Palladium-Catalyzed Coupling of Naphthoquinone Triflates with Stannanes. Unprecedented Nucleophilic Aromatic Substitution on a Hydroxynaphthoquinone Triflate

Full text of DOI:10.1021/jo9621027

4524
J . Org. Chem. 1997, 62, 4524-4527
Sch em e 1
P a lla d iu m -Ca ta lyzed Cou p lin g of
Na p h th oqu in on e Tr ifla tes w ith Sta n n a n es.
Un p r eced en ted Nu cleop h ilic Ar om a tic
Su bstitu tion on a Hyd r oxyn a p h th oqu in on e
Tr ifla te
Antonio M. Echavarren,*,1a OÄ scar de Frutos,1a
Nuria Tamayo,1b Pedro Noheda,1c and Paloma Calle1d
Departamento de Quı´mica Orga´nica, Universidad
Auto´noma de Madrid, Cantoblanco, 28049 Madrid, Spain,
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva 3,
28006 Madrid, Spain, and Departamento de Quı´mica Fı´sica
Aplicada, Universidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain
donor phosphine ligands. Thus, by using Pd2(dba)3‚dba
as the catalyst in NMP (N-methylpyrrolidone) as the
solvent, 1 and 4 coupled at room temperature to give 6
in 73% yield. Under these conditions, triflate 2 reacted
with stannane 4 to give 75a,c in 67% yield. Similarly,
coupling of 2 with alkenylstannane 5 furnished 85a,c in
61% yield. Triflate 3 coupled uneventfully with 4 to give
2-phenylnaphthazarine (9) in 45% yield. It is worth
noting that this coupling reaction proceeds in the absence
of added halide sources. In fact, in these cases addition
of LiCl, the usual additive employed in the cross coupling
of triflates,2,3 led to the formation of 2-chloro-1,4-naph-
thoquinones as a result of an addition-elimination
reaction,9 which did not couple with the stannanes under
these mild reaction conditions. Thus, for example, a
coupling attempted between triflate 3 and stannane 4
with Pd(dppf)Cl2 as the catalyst in DMF in the presence
of excess LiCl afforded 2-chloronaphthazarin in good
yield.
Received November 11, 1996
Aryl trifluoromethanesulfonates (triflates), readily pre-
pared from phenols, have been extensively used in recent
years as electrophiles in the Stille palladium-catalyzed
coupling with organostannanes.2,3 We have recently
applied this type of coupling reaction for the formation
of carbon-carbon bonds from anthraquinone triflates.4
As an extension of this coupling, and as an alternative
to the use of 2-bromoquinone electrophiles in palladium-
catalyzed coupling reactions,5 we decided to examine the
palladium-catalyzed coupling reaction of 2-[(trifluoro-
methanosulfonyl)oxy]-1,4-naphthoquinones (2-hydroxy-
naphthoquinone triflates). As expected, the desired
coupling with stannanes proceeds very readily by using
a palladium catalyst in the absence of phosphine ligands
and LiCl, a common additive in the coupling of triflates.2,3
Additionally, we have also uncovered an unexpected
nucleophilic aromatic substitution on one of the hydroxy-
naphthoquinone triflates that proceeds under surpris-
ingly mild conditions.
The starting 1,4-naphthoquinone triflates 1-3 were
readily prepared from 2-hydroxynaphthoquinone,6 2-hy-
droxyjuglone (2,5-dihydroxy-1,4-naphthoquinone),7 and
2-hydroxynaphthazarine (2,5,8-trihydroxy-1,4-naphtho-
quinone),8 respectively, by reaction with triflic anhydride
and 2,6-lutidine (1 equiv each) as the base. Phenyltri-
butylstannane (4) and dihydropyranyltributylstannane
(5) were selected as representative aryl- and alkenyl-
stannanes. Triflate 1 reacted with stannane 4 with
Pd(PPh3)4 as the catalyst to give 2-phenylnaphthoquinone
(6) in 46% yield (Scheme 1). The best coupling yields
were realized by using a palladium catalyst without
1
The H and 13C NMR spectra of 3 were consistent with
the existence of an equilibrium between two tautomers
3a and 3b shifted toward this last structure.10,11 It is
interesting to note that, in contrast with related naph-
thazarins,12 the 13C NMR spectrum of 3 in CDCl3 at 23
°C showed the carbons, except for C-2 and C-3,13 coupled
to the OH hydrogens (J ) 2.3-3.5 Hz).
Surprisingly, as part of the studies on the stability of
the naphthoquinone triflates toward nucleophiles, we
found that triflate 3 reacted very cleanly with methanol
in DMF in the presence of 3 equiv of Et3N at 23 °C for 3
h to give methyl ether 10 in 86% yield (Scheme 2). A
reaction carried out in the absence of DMF as cosolvent
led to the formation of a 1:6 mixture of 10 and 2-meth-
oxynaphthazarin, the expected product of addition-
elimination reaction.9 The structure of 10 was supported
by the NMR data. In addition, methylation of the free
hydroxyl of 10 with methyl iodide and silver oxide yielded
1
dimethyl ether 11 (68%), which showed H and 13C NMR
(1) (a) Universidad Auto´noma de Madrid, Departamento de Qu´ımica
Orga´nica (b) Present address: AMGEN Inc., Thousand Oaks, CA. (c)
Instituto de Qu´ımica Orga´nica, CSIC. (d) Universidad Auto´noma de
Madrid, Departamento de Qu´ımica F´ısica Aplicada.
(2) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987, 109,
5478.
(3) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Mitchell, T. N. Synthesis 1992, 803. (c) Ritter, K. Synthesis 1993, 735.
(d) Farina, V. In Comprehensive Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995;
Vol. 12, Chapter 3.4.
data fully consistent with the assigned structure. Qui-
none 11 and its regioisomer 5,7-dimethoxy-8-hydroxy-1,4-
naphthoquinone were proposed as reasonable structures
for one of the methylation products of 2-methoxynaph-
thazarin.14 The preparation of 11, with NMR data
different from those reported for the dimethyl ether
(4) Tamayo, N.; Echavarren, A. M.; Paredes, M. C.; Farin˜a, F.;
Noheda, P. Tetrahedron Lett. 1990, 31, 5189.
(5) (a) Tamayo, N.; Echavarren, A. M.; Paredes, M. C. J . Org. Chem.
1991, 56, 6488. (b) Echavarren, A. M.; Tamayo, N.; Paredes, M. C.
Tetrahedron Lett. 1993, 34, 4713. (c) Echavarren, A. M.; Tamayo, N.;
Ca´rdenas, D. J . J . Org. Chem. 1994, 59, 6075. (d) Frutos, O.;
Echavarren, A. M. Tetrahedron Lett. 1996, 37, 8953.
(9) Ulrich, H.; Richter, R. In Methoden der Organischen Chemie
(Houben-Weyl); Thieme: Stuttgart, 1977; Vol. 7/3a.
(10) Moore, R. E.; Scheuer, P. J . J . Org. Chem. 1966, 31, 3272.
(11) Carren˜o, M. C.; Garc´ıa-Ruano, J . L.; Urbano, A. Tetrahedron
1994, 50, 5013.
(12) For example, the 13C NMR spectrum of 2-chloronaphthazarin
did not show any coupling with the OH hydrogens under the same
conditions (CDCl3, 23 °C).
(6) Fieser, L. F. J . Am. Chem. Soc. 1948, 70, 3165.
(7) (a) Thomson, R. H. J . Org. Chem. 1948, 13, 870. (b) Chaker, L.;
Pautet, F.; Fillion, H. Chem. Pharm. Bull. 1994, 42, 2238.
(8) (a) Zahn, K.; Ochwat, P. Liebigs Ann. Chem. 1928, 462, 72. (b)
Kuroda, C. J . Sci. Res. Int. 1951, 45, 166.
(13) Assignments were made by comparison with related com-
pounds. See: Ho¨fle, G. Tetrahedron 1977, 33, 1963.
(14) Farin˜a, F.; Mart´ınez-Utrilla, R.; Paredes, M. C. Tetrahedron
1982, 38, 1531.
S0022-3263(96)02102-0 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 13, 1997 4525
Sch em e 2
Sch em e 3
F igu r e 1. (a) ESR spectrum of the radical anion 16 generated
from triflate 3 and Et3N in DMF. Spectrometer settings:
modulation amplitude 2.5 × 10-2 G, receiver gain 6.3 × 103,
scan time 16 s. (b) Computer simulation (peak to-peak width
of 0.35 G).
derived from 2-methoxynaphthazarin, allows the assign-
ment of its structure as 5,7-dimethyl-8-hydroxy-1,4-
naphthoquinone. Interestingly, 11 is the only dimethyl
ether that could not be prepared by direct methylation
of 2-methoxynaphthazarin with methyl iodide and silver
oxide.14
not equilibrate after being heated in toluene or DMF for
several hours.
A strong coloration appeared immediately after dis-
solving quinone 3 with Et3N in DMF, which suggests the
formation of a charge-transfer complex.18 Dissociation
of the charge-transfer complex at room temperature led
to an ESR-active species for which was assigned structure
16, the radical anion of 3. Radical anion 16 gave rise to
a signal whose intensity increased with time and was
analyzed in terms of six hyperfine splitting constants,
a1 ) 6.70 G (1H), a2 ) 3.53 (1H), a3 ) 3.20 G (1H), a4 )
1.0 G (2H), a5 ) 0.50 G (3F), by comparing the experi-
mental spectrum with that obtained by computer simula-
tion (Figure 1). Although 16 was stable under the
conditions of the ESR experiment, a homolytic cleavage
Formation of 10 formally implies a nucleophilic sub-
stitution on 12, which may arise by an intramolecular
triflate rearrangement from 3 (Scheme 3). However,
such a sulfonyl migration is, to the best of our knowledge,
unprecedented.15 Additionally, although nucleophilic
substitutions at the peri position of quinones, particularly
anthraquinones, are precedented, these reactions usually
proceed under harsh conditions.9 Furthermore, bistri-
flate 13, prepared from naphthazarin by reaction with
excess triflic anhydride, did not suffer substitution after
being treated with methanol under the conditions in
which 3 gives 10.16 On the other hand, tristriflates 14
and 15, obtained by reaction of 3 with excess triflic
anhydride or directly from 2-hydroxynaphthazarin, were
stable compounds that, unlike their acyl analogues,17 did
(16) Traces of product tentatively assigned as 2-methoxy-5,8-bis-
[(trifluoromethanesulfonyl)oxy]-1,4-naphthoquinone (ca. 10%) were
occasionally obtained in these experiments: 1H NMR (CDCl3, 200 MHz)
δ 7.65 (s, 2H), 6.22 (s, 1H), 3.93 (s, 3H).
(17) Acyl migration: (a) Alvarado, S.; Farin˜a, F.; Mart´ın, J . L.
Tetrahedron Lett. 1970, 3377. (b) Brockmann, H.; Greve, H.; Zeeck, A.
Tetrahedron Lett. 1971, 1929.
(18) See: Mukherjee, A. K.; Chattopadhyay, A. K. J . Chem. Soc.,
Perkin Trans. 2 1992, 1081.
(15) We have recently uncovered another case of sulfonyl migration
on calixarene derivatives that proceeds intermolecularly: Gonza´lez,
J . J .; Nieto, P. M.; Prados, P.; Echavarren, A. M.; de Mendoza, J . J .
Org. Chem. 1995, 60, 7419.

4526 J . Org. Chem., Vol. 62, No. 13, 1997
Notes
7.73-7.65 (m, 2H), 7.34 (dd, J ) 6.8, 3.0 Hz, 1H), 6.91 (s, 1H);
13C{1H} NMR (CDCl3, 50 MHz) δ 188.1, 176.3, 161.8, 152.0,
137.0, 127.0, 126.1, 120.5, 118.5 [q, J (13C-19F) ) 321 Hz], 114.3
(one carbon signal was not observed). Anal. Calcd for C11H5F3O
S: C, 41.00; H, 1.56. Found: C, 41.05; H, 1.49.
Sch em e 4
5,8-Dih yd r oxy-6-[(t r iflu or om et h a n esu lfon yl)oxy]-1,4-
n a p h th oqu in on e (3). To a solution of 2,5,8-trihydroxy-1,4-
naphthoquinone (2-hydroxynaphthazarine) (260 mg, 1.26 mmol)
in CH2Cl2 (20 mL) at 0 °C were added 2,6-lutidine (0.15 mL,
138 mg, 1.29 mmol) and triflic anhydride (0.22 mL, 369 mg, 1.30
mmol). The mixture was stirred at 0 °C for 5 min and at 23 °C
for 1 h. After the usual workup and chromatography (5:1
hexane-EtOAc), 3 was obtained as a dark red solid (355 mg,
83%): mp 142-143 °C; IR (KBr) 1625, 1570 cm-1 1H NMR
;
(CDCl3, 200 MHz) δ 12.27 (s, 1H), 12.20 (s, 1H), 7.23 (part A,
AB system, J ) 9.8 Hz, 1H), 7.19 (part B, AB system, J ) 9.8
Hz, 1H), 7.13 (s, 1H); 13C NMR (CDCl3, 50 MHz) δ 173.8 (ddd,
J ) 6.1, 2.9, 2.7 Hz), 173.3 (ddd, J ) 5.6, 3.2, 3.0 Hz), 170.9 (dd,
J ) 2.9, 2.8 Hz), 164.1 (dd, J ) 6.8, 2.3 Hz), 148.0 (dd, J ) 6.1,
3.6 Hz), 135.9 (dd, J ) 168.5, 3.5 Hz), 134.9 (dd, J ) 168.8, 3.5
Hz), 124.5 (dd, J ) 169.8, 3.8 Hz), 118.5 (q, J ) 320.8 Hz), 112.3
(m), 111.56 (m); 13C NMR (CDCl3 + D2O, 50 MHz) δ 173.8 (dd,
J ) 6.1, 3.0 Hz), 173.3 (dd, J ) 5.6, 3.2 Hz), 170.9 (d, J ) 3.0
Hz), 164.1 (d, J ) 7.0 Hz), 148.0 (d, J ) 5.8 Hz), 135.9 (d, J )
168.5 Hz), 134.9 (d, J ) 168.8 Hz), 124.5 (d, J ) 168.8 Hz), 118.5
(q, J ) 320.8 Hz), 112.3 (m), 111.6 (m); EI-MS m/ z 338 (M+,
100), 261 (8), 205 (32), 177 (95). Anal. Calcd for C11H5F3O7S:
C, 39.06; H, 1.49. Found: C, 38.69; H, 1.59.
P a lla d iu m -Ca ta lyzed Cou p lin g of 1-3. Gen er a l P r oce-
d u r e. The triflate and Pd2(dba)3‚dba (2.5 mol%) were dissolved
in NMP (1.5 mL). After 5 min, the stannane was added (1.2
equiv) dissolved in NMP (1 mL), and the resulting mixture was
stirred at 23 °C for 16 h. Usual workup and chromatography
(EtOAc-hexane mixtures) furnished the coupled products as
orange solids (6, 73%; 7, 67%; 8, 61%) identical with previously
prepared compounds.5a,c
of the triflate leading to an intermediate sulfonyl radical19
following by recombination could lead to the formation
of 17 (Scheme 4). Further reaction of 17 with methanol
by a SRN1-type mechanism20 could account for the forma-
tion of 10.
In summary, we have shown that 2-hydroxynaphtho-
quinones are suitable starting materials for the synthesis
of substituted naphthoquinones. In addition, we have
found a surprisingly facile nucleophilic aromatic substi-
tution on one of the hydroxynaphthoquinone triflates that
may proceed through its radical anion.
Exp er im en ta l Section
5,8-Dih yd r oxy-2-p h en yl-1,4-n a p h th oqu in on e (9). This
new quinone was prepared according with the general procedure
in 45% yield as a red solid: mp 147-148 °C; Rf ) 0.53 (5:1
hexane-EtOAc); 1H NMR (CDCl3, 200 MHz) δ 12.85 (s, 1H),
12.57 (s, 1H), 7.63-7.58 (m, 2H), 7.51-7.48 (m, 3H), 7.24 (s,
2H), 7.16 (s, 1H); 13C{1H} NMR (CDCl3, 50 MHz) δ 179.6, 179.1,
166.3, 165.4, 147.7, 134.3, 133.2, 132.3 (2C), 130.0, 129.3, 128.5,
112.2, 111.9; EI-MS m/ z 266 (M+, 100), 237 (32).
Only the most significant IR absortions and the molecular ions
and/or base peaks in the MS are given. “Usual workup” means
aqueous treatment, extraction with EtOAc or CH2Cl2, drying
with Na2SO4, filtration, and evaporation. Chromatography was
performed with flash grade silica gel. All reactions were carried
out under an atmosphere of Ar.
2-Hydroxy-1,4-naphthoquinone,6 2,5-dihydroxy-1,4-naphtho-
quinone,7 2,5,8-trihydroxy-1,4-naphthoquinone,8 and (2,3-dihy-
dro-4H-pyran-6-yl)tri-n-butylstannane21 were prepared accord-
ing to known procedures.
2-Ch lor o-5,8-d ih yd r oxy-1,4-n a p h th oqu in on e. A solution
of 3 (30 mg, 0.09 mmol), Pd(dppf)Cl2 (4 mg, 0.005 mmol), LiCl
(11 mg, 0.27 mmol), and phenyltributylstannane (40 mg, 0.11
mmol) was stirred at 23 °C in DMF (3 mL) for 1.5 h. After the
usual workup and chromatography, 2-chloronaphthazarin (17
mg, 85%) was obtained as a dark red solid: mp 178-179 °C (lit.22
179 °C); IR (KBr) 1620, 1575 cm-1; 1H NMR (CDCl3, 200 MHz)
δ 12.41 (s, 1H), 12.37 (s, 1H), 7.29 (s, 1H), 7.29 (part A, AB
system, J ) 9.6 Hz, 1H), 7.21 (part B, AB system, J ) 9.6 Hz,
1H); 13C NMR (CDCl3, 50 MHz) δ 177.4 (s), 173.2 (d, J ) 7.8
Hz), 167.2 (dd, J ) 7.3, 2.2 Hz), 166.5 (dd, J ) 7.3, 1.5 Hz), 143.0
(d, J ) 5.2 Hz), 134.5 (d, J ) 171.2 Hz), 133.3 (dd, J ) 167.3,
132.3 Hz), 132.3 (br d, J ) 165.8 Hz), 111.5 (br s), 111.34 (m).
5,7-Dih yd r oxy-8-m eth oxy-1,4-n a p h th oqu in on e (10). To
a solution of triflate 3 (45 mg, 0.13 mmol) in DMF (6 mL) and
methanol (3 mL) at 23 °C was added triethylamine (0.045 mL,
0.32 mmol). The mixture was stirred at this temperature for 3
h. After the usual workup (washing with aqueous tartaric acid
solution) and chromatography (2:1 hexane-EtOAc), 10 was
obtained as an orange solid (25 mg, 86%): mp 173-175 °C; IR
(KBr) 1665, 1635, 1575 cm-1; 1H NMR (CDCl3, 300 MHz) δ 12.81
(s, 1H), 11.25 (br s, 1H), 6.94 (part A, AB system, J ) 10.3 Hz,
1H), 6.84 (part B, AB system, J ) 10.3 Hz, 1H), 6.66 (s, 1 H),
2-[(Tr iflu or om e t h a n e su lfon yl)oxy]-1,4-n a p h t h oq u i-
n on e (1). To a solution of 2-hydroxy-1,4-naphthoquinone (308
mg, 1.77 mmol), 2,6-lutidine (0.227 mL, 208 mg, 1.95 mmol),
and 4-(N,N-dimethylamino)pyridine (21 mg, 0.18 mmol) in
CH2Cl2 (35 mL) at 0 °C was slowly added triflic anhydride (0.315
mL, 529 mg, 1.88 mmol). The resulting mixture was stirred at
23 °C for 3 h. After the usual workup and chromatography (20:1
hexane-EtOAc), 1 was isolated as a red solid (353 mg, 65%):
mp 101-102 °C; Rf ) 0.23 (24:1 hexane-EtOAc); 1H NMR
(CDCl3, 200 MHz) δ 8.25-8.10 (m, 2H), 7.90-7.81 (m, 2H), 6.94
(s, 1H); 13C{1H} NMR (CDCl3, 50 MHz) δ 183.1, 177.1, 151.7,
135.2, 134.7, 131.5, 130.2, 127.3, 126.8 (2C), 118.5 [q, J (13C-
19F) ) 321 Hz]. Anal. Calcd for C11H5F3O5S: C, 43.14; H, 1.65.
Found: C, 43.36; H, 1.55.
5-Hyd r oxy-2-[(tr iflu or om eth a n esu lfon yl)oxy]-1,4-n a p h -
th oqu in on e (2). To a solution of 2,5-dihydroxy-1,4-naphtho-
quinone (290 mg, 1.53 mmol), 2,6-lutidine (0.196 mL, 180 mg,
1.68 mmol), and 4-(N,N-dimethylamino)pyridine (19 mg, 0.15
mmol) in CH2Cl2 (35 mL) at 0 °C was slowly added triflic
anhydride (0.272 mL, 456 mg, 1.62 mmol). The resulting
mixture was stirred at 23 °C for 3 h. After the usual workup
and chromatography (10:1 hexane-EtOAc), 2 was obtained as
a red solid (391 mg, 79%): mp 109-110 °C; Rf ) 0.41 (9:1
hexane-EtOAc); 1H NMR (CDCl3, 200 MHz) δ 11.66 (s, 1H),
1
3.94 (s, 3H); H NOEDIFF (CDCl3, 300 MHz) (i) irradiation at
3.94 ppm (OMe) led to enhancements of the signals at 6.66 (H-
6, 13%), 11.25 (OH, -45%), and 12.81 (OH, -38%), (ii) irradia-
tion at 6.66 (H-6) led to enhancements of the signals at 11.25
(OH, 2%) and 12.81 (OH, 2%); 13C{1H} NMR (10:1 CDCl3-
CD3OD, 50 MHz) δ 188.0, 184.2, 161.2, 159.9, 139.7, 137.9, 130.5,
129.0, 110.2, 109.0, 61.1; EI-MS m/ z 220 (M+, 100), 205 (8), 177
(38), 160 (35). Anal. Calcd for C11H8O5: C, 60.00; H, 3.66.
Found: C, 59.71; H, 3.56.
(19) For a lead reference on the formation of sulfonyl radicals, see:
Quiclet-Sire, B.; Zard, S. Z. J . Am. Chem. Soc. 1996, 118, 1209.
(20) March, J . Advanced Organic Chemistry, 4th ed.; Wiley: New
York, 1992; pp 648-649.
(21) Ghosal, S.; Luke, G. P.; Kyler, K. S. J . Org. Chem. 1987, 52,
4296.
(22) Bruce, D. B.; Thomson, R. H. J . Chem. Soc. 1955, 1089.

Notes
5,6-Dim et h oxy-8-h yd r oxy-1,4-n a p h t h oq u in on e (11).
J . Org. Chem., Vol. 62, No. 13, 1997 4527
A
AB system, J ) 11.4 Hz, 1H), 7.06 (part B, AB system, J ) 11.4
Hz, 1H); 13C{1H} NMR (CDCl3, 50 MHz) δ 180.4, 180.0, 146.0,
144.8, 138.9, 138.8, 138.6, 138.3, 123.4 (2C), 118.6 [q, J (13C-
19F) ) 321 Hz], 118.51 [q, J (13C-19F) ) 321 Hz], 118.46 [q, J (13C-
19F) ) 321 Hz]; EI-MS m/ z 602 (M+, 17), 382 (11), 341 (24), 203
(20); HRMS calcd for C13H3F9O11S3 601.8694, found 601.8691.
15: mp 185-190 °C; IR (KBr) 1690, 1680 cm-1; 1H NMR (CDCl3,
300 MHz) δ 7.80 (s, 2H), 7.01 (s, 1H); 13C{1H} NMR (CDCl3, 50
MHz) δ 179.4, 173.7, 150.4, 146.7, 146.2, 131.5, 130.9, 127.0,
125.6, 124.3, 118.7 [q, J (13C-19F) ) 321 Hz, 2C], 118.5 [q, J (13C-
19F) ) 321 Hz]; EI-MS m/ z 602 (M+, 34), 533 (13), 341 (44) 203
(39); HRMS calcd for C13H3F9O11S3 601.8694, found 601.8672.
Meth od b. To a solution of triflate 3 (100 mg, 0.29 mmol) in
CH2Cl2 (10 mL) at 0 °C were added 2,6-lutidine (0.48 mL, 0.44
g, 3.26 mmol) and triflic anhydride (0.55 mL, 0.92 g, 3.26 mmol).
The mixture was stirred at 0 °C for 10 min and at 23 °C for 24
h. After the usual workup and chromatography (7:1 hexane-
EtOAc), 14 (48 mg, 27%) and 15 (53 mg, 30%) were obtained as
yellow solids.
mixture of quinone 10 (90 mg, 0.41 mmol), Ag2O (116 mg, 0.50
mmol), and iodomethane (0.031 mL, 0.50 mmol) in acetonitrile
(10 mL) was heated at 70 °C for 3 h. The solvent was
evaporated, and the residue was chromatographed (7:1 hexane-
EtOAc) to yield 11 as an orange solid (65 mg, 68%): mp 180-
1
181 °C; IR (KBr) 1660, 1640, 1590 cm-1; H NMR (CDCl3, 300
MHz) δ 12.97 (s, 1H), 6.86 (part A, AB system, J ) 10.2 Hz,
1H), 6.79 (part B, AB system, J ) 10.2 Hz, 1H), 6.68 (s, 1 H),
3.95 (s, 3H), 3.67 (s, 3H); 1H NOEDIFF (CDCl3, 300 MHz) (i)
irradiation at 3.95 (OMe) led to an enhancement of the signal
at 6.68 (H-6, 11%), (ii) no enhancement was observed after
irradiation at 3.68 (OMe); 13C NMR (CDCl3, 50 MHz) δ 188.3
(d, J ) 10.1 Hz), 183.7 (dd, J ) 8.8, 1.9 Hz), 161.6 (d, J ) 10.4
Hz), 161.6 (d, J ) 1.1 Hz), 145.1 (m), 140.6 (dd, J ) 169.0, 1.4
Hz), 137.6 (dd, J ) 169.2, 1.2 Hz), 123.0 (d, J ) 3.5 Hz), 107.9
(q, J ) 3.6 Hz), 105.5 (dd, J ) 162.1, 7.8 Hz), 61.2 (q, J ) 145.5
Hz), 56.5 (q, J ) 145.8 Hz). Anal. Calcd for C12H10O5: C, 61.54;
H, 4.30. Found: C, 61.35; H, 4.60.
5,8-Bis[(t r iflu or om e t h a n e su lfon yl)oxy]-1,4-n a p h t h o-
qu in on e (13). To a solution of 5,8-dihydroxy-1,4-naphtho-
quinone (300 mg, 1.58 mmol) in CH2Cl2 (40 mL) at 23 °C were
added 2,6-lutidine (2.24 mL, 2.06 g, 19.2 mmol) and triflic
anhydride (3.22 mL, 5.40 mL, 19.1 mmol). The mixture was
stirred at 23 °C for 18 h. After the usual workup and chroma-
tography (5:1 hexane-EtOAc), 13 was obtained as a yellow solid
Ra d ica l An ion 16. The paramagnetic species were gener-
ated by reaction of a nitrogen-purged solution of 3 (3.4 mg, 1
mmol) with Et3N (0.2 mL). The mixture, which immediately
turned from red to intense violet, was transferred to the ESR
cell. The ESR spectrum was recorded at 23 °C on a Varian E-12
spectrometer with 100 kHz field modulation operating at 9.5
GHz microwave frequency, in a flat quartz cell (4 × 1 × 0.1 cm).
The microwave power level was kept at 1 mW, the time constant
was 0.3 s, the modulation amplitude was 100 kHz, and the scan
range was 20 G.
1
(444 mg, 62%): mp 148-150 °C; IR (KBr) 1670 cm-1; H NMR
(CDCl3, 200 MHz) δ 7.69 (s, 2H), 7.02 (s, 2H); 13C{1H} NMR
(CDCl3, 50 MHz) δ 181.1, 146.1, 138.7, 130.0, 125.9, 118.9 [q,
J (13C-19F) ) 321 Hz]; EI-MS m/ z 454 (M+, 7), 298 (6), 270 (11),
257 (15), 201 (46); HRMS calcd for C12H4F6O8S2 453.9252, found
453.9251. Anal. Calcd for C12H4F6O8S2: C, 31.72; H, 0.89; S,
14.11. Found: C, 31.79; H, 1.10; S, 13.97.
Ack n ow led gm en t. This work was supported by the
DGICYT (Project PB-94-0163). OÄ .F. is a recipient of a
predoctoral fellowship by the Ministerio de Educacio´n
y Ciencia. We acknowledge Dr. A. M. Castan˜o for the
developping of conditions for the bistriflation of naph-
thazarin.
5,6,8-Tr is[(tr iflu or om eth a n esu lfon yl)oxy]-1,4-n a p h th o-
qu in on e (14) a n d 2,5,8-Tr is[(tr iflu or om eth a n esu lfon yl)-
oxy]-1,4-n a p h th oqu in on e (15). Meth od a . To a solution of
2,5,8-trihydroxy-1,4-naphthoquinone (100 mg, 1.58 mmol) in
CH2Cl2 (10 mL) at 0 °C were added 2,6-lutidine (0.56 mL, 0.52
g, 4.85 mmol) and triflic anhydride (0.80 mL, 1.34 g, 4.75 mmol).
The mixture was stirred at 0 °C for 10 min and at 23 °C for 24
h. After the usual workup and chromatography (7:1 hexane-
EtOAc), 14 (73 mg, 25%; Rf ) 0.6, 3:1 hexane-EtOAc) and 15
(88 mg, 31%; Rf ) 0.5, 3:1 hexane-EtOAc) were obtained as a
yellow solids. 14: mp 234-235 °C dec; IR (KBr) 1720, 1600
Su p p or tin g In for m a tion Ava ila ble: Copies of the NMR
spectra for 9, 14, and 15 (6 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
cm-1
;
1H NMR (CDCl3, 300 MHz) δ 7.73 (s, 1H), 7.14 (part A,
J O9621027