢂArH), 7.44–7.38 (1H, m, ArH), 7.26–7.23 (2H,
m, 2ꢂArH), 7.11–7.05 (2H, m, 2ꢂArH), 4.46–4.38 (1H, m,
OCH(CH3)2), 1.06 (3H, d, J¼6.0 Hz, OCH(CH3)2), 0.97 (3H, d,
[OCH(CH3)2]); 13C NMR
d/ppm 193.4 (CHO), 160.1 (C), 156.4 (C),
144.1 (C), 138.5 (C), 133.2 (CH), 130.3 (CH), 130.0 (C), 129.3 (CH),
128.1 (C), 127.2 (CH), 125.5 (C), 123.2 (CH), 120.6 (CH), 119.4 (CH),
114.2 (CH), 106.7 (CH), 70.8 (OCH(CH3)2), 55.8 (OCH3), 22.3
(OCH(CH3)2); MS (EI) m/z (%) 320 (Mþ, 2), 263 (21), 218 (100), 131
(31), 100 (9), 69 (62); HRMS calculated for C21H20O3 Mþ 320.1412,
found 320.1399.
J¼6.0 Hz, OCH(CH3)2); 13C NMR
d/ppm 193.2 (CHO), 156.0 (C), 143.6
(C), 136.2 (C), 132.8 (CH), 132.5 (C), 132.0 (C), 131.2 (C), 129.9 (CH),
128.4 (CH), 128.1 (CH), 128.0 (CH), 127.5 (CH), 126.4 (CH), 124.9 (C),
121.9 (CH), 120.2 (CH), 113.7 (CH), 70.4 (OCH(CH3)2), 21.8
(OCH(CH3)2), 21.7 (OCH(CH3)2); MS (EI) m/z (%) 292 (Mþ2, 18), 291
(Mþ1, 15), 290 (Mþ, 63), 249 (40), 248 (72), 247 (50), 231 (100), 219
(31), 202 (28), 189 (28); HRMS calculated for C20H18O2 Mþ
290.1307, found 290.1295.
3.15. (2-Isopropoxynaphthyl)-6-methoxy-2-
naphthaldehyde 27b
3.12. 1-(2-Isopropoxynaphthyl)-2-naphthaldehyde 26b
Suzuki coupling of bromomethoxynaphthaldehyde 16 (1.00 g,
3.77 mmol) in DME (10 ml) with 2-isopropoxynaphthylboronic
acid 23 (1.30 g, 5.66 mmol) in ethanol (7 ml) using catalytic
[Pd(PPh3)4] (0.59 g, 0.377 mmol) gave naphthaldehyde 27b (1.22 g,
87% yield) as a thick light brown oil. IR nmax (cmꢀ1) 1694 (vs, C]O),
Similarly, 1-bromo-2-naphthaldehyde 14 (1.00 g, 4.25 mmol) in
DME (15 ml) was stirred together with 2-isopropoxynaphthy-
lboronic acid 23 (1.28 g, 6.38 mmol) in ethanol (7 ml) using cata-
lytic [Pd(PPh3)4] (0.48 g, 0.425 mmol) and sodium carbonate
(3.71 g, 36.2 mmol in 16 ml of water) to give naphthaldehyde 26b
as a thick light brown oil (1.52 g, 79%). IR nmax (cmꢀ1) 1687 (s, C]O),
1595 (s, C]C stretch); 1H NMR
d/ppm 9.62 (1H, s, CHO), 8.12 (1H, d,
J¼8.6 Hz, ArH), 7.99 (1H, d, J¼9.0 Hz, ArH), 7.87 (2H, d, J¼9.0 Hz,
2ꢂArH), 7.40 (1H, d, J¼9.0 Hz, ArH), 7.35–7.30 (1H, m, ArH), 7.25–
7.21 (3H, m, 3ꢂArH), 6.98–6.92 (2H, m, 2ꢂArH), 4.55 (1H, septet,
J¼6.0 Hz, OCH(CH3)2), 3.93 (3H, s, OCH3), 1.06 (3H, d, J¼6.0 Hz,
1623, 1594 (s, C]C stretch); 1H NMR
d/ppm 9.69 (1H, s, CHO), 8.15
(1H, d, J¼8.6 Hz, ArH), 8.01–7.86 (4H, m, 4ꢂArH), 7.59–7.54 (1H, m,
ArH), 7.42 (1H, d, J¼9.0 Hz, ArH), 7.35–7.23 (4H, m, 4ꢂArH), 6.96
(1H, d, J¼8.3 Hz, ArH), 4.61–4.49 (1H, m, OCH(CH3)2), 1.06 (3H, d,
J¼5.9 Hz, OCH(CH3)2), 0.94 (3H, d, J¼5.9 Hz, OCH(CH3)2); 13C NMR
OCH(CH3)2), 0.96 (3H, d, J¼6.0 Hz, OCH(CH3)2); 13C NMR
d/ppm
192.8 (CHO), 159.8 (C), 153.8 (C), 142.2 (C), 138.1 (C), 134.7 (C), 130.5
(C), 130.3 (CH), 129.1 (CH), 128.7 (C), 128.0 (C), 127.9 (CH), 127.0
(CH), 126.9 (CH), 125.2 (CH), 123.9 (CH), 122.9 (CH), 119.2 (CH), 118.9
(C), 115.8 (CH), 106.3 (CH), 71.3 (OCH(CH3)2), 55.4 (OCH3), 22.1
(OCH(CH3)2), 21.9 (OCH(CH3)2); MS (EI) m/z (%) 371 (Mþ1, 17), 370
(Mþ, 64), 328 (100), 311 (32), 268 (17), 255 (29), 239 (39), 226 (48),
185 (10); HRMS calculated for C25H22O3 Mþ 370.1569, found
370.1574.
d/ppm 192.8 (CHO), 153.7 (C), 142.0 (C), 136.2 (C), 134.6 (C), 132.7
(C), 132.1 (C), 130.3 (CH), 128.6 (C), 128.5 (CH), 128.2 (CH), 128.1
(CH), 127.9 (CH), 127.2 (CH), 126.9 (CH), 126.5 (CH), 125.0 (CH), 123.8
(CH), 121.9 (CH), 118.6 (C), 115.6 (CH), 71.0 (OCH(CH3)2), 21.9
(OCH(CH3)2); MS (EI) m/z (%) 342 (Mþ2, 16), 341 (Mþ1, 16), 340
(Mþ, 62), 298 (88), 281 (28), 269 (32), 252 (34), 239 (69), 155 (13),
144 (100), 127 (17); HRMS calculated for C24H20O2 Mþ 340.1463,
found 340.1463.
3.16. 6,7-Dimethoxy-1-(2-isopropoxyphenyl)-2-
naphthaldehyde 28a
3.13. 1-(2-Benzyloxyphenyl)-2-naphthaldehyde 26c
Similarly, bromodimethoxynaphthaldehyde 17 (0.50 g, 1.69 mmol)
in DME (10 ml) was reacted with 2-isopropoxyphenylboronic acid
25 (0.46 g, 2.54 mmol) in ethanol (7 ml) using catalytic [Pd(PPh3)4]
(0.20 g, 0.169 mmol) to give product 28a as a thick light brown oil
(0.47 g, 80% yield). IR nmax (cmꢀ1) 1678 (s, C]O), 1598 (s, C]C
Using the same experimental procedure as described above
bromonaphthaldehyde 14 (1.50 g, 6.81 mmol) in DME (15 ml) was
stirred together with 2-benzyloxyphenyl boronic acid 24 (2.17 g,
9.57 mmol) in ethanol (10 ml) using [Pd(PPh3)4] (0.74 g,
0.681 mmol) as catalysttoobtain the desired naphthaldehyde 26c as
a thick light brown oil (2.04 g, 94% yield). IR nmax (cmꢀ1) 1675 (s,
stretch); 1H NMR
d
/ppm 9.81 (1H, s, CHO), 7.94 (1H, d, J¼8.5 Hz,
ArH), 7.75 (1H, d, J¼8.5 Hz, ArH), 7.48–7.42 (1H, m, ArH), 7.26–
7.24 (1H, m, ArH), 7.18 (1H, s, ArH), 7.11–7.06 (2H, m, 2ꢂArH),
6.87 (1H, s, ArH), 4.46–4.38 (1H, m, OCH(CH3)2), 4.04 (3H, s,
OCH3), 3.74 (3H, s, OCH3), 1.07 (3H, d, J¼6.0 Hz, OCH(CH3)2), 1.01
C]O), 1618 (s, C]C stretch); 1H NMR
d/ppm 9.90 (1H, s, CHO), 8.07
(1H, d, J¼8.6 Hz, ArH), 7.93–7.89 (2H, m, 2ꢂArH), 7.63–7.56 (2H, m,
2ꢂArH), 7.47–7.39 (2H, m, 2ꢂArH), 7.28–7.25 (1H, m, 1ꢂArH), 7.15–
7.08 (5H, m, 5ꢂArH), 6.95–6.93 (2H, m, 2ꢂArH), 5.04 (1H, d,
J¼18.1 Hz, one of OCH2), 4.92 (1H, d, J¼18.1 Hz, one of OCH2); 13C
(3H, d, J¼6.0 Hz, OCH(CH3)2); 13C NMR
d/ppm 193.2 (CHO),
155.9 (C), 151.4 (C), 149.6 (C), 142.0 (C), 132.8 (C), 132.6 (CH),
130.0 (C), 129.8 (CH), 128.0 (C), 126.2 (CH), 125.3 (C), 120.8 (CH),
120.3 (CH), 113.8 (CH), 106.5 (CH), 106.0 (CH), 69.9 (OCH(CH3)2),
55.9 (OCH3), 55.6 (OCH3), 21.8 (OCH(CH3)2); MS (EI) m/z (%) 351
(Mþ1, 25), 350 (Mþ, 100), 307 (90), 306 (41), 290 (95), 280
(29), 205 (12), 120 (18), 83 (10); HRMS calculated for C22H22O4
Mþ 350.1518, found 350.1507.
NMR d/ppm 192.9 (CHO), 156.5 (C), 144.3 (C), 136.6 (C), 136.2 (C),
132.6 (CH), 132.5 (C), 131.3 (C), 130.0 (CH), 128.5 (CH), 128.2 (2ꢂCH),
128.1 (CH),127.6 (CH),127.6 (CH),126.6 (2ꢂCH),124.5 (C),121.9 (CH),
120.8 (CH), 112.8 (CH), 70.0 (OCH2), two CH carbons not observed;
MS (EI) m/z (%) 338 (Mþ, 5), 276 (3), 231 (8), 200 (4),184 (4), 91 (100),
65 (12); HRMS calculated for C24H18O2 Mþ 338.1307, found 338.1298.
3.14. 1-(2-Isopropoxyphenyl)-6-methoxy-2-
naphthaldehyde 27a
3.17. 6,7-Dimethoxy-1-(2-isopropoxynaphthyl)-2-
naphthaldehyde 28b
Bromomethoxynaphthaldehyde 16 (1.35 g, 5.09 mmol) in DME
(10 ml) was mixed with 2-isopropoxyphenylboronic acid 25 (1.74 g,
7.64 mmol) in ethanol (7 ml) and using [Pd(PPh3)4] (0.59 g,
0.509 mmol) as catalyst to give product 27a as a light brown oil
Suzuki coupling of bromodimethoxynaphthaldehyde 17 (1.00 g,
3.65 mmol) in DME (10 ml) with 2-isopropoxynaphthylboronic
acid 23 (1.07 g, 5.05 mmol) in ethanol (7 ml) using catalytic
[Pd(PPh3)4] (0.36 g, 0.365 mmol) gave naphthaldehyde 28b as

10578
S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
yellow flakes (0.81 g, 60% yield). Mp¼64–67 ꢁC; IR nmax (cmꢀ1
)
mixture was filtered and ethyl acetate removed on a rotary evap-
orator to give a white solid that was crystallized from dichloro-
methane and hexane. The resultant crystalline solid proved to be
product 30 (0.81 g, 73% yield). Mp¼61–62 ꢁC; IR nmax (cmꢀ1) 3538
1679 (vs, C]O), 1621, 1594 (s, C]C stretch); 1H NMR
d/ppm 9.61
(1H, s, CHO), 8.04 (1H, d, J¼8.5 Hz, ArH), 7.99 (1H, d, J¼9.1 Hz, ArH),
7.85 (1H, d, J¼7.9 Hz, ArH), 7.82 (1H, d, J¼7.9 Hz, ArH), 7.42 (1H, d,
J¼9.1 Hz, ArH), 7.36–7.30 (1H, m, ArH), 7.24–7.20 (2H, m, 2ꢂArH),
7.00 (1H, d, J¼8.4 Hz, ArH), 6.58 (1H, s, ArH), 4.56–4.49 (1H, m,
OCH(CH3)2), 4.04 (3H, s, OCH3), 3.47 (3H, s, OCH3), 1.07 (3H, d,
J¼6.0 Hz, [OCH(CH3)2]), 0.99 (3H, d, J¼6.0 Hz, [OCH(CH3)2]); 13C
(vs, br, O–H stretch),1575 (s, C]C stretch); 1H NMR
d/ppm 7.65 (1H,
d, J¼8.3 Hz, ArH), 7.39–7.32 (1H, m, ArH), 7.29 (1H, d, J¼8.3 Hz,
ArH), 7.15–7.03 (4H, m, 4ꢂArH), 6.68 (1H, s, ArH), 3.99 (3H, s, OCH3),
3.71 (3H, s, OCH3), 2.21 (3H, s, CH3); 13C NMR
d/ppm 152.9 (C), 149.7
NMR
d
/ppm 192.3 (CHO), 153.7 (C), 151.5 (C), 149.7 (C), 140.0 (C),
(C), 148.9 (C), 133.5 (C), 130.2 (CH), 129.9 (C), 129.2 (CH), 128.6 (C),
127.8 (C), 126.8 (CH), 126.7 (CH), 125.2 (C), 120.6 (CH), 115.4 (CH),
106.4 (CH), 104.1 (CH), 55.7 (OCH3), 55.4 (OCH3), 20.1 (CH3); MS (EI)
m/z (%) 295 (Mþ1, 21), 294 (Mþ, 100), 264 (4), 221 (3), 189 (3), 94
(2); HRMS calculated for C19H18O3 Mþ 294.1256, found 294.1252.
134.5 (CH), 132.8 (CH), 130.9 (CH), 130.3 (C), 130.2 (C), 128.7 (CH),
128.3 (CH), 127.9 (C), 127.8 (C), 126.9 (CH), 125.2 (CH), 123.9 (C),
121.0 (CH), 119.2 (CH), 115.8 (C), 106.6 (CH), 105.9 (CH), 55.9
(OCH(CH3)2), 55.5 (OCH3), 55.4 (OCH3), 22.3 (OCH(CH3)2), 22.2
(OCH(CH3)2); MS (EI) m/z (%) 401 (Mþ1, 18), 400 (Mþ, 62), 359 (25),
358 (100), 298 (14), 293 (22), 271 (13), 239 (16), 226 (22), 213 (20);
HRMS calculated for C26H24O4 Mþ 400.1675, found 400.1681.
3.21. 2-(2-Hydroxymethyl-naphthalen-1-yl)-phenol 32a
Naphthaldehyde 26a (1.00 g, 3.44 mmol) was treated with alu-
minum trichloride (0.92 g, 6.89 mmol) in dichloromethane (20 ml)
at room temperature for 1 h. Water was added to the mixture and
the organic material extracted into dichloromethane (2ꢂ40 ml).
After separation of the organic layer it was dried (MgSO4) and the
solvent evaporated. The resultant phenol/lactol was exposed to
sodium borohydride (16 mg, 4.30 mmol) in ethanol (10 ml) for
30 min. Water was added to the reaction mixture before diethyl
ether was used to extract the organic material. Separation of the
organic layer and drying (MgSO4) followed by evaporation of the
organic layer afford diol 32a as a white solid (0.39 g, 45% yield).
3.18. 6,7-Dimethoxy-1-(2-benzyloxyphenyl)-2-
naphthaldehyde 28c
In a similar manner as described above bromodimethox-
ynaphthaldehyde 17 (1.00 g, 3.37 mmol) in DME (15 ml) was stirred
with to 2-benzyloxyphenyl boronic acid 24 (1.16 g, 5.05 mmol) in
ethanol (7 ml) using catalytic [Pd(PPh3)4] (0.39 g, 0.337 mmol) to
afford naphthaldehyde 28c as a thick light yellow oil (1.30 g, 97%
yield). IR nmax (cmꢀ1) 1677 (s, C]O), 1620, 1595 (s, C]C stretch); 1H
NMR
d
/ppm 9.84 (1H, s, CHO), 7.97 (1H, d, J¼8.5 Hz, ArH), 7.77 (1H,
d, J¼8.5 Hz, ArH), 7.46–7.41 (1H, m, ArH), 7.28 (1H, dd, J¼1.6, 7.3 Hz,
ArH), 7.19 (1H, s, ArH), 7.18–7.09 (5H, m, 5ꢂArH), 6.99–6.97 (2H, m,
2ꢂArH), 6.81 (1H, s, ArH), 4.99 (2H, s, OCH2), 4.04 (3H, s, OCH3),
Mp¼165–167 ꢁC (lit. 117–118 ꢁC or 167–168 ꢁC);17 1H NMR
d/ppm
7.82 (1H, d, J¼8.0 Hz, ArH), 7.80 (1H, d, J¼8.4 Hz, ArH), 7.54 (1H, d,
J¼8.5 Hz, ArH), 7.47–7.26 (4H, m, 4ꢂArH), 7.06–6.95 (3H, m,
3ꢂArH), 4.44 (1H, d, J¼12.6 Hz, CHaHbOH), 4.39 (1H, d, J¼12.5 Hz,
CHaHbOH).
3.68 (3H, s, OCH3), one CH not apparent; 13C NMR
d/ppm 192.9
(CHO), 156.4 (C), 151.5 (C), 149.7 (C), 141.6 (C), 136.7 (C), 132.8 (C),
132.4 (CH), 130.2 (C), 129.9 (CH), 128.3 (2ꢂCH), 128.0 (C), 127.6 (CH),
126.6 (2ꢂCH), 126.5 (CH), 124.9 (C), 120.9 (CH), 112.9 (CH), 106.6
(CH), 105.9 (CH), 69.9 (OCH2), 56.0 (OCH3), 55.6 (OCH3); MS (EI) m/z
(%) 399 (Mþþ1, 19), 398 (Mþ, 64), 307 (21), 291 (100), 279 (11), 248
(11), 91 (85); HRMS calculated for C26H22O4 Mþ 398.1518, found
398.1526.
3.22. 2-(2-Hydroxymethyl-6-methoxynaphthalen-1-yl)-
phenol 32b
Using the same procedure as described above, isopropyl ether
27a (1.00 g, 3.57 mmol) was deprotected using aluminum tri-
chloride (0.95 g, 7.14 mmol) in dichloromethane (20 ml) and then
reduced to the diol 32b (0.36 g, 41% yield) using sodium borohy-
dride (0.17 g, 4.46 mmol) in ethanol (10 ml). The product was
3.19. 2-(2-Methyl-naphthalen-1yl)-phenol 29
Naphthaldehyde 26c (1.00 g, 3.13 mmol) together with ethyl
acetate (15 ml) and 10% Pd/C (35 mg, 0.313 mmol) was stirred un-
der an atmosphere of hydrogen gas for 8 h. After filtering off the Pd/
C the excess solvent was removed on a rotary evaporator. After
column chromatography of the residue product 29 (0.47 g, 68%
yield) was produced as a yellowish oil. IR nmax (cmꢀ1) 3411 (br s, O–
obtained as a white crystalline solid. Mp¼66–68 ꢁC; IR nmax (cmꢀ1
)
3316 (br s, O–H stretch), 1624 (s, C]C stretch); 1H NMR
d/ppm 7.69
(1H, d, J¼8.5 Hz, ArH), 7.49 (1H, d, J¼8.4 Hz, ArH), 7.31–7.26 (2H, m,
2ꢂArH), 7.10–6.95 (5H, m, 5ꢂArH), 4.42 (1H, d, J¼12.4 Hz, CHaH-
bOH), 4.32 (1H, d, J¼13.3 Hz, CHaHbOH), 3.88 (3H, s, OCH3); 13C NMR
d/ppm 157.6, 153.5, 134.6, 134.4, 132.7, 131.4, 129.4, 128.1, 127.8,
H stretch), 1581 (s, C]C stretch); 1H NMR
2ꢂArH), 7.42–7.31 (5H, m, 5ꢂArH), 7.10–6.99 (3H, m, 3ꢂArH), 2.22
(3H, s, CH3);16 13C NMR
/ppm 153.2 (C), 135.5 (C), 132.9 (C), 132.2
d/ppm 7.83–7.78 (2H, m,
127.5, 127.1, 124.6, 120.5, 118.9, 116.3, 105.9, 63.6 (CH2OH), 55.2
(OCH3); MS (EI) m/z (%) 281 (Mþ1, 5), 280 (Mþ, 28), 262 (86), 261
(100), 220 (16), 189 (16), 188 (17), 85 (49), 84 (76), 47 (17), 43 (14);
HRMS calculated for C18H16O3 Mþ 280.1099, found 280.1085.
d
(C), 131.4 (C), 130.9 (CH), 129.2 (CH), 128.6 (CH), 128.3 (CH), 127.8
(CH), 126.4 (CH), 125.4 (CH), 125.2 (CH), 125.0 (C), 120.5 (CH), 115.5
(CH), 20.6 (CH3).
3.23. 2-(2-Hydroxymethyl-6,7-dimethoxynaphthalen-1-yl)-
phenol 32c
3.20. 2-(6,7-Dimethoxy-2-methyl-naphthalen-1yl)-phenol 30
In the same manner as outlined above, naphthaldehyde 28a
(1.05 g, 3.38 mmol) was treated with aluminum trichloride (0.90 g,
6.77 mmol) in dichloromethane (25 ml) and then with sodium
borohydride (0.16 g, 4.22 mmol) in ethanol (10 ml) to give the diol
32c as white flakes (0.46 g, 52% yield). Mp¼66–68 ꢁC; IR nmax
(cmꢀ1) 3460 (br s, O–H stretch), 1577 (s, C]C stretch); 1H NMR
To a solution of naphthaldehyde 28c (1.50 g, 3.76 mmol) in ethyl
acetate (20 ml) was added 10% Pd/C (0.04 g, 0.376 mmol) in one
portion. After evacuating the system, hydrogen gas was allowed to
diffuse slowly from a balloon into the stirred reaction vessel. The
reaction was then stirred for a period of 8 h. An aliquot of the re-
action was taken and characterized by NMR spectroscopy and the
results showed that the O-benzyl group was still intact but the
aromatic aldehyde had been reduced to an alcohol. Therefore, extra
Pd/C was added to the reaction and the reaction mixture stirred
under a hydrogen atmosphere over a period of another 8 h. The
d
/ppm 7.71 (1H, d, J¼8.4 Hz, ArH), 7.47 (1H, d, J¼8.3 Hz, ArH), 7.38–
7.32 (1H, m, ArH), 7.13 (1H, s, ArH), 7.12 (1H, d, J¼6.8 Hz, ArH), 7.05
(2H, d, J¼7.7 Hz, 2ꢂArH), 6.66 (1H, s, ArH), 4.42 (2H, s, CH2OH), 3.99
(3H, s, OCH3), 3.69 (3H, s, OCH3); 13C NMR
d/ppm 153.5 (C), 149.9
(C), 149.7 (C), 135.3 (C), 131.2 (CH), 130.9 (C), 129.7 (CH), 129.3 (C),

S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
10579
128.6 (C), 127.3 (CH), 124.9 (CH), 124.8 (C), 120.8 (CH), 116.4 (CH),
3.27. 20-Hydroxymethyl-[1,10]binaphthalenyl-2-ol 34a
106.4 (CH), 104.7 (CH), 63.9 (CH2OH), 55.8 (OCH3), 55.5 (OCH3); MS
(EI) m/z (%) 310 (Mþ, 15), 292 (35), 291 (29), 263 (18), 218 (100), 214
(10), 149 (11), 130 (27), 68 (77), 41 (11); HRMS calculated for
To a solution of naphthaldehyde 33a (0.77 g, 2.58 mmol) in
ethanol (5 ml) was added sodium borohydride (0.12 g, 3.23 mmol)
portion-wise. The reaction mixture warmed up and was stirred at
room temperature for 5 min before being poured into a separating
funnel containing water (50 ml). The organic material was extrac-
ted with dichloromethane (3ꢂ100 ml) and the organic extracts
combined, dried (MgSO4) before being filtered through a Celite
plug. The excess dichloromethane was removed on a rotary evap-
orator and the resultant oil purified by column chromatography
using 30–50% ethyl acetate/hexane as an eluent to obtain the diol
34a as cream-white flakes (0.76 g, 99% yield). Mp¼162–164 ꢁC (lit.
Mp¼172–173 ꢁC);18 IR nmax (cmꢀ1) 3321 (br s, O–H stretch), 1579 (s,
C
19H18O4 Mþ 310.1205, found 310.1201.
3.24. 1-(20-Hydroxynaphthalen-2-yl)-2-naphthaldehyde 33a
To a solution of naphthaldehyde 26b (0.96 g, 2.69 mmol) in
dichloromethane (10 ml) was added aluminum trichloride (0.75 g,
5.39 mmol) in one portion. The reaction mixture immediately
turned deep red whilst warming up in the process. The mixture was
stirred at room temperature for 15 min after which time water was
added dropwise until the effervescence had stopped. The mixture
was then extracted with dichloromethane (3ꢂ100 ml) and the or-
ganic extracts combined before being dried (MgSO4), filtered
through a Celite plug and then the excess solvent was removed
using a rotary evaporator. The resultant brown oil was purified
using column chromatography with 10% ethyl acetate/hexane as an
eluent to obtain naphthaldehyde 33a as white flakes (0.78 g, 98%
C]C stretch); 1H NMR
d/ppm 7.90–7.82 (4H, m, 4ꢂArH), 7.67 (1H, d,
J¼8.5 Hz, ArH), 7.45–7.41 (1H, m, ArH), 7.31–7.13 (5H, m, 5ꢂArH),
6.87 (1H, d, J¼8.4 Hz, ArH), 4.31 (2H, s, CH2OH); 13C NMR
d/ppm
151.1 (C), 138.3 (C), 133.7 (C), 133.3 (CH), 132.9 (C), 129.9 (CH), 129.8
(C), 129.2 (CH), 128.9 (C), 128.1 (2ꢂCH), 127.4 (C), 126.7 (CH), 126.3
(CH), 126.1 (CH), 125.9 (CH), 124.4 (CH), 123.5 (CH), 117.9 (CH), 116.8
(C), 63.4 (CH2OH); MS (EI) m/z (%) 300 (Mþ, 27), 284 (22), 283 (28),
281 (100), 252 (30), 239 (19), 126 (12), 113 (6), 43 (8); HRMS cal-
culated for C21H16O2 Mþ 300.1150, found 300.1164.
yield). Mp¼97–98 ꢁC (lit. 70–71 ꢁC);18 1H NMR
d/ppm 9.67 (1H, s,
CHO), 8.16 (1H, d, J¼8.6 Hz, ArH), 8.04 (1H, d, J¼8.6 Hz, ArH), 7.96
(2H, d, J¼8.7 Hz, 2ꢂArH), 7.89–7.87 (1H, m, ArH), 7.65–7.59 (1H, m,
ArH), 7.45 (1H, d, J¼8.2 Hz, ArH), 7.39–7.22 (4H, m, 4ꢂArH), 6.93
(1H, d, J¼8.4 Hz, ArH).
3.28. 20-Hydroxymethyl-60-methoxy-[1,10]binaphth-
alenyl-2-ol 34b
3.25. 1-(20-Hydroxynaphthalen-2-yl)-6-methoxy-2-
naphthaldehyde 33b
In a similar manner as outlined above, naphthaldehyde 33b
(0.60 g, 1.83 mmol) in ethanol (5 ml) was reduced to yield the diol
34b (0.55 g, 92% yield) as white flakes, using sodium borohydride
(0.09 g, 2.28 mmol) as the reductant. Mp¼89–92 ꢁC; IR nmax (cmꢀ1
)
In
a similar manner as described above, methoxynaph-
3372 (br s, O–H stretch),1617 (s, C]C stretch); 1H NMR
d/ppm 7.86–
thaldehyde 27b (1.10 g, 2.97 mmol) in dichloromethane (15 ml) was
converted to naphthaldehyde 33b (0.79 g, 81% yield), using alu-
minum trichloride (0.79 g, 5.94 mmol) to afford the product as
a brown solid. Mp¼187–190 ꢁC; IR nmax (cmꢀ1) 3372 (br s, O–H
7.79 (3H, m, 3ꢂArH), 7.63 (1H, d, J¼8.5 Hz, ArH), 7.32–7.16 (4H, m,
4ꢂArH), 7.08 (1H, d, J¼9.2 Hz, ArH), 6.93–6.87 (2H, m, 2ꢂArH), 4.35
(2H, br s, CH2OH), 3.90 (3H, s, OCH3); 13C NMR
d/ppm 157.9 (C),
stretch), 1683 (s, C]O), 1618 (s, C]C stretch); 1H NMR
d/ppm 9.63
151.2 (C), 136.2 (C), 134.8 (C), 133.7 (C), 130.0 (CH), 129.7 (C), 129.0
(C), 128.4 (C), 128.2 (CH), 128.1 (CH), 127.6 (CH), 127.3 (CH), 126.8
(CH), 124.4 (CH), 123.5 (CH), 119.4 (CH), 117.9 (CH), 117.0 (C), 106.2
(CH), 63.6 (CH2OH), 55.3 (OCH3); MS (EI) m/z (%) 330 (Mþ, 18), 312
(100), 311 (70), 239 (15), 113 (5); HRMS calculated for C22H18O3 Mþ
330.1256, found 330.1254.
(1H, s, CHO), 8.17 (1H, d, J¼8.7 Hz, ArH), 7.96 (2H, d, J¼8.8 Hz,
2ꢂArH), 7.88 (1H, d, J¼7.7 Hz, ArH), 7.37–7.23 (5H, m, 5ꢂArH), 7.03
(1H, dd, J¼2.5, 9.2 Hz, ArH), 6.96 (1H, d, J¼8.4 Hz, ArH), 3.96 (3H, s,
OCH3); 13C NMR
d/ppm 191.9 (CHO), 160.5 (C), 151.6 (C), 138.7 (C),
134.4 (C), 131.5 (C), 130.9 (CH), 128.8 (C), 128.6 (CH), 128.4 (CH),
128.2 (CH), 127.8 (C), 127.4 (CH), 124.6 (CH), 123.9 (CH), 123.5 (CH),
120.3 (CH), 117.4 (CH), 113.8 (C), 106.7 (CH), 55.5 (OCH3); MS (EI) m/z
(%) 329 (Mþ1, 25), 328 (Mþ, 100), 311 (26), 220 (29), 186 (51), 185
(36), 144 (24), 68 (36); HRMS calculated for C22H16O3 Mþ 328.1099,
found 328.1110.
3.29. 20-Hydroxymethyl-60,70-dimethoxy-[1,10]binaphth-
alenyl-2-ol 34c
Using the same experimental procedure as described above,
aldehyde 33c (0.65 g, 1.81 mmol) in ethanol (5 ml) was reduced to
afford the diol 34c (0.64 g, 98% yield) as brownish flakes using
sodium borohydride (0.09 g, 2.27 mmol) as the reducing agent.
Mp¼88–90 ꢁC; IR nmax (cmꢀ1) 3319 (br s, O–H stretch), 3026 (s, C–H
3.26. 1-(20-Hydroxynaphthalen-2-yl)-6,7-dimethoxy-2-
naphthaldehyde 33c
stretch),1581 (s, C]C stretch),1040 (s, C–H stretch); 1H NMR
d/ppm
Naphthaldehyde 28b (0.70 g, 1.75 mmol) in dichloromethane
(10 ml) was converted to the desired product 33c (0.54 g, 86%
yield), as white flakes, using aluminum trichloride (0.47 g,
3.49 mmol) in the same manner as described above to yield the
product as white crystals. Mp¼195–197 ꢁC; IR nmax (cmꢀ1) 3376
(br s, O–H stretch), 1681 (s, C]O), 1601 (s, C]C stretch); 1H NMR
7.89–7.82 (2H, m, ArH), 7.76 (1H, d, J¼8.3 Hz, ArH), 7.56 (1H, d,
J¼8.4 Hz, ArH), 7.32–7.15 (4H, m, 4ꢂArH), 6.93 (1H, d, J¼8.4 Hz, ArH),
6.41 (1H, s, ArH), 5.67 (1H, br s, OH), 4.31 (2H, br s, CH2OH), 3.94 (3H,
s, OCH3), 3.44 (3H, s, OCH3); 13C NMR
d/ppm 151.1 (C),150.1 (C),149.7
(C),136.7 (C),133.5 (C),129.9 (CH),129.4 (C),128.9 (C),128.8 (C),128.1
(C), 128.0 (CH), 127.6 (CH), 126.7 (CH), 124.9 (CH), 124.3 (CH), 123.5
(CH), 117.9 (CH), 117.1 (C), 106.5 (CH), 104.6 (CH), 63.7 (CH2OH), 55.8
(OCH3), 55.4 (OCH3); MS (EI) m/z (%) 361 (Mþ1, 5), 360 (Mþ,18), 343
(21), 342 (100), 311 (21), 309 (11), 283 (6), 226 (6), 113 (6); HRMS
calculated for C23H20O4 Mþ 360.1362, found 360.1362.
d
/ppm 9.60 (1H, s, CHO), 8.08 (1H, d, J¼8.5 Hz, ArH), 7.97 (1H, d,
J¼8.9 Hz, ArH), 7.93 (1H, d, J¼8.6 Hz, ArH), 7.89 (1H, d, J¼8.2 Hz,
ArH), 7.38–7.26 (4H, m, 4ꢂArH), 6.99 (1H, d, J¼8.4 Hz, ArH), 6.66
(1H, s, ArH), 4.05 (3H, s, OCH3), 3.96 (3H, s, OCH3); 13C NMR
d/ppm
192.1 (CHO), 160.3 (C), 151.6 (C), 138.9 (C), 134.7 (C), 132.1 (C),
130.9 (CH), 128.8 (C), 128.3 (C), 128.2 (CH), 127.9 (CH), 127.3 (CH),
124.6 (CH), 123.8 (CH), 121.6 (CH), 117.4 (CH), 106.9 (CH), 106.4 (C),
104.9 (CH), 55.5 (OCH3), two carbons not visible; MS (EI) m/z (%)
359 (Mþ1, 27), 358 (Mþ, 100), 341 (17), 215 (10), 113 (7); HRMS
calculated for C23H18O4 Mþ 358.1205, found 358.1202.
Acknowledgements
This work was supported by the National Research Foundation
(NRF, GUN 2053652 and IRDP of the NRF (South Africa) for

10580
S.S. Moleele et al. / Tetrahedron 64 (2008) 10573–10580
8. See, for example Li, X.; Hewgley, J. B.; Mulrooney, C. A.; Yang, J.; Kozlowski, M. C.
J. Org. Chem. 2003, 68, 5500–5511 and references therein.
financial support provided by the Research Niche Areas pro-
gramme), Pretoria, and the University of the Witwatersrand (Sci-
ence Faculty Research Council). Professor WAL van Otterlo is
thanked for many helpful discussions and in the preparation of the
manuscript. We also gratefully acknowledge the Mellon Post-
graduate Mentoring Programme (sponsored by the Andrew W.
Mellon Foundation) for generous funding to Mr. S.S.M. and for
funding some of the running expenses. Mr. R. Mampa and Mr. T.
van der Merwe are also thanked for providing the NMR and MS
spectroscopy services, respectively.
9. Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419–2440.
10. See, for example: (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; (b) Metal-Catalyzed Cross-Cou-
pling Reactions, 2nd rev. ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004.
11. Cross-coupling Reactions: A Practical Guide; Miyaura, N., Ed.; Springer: Berlin,
2002.
12. Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 8153–
8156.
13. Moleele, S. S.; Michael, J. P.; de Koning, C. B. Tetrahedron 2006, 62, 2831–2844.
14. (a) A review on the use of halovinyl aldehydes as synthetic intermediates has
recently appeared. Brahma, S.; Ray, J. K. Tetrahedron 2008, 64, 2883–2896; (b)
Halovinyl aldehydes have also been used extensively by Kirsch in synthesis see,
for example Hesse, S.; Kirsch, G. Tetrahedron 2005, 61, 6534–6539.
15. The formation of lactols has been investigated and reported by Professor
Bringmann. Bringmann, G.; Breuning, M.; Endress, H.; Vitt, D.; Peters, K.; Peters,
E.-M. Tetrahedron 1998, 54, 10677–10690.
16. Blum, J.; Yona, I.; Tsaroom, S.; Sasson, Y. J. Org. Chem. 1979, 44, 4178–4182.
17. (a) Bringmann, G.; Hartung, T.; Go¨bel, L.; Schupp, O.; Peters, K.; von Schnering,
H. G. Liebigs Ann. Chem. 1992, 769–776; (b) Shi, Y.; Wan, P. Can. J. Chem. 2005, 83,
1306–1323 The 1H NMR spectra of these products were run in CD3CN while the
1H NMR spectra of our products were run in CDCl3. However, there were
general agreements between both sets of data.
References and notes
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2. For some ligand structures see, for example: (a) Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; Wiley-VCH: Weinheim, 2000; pp 801–854.
3. Kano, T.; Ueda, U.; Takai, J.; Maruoka, K. J. Am. Chem. Soc. 2006, 128, 6046–6047.
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