Suzuki-Miyaura homocoupling of naphthyl triflates using bis(pinacolato)diboron: Approaches to the biaryl skeleton of crisamicin A

Article abstract of DOI:10.1039/b303070a

Homocoupling of naphthyl triflates 27, 16, 17 to the respective binaphthyls 28, 31 and 35 has been achieved in a one-pot procedure using bis(pinacolato)diboron and PdCl₂(dppf). Use of potassium acetate as the base provides access to the initial naphthylboronate intermediates whereas the stronger base potassium phosphate is required in order to promote subsequent coupling of the naphthylboronate with a second equivalent of the naphthyl triflate. Attempts to convert binaphthyl 35 into bis-acetylnaphthalene 14, a key intermediate for the synthesis of the dimeric pyranonaphthoquinone antibiotic crisamicin A 2, via double Fries rearrangement of bis-acetate 37 derived from binaphthyl 35, were unsuccessful. Attempts to introduce the acetyl groups at C-7 and C-7′ on bis-acetylnaphthalene 14 via Fries rearrangement of the monomeric precursors 21 and 15, before effecting homocoupling to a biaryl were unsuccessful. Introduction of an acetyl group via initial bromination ortho to the hydroxyl group in naphthol 18, which bears an electron rich benzyl ether at C-7, was plagued by the formation of phenolic coupling product 42 and naphthoquinone 43. Bromination of naphthol 45, bearing a less electron rich triflate group at C-7, also afforded binaphthol 47 resulting from phenolic coupling as well as naphthoquinone 48 when using N-bromosuccinimide at low temperature.

Full text of DOI:10.1039/b303070a

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Suzuki–Miyaura homocoupling of naphthyl triflates using
bis(pinacolato)diboron: approaches to the biaryl skeleton of
crisamicin A
Margaret A. Brimble* and Michelle Y. H. Lai
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland, New Zealand
Received 17th March 2003, Accepted 1st May 2003
First published as an Advance Article on the web 13th May 2003
Homocoupling of naphthyl triflates 27, 16, 17 to the respective binaphthyls 28, 31 and 35 has been achieved in a one-
pot procedure using bis(pinacolato)diboron and PdCl2(dppf ). Use of potassium acetate as the base provides access
to the initial naphthylboronate intermediates whereas the stronger base potassium phosphate is required in order to
promote subsequent coupling of the naphthylboronate with a second equivalent of the naphthyl triflate. Attempts
to convert binaphthyl 35 into bis-acetylnaphthalene 14, a key intermediate for the synthesis of the dimeric
pyranonaphthoquinone antibiotic crisamicin A 2, via double Fries rearrangement of bis-acetate 37 derived from
binaphthyl 35, were unsuccessful. Attempts to introduce the acetyl groups at C-7 and C-7Ј on bis-acetylnaphthalene
14 via Fries rearrangement of the monomeric precursors 21 and 15, before effecting homocoupling to a biaryl were
unsuccessful. Introduction of an acetyl group via initial bromination ortho to the hydroxyl group in naphthol 18,
which bears an electron rich benzyl ether at C-7, was plagued by the formation of phenolic coupling product 42 and
naphthoquinone 43. Bromination of naphthol 45, bearing a less electron rich triflate group at C-7, also afforded
binaphthol 47 resulting from phenolic coupling as well as naphthoquinone 48 when using N-bromosuccinimide at
low temperature.
Introduction
Members of the pyranonaphthoquinone family of anti-
biotics contain
a
basic naphtho[2,3-c]pyran-5,10-dione
skeleton that is built up from acetate/malonate units via a
polyketide pathway.1 These antibiotics exhibit activity against a
variety of Gram-positive bacteria, pathogenic fungi and yeasts,
as well as antiviral activity. In addition, they have been
proposed to act as bioreductive alkylating agents.2 The diver-
sity of chemical structures found within the pyrano-
naphthoquinone family of antibiotics has prompted a number
of syntheses of this class of compound.3 Our initial synthetic
work in this area focused on the synthesis of the monomeric
pyranonaphthoquinone antibiotics via addition of 2-trimethyl-
silyloxyfuran to a 2-acetyl-1,4-naphthoquinone followed by
rearrangement of the resultant furonaphthofuran ring system
to a furonaphthopyran ring system using ceric ammonium
nitrate (CAN). This approach has been successfully used to
prepare analogues of the carbohydrate containing pyrano-
naphthoquinone antibiotics griseusin A4 and medermycin5 as
well as simpler members of the family such as the arizonins6
and kalafungin.7 The focus of the work reported herein is
directed towards the synthesis of the more complex dimeric
pyranonaphthoquinones such as actinorhodin 1 and the
crisamicins A 2 and C 3.
Whilst efficient syntheses of several monomeric pyrano-
naphthoquinones have been achieved, only one synthesis of a
dimeric pyranonaphthoquinone has been reported in which a
novel double furofuran annulation—oxidative rearrangement
strategy was used to prepare an analogue 4 (Scheme 1) of the
aphid pigment actinorhodin 1.8 In this case Suzuki–Miyaura
coupling of a bromonaphthalene 5 allowed construction of the
key biaryl linkage in 6 ortho to a methoxy group on the naph-
thalene ring, before the ensuing double furofuran annulation of
the bis-quinone 7 with 2-trimethylsilyloxyfuran 8 and oxidative
rearrangement of the resultant adduct 9 to the bis-lactol 10. In
this case the bromine in naphthalene 5 was strategically placed
via ortho-selective bromination of a naphthol precursor, at the
position where biaryl formation later took place.
It was envisaged that previous methodology employed for the
synthesis of the actinorhodin analogue 4 could be applied to
the synthesis of crisamicins A 2 and C 3, that were isolated from
the microorganism Micromonospora purpureochromogenes.9
Crisamicin A 2 exhibits activity against B16 murine melanoma
cells, herpes simplex virus and vesicular stomatitis virus.10 Our
strategy for the synthesis of crisamicin A 2 is outlined in
retrosynthetic terms (Scheme 2) and features the double oxid-
ative rearrangement of furonaphthofuran 12 to furonaphtho-
pyran 11 as a key step. In turn bisfuronaphthofuran 12 is
formed by double furofuran annulation of bis-naphthoquinone
13 with 2-trimethylsilyloxyfuran 8. The precursor to bis-
naphthoquinone 13 is bis-naphthalene 14 for which it is
envisaged that the critical biaryl linkage be constructed via
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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Scheme 1
Scheme 2
Suzuki–Miyaura homocoupling of one of the protected naph-
triflates 15, 16 or 17 with the ‘in-situ’ generated boronates
thyl triflates 15,16 or 17 that are derived from readily prepared
benzyl ether 18.11 Thus, in the case of crisamicin A 2 the lack of
an oxygen substituent ortho to the biaryl linkage precluded the
possibility of using a bromine atom to construct a biaryl hence
the use of a triflate to achieve this was a critical goal in the
present work.
derived from the same triflate, would provide an efficient entry
to the bis-naphthalene skeleton of crisamicin A 2. An import-
ant consideration was the choice of protecting group for the
hydroxyl group at the alpha position that is compatible with the
Suzuki–Miyaura coupling hence triflates 15, 16 and 17 bear-
ing an acetate, tert-butyldimethylsilyl or isopropyl ether were
selected. It was envisaged that after Suzuki–Miyaura coupling
and removal of the protecting group the resultant hydroxyl
group would provide functionality for introduction of an acetyl
group to the two ortho positions. Alternatively, it was hoped
that acetate 15 would undergo homocoupling and the acetate
groups on the resultant biaryl could then be subjected to double
Fries rearrangement in order to introduce the ortho-acetyl
groups in bis-naphthalene 14.
Results and discussion
Miyaura and co-workers12 have reported the use of bis(pinaco-
lato)diboron and PdCl2(dppf†)–KOAc as a method to prepare
aryl boronates from aryl triflates. In the same paper they also
report the synthesis of unsymmetrical biaryls by cross-coupling
the ‘in-situ’ generated boronate esters with another triflate in
the presence of potassium phosphate. As an extension to this
work we proposed that homocoupling of one of the protected
Triflates 15, 16 and 17 were prepared from benzyl ether 18
which in turn is available in seven steps from 5-bromovanillin
via acid catalysed fragmentation of the Diels–Alder adduct
formed from addition of benzyne 19 to 2-methoxyfuran 20
(Scheme 3).11 Protection of the hydroxyl group as either an
† dppf = 1,1Ј-Bis(diphenylphosphino)ferrocene.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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Scheme 3 Reagents, conditions and yields: (i) see ref. 11; (ii) 21, Ac2O, py, 18 h, 73%; 22, ClSitBuMe2, imid., DMAP, CH2Cl2, room temp., 20 h, 67%;
23, NaH, DMF, 1 h, then 2-bromopropane, room temp., 3.5 h, 89%; (iii) 10% Pd/C, H2, EtOAc, 24, 5 h, 81%; 25, 1 h, 89%; 26, 1.5 h, 78%; (iv) 15,
Tf2O, Et3N, CH2Cl2, Ϫ20 ЊC, 18.5 h, 82%; 16, 23.5 h, 96%; 17, PhNTf2, Et3N, CH2Cl2, Ϫ25 ЊC, 15 h, 81%.
acetate 21, a tert-butyldimethylsilyl ether 22 or an isopropyl
ether 23 was then effected under standard conditions. Removal
of the benzyl ether by hydrogenolysis over palladium on char-
coal afforded naphthols 24, 25 or 26 respectively, that were then
treated with trifluoromethanesulfonic anhydride or N-phenyl-
trifluoromethanesulfonimide to afford triflates 15, 16 and 17 in
good yield.
In preparation for the key Suzuki–Miyaura coupling of tri-
flates 15, 16 and 17 to binaphthyls it was initially decided to
investigate the homocoupling of 2-naphthyl triflate 2713 into
binaphthyl 28. One method for direct reduction of 2-naphthyl
triflate 27 using zinc metal catalysed by palladium() acetate
and ( )-1,1Ј-BINAP, as reported by Jutand and Mosleh,14
afforded binaphthyl 28 in 67% yield (Scheme 4).
one-pot ‘in situ’ coupling directly to the biaryl. Potassium acet-
ate is used as the base to form the naphthylboronate whereas
the stronger base potassium phosphate is required to effect
formation of the biaryl. Comparison of these two procedures
described by Miyaura et al.12 using 2-naphthyl triflate 27 led to
the conclusion that the best yielding method was the one-pot
‘in situ’ coupling of boronate 29 with 2-naphthyl triflate 27
affording binaphthyl 28 in 84% yield compared to 31% yield
when using the stepwise coupling. The use of potassium acetate
for the initial formation of the naphthylboronate 29 was import-
ant in order to minimize the formation of the by-product,
naphthalene.
Having established the optimum method for effecting homo-
coupling of 2-naphthyl triflate 27 attention turned to the homo-
coupling of triflates 15, 16 and 17 using similar conditions.
Treatment of triflate 15 bearing an acetate group at C-1, with
zinc and palladium() acetate afforded mainly recovered start-
ing material as did attempts to effect Suzuki–Miyaura homo-
coupling using bis(pinacolato)diboron. On the other hand, silyl
ether 16 underwent smooth conversion into naphthylboronate
30 (Scheme 5) with bis(pinacolato)diboron and subsequent
coupling of 30 with triflate 16 afforded biaryl 31 in low yield
together with deprotected material 32 and reduced product 33.
In this case use of the one pot method did not improve the yield
of biaryl 31.
In the case of the isopropyl protected triflate 17, naphthyl-
boronate 34 was prepared in 50% yield by treatment with
bis(pinacolato)diboron in 1,2-dichloroethane using PdCl2(dppf )
Scheme 4 Reagents, conditions and yields: (i) Zn, Pd(OAc)2, ( )-1,1Ј-
BINAP, DMF, 120 ЊC, 1.5 h, 67%; (ii) pinacolborane (3.0 equiv., 1.0 M
in THF), PdCl2(dppf ), Et3N, 1,2-dichloroethane, 110 ЊC, 53%; pina-
colborane (1.5 equiv., 97%), PdCl2(dppf ), Et3N, 1,2-dichloroethane,
110 ЊC, 50%; bis(pinacolato)diboron (1.1 equiv.), PdCl2(dppf ), dppf,
KOAc, dioxane, reflux, 2.5 h, 54%; (iii) triflate 27, PdCl2(dppf ), K3PO4,
dioxane, reflux, 5 h, 58%; (iv) bis(pinacolato)diboron (1.1 equiv.),
PdCl2(dppf ), dppf, KOAc, dioxane, reflux, 2.5 h, then K3PO4, heat,
18 h, 84%.
In an attempt to improve the yield of binaphthyl 28 we next
turned to Suzuki–Miyaura coupling using pinacolboronate 29
(Scheme 4). Pinacolboronate 29 was generated from 2-naphthyl
triflate 27 using pinacolborane in 50–53% yield using pinacol-
borane (1.0 M in THF, 3.0 equiv.), triethylamine and PdCl2-
(dppf ) in 1,2-dichloroethane at 110 ЊC following the method of
Murata et al.15 Use of neat pinacolborane (1.5 equiv., 97%) did
not improve the yield of naphthylboronate 29 with substantial
formation of naphthalene as a by-product also being formed in
this case. This observation may be attributed to the pinacol-
borone acting as a hydride source and effecting cross-coupling
with the pinacolboronate.15,16
We next focussed on the use of bis(pinacolato)diboron as the
boronating agent following the method reported by Miyaura
et al.12 In this case one can either form the arylboronate first
and then effect homocoupling to the biaryl or one can employ a
Scheme 5 Reagents, conditions and yields: (i) bis(pinacolato)diboron
(1.1 equiv.), PdCl2(dppf ), dppf, KOAc, dioxane, reflux, 1.5 h, 80%;
(ii) triflate 16, PdCl2(dppf ), K3PO4, dioxane, reflux, 1.5 h, 31, 22%; 32,
16%; 33, 4%.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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Scheme 6 Reagents, conditions and yields: (i) bis(pinacolato)diboron (1.1 equiv.), PdCl2(dppf ), Et3N, 1,2-dichloroethane, reflux, 1.5 h, 50%;
(ii) triflate 17, PdCl2(dppf ), K3PO4, dioxane, reflux, 21.5 h, 59%; (iii) bis(pinacolato)diboron (1.1 equiv.), PdCl2(dppf ), dppf, KOAc, dioxane, reflux,
1.5 h, then triflate 17, PdCl2(dppf ), K3PO4, reflux, 18 h, 77%.
Scheme 7 Reagents, conditions and yields: (i) AgO (16 equiv.), 6 M HNO3, dioxane, 10 min, then AgO (16 equiv.), 100%; (ii) Ac2O, py, Zn, CHCl3,
heat, 10 min, 71%; (iii) dimethyl sulfate, acetone, reflux, 7 h, 67%.
with triethylamine as the base (Scheme 6). Subsequent
conversion to binaphthyl 35 took place in 59% yield by further
reaction with triflate 17 and PdCl2(dppf ) using potassium
phosphate as base in dioxane. The homocoupling was then
achieved in better yield (77%) using a one-pot procedure
wherein naphthylboronate 34 was generated in dioxane with
PdCl2(dppf ) using potassium acetate as base, triflate 17 was
added with a second portion of PdCl2(dppf ) together with the
stronger base potassium phosphate. Attempts to optimize
this homocoupling further using Pd2(dba)3 rather than PdCl2-
(dppf ) using the phosphine ligands (dicyclohexylphosphino)-
biphenyl and 2-(dimethylamino)-2Ј-(dicyclohexylphosphino)-
biphenyl did not offer any improvement in the yield of
binaphthyl 35 obtained, rather substantial quantities of the
reduced product 36 were afforded.
With binaphthyl 35 in hand, attention turned to introduction
of acetyl groups at C-7 and C-7Ј in order to provide binaphthyl
14 as required for the proposed synthesis of crisamicin A 2
(Scheme 2). It was initially envisaged that selective removal of
the isopropyl ethers and acetylation of the resultant bis-naph-
thol would provide bis-acetate 37 that would undergo double
Fries rearrangement to the bis-acetylnaphthalene 14 (Scheme
7). This approach was put on hold when attempts to selectively
deprotect the isopropyl groups in binaphthyl 35 using alu-
minium trichloride,17 boron trichloride,18 trifluoroacetic acid,19
iron trichloride20 and ruthenium trichloride21 were not selective
for removal of the isopropyl groups and afforded complex
mixtures of products.
bis-naphthoquinone 38 that would then undergo reductive
acetylation and methylation to bis-acetate 37 (Scheme 7). Bis-
acetate 37 would then provide bis-acetylnaphthalene 14 upon
double Fries rearrangement. Towards this end binaphthyl
35 was oxidized quantitatively with silver() oxide and nitric
acid to bis-naphthoquinone 38 that then underwent double
selective reductive acetylation to 39 in 71% yield using zinc and
acetic anhydride. Finally methylation of 39 by heating with di-
methyl sulfate and potassium carbonate in acetone22 afforded
bis-acetate 37 in 67% yield.
Considerable effort was made to effect a double Fries
rearrangement of bis-acetate 37 to the desired bis-acetyl-
naphthalene 14 using boron trifluoride, aluminium trichloride
and scandium triflate using a variety of solvents and conditions,
however these attempts were fruitless. Similarly, attempts
to effect introduction of acetyl groups at C-7 and C-7Ј on
binaphthyl 35 using trifluoroacetic anhydride in acetic acid22
and acetic anhydride with ruthenium trichloride21 afforded
complex mixtures.
Given that the acetyl groups at C-7 and C-7Ј in binaphthyl 14
that are required for our proposed synthesis of crisamicin A 2,
could not be effectively introduced onto binaphthyl 35, an
alternative pathway was adopted wherein the required acetyl
groups were introduced onto a monomeric naphthalene before
effecting construction of the biaryl linkage.
With acetate 21 already in hand, its conversion to 2-acetyl-
naphthalene 40 was investigated (Scheme 8). Disappointingly,
attempts to effect Fries rearrangement of 21 to 40 were
frustrated by the formation of complex mixtures in which
loss of the benzyl and methyl ethers were observed. Altern-
atively, 2-acetylnaphthalene 40 could be prepared from acetate
In light of the inability to effect deprotection of the isopropyl
ethers in binaphthyl 35, as required for preparation of bis-acet-
ate 37, we next decided to effect oxidation of binaphthyl 35 to
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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i
Scheme 8 Reagents, conditions and yields: (i) NBS (1.0 equiv.), DMF, 1.5 h, 75%; (ii) NBS (1.0 equiv.). Pr2EtN, CH2Cl2, 2 h, 79%; (iii) NBS
(1.0 equiv.), DMF, 22 h, 37%.
Scheme 9 Reagents, conditions and yields: (i) K2CO3, MeOH–THF (95 : 5), 15 min, 91%; (ii) NBS, toluene, Ϫ78 ЊC, 1 h, 47, 22%; 48, 14%.
21 via selective bromination at C-2 followed by Stille coupling
with α-(ethoxyvinyl)tributylstannane as used by this research
group in the synthesis of C-glycosylpyranonaphthoquinones.5
Unfortunately bromination of acetate 21 took place in the more
electron rich ring affording the undesired C-8 bromide 41. In an
attempt to direct bromination to the C-2 position naphthol 18
was treated with N-bromosuccinimide and diisopropylamine in
dichloromethane, however this resulted in a 79% yield of dimer
42, a product of phenolic coupling formed due to the presence
of electron donating groups on naphthol 18. Use of N-bromo-
succinimide in DMF afforded naphthoquinone 43 in 37% yield
whereas use of molecular bromine and iodine afforded complex
mixtures of products.
The electron donating effects of the two methoxy groups at
C-4 and C-5 in benzyl ether 21 resulted in increased electron
density at C-8 that was reinforced by the benzyloxy group at
C-7. It was therefore decided to focus on electrophilic aromatic
substitution of triflate 15 as a method for introduction of an
acetyl group at C-2, hoping that the presence of the more elec-
tron withdrawing triflate group at C-7 would direct reaction to
the hydroquinonoid ring (Scheme 9). Numerous attempts to
effect Fries rearrangement of triflate 15 to acetylnaphthalene 44
only afforded naphthol 45. Naphthol 45, however, could poten-
tially undergo ortho-selective bromination to bromide 46 that
could then serve as precursor for introduction of an acetyl
group at this position.
quinone 48 upon treatment of naphthol 45 with N-bromo-
succinimide in toluene at low temperature. It was therefore con-
cluded that introduction of an acetyl group at C-2 on naphthol
45 via ortho-bromination followed by Stille coupling using
α-(ethoxyvinyl)tributylstannane was not viable due to the initial
inability to successfully brominate naphthol 45 at C-2.
In summary, the homocoupling of naphthyl triflates 27, 16,
17 to the binaphthyls 28, 31 and 35 respectively, has been
achieved providing the first examples of the use of a Suzuki–
Miyaura coupling using bis(pinacolato)diboron and PdCl2-
(dppf ) to effect homocoupling of aryl triflates to biaryls.
Although the main focus of the present work was to prepare
bis-acetylnaphthalene 14 as a key intermediate for our pro-
posed synthesis of crisamicin A 2 using a double furofuran
annulation–double oxidative rearrangement strategy, it tran-
spired that attempts to introduce the required acetyl groups at
C-7 and C-7Ј in bis-acetylnaphthalene 14 via double Fries
rearrangement of acetate 37, Fries rearrangement of mono-
meric acetates 21 and 15, or regioselective bromination of
monomeric benzyl ether 8 and triflate 45, proved problematic
thereby prompting a rethink of our synthetic approach to
crisamicin A 2.
Experimental
General
In order to investigate this approach larger quantities of
naphthol 45 were prepared by hydrolysis of acetate 15 using
potassium carbonate in methanol–THF (Scheme 9). Unfortu-
nately attempts to effect ortho-bromination of naphthol 45 gave
complex mixtures of phenolic coupling products and naphtho-
quinonesasexemplifiedbytheformationofdimer47andnaphtho-
Mps were determined on a Kofler hot-stage apparatus and are
uncorrected. IR spectra were recorded using a Perkin-Elmer
1600 Fourier Transform IR spectrophotometer as thin films
between sodium chloride plates. Absorption spectra are
expressed in wavenumbers (cmϪ1) with the following abbrevi-
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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1
ations: s = strong, m = medium, w = weak and br = broad. H
(20 mL) and water (20 mL) then dried over magnesium sulfate,
NMR spectra were recorded on a Bruker AC 200 (200 MHz) or
a Bruker DRX 400 (400 MHz) spectrometer at ambient tem-
perature. All J-values are given in Hz. Chemical shifts are
expressed in parts per million downfield shift from tetramethyl-
silane as an internal standard, and reported as position (δH),
relative integral, multiplicity (s = singlet, br s = broad singlet,
d = doublet, dd = double doublet, ddd = double double doublet,
t = triplet, q = quartet, m = multiplet) and assignment. 13C
NMR spectra were recorded on a Bruker AC 200 (50.3 MHz)
or a Bruker DRX 400 (100.5 MHz) spectrometer at ambient
temperature with complete proton decoupling. Low resolution
mass spectra were recorded on a VG70-250S, a VG70-SD or a
AEI model MS902 double focusing magnetic sector mass
spectrometer operating with an ionisation potential of 70 eV
(EI, DEI, CI and DCI). High resolution mass spectra were
recorded at nominal resolution of 5000 or 10000 as appropri-
ate. Major fragments are given as percentages relative to the
base peak and assigned where possible. Ionisation methods
employed were either electron impact or chemical ionisation
with ammonia or methane as reagent gas (CI). Low resolution
chemical ionisation mass spectra were also recorded on a
Hewlett Packard 5989A mass spectrometer using ammonia as
reagent gas with the sample dissolved in methanol. Flash chro-
matography was performed using Merck Kieselgel 60 (230–
400 mesh) with the indicated solvents. Thin layer chromato-
graphy (TLC) was performed using 0.2 mm thick pre-coated
silica gel plates (Merck Kieselgel 60 F254 or Riedel-de Haen
Kieselgel S F254). Compounds were visualised by ultraviolet
fluorescence or by staining with iodine or vanillin in methanolic
sulfuric acid.
and evaporated to dryness to give a brown oil which was puri-
fied by flash column chromatography using 1 : 9 ethyl acetate–
hexane as eluent to give the title compound 27 (0.556 g, 97%)
as a colourless solid, mp 32–33 ЊC, lit.13 mp 31–32 ЊC; δH (200
MHz, CDCl3) 7.39 (1 H, dd, J 2.5, 9.0 Hz, H-3), 7.53–7.63
(2 H, m, ArH), 7.76 (1 H, d, J 2.4 Hz, H-1), 7.86–7.95 (3H, m,
ArH).
4,4,5,5-Tetramethyl-2-naphthalen-2-yl-1,3,2-dioxaborolane (29)
a) Using pinacolborane (1.0 M solution in tetrahydro-
furan).15 To a stirred solution of PdCl2(dppf ) (14 mg, 0.017
mmol) in dry 1,2-dichloroethane (1.2 mL) was added naph-
thalen-2-yl trifluoromethanesulfonate 27 (76 mg, 0.275 mmol),
dry triethylamine (0.23 mL, 1.65 mmol) and pinacolborane
(0.83 mL of a 1.0 M solution in tetrahydrofuran, 0.83 mmol)
under an atmosphere of argon and the mixture stirred at
reflux for 2 h. The reaction mixture was extracted with ethyl
acetate (2 × 20 mL). The combined organic extracts were
washed with water (10 mL), dried over magnesium sulfate,
and concentrated in vacuo to give a dark brown oil which
was purified by flash column chromatography on florisil
using gradient elution (from hexane to 5 : 95 ethyl acetate–
hexane) to yield boronate 29 (37 mg, 53%) as colourless needles,
mp 44–46 ЊC; δH (200 MHz, CDCl3) 1.41 (12 H, s, 4 × CH3),
7.50 (2 H, m, ArH), 7.85 (4 H, m, ArH), 8.40 (1 H, s, H-1). The
1H NMR data were in agreement with that reported in the
literature.15
b) Using 97% pure pinacolborane. To a stirred solution of
PdCl2(dppf ) (18 mg, 0.022 mmol) in dry dichloroethane
(1.4 mL) was added naphthalen-2-yl trifluoromethanesulfonate
27 (94 mg, 0.34 mmol), dry triethylamine (0.142 mL, 1.02
mmol) and pinacolborane (0.076 mL, 0.51 mmol) under
an atmosphere of argon and the mixture stirred at reflux for 3 h.
The reaction mixture was extracted with ethyl acetate (2 ×
20 mL). The combined organic extracts were washed with water
(10 mL), dried over magnesium sulfate, and concentrated in
vacuo to give a dark brown oil which was purified by flash
column chromatography on florisil using gradient elution (from
hexane to 5 : 95 ethyl acetate–hexane) to yield boronate 29
43.2 mg, 50%) as colourless needles. The 1H NMR data were in
agreement with those reported above.
7-Benzyloxy-4,5-dimethoxynaphthalen-1-ol (18)
The following procedure is adapted from the method of Giles,
Hughes and Sargent.23
A solution of n-butyllithium (0.54 mL of a 1.6 M solution in
hexane, 0.857 mmol) was added to a stirred solution of 4-benzy-
loxy-2-bromo-6-methoxyphenyl toluene-p-sulfonate11 (0.209 g,
0.451 mmol) and 2-methoxyfuran 20 (0.084 mL, 0.90 mmol) in
dry tetrahydrofuran (10 mL), under an atmosphere of nitrogen
at Ϫ100 ЊC. The solution was stirred at Ϫ100 ЊC for 13 min then
allowed to warm to room temperature for 2 h. The mixture was
acidified by the addition of conc. HCl (∼6 drops), stirred at
room temperature for 15 min. then poured into water (2 mL),
extracted with ethyl acetate (2 × 50 mL), washed with water
(20 mL) and brine (20 mL) then dried over magnesium sulfate.
Concentration under reduced pressure afforded a red–orange
oil which was purified by flash column chromatography using
2:8 ethyl acetate–hexane as eluent to yield naphthol 18 (84 mg,
c) Using bis(pinacolato)diboron. A mixture of potassium
acetate (16 mg, 0.163 mmol), dry dioxane (0.33 mL), PdCl2-
(dppf ) (1.3 mg, 0.0016 mmol), dppf (0.9 mg, 0.0016 mmol),
bis(pinacolato)diboron (15 mg, 0.06 mmol) and naphthalen-
2-yl trifluoromethanesulfonate 27 (15 mg, 0.054 mmol) was
heated and stirred under argon, at reflux for 2 h. The reaction
mixture was diluted with ethyl acetate (10 mL), washed with
water (5 mL), dried over magnesium sulfate and concentrated
in vacuo to a dark brown oil which was purified by flash column
chromatography on florisil using gradient elution (from hexane
to 5 : 95 ethyl acetate–hexane) to yield boronate 29 (7.5 mg,
54%) as colourless needles. The 1H NMR data were in
agreement with that reported above.
1
60%) as a dark green solid, mp 155.2–156.8 ЊC. The H NMR
data were in agreement with those reported in the literature.11
δH (200 MHz, CDCl3) 3.90 (3 H, s, 4-OCH3), 3.95 (3 H, s,
5-OCH3), 5.18 (2 H, s, OCH2), 6.57 (1 H, d, J3,2 8.3 Hz, H-3),
6.63 (1 H, d, J6,8 2.4 Hz, H-6), 6.73 (1 H, d, J2,3 8.3 Hz, H-2),
7.18 (1 H, d, J8,6 2.3 Hz, H-8), 7.34–7.52 (5 H, m, PhH); δC (50
MHz, CDCl3) 56.2 (CH3, OCH3), 57.3 (CH3, OCH3), 69.7
(CH2, OCH2), 94.0 (CH, C-6), 99.8 (CH, C-8), 104.9 (CH,
C-3), 109.5 (CH, C-2), 114.3 (quat., C-4a), 127.8 (CH, C-2Ј and
C-6Ј), 128.0 (CH, C-4Ј), 128.3 (quat., C-8a), 128.5 (CH, C-3Ј
and C-5Ј), 136.8 (quat., C-1Ј), 144.7 (quat., C-1), 151.3 (quat.,
C-4), 157.1 (quat., C-7), 158.1 (quat., C-5).
2,2Ј-Binaphthalenyl (28)
a) Stepwise homocoupling of triflate 27 and boronate 29.12
To a solution of boronate 29 (44.1 mg, 0.174 mmol) in dry
dioxane (0.86 mL) was added potassium phosphate (111 mg,
0.523 mmol), PdCl2(dppf ) (4.3 mg, 0.005 mmol) and naph-
thalen-2-yl trifluoromethanesulfonate 27 (48 mg, 0.174 mmol).
The mixture was stirred and heated at reflux under an atmos-
phere of argon for 5 h. The reaction mixture was concentrated
in vacuo then diluted with ethyl acetate (50 mL), washed with
water (30 mL), brine (30 mL), dried over magnesium sulfate
and concentrated in vacuo to give a dark brown oil. Further
Naphthalen-2-yl trifluoromethanesulfonate (27)
Trifluoromethanesulfonic anhydride (0.35 mL, 2.50 mmol) was
added to a mixture of 2-naphthol (0.300 g, 2.08 mmol) and
dry triethylamine (0.35 mL, 2.50 mmol) in dry dichloromethane
(10 mL). The mixture was stirred at Ϫ20 ЊC for 2 h, poured into
water (20 mL) then extracted with chloroform (2 × 40 mL).
The combined organic extracts were washed with dilute HCl
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
2089

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purification by flash column chromatography using hexane as
eluent yielded the title compound 28 (26 mg, 58%) as a white
solid, mp 186–188 ЊC, lit.24 mp 185–187 ЊC.
The mixture was stirred at Ϫ20 ЊC for 18.5 h, then the solvent
was removed under reduced pressure and chloroform (50 mL)
added. The organic layer was washed with water (25 mL) and
separated. The aqueous layer was extracted with chloroform
(50 mL). The combined organic layers were dried over mag-
nesium sulfate and concentrated at reduced pressure to give a
dark brown–orange oil which was purified by flash column
chromatography using 3 : 7 ethyl acetate–hexane as eluent to
give the title compound 15 (10.6 mg, 82%) as a colourless solid,
mp 132–134 ЊC (Found: C, 45.9; H, 3.6. C15H13F3O7S requires
C, 45.7; H, 3.3%) [Found (EI): Mϩ, 394.0331; C15H13F3O7S
b) Generation of boronate 29 followed by in situ coupling
with triflate 27.12 A mixture of potassium acetate (37 mg,
0.38 mmol), dry dioxane (0.8 mL), PdCl2(dppf ) (3.1 mg, 0.0038
mmol), dppf (2.1 mg, 0.0038 mmol), bis(pinacolato)-
diboron (35 mg, 0.138 mmol) and naphthalen-2-yl trifluoro-
methanesulfonate 27 (35 mg, 0.127 mmol) under argon was
heated with stirring at reflux for 2.5 h. Potassium phosphate
(81 mg, 0.382 mmol), PdCl2(dppf ) (3.1 mg, 0.0038 mmol) and
naphthalen-2-yl trifluoromethanesulfonate 27 (35 mg, 0.127
mmol) were added and the reaction mixture heated at reflux for
18 h. The reaction mixture was diluted with ethyl acetate
(12 mL), washed with water (6 mL), dried over magnesium
sulfate then concentrated in vacuo to a dark brown oil. Further
purification by flash column chromatography using hexane as
eluent yielded the title compound 28 (27 mg, 84%) as a white
solid, mp 186–188 ЊC, lit.24 mp 185–187 ЊC.
requires Mϩ, 394.0334]; νmax(CH2Cl2 solution) 1763 (C᎐O),
᎐
1422 (SO2–O), 1215 (C–F), 1040 (C–O) cmϪ1; δH (200 MHz,
CDCl3) 2.42 (3 H, s, COCH3), 3.94 (3 H, s, 4-OCH3), 3.97 (3 H,
s, 5-OCH3), 6.69 (1 H, d, J6,8 2.2 Hz, H-6), 6.85 (1 H, d,
J3,2 8.3 Hz, H-3), 7.24 (1 H, d, J2,3 8.3 Hz, H-2), 7.25 (1 H, d,
J8,6 2.2 Hz, H-8); δC (50 MHz, CDCl3) 20.9 (CH3, COCH3), 56.7
(CH3, 2 × OCH3), 100.2 (CH, C-8), 104.9 (CH, C-6), 106.4
(CH, C-3), 117.3 (quat., C-4a), 120.5 (CH, C-2), 129.7 (quat.,
C-8a), 139.7 (quat., C-1), 148.1 (quat., C-4), 155.4 (quat., C-7),
159.7 (quat., C-5), 169.5 (quat., C᎐O); m/z 394 (Mϩ, 14%), 352
᎐
(M Ϫ C3H6, 100), 191 (67).
7-Benzyloxy-4,5-dimethoxynaphthalen-1-yl acetate (21)
(7-Benzyloxy-4,5-dimethoxynaphthalen-1-yloxy)-tert-butyl-
dimethylsilane (22)
To a stirred solution of 7-benzyloxy-4,5-dimethoxynaphthalen-
1-ol 18 (78 mg, 0.251 mmol) in dry pyridine (1.5 mL) under a
nitrogen atmosphere was added acetic anhydride (0.036 mL,
0.377 mmol) and the mixture left to stir overnight at room tem-
perature. Diethyl ether (60 mL) and water (15 mL) were then
added. The aqueous layer was removed and the organic layer
was washed with 1 M HCl (30 mL), water (30 mL), sat. sodium
bicarbonate (30 mL), water (30 mL), brine (30 mL) then dried
over magnesium sulfate and concentrated at reduced pressure
to yield a yellow–brown solid. Further purification by flash
column chromatography using 3 : 7 ethyl acetate–hexane as
eluent gave the title compound 21 (65 mg, 73%) as a yellow
tert-Butylchlorodimethylsilane (61.2 mg, 0.406 mmol) was
added to a solution of 7-benzyloxy-4,5-dimethoxynaphthalen-
1-ol 18 (70 mg, 0.226 mmol), imidazole (38.4 mg, 0.564 mmol)
and 4-(dimethylamino)pyridine (5%) (1.38 mg, 0.0113 mmol) in
dry dichloromethane (4.5 mL). The mixture was stirred at room
temperature under nitrogen for 20 h. The reaction mixture
was diluted with dichloromethane (10 mL), washed with brine
(10 mL) then dried over magnesium sulfate and concentrated
in vacuo to give a yellow–green oil. Further purification by flash
column chromatography using 1 : 9 ethyl acetate–hexane as
eluent gave the title compound 22 (64 mg, 67%) as a pale yellow
solid, mp 93–94 ЊC [Found (EI): Mϩ, 424.2072; C25H32O4Si
1
solid, mp 108–109 ЊC, lit.11 mp 109–109.5 ЊC. The H and 13C
NMR data were in agreement with those reported in the
literature.11
requires Mϩ, 424.2070]; νmax(CH Cl solution) 1620 (C᎐C) 1252
᎐
2
2
(SiMe), 1061 (Si–O), 838 (SiMe2) cmϪ1; δH (200 MHz, CDCl3)
0.25 (6 H, s, SiCH3), 1.10 (9 H, s, t-Bu), 3.92 (3 H, s, 4-OCH3),
3.96 (3 H, s, 5-OCH3), 5.18 (2 H, s, OCH2), 6.61 (1 H, d, J3,2
8.4 Hz, H-3), 6.66 (1 H, d, J6,8 2.4 Hz, H-6), 6.79 (1 H, d, J2,3
8.4 Hz, H-2), 7.22 (1 H, d, J8,6 2.4 Hz, H-8), 7.34–7.54 (5 H,
m, PhH); δC (50 MHz, CDCl3) Ϫ4.3 (CH3, SiCH3), 18.3 (quat.,
t-Bu), 25.9 (CH3, t-Bu), 56.3 (CH3, OCH3), 57.0 (CH3, OCH3),
69.8 (CH2, OCH2), 94.8 (CH, C-6), 99.5 (CH, C-8), 104.6 (CH,
C-3), 113.4 (CH, C-2), 114.2 (quat., C-4a), 127.6 (CH, C-2Ј and
C-6Ј), 128.0 (CH, C-4Ј), 128.6 (CH, C-3Ј and C-5Ј), 131.6
(quat., C-8a), 136.8 (quat., C-1Ј), 144.4 (quat., C-1), 151.6
(quat., C-4), 157.0 (quat., C-7), 158.3 (quat., C-5); m/z 424 (Mϩ,
100%), 409 (M Ϫ CH3, 2), 305 (84), 91 (39), 73 (26).
7-Hydroxy-4,5-dimethoxynaphthalen-1-yl acetate (24)
A solution of 7-benzyloxy-4,5-dimethoxynaphthalen-1-yl acet-
ate 21 (63 mg, 0.179 mmol) in ethyl acetate (8 mL) was stirred
under an atmosphere of hydrogen over palladium on charcoal
(10%, 80 mg, 0.75 mmol). After 5 h, the mixture was filtered
through Celite and the solvent was removed in vacuo to give
a green-white solid. The solid was purified by flash column
chromatography using gradient elution (from 3 : 7 to 6 : 4 to
8 : 2 ethyl acetate-hexane) to afford the title compound 24
(38 mg, 81%) as a colourless solid, mp 178–180 ЊC [Found (EI):
Mϩ, 262.0840; C14H14O5 requires Mϩ, 262.0841]; νmax(CH2Cl2
solution) 3200 (OH), 1765 (C᎐O) cmϪ1; δH (200 MHz, CDCl3)
᎐
2.35 (3 H, s, COCH3), 3.88 (3 H, s, 4-OCH3), 3.93 (3 H, s,
5-OCH3), 5.71 (1 H, s, OH), 6.47 (1 H, d, J6,8 2.3 Hz, H-6), 6.62
(1 H, d, J3,2 8.5 Hz, H-3), 6.64 (1 H, d, J8,62.3 Hz, H-8), 7.06
(1 H, d, J2,3 8.5 Hz, H-2); δC (50 MHz, CDCl3) 20.9 (CH3,
COCH3), 56.3 (CH3, OCH3), 56.5 (CH3, OCH3), 95.9 (CH,
C-8), 98.9 (CH, C-6), 102.9 (CH, C-3), 113.6 (quat., C-4a),
119.2 (CH, C-2), 130.9 (quat., C-8a), 139.0 (quat., C-1), 155.0
(quat., C-4), 155.4 (quat., C-7), 159.1 (quat., C-5), 170.2 (quat.,
8-(tert-Butyldimethylsilyloxy)-4,5-dimethoxynaphthalen-2-ol
(25)
A solution of benzyl ether 22 (1.36 g, 3.21 mmol) in ethyl acet-
ate (80 mL) was stirred over palladium on charcoal (10%, 1.43
g, 13.5 mmol) under an atmosphere of hydrogen. After 1 h, the
mixture was filtered through Celite and the solvent removed in
vacuo to give a pale green solid. The solid was purified by flash
column chromatography using gradient elution (from 2.5 : 7.5
to 3 : 7 ethyl acetate–hexane) to afford the title compound 25
(0.96 g, 89%) as a colourless solid, mp 222.2–224 ЊC [Found
C᎐O); m/z 262 (Mϩ, 28%), 220 (M Ϫ C H O, 100), 205 (7), 177
᎐
2
2
(11), 147 (7).
(EI): Mϩ, 334.1599; C18H26O4Si requires Mϩ, 334.1600]; νmax
-
4,5-Dimethoxy-7-trifluoromethanesulfonyloxynaphthalen-1-yl
acetate (15)
(CH Cl solution) 3370 (O–H), 1635 (C᎐C), 1275 (SiMe), 1054
᎐
2
2
(SiO), 842 (SiMe2) cmϪ1; δH (400 MHz, CDCl3) 0.244 (6 H, s,
SiCH3), 1.07 (9 H, s, t-Bu), 3.89 (3 H, s, 5-OCH3), 3.94 (3 H, s,
4-OCH3), 5.10 (1 H, s, OH), 6.51 (1 H, d, J3,1 2.4 Hz, H-3), 6.55
(1 H, d, J6,7 8.4 Hz, H-6), 6.73 (1 H, d, J7,6 8.4 Hz, H-7), 7.06
(1 H, d, J1,3 2.4 Hz, H-1); δC (100 MHz, CDCl3) Ϫ4.2 (CH3,
Trifluoromethanesulfonic anhydride (0.007 mL, 0.04 mmol)
was added to a mixture of 7-hydroxy-4,5-dimethoxynaph-
thalen-1-yl acetate 24 (8.6 mg, 0.033 mmol) and dry triethyl-
amine (0.006 mL, 0.04 mmol) in dry dichloromethane (0.8 mL).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
2090

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SiCH3), 18.4 (quat., t-Bu), 26.0 (CH3, t-Bu), 56.4 (CH3, OCH3),
57.0 (CH3, OCH3), 97.6 (CH, C-1), 98.5 (CH, C-3), 104.3 (CH,
C-6), 113.2 (CH, C-7), 114.1 (quat., C-4a), 131.8 (quat., C-8a),
144.2 (quat., C-8), 151.6 (quat., C-5), 153.7 (quat., C-4), 158.8
(quat., C-2); m/z 334 (Mϩ, 100%), 319 (M Ϫ CH3, 10), 277 (60),
246 (22), 73 (37).
PdCl2(dppf ) (5.2 mg, 0.0063 mmol) and triflate 16 (98 mg,
0.21 mmol). The mixture was heated under reflux under argon
for 15 h. The reaction mixture was concentrated in vacuo,
diluted with ethyl acetate (100 mL), washed with water (50 mL)
and brine (50 mL) then dried over magnesium sulfate and con-
centrated in vacuo to give a dark green oil. Further purification
by flash column chromatography using gradient elution (from
1 : 9 to 1.5 : 8.5 to 5 : 5 ethyl acetate–hexane) yielded 1-tert-
butyldimethylsilyloxy-4,5-dimethoxynaphthalene 33 (3 mg, 4%)
as a light brown oil [Found (EI): Mϩ, 318.1652; C18H26O3Si
requires Mϩ, 318.1651]; m/z 318 (Mϩ, 100%), 261 [M Ϫ (C4H9),
64], 246 (10), 203 (7), 73(50).
8-(tert-Butyldimethylsilyloxy)-4,5-dimethoxynaphthalen-2-yl
trifluoromethanesulfonate (16)
Trifluoromethanesulfonic anhydride (0.45 mL, 2.69 mmol) was
added to a mixture of naphthol 25 (0.5 g, 1.49 mmol) and dry
triethylamine (0.38 mL, 2.69 mmol) in dry dichloromethane
(80 mL). The mixture was stirred at Ϫ20 ЊC for 23.5 h, concen-
trated in vacuo and chloroform (100 mL) added. The organic
layer was washed with water (80 mL) and separated. The aque-
ous layer was extracted with chloroform (100 mL). The com-
bined organic extracts were dried over magnesium sulfate and
concentrated at reduced pressure to give a dark pink oil which
was purified by flash column chromatography using 2 : 8 ethyl
acetate–hexane as eluent to give the title compound 16 (0.67 g,
96%), as a pale yellow solid, mp 64–66 ЊC (Found: C, 48.8; H,
5.5. C19H25F3O6SSi requires C, 48.9; H, 5.4%) [Found (EI): Mϩ,
466.1599; C19H25F3O6SSi requires Mϩ, 466.1600]; νmax(CH2Cl2
solution) 1422 (SO2–O), 1383 [C(CH3)3], 1266 (SO2–O), 1215
(C–F), 1051 (C–O) cmϪ1; δH (400 MHz, CDCl3) 0.24 (6 H, s,
SiCH3), 1.07 (9 H, s, t-Bu), 3.90 (3 H, s, 5-OCH3), 3.99 (3 H, s,
4-OCH3), 6.70 (1 H, d, J3,1 2.4 Hz, H-3), 6.78 (1 H, d, J6,7
8.5 Hz, H-6), 6.86 (1 H, d, J7,6 8.5 Hz, H-7), 7.67 (1 H, d, J1,3 2.4
Hz, H-1); δC (100 MHz, CDCl3) Ϫ4.4 (CH3, SiCH3), 18.3
(quat., t-Bu), 25.8 (CH3, t-Bu), 56.7 (CH3, OCH3), 57.3 (CH3,
OCH3), 100.3 (CH, C-1), 106.5 (CH, C-3), 108.2 (CH, C-6),
114.4 (CH, C-7), 117.7 (quat., C-4a), 120.4 (quat., C-8a), 130.4
(quat., C-8), 145.3 (quat., C-5), 147.3 (quat., C-4), 151.5 (quat.,
C–F), 159.1 (quat., C-2); m/z 466 (Mϩ, 100%), 319 (M, 10), 277
(60), 246 (22), 73 (37).
8,8Ј-Bis(tert-butyldimethylsilyloxy)-4,5,4Ј,5Ј-tetramethoxy-
2,2Ј-binaphthalenyl 31 (29 mg, 22%) as a colourless solid, mp
205–207 ЊC [Found (EI): Mϩ, 634.3144; C36H50O6Si2 requires
Mϩ, 634.3146]; νmax(CH2Cl2 solution) 1592 (C᎐C), 1381
᎐
[C(CH3)3], 1264 (SiMe), 1046 (SiO), 839 (SiMe2) cmϪ1; δH (400
MHz, CDCl3) 0.29 (6 H, s, SiCH3), 1.12 (9 H, s, t-Bu), 3.96
(3 H, s, 4-OCH3), 4.08 (3 H, s, 5-OCH3), 6.75 (1 H, d, J6,7
8.2 Hz, H-6), 6.82 (1 H, d, J7,6 8.2 Hz, H-7), 7.33 (1 H, s, H-3),
8.18 (1 H, s, H-1); δC (100 MHz, CDCl3) Ϫ4.3 (CH3, SiCH3),
18.4 (quat., t-Bu), 26.0 (CH3, t-Bu), 56.3 (CH3, OCH3), 57.3
(CH3, OCH3), 105.8 (CH, C-3), 107.1 (CH, C-6), 113.1 (CH,
C-7), 113.6 (CH, C-1), 117.8 (quat., C-4a), 131.2 (quat., C-8a),
138.1 (quat., C-2), 145.7 (quat., C-5), 151.3 (quat., C-8), 157.4
(quat., C-4); m/z 634 (Mϩ, 100%), 577 [M Ϫ (C4H9),8], 497 (9),
440 (11), 371 (8), 73 (31).
8Ј-(tert-Butyldimethylsilyloxy)-4,5,4Ј,5Ј-tetramethoxy-2,2Ј-
binaphthalenyl-8-ol 32 (18 mg, 16%) as a light yellow oil [Found
(EI): Mϩ, 520.2284; C30H36O6Si requires Mϩ, 520.2281]; νmax
-
(CH Cl solution) 3412 (O–H), 1594 (C᎐C), 1382 [C(CH ) ],
᎐
2
2
3 3
1270 (SiMe), 1058 (SiO), 838 (SiMe2) cmϪ1; δH (400 MHz,
CDCl3) 0.28 (6 H, s, SiCH3), 1.12 (9 H, s, t-Bu), 3.94 (3H, s, 5-
OCH3), 3.95 (3 H, s, 5Ј-OCH3), 4.076 (3 H, s, 4Ј-OCH3), 4.084
(3 H, s, 4-OCH3), 5.25 (1 H, br s, OH), 6.72 (1 H, d, J6,7 8.8 Hz,
H-6), 6.74 (1 H, d, J6Ј,7Ј 8.8 Hz, H-6Ј), 6.80 (1 H, d, J7,6 8.8 Hz,
H-7), 6.82 (1 H, d, J7Ј,6Ј 8.8 Hz, H-7Ј), 7.32 (1 H, d, J3,1 1.5 Hz,
H-3), 7.33 (1 H, d, J3Ј,1Ј 1.5 Hz, H-3Ј), 8.16 (1 H, d, J1,3 1.5 Hz,
H-1), 8.19 (1 H, d, J1Ј,3Ј 1.5 Hz, H-1Ј); δC (100 MHz, CDCl3)
Ϫ4.3 (CH3, SiCH3), 18.4 (quat., t-Bu), 26.0 (CH3,t-Bu), 56.4
(CH3, OCH3), 56.8 (CH3, OCH3), 57.4 (CH3, OCH3), 57.5
(CH3, OCH3), 106.3 (CH, C-3Ј), 106.4 (CH, C-3), 107.3 (CH,
C-6Ј), 107.4 (CH, C-6), 109.4 (CH, C-7Ј), 112.7 (CH, C-7),
113.2 (CH, C-1Ј), 114.0 (CH, C-1), 117.7 (quat., C-4aЈ), 118.0
(quat., C-4a), 128.0 (quat., C-8a), 131.2 (quat., C-8aЈ), 138.1
(quat., C-2Ј), 138.5 (quat., C-2), 145.7 (quat., C-5Ј), 145.9
(quat., C-5), 151.0 (quat., C-8), 151.2 (quat., C-8Ј), 157.3 (quat.,
C-4), 157.4 (quat., C-4Ј); m/z 520 (Mϩ, 96%), 505 [M Ϫ (CH3), 6],
463 [M Ϫ (C4H9),15], 371 (12), 330 (20), 127 (34), 99 (31),
59 (73), 57 (100).
2-[8-(tert-Butyldimethylsilyloxy)-4,5-dimethoxynaphthalen-2-
yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (30)
A mixture of potassium acetate (63.1 mg, 0.643 mmol), dry
dioxane (1.8 mL), PdCl2(dppf ) (5.3 mg, 0.0064 mmol), dppf
(3.6 mg, 0.0064 mmol), bis(pinacolato)diboron (0.0599 mg,
0.236 mmol) and triflate 16 (100 mg, 0.214 mmol) was heated
under argon, with stirring at reflux for 1.5 h. The reaction mix-
ture was diluted with ethyl acetate (30 mL), washed with water
(10 mL), dried over magnesium sulfate and concentrated
in vacuo to a yellow–brown oil. Further purification by flash
column chromatography using gradient elution (from 1 : 9 to
1.5 : 8.5 ethyl acetate–hexane) as eluent to give the title
compound 30 (76 mg, 80%) as a light yellow-green oil [Found
(EI): Mϩ, 444.2501; C24H37BO5Si requires Mϩ, 444.2503];
b) Generation of boronate 30 followed by in situ coupling
with triflate 16. A mixture of potassium acetate (63.1 mg,
0.643 mmol), dry dioxane (1.8 mL), PdCl2(dppf ) (5.3 mg,
0.0064 mmol), dppf (3.6 mg, 0.0064 mmol), bis(pinacolato)-
diboron (59.9 mg, 0.236 mmol) and triflate 16 (100 mg, 0.214
mmol) was heated under argon, with stirring at reflux for 1 h.
Potassium phosphate (137 mg, 0.8643 mmol), PdCl2(dppf )
(5.3 mg, 0.0064 mmol) and triflate 16 (100 mg, 0.214 mmol)
were then added and the resultant mixture heated with stirring
at reflux for 20.5 h. The reaction mixture was diluted with ethyl
acetate (30 mL), washed with water (10 mL), dried over mag-
nesium sulfate and concentrated in vacuo to a dark brown oil.
Further purification by flash column chromatography using
gradient elution (from 1 : 9 to 2 : 8 to 3 : 7 to 5 : 5 ethyl acetate–
hexane) yielded binaphthyl 31 (34 mg, 22%) as an off-white
νmax(neat) 1595 (C᎐C), 1380 [C(CH ) ], 1339 (B–O), 1264 (B–C
᎐
3
3
and SiMe), 1052 (SiO), 839 (SiMe2) cmϪ1; δH (400 MHz, CDCl3)
0.23 (6 H, s, SiCH3), 1.12 (9 H, s, t-Bu), 1.37 (12 H, s, 4 × CH3),
3.91 (3 H, s, 5-OCH3), 4.02 (3 H, s, 4-OCH3), 6.78 (2 H, s, H-6
and H-7), 7.20 (1 H, s, H-3), 8.38 (1 H, s, H-1); δC (100 MHz,
CDCl3) Ϫ4.4 (CH3, SiCH3), 18.4 (quat., t-Bu), 24.9 (CH3,t-Bu),
25.9 (CH3, CH3of boronate), 56.5 (CH3, OCH3), 57.4 (CH3,
OCH3), 83.7 (quat., boronate), 108.5 (CH, C-6), 110.4 (CH,
C-3), 113.0 (CH, C-7), 120.1 (quat., C-4a), 124.4 (CH,
C-1), 126.0 (quat., C-8a), 130.5 (quat., C-2), 146.0 (quat., C-5),
151.2 (quat., C-8), 156.1 (quat., C-4); m/z 444 (Mϩ, 100%), 429
[M Ϫ (CH3), 5], 372 (11), 287 (43), 73 (27).
8,8Ј-Bis(tert-butyldimethylsilyloxy)-4,5,4Ј,5Ј-tetramethoxy-2,2Ј-
binaphthalenyl (31)
1
solid, mp 205–207 ЊC for which the H NMR data were in
a) Stepwise homocoupling of triflate 16 and boronate 30. To
a solution of boronate 30 (93.5 mg, 0.210 mmol) in dry dioxane
(3 mL) was added potassium phosphate (0.134 g, 0.631 mmol),
agreement with that reported above and binaphthyl 32 (27 mg,
24%) as a yellow oil for which the 1H NMR data were in
agreement with that reported above.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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3-Benzyloxy-5-isopropoxy-1,8-dimethoxynaphthalene (23)
by flash column chromatography using 2 : 8 ethyl acetate–
hexane as eluent to give the title compound 17 (14 mg, 91%) as a
pale yellow solid, mp 58–60 ЊC (Found: C, 48.6; H, 4.2.
C16H17F3O6S requires C, 48.7; H, 4.3) [Found (EI): Mϩ,
394.0696; C16H17F3O6S requires Mϩ, 394.0698]; νmax(CH2Cl2
solution) 1421 (SO2–O), 1383 [C(CH3)2], 1265 (SO2–O), 1216
(C–F), 1050 (C–O) cmϪ1; δH (200 MHz, CDCl3) 1.40 (6 H, d,
J 6.1 Hz, CH3 of isopropyl), 3.91 (3 H, s, 5-OCH3), 3.98 (3 H, s,
4-OCH3), 4.60 (1 H, septet, J 6.1 Hz, CH of isopropyl), 6.70
(1 H, d, J3,1 2.4 Hz, H-3), 6.82 (1 H, d, J6,7 8.3 Hz, H-6), 6.87
(1 H, d, J7,6 8.3 Hz, H-7), 7.74 (1 H, d, J1,3 2.4 Hz, H-1);
δC (50 MHz, CDCl3) 22.1 (CH3, 2 × CH3 of isopropyl), 56.6
(CH3, OCH3), 57.4 (CH3, OCH3), 71.8 (CH, CH of isopropyl),
100.3 (CH, C-6), 106.5 (CH, C-7), 108.3 (CH, C-3), 109.8 (CH,
C-1), 117.7 (quat., C-4a), 129.4 (quat., C-8a), 147.3 (quat., C-2),
147.6 (quat., C-8), 151.0 (quat., C-5), 158.9 (quat., C-4); m/z
394 (Mϩ, 29%), 352 (M Ϫ C3H6,65), 219 (7), 191 (100), 175 (10),
147 (8), 119 (5), 91(7).
A mixture of 7-benzyloxy-4,5-dimethoxynaphthalen-1-ol 18
(110 mg, 0.354 mmol) and sodium hydride (25.4 mg, 1.06
mmol) in dry N,N-dimethylformamide (12 mL) was stirred
at room temperature under a nitrogen atmosphere for 1 h.
2-Bromopropane (0.17 mL, 1.77 mmol) was then added and the
reaction mixture left to stir at room temperature for 4.5 h. The
reaction mixture was poured into water (3 mL) and extracted
with ethyl acetate (4 × 30 mL). The combined organic extracts
were washed with water (50 mL) and brine (50 mL) then dried
over magnesium sulfate and evaporated to dryness to give a
brownish-yellow oil, which was purified by flash column chro-
matography using 2 : 8 ethyl acetate–hexane as eluent to give
the title compound 23 (0.11 g, 89%) as a light yellow solid, mp
79.5–81.5 ЊC [Found (EI): Mϩ, 352.1672; C22H24O4 requires Mϩ,
352.1675]; νmax(CH Cl solution) 1620 (C᎐C), 1382 [C(CH ) ],
᎐
2
2
3 2
1059 (C–O) cmϪ1; δH (200 MHz, CDCl3) 1.38 (6 H, d, J 6.5 Hz,
CH3 of isopropyl), 3.91 (3 H, s, 8-OCH3), 3.94 (3 H, s, 1-OCH3),
4.53 (1 H, septet, J 6.5 Hz, CH of isopropyl), 5.19 (2 H, s,
OCH2), 6.62 (1 H, d, J7,6 8.5 Hz, H-7), 6.63 (1 H, d, J2,4 2.4 Hz,
H-2), 6.78 (1 H, d, J6,7 8.5 Hz, H-6), 7.27 (1 H, d, J4,2 2.4 Hz,
H-4), 7.36–7.53 (5 H, m, PhH); δC(50 MHz, CDCl3) 22.3 (CH3,
2 × CH3 of isopropyl), 56.3 (CH3, OCH3), 57.2 (CH3, OCH3),
70.0 (CH2, OCH2), 71.5 (CH, CH of isopropyl), 94.8 (CH, C-2),
99.6 (CH, C-4), 104.6 (CH, C-7), 109.4 (CH, C-6), 114.8 (quat.,
C-8a), 127.8 (CH, C-2Ј and C-6Ј), 128.0 (CH, C-4Ј), 128.6 (CH,
C-3Ј and C-5Ј), 130.8 (quat., C-4a), 137.0 (CH, C-1Ј), 146.9
(quat., C-5), 151.3 (quat., C-8), 157.0 (quat., C-3), 158.2
(quat., C-1); m/z 352 (Mϩ, 42%), 309 [M Ϫ CH(CH3)2, 37], 281
(M Ϫ C3H7CO, 1), 219 (13), 191 (19), 149 (5), 91 (100).
2-(8-Isopropoxy-4,5-dimethoxynaphthalen-2-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (34)
To a stirred solution of PdCl2(dppf ) (43 mg, 0.0053 mmol) in
dry 1,2-dichloroethane (0.52 mL), was added triflate 17 (35 mg,
0.089 mmol), dry triethylamine (0.074 mL, 0.533 mmol) and
pinacolborane (0.040 mL, 0.266 mmol) under an atmosphere of
argon and the mixture heated with stirring at reflux for 1.5 h.
The reaction mixture was extracted with ethyl acetate (2 ×
20 mL). The combined organic extracts were washed with water
(10 mL), dried over magnesium sulfate then concentrated
in vacuo to give a dark brown oil. Further purification by flash
column chromatography on florisil using gradient elution (from
hexane to 5 : 95 ethyl acetate–hexane) yielded 1-isopropoxy-4,5-
dimethoxynaphthalene 36 (3 mg) as a light yellow oil [Found
(EI): Mϩ, 246.1258; C15H18O3 requires Mϩ, 246.1256]; δH (400
MHz, CDCl3) 1.41 (6 H, d, J 6.1 Hz, CH3 of isopropyl), 3.92 (3
H, s, 4-OCH3), 3.97 (3H, s, 5-OCH3), 4.61 (1 H, septet, J 6.1 Hz,
CH of isopropyl), 6.79 (2 H, m, H-2, H-3), 6.90 (1 H, d, J6,7 7.6
Hz, H-6), 7.37 (1 H, dd, J7,6 and J7,8 8.1 Hz, H-7), 7.88 (1 H, d,
J8,7 8.1 Hz, H-8); δC (100 MHz, CDCl3) 22.2 (CH3, 2 × CH3 of
isopropyl), 56.5 (CH3, OCH3), 57.5 (CH3, OCH3), 71.2 (CH,
CH of isopropyl), 107.0 (CH, C-3), 107.1 (CH, C-6), 108.2
(CH, C-2), 115.1 (CH, C-8), 118.7 (quat., C-4a), 125.7 (CH,
C-7), 130.1 (quat., C-8a), 147.7 (quat., C-4), 150.9 (quat., C-1),
156.8 (quat., C-5); m/z 246 (Mϩ, 63%), 204 (M Ϫ C3H6, 100),
189 (16), 161 (17), 131 (13), 115 (10).
8-Isopropoxy-4,5-dimethoxynaphthalen-2-ol (26)
A
solution of 3-benzyloxy-5-isopropoxy-1,8-dimethoxy-
naphthalene 23 (88.3 mg, 0.251 mmol) in ethyl acetate (8 mL)
was stirred under an atmosphere of hydrogen over 10%
palladium on charcoal (112 mg, 1.05 mmol). After 1.5 h, the
mixture was filtered through Celite and the solvent removed
in vacuo to give a green–white solid. The solid was purified
by flash column chromatography using gradient elution (from
3 : 7 to 6 : 4 to 8 : 2 ethyl acetate–hexane) to afford the title
compound 26 (50 mg, 78%) as a pale yellow green solid, mp 161–
163 ЊC [Found (EI): Mϩ, 262.12052; C15H18O4 requires Mϩ,
262.12051]; νmax(CH2Cl2 solution) 3370 (OH), 1384 [C(CH3)2],
1051 (C–O) cmϪ1; δH (200 MHz, CDCl3) 1.36 (6 H, d, J 6.1 Hz,
CH3 of isopropyl), 3.86 (3 H, s, 5-OCH3), 3.89 (3 H, s, 4-OCH3),
4.54 (1 H, septet, J 6.1 Hz, CH of isopropyl), 5.66 (1 H, s, OH),
6.49 (1H, d, J3,1 2.3 Hz, H-3), 6.59 (1 H, d, J6,7 8.5 Hz, H-6),
6.74 (1 H, d, J7,6 8.5 Hz, H-7), 7.18 (1 H, d, J1,3 2.3 Hz, H-1);
δC (50 MHz, CDCl3) 22.2 (CH3, 2 × CH3 of isopropyl), 56.2
(CH3, OCH3), 57.1 (CH3, OCH3), 71.2 (CH, CH of isopropyl),
97.4 (CH, C-3), 98.7 (CH, C-1), 104.3 (CH, C-6), 109.0 (CH,
C-7), 113.9 (quat., C-4a), 131.0 (quat., C-8a), 146.5 (quat.,
C-8), 151.2 (quat., C-5), 154.0 (quat., C-2), 158.5 (quat., C-4);
m/z 262 (Mϩ, 59%), 219 [M Ϫ CH(CH3)2, 100], 205 (12), 191
(M Ϫ C3H7CO, 8), 177 (25), 147 (8), 45 (9).
2-(8-Isopropoxy-4,5-dimethoxynaphthalen-2-yl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane 34 (43 mg, 50%) as a colourless
oil [Found (EI): Mϩ, 372.2107; C21H29BO5 requires Mϩ,
372.2108]; νmax(neat) 1598 (C᎐C), 1379 [C(CH ) ], 1343 (B–O),
᎐
3
2
1265 (B–C) cmϪ1; δH (400 MHz, CDCl3) 1.38 (12 H, s, 4 × CH3),
1.43 (6 H, d, J 6.1 Hz, CH3 of isopropyl), 3.90 (3 H, s, 5-OCH3),
4.01 (3 H, s, 4-OCH3), 4.63 (1 H, septet, J 6.1 Hz, CH of iso-
propyl), 6.76 (1 H, d, J6,7 8.5 Hz, H-6), 6.82 (1 H, d, J7,6 8.5 Hz,
H-7), 7.23 (1 H, br s, H-3), 8.37 (1 H, br s, H-1); δC (100 MHz,
CDCl3) 22.1 (CH3, CH3 of isopropyl), 24.9 (CH3, CH3 of boro-
nate), 56.5 (CH3, OCH3), 57.6 (CH3, OCH3), 70.8 (CH, CH of
isopropyl), 83.8 (quat., boronate), 107.4 (CH, C-6), 108.7 (CH,
C-3), 111.0 (CH, C-7), 123.2 (CH, C-1), 127.6 (C-4a), 128.1
(quat., C-2), 129.3 (quat., C-8a), 148.3 (quat., C-5), 150.5
(quat., C-8), 155.9 (quat., C-4); m/z 262 (Mϩ, 59%), 219
[M Ϫ CH(CH3)2,100], 205 (12), 191 (M Ϫ C3H7CO, 8), 177 (25),
147 (8), 45 (9).
8-Isopropoxy-4,5-dimethoxynaphthalen-2-yl trifluoro-
methanesulfonate 17
To a solution of 8-isopropoxy-4,5-dimethoxynaphthalen-2-ol
26 (10.4 mg, 0.040 mmol) in dry dichloromethane (1 mL) was
added dry triethylamine (0.011 mL, 0.079 mmol), N-phenyltri-
fluoromethanesulfonimide (17 mg, 0.048 mmol) and 4-(di-
methylamino)pyridine (2 mg) and the mixture stirred at Ϫ25 ЊC
under an atmosphere of nitrogen for 15 h. The mixture was
poured into water (2 mL), and extracted with chloroform (25
mL). The organic extract was washed with dilute HCl (10 mL)
and water (10 mL) then dried over magnesium sulfate and con-
centrated in vacuo to give a green solid. This solid was purified
8,8Ј-Diisopropoxy-4,5,4Ј,5Ј-tetramethoxy-2,2Ј-binaphthalenyl
(35)
a) Stepwise homocoupling of triflate 17 and boronate 34. To
a solution of boronate 34 (40 mg, 0.107 mmol) in dry dioxane
(0.7 mL) was added potassium phosphate (68 mg, 0.32 mmol),
PdCl2(dppf ) (2.6 mg, 0.003 mmol) and triflate 17 (40 mg, 0.101
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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mmol). The mixture was heated under reflux under argon for
21.5 h. The reaction mixture was concentrated in vacuo, diluted
with ethyl acetate (50 mL), washed with water (30 mL) and
brine (30 mL) then dried over magnesium sulfate and concen-
trated in vacuo to give a dark brown oil. Further purification by
flash column chromatography using 2 : 8 ethyl acetate–hexane
as eluent yielded binaphthyl 35 (29 mg, 59%) as a yellow solid,
mp 133.5–135 ЊC (Found: C, 73.2; H, 6.9. C30H34O6 requires C,
73.5; H, 7.0) [Found (EI): Mϩ, 490.2364; C30H34O6 requires Mϩ,
magnesium sulfate and concentration in vacuo, the residue
obtained was purified by flash chromatography using 6 : 4 ethyl
acetate–hexane as eluent to yield the title compound 39 (21 mg,
71%) as a pale yellow solid, mp 256.5–258 ЊC [Found (FAB):
Mϩ, 462.1308; C26H22O8 requires Mϩ, 462.1315]; νmax(CH2Cl2
solution) 3400 (OH), 1760 (C᎐O), 1633 (C᎐C) and 1047 (C–O)
᎐
᎐
cmϪ1; δH (200 MHz, CDCl3) 2.43 (3 H, s, COCH3), 4.15 (3 H, s,
OCH3), 6.88 (1 H, d, J6,7 8.4 Hz, H-6), 7.02 (1 H, d, J1,3 1.3 Hz,
H-1), 7.18 (1 H, d, J7,6 8.4 Hz, H-7), 7.53 (1 H, d, J3,1 1.3 Hz,
H-3), 9.24 (1 H, s, OH); δC (50 MHz, CDCl3) 20.9 (CH3,
COCH3), 56.4 (CH3, OCH3), 104.5 (CH, C-6), 109.9 (CH, C-7),
113.7 (CH, C-1), 114.6 (quat., C-4a), 120.8 (CH, C-3), 129.2
(quat., C-8a), 138.9 (quat., C-2), 139.4 (quat., C-8), 152.5
490.2355]; νmax(CH Cl solution) 1596 (C᎐C), 1382 [C(CH ) ],
᎐
2
2
3 2
1059 (C–O) cmϪ1; δH (400 MHz, CDCl3) 1.45 (6 H, d, J 6.0 Hz,
CH3 of isopropyl), 3.96 (3 H, s, 5-OCH3), 4.09 (3 H, s, 4-OCH3),
4.63 (1 H, septet, J 6.0 Hz, CH of isopropyl), 6.80 (1 H, d, J6,7
8.4 Hz, H-6), 6.86 (1 H, d, J7,6 8.4 Hz, H-7), 7.29 (1 H, d, J3,1 1.4
Hz, H-3), 8.25 (1 H, d, J1,3 1.4 Hz, H-1); δC (100 MHz, CDCl3)
22.3 (CH3, CH3 of isopropyl), 56.8 (CH3, OCH3), 57.5 (CH3,
OCH3), 71.7 (CH, CH of isopropyl), 106.8 (CH, C-6), 107.2
(CH, C-7), 109.2 (CH, C-3), 113.7 (CH, C-1), 117.9 (quat.,
C-4a), 130.4 (quat., C-8a), 138.6 (quat., C-2), 148.1 (quat., C-8),
151.0 (quat., C-5), 157.2 (quat., C-4); m/z 490 (Mϩ, 100%), 447
[M Ϫ CH(CH3)2,70], 405 (66), 390 (45), 203 (30), 199 (7), 129
(8), 69 (22).
(quat., C-5), 156.8 (quat., C-4), 169.8 (quat., C᎐O); m/z 462
᎐
(Mϩ, 36%), 420 (24), 378 (31), 338 (64).
8Ј-Acetoxy-4,5,4Ј,5Ј-tetramethoxy-2,2Ј-binaphthalenyl-8-yl
acetate (37)
A mixture of naphthol 39 (79 mg, 0.171 mmol), potassium
carbonate (0.397 g, 2.87 mmol) and dimethyl sulfate (0.35 mL,
3.67 mmol) in dry acetone (8 mL) was heated under reflux with
vigorous stirring for 7 h. The mixture was cooled and filtered.
The filtrate was concentrated under reduced pressure and the
resultant residue was dissolved in ethyl acetate (15 mL)
and washed with concentrated ammonia (5 mL) and water
(5 mL). The organic layer was dried over magnesium sulfate
and concentrated. The residue was purified by flash chromato-
graphy using 6 : 4 ethyl acetate–hexane as eluent to yield the
title compound 37 (55 mg, 67%) as a yellow solid, mp 231–233
ЊC [Found (EI): Mϩ, 490.16284; C28H26O8 requires Mϩ,
b) Generation of boronate 34 followed by in situ coupling
with triflate 17. A mixture of potassium acetate (86 mg, 0.88
mmol), dry dioxane (2 mL), PdCl2(dppf ) (7.1 mg, 0.0088
mmol), dppf (4.9 mg, 0.0088 mmol), bis(pinacolato)diboron
(81.5 mg, 0.321 mmol) and triflate 17 (115 mg, 0.292 mmol) was
heated under argon, with stirring at reflux for 1.5 h. Potassium
phosphate (186 mg, 0.875 mmol), PdCl2(dppf ) (7.1 mg, 0.009
mmol) and triflate 17 (115 mg, 0.292 mmol) were then added
and the resultant mixture heated with stirring at reflux for 18 h.
The reaction mixture was diluted with ethyl acetate (30 mL),
washed with water (10 mL), dried over magnesium sulfate and
concentrated in vacuo to afford a dark brown oil. Further puri-
fication by flash column chromatography using 2 : 8 ethyl acet-
ate–hexane as eluent yielded binaphthyl 35 (110 mg, 77%) as a
yellow solid, mp 133.5–135 ЊC for which the 1H NMR data were
in agreement with that reported above.
490.16277]; νmax(CH2Cl2 solution) 1760 (C᎐O), 1598 (C᎐C),
᎐
᎐
1071 (C–O) cmϪ1; δH (400 MHz, CDCl3) 2.44 (3 H, s, COCH3),
4.00 (3 H, s, OCH3), 4.06 (3 H, s, OCH3), 6.84 (1 H, d, J6,7
8.4 Hz, H-6), 7.15 (1 H, d, J3,1 1.3 Hz, H-3), 7.20 (1 H, d, J7,6
8.4 Hz, H-7), 7.59 (1 H, d, J1,3 1.3 Hz, H-1); δC (100 MHz,
CDCl3) 21.0 (CH3, COCH3), 56.76 (CH3, OCH3), 56.82 (CH3,
OCH3), 105.5 (CH, C-6), 107.0 (CH, C-7), 112.5 (CH, C-1),
117.6 (quat., C-4a), 119.1 (CH, C-3), 130.2 (quat., C-8a), 140.18
(quat., C-2), 140.20 (quat., C-8), 155.2 (quat., C-5), 157.8
(quat., C-4), 169.8 (quat., C᎐O); m/z 490 (Mϩ, 27%), 448
᎐
4,4Ј-Dimethoxy-2,2Ј-binaphthalenyl-5,8,5Ј,8Ј-tetraone (38)
(M Ϫ C2H2O, 43), 406 (M Ϫ C4H4O2, 100), 390 (M Ϫ C4H4O3,
Binaphthyl 35 (26 mg, 0.053 mmol) and freshly prepared AgO
(105 mg, 0.848 mmol) were mixed in dioxane (4 mL). To this
was added HNO3 (0.074 mL of a 6 M solution) and the reac-
tion mixture stirred for 10 min, after which time further AgO
(105 mg, 0.848 mmol) and HNO3 (0.074 mL of a 6 M solution)
were added. After stirring an additional 10 min the reaction
mixture was quenched with water (8 mL) and extracted into
dichloromethane (4 × 15 mL). The organic layer was washed
with water (30 mL), dried over magnesium sulfate and the
solvent removed under reduced pressure to yield the title
compound 38 (21 mg) as an orange oil which was not purified
further [Found (EI): Mϩ, 374.0784; C22H14O6 requires Mϩ,
16), 203 (12).
7-Benzyloxy-8-bromo-4,5-dimethoxynaphthalen-1-yl acetate
(41)
A solution of N-bromosuccinimide (46 mg, 0.258 mmol) in dry
N,N-dimethylformamide (1.8 mL) was added to a solution of
acetate 21 (91 mg, 0.258 mmol) in dry N,N-dimethylformamide
(1.8 mL) and stirred at room temperature under a nitrogen
atmosphere for 1.5 h. The mixture was poured into water
(20 mL) and extracted with dichloromethane (2 × 20 mL). The
combined organic extracts were washed with water (20 mL)
then dried over magnesium sulfate and concentrated in vacuo to
give a yellow–brown solid. Further purification by flash column
chromatography using 3 : 7 ethyl acetate–hexane as eluent
afforded the title compound 41 (34 mg, 75%) as a light yellow
solid, mp 96–98 ЊC [Found (EI): Mϩ, 430.0413 and 432.0387;
C21H1979BrO5 and C21H1981BrO5 require Mϩ, 430.0416 and
374.0790]; νmax(neat) 1656 (C᎐O, quinone), 1594 (C᎐C) and
᎐
᎐
1017 (C–O) cmϪ1; δH (200 MHz, CDCl3) 4.12 (3 H, s, OCH3),
6.93 (2 H, s, H-6 and H-7), 7.53 (1 H, d, J3,1 1.4 Hz, H-3), 7.99
(1 H, d, J1,3 1.4 Hz, H-1); m/z 374 (Mϩ, 41%), 357 (4).
8Ј-Acetoxy-5,5Ј-dihydroxy-4,4Ј-dimethoxy-2,2Ј-binaphthalenyl-
8-yl acetate (39)
432.0395]; νmax(CH Cl solution) 1654 (C᎐O), 1594 (C᎐C), 1026
᎐
᎐
2
2
(C–O) cmϪ1; δH (400 MHz, CDCl3) 2.42 (3 H, s, COCH3), 3.86
(3 H, s, 4-OCH3), 3.91 (3 H, s, 5-OCH3), 5.25 (2 H, s, OCH2),
6.65 (1 H, s, H-6), 6.74 (1 H, d, J3,2 8.5 Hz, H-3), 7.08 (1 H, d,
J2,3 8.5 Hz, H-2), 7.30–7.52 (5 H, m, PhH); δC (100 MHz,
CDCl3) 22.0 (CH3, COCH3), 56.7 (CH3, OCH3), 57.8 (CH3,
OCH3), 71.8 (CH2, OCH2), 95.1 (quat., C-8), 98.0 (CH,
C-6), 104.6 (CH, C-3), 116.1 (quat., C-4a), 122.8 (CH, C-2),
127.2 (CH, C-2Ј and C-6Ј), 128.0 (CH, C-4Ј), 128.2 (quat.,
C-8a), 128.6 (CH, C-3Ј and C-5Ј), 136.5 (quat., C-1), 138.8
(quat., C-1Ј), 154.5 (quat., C-4), 155.8 (quat., C-5), 158.5
Bis-naphthoquinone 38 (22 mg, 0.059 mmol) in dry chloroform
(2 mL) was treated with acetic anhydride (0.03 mL, 0.317
mmol), dry pyridine (0.03 mL, 0.364 mmol) and zinc powder
(0.09 g, 1.30 mmol). The mixture was gently heated under
nitrogen with vigorous stirring for 15 min. The mixture was
cooled and filtered. The filtrate was poured into water (2 mL)
and stirred for 10 min. The organic phase was briefly shaken
with water (10 mL) containing concentrated hydrochloric acid
(0.33 mL), followed by water (2 × 10 mL). After drying over
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 0 8 4 – 2 0 9 5
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(quat., C-7), 170.7 (quat., C᎐O); m/z 432/430 (Mϩ, 9%), 390/388
3-Bromo-1,1Ј-dihydroxy-4,5,4Ј,5Ј-tetramethoxy-7Ј-trifluoro-
᎐
(M Ϫ C2H2O, 18), 91(100).
methanesulfonyloxy-2,2Ј-binaphthalenyl-7-yl trifluoromethane-
sulfonate (47) and 4-methoxy-5,8-dioxo-5,8-dihydronaphthalen-
2-yl trifluoromethanesulfonate (48)
7,7Ј-Bis(benzyloxy)-4,5,4Ј,5Ј-tetramethoxy-2,2Ј-binaphthalenyl-
1,1Ј-diol (42)
To a suspension of N-bromosuccinimide (23.9 mg, 0.134 mmol)
in dry toluene (0.5 mL) cooled to Ϫ78 ЊC under an atmosphere
of nitrogen, was added a solution of naphthol 45 (53 mg,
0.134 mmol) in dry dichloromethane (0.5 mL) drop-wise over
10 min. with stirring. After stirring at Ϫ78 ЊC for 1 h, the yellow
slurry was allowed to warm to room temperature and stirred for
17 h. The reaction mixture was poured into water (10 mL) and
extracted with diethyl ether (4 × 20 mL). The combined organic
extracts were washed with water (2 × 40 mL), dried over mag-
nesium sulfate and the solvent removed under reduced pressure
to give a brown oil. Purification by flash column chromato-
graphy using ethyl acetate–hexane (2 : 8) as eluent afforded the
title compound 47 (25 mg, 22%) as a brown oil [Found (EI): Mϩ,
779.9399 and 781.9393; C26H1979BrF6O12S2 and C26H1981BrF6-
O12S2require Mϩ, 779.9406 and 781.9385]; νmax(CH2Cl2 solu-
tion) 3415 (OH), 1424 (SO2–O), 1213 (C–F), 1046 (C–Br), 1028
(C–O) cmϪ1; δH(400 MHz, CDCl3) 3.79 (3 H, s, 5Ј-OCH3), 3.86
(3 H, s, 4Ј-OCH3), 3.93 (3 H, s, 5-OCH3), 3.95 (3 H, s, 4-OCH3),
6.57 (1 H, s, H-3Ј), 6.69 (1 H, d, J6,8 2.4 Hz, H-6), 7.02 (1 H, d,
J6Ј,8Ј 2.4 Hz, H-6Ј), 7.45 (1 H, d, J8,6 2.4 Hz, H-8), 7.64 (1 H, d,
J8Ј,6Ј 2.4 Hz, H-8Ј); δC(100 MHz, CDCl3) 56.7, 56.9, 57.1, 57.2
(CH3, 4 × OCH3), 99.3 (quat., C-3), 101.2 (CH, C-8), 105.2
(CH, C-8Ј), 105.4 (CH, C-6Ј), 110.2 (CH, C-6), 111.3
(quat., C-4a), 112.0 (CH, C-3Ј), 112.7 (quat., C-4aЈ), 113.0
(quat., C-2Ј), 117.5 (quat., C-2), 120.7 (quat., C-8aЈ), 124.2
(quat., C-8a), 127.7 (quat., C-1Ј), 132.4 (quat., C-1), 142.1
(quat., C-4Ј), 142.3 (quat., C-4), 148.0 (quat., C-5), 152.6 (quat.,
C-5Ј), 159.4 (quat., C-7Ј), 160.9 (quat., C-7); m/z 780/782 (Mϩ,
19%), 701/703 (M Ϫ Br, 100).
To a solution of naphthol 18 (85 mg, 0.274 mmol) in dichloro-
methane (1.5 mL) was added a solution of N,N-diisopropyl-
amine (0.0042 mL, 0.030 mmol) in dichloromethane (0.15 mL).
To this mixture was added a solution of N-bromosuccinimide
(49 mg, 0.274 mmol) in dichloromethane (1.5 mL) dropwise
with stirring over 20 min. After stirring for a further 2 h at room
temperature, dilute sulfuric acid (2 M solution) was added until
the solution became acidic. The organic layer was washed with
water (2 × 1.5 mL) then dried over magnesium sulfate and con-
centrated in vacuo to give a dirty green solid. Further purifi-
cation by flash column chromatography using gradient elution
(from 3 : 7 to 5 : 5 ethyl acetate–hexane) yielded the title com-
pound 42 (67 mg, 79%), mp 164.4–166.0 ЊC [Found (EI): Mϩ,
618.2258; C38H34O8 requires Mϩ, 618.2254]; δH (400 MHz,
CDCl3) 3.98 (6H, s, 2 × OCH3), 5.21 (2 H, s, OCH2), 7.31–7.43
(5 H, m, PhH), 7.48 (1 H, s, H-6), 7.51 (1 H, s, H-3), 7.53 (1 H, s,
H-8); m/z 618 (Mϩ, 26%), 505 [M Ϫ (C7H6),3], 497 (7), 460 (4),
391 (4), 120 (13), 91 (41).
7-Benzyloxy-5-methoxy-1,4-naphthoquinone (43)
A solution of N-bromosuccinimide (48.8 mg, 0.274 mmol) in
dry N,N-dimethylformamide (1.5 mL) was added to a solution
of naphthol 18 (85 mg, 0.274 mmol) in dry N,N-dimethyl-
formamide (1.5 mL) and stirred at room temperature under
a nitrogen atmosphere for 22 h. The mixture was poured
into water (15 mL) and extracted with dichloromethane (2 ×
15 mL). The combined organic extracts were washed with water
(15 mL) then dried over magnesium sulfate and concentrated
in vacuo to give a yellow oil. Further purification by flash col-
umn chromatography using gradient elution (from 1 : 9 to 2.5
: 7.5 to 4 : 6 ethyl acetate–hexane) afforded the title compound
43 (30 mg, 37%) as an orange–yellow oil [Found (EI): Mϩ,
294.0890; C18H14O4 requires Mϩ, 294.0892]; νmax(CH2Cl2
The title compound 48 (7 mg, 14%) was also isolated as a
yellow solid, mp 115–117 ЊC [Found (EI): Mϩ 335.9910;
C12H7F3O6S requires Mϩ 335.9915]; νmax(CH2Cl2 solution) 1658
(C᎐O, quinone) 1423 (SO –O), 1208 (C–F), 1038 (C–O) cmϪ1
;
᎐
2
δH(300 MHz, CDCl3) 4.03 (3 H, s, OCH3), 6.90 (1 H, d, J7,6
10.3 Hz, H-7), 6.95 (1 H, d, J6,7 10.3 Hz, H-6), 7.16 (1 H, d, J3,1
2.4 Hz, H-3), 7.60 (1 H, d, J1,3 2.4 Hz, H-1); δC(75 MHz, CDCl3)
57.1 (CH3, OCH3), 110.7 (CH, C-6), 111.4 (CH, C-7) 116.5
(quat., C-4a), 136.0 (quat., C-8a), 136.1 (CH, C-3), 141.0 (CH,
C-1), 153.2 (quat., C-2), 161.5 (quat., C-4), 182.6, 183.1 (quat.,
C-5 and C-8); m/z 336 (Mϩ, 98%), 203 (M Ϫ CF3SO2, 65), 188
(43), 175 (100).
solution) 1654 (C᎐O, quinone), 1594 (C᎐C), 1057 (C–O) cmϪ1
;
᎐
᎐
δH (200 MHz, CDCl3) 3.94 (3 H, s, OCH3), 5.24 (2 H, s, OCH2),
6.81 (2 H, s, H-2 and H-3), 7.32–7.45 (7 H, m, H-6, H-8 and
ArH); m/z 294 (Mϩ, 15%), 91(100).
8-Hydroxy-4,5-dimethoxynaphthalen-2-yl trifluoromethane-
sulfonate (45)
To a solution of acetate 15 (64 mg, 0.162 mmol) in methanol–
THF (10 mL, 9.5 : 0.5) was added potassium carbonate (25 mg,
0.179 mmol) and the mixture stirred for 15 min under an
atmosphere of nitrogen at room temperature. The reaction mix-
ture was concentrated in vacuo, and water (5 mL) added and the
solution acidified with 1 M hydrochloric acid solution (3 mL).
The mixture was extracted with ethyl acetate (2 × 20 mL) and
the combined organic extracts washed with water (10 mL),
brine (10 mL), dried over magnesium sulfate and concentrated
to give a dark brown oil. Purification by flash column chrom-
atography using ethyl acetate–hexane (3 : 7) as eluent afforded
the title compound 45 (52 mg, 91%) as a pale yellow solid, mp
66–68 ЊC [Found (EI): Mϩ, 352.0229; C13H11F3O6S requires Mϩ,
352.0228]; νmax(CH2Cl2 solution) 3408 (free OH), 1422 (SO2–O),
1214 (C–F), 1041 (C–O) cmϪ1; δH (400 MHz, CDCl3) 3.90 (3 H,
s, 5-OCH3), 3.98 (3 H, s, 4-OCH3), 5.41 (1 H, s, OH), 6.72 (1 H,
d, J3,1 2.2 Hz, H-3), 6.76 (1 H, d, J6,7 8.4 Hz, H-6), 6.81 (1 H, d,
J7,6 8.4 Hz, H-7), 7.70 (1 H, d, J1,3 2.2 Hz, H-1); δC (100 MHz,
CDCl3) 56.6 (CH3, OCH3), 57.5 (CH3, OCH3), 100.5 (CH, C-1),
106.2 (CH, C-3), 108.4 (CH, C-6), 110.6 (CH, C-7), 117.6
(quat., C-4a), 127.1 (quat., C-8a), 145.4 (quat., C-8), 147.2
(quat., C-5), 151.3 (quat., C-4), 158.9 (quat., C-2); m/z 352 (Mϩ,
58%), 191 (100).
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