A novel nickel(0)-catalyzed cascade Ullmann-pinacol coupling: From o-bromobenzaldehyde to trans-9,10-dihydroxy-9,10-dihydrophenanthrene

Article abstract of DOI:10.1055/s-2007-984543

Using 5 mol% of (Ph₃P)₂NiCl₂ as a catalyst, Zn powder as a reductant, ortho-carbonyl-substituted aryl halides could be coupled to form trans-9,10-dihydroxy-9,10-dihydrophenanthrenes in a one-pot cascade reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984543

LETTER
2101
A Novel Nickel(0)-Catalyzed Cascade Ullmann–Pinacol Coupling: From
o-Bromobenzaldehyde to trans-9,10-Dihydroxy-9,10-dihydrophenanthrene
A
Novel
Nick
h
el(0)-Catalyz
u
ed
C
ascade
a
U
llmann–P
n
inacol Coupl
g
ing -zheng Lin, Qing-an Chen, Tian-pa You*
Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. of China
E-mail: ytp@ustc.edu.cn
Received 9 April 2007
trans-phendiol was really obtained as the major product in
the homocoupling reaction of o-bromobenzaldehyde
under the conditions of Ni-catalyzed Ullmann reaction in
the presence of Zn metal (Scheme 1).9
Abstract: Using 5 mol% of (Ph3P)2NiCl2 as a catalyst, Zn powder
as a reductant, ortho-carbonyl-substituted aryl halides could be
coupled to form trans-9,10-dihydroxy-9,10-dihydrophenanthrenes
in a one-pot cascade reaction.
Key words: Nickel catalysis, Ullmann–pinacol coupling, cascade
reaction, trans-selectivity, trans-9,10-dihydroxy-9,10-dihydro-
phenanthrene
(Ph3P)2NiCl2 (0.05 equiv)
Zn (3 equiv)
CHO
Br
OH
OH
DMF, 60 °C
Chiral diols, especially TADDOL1 and BINOL,2 are ver-
satile chiral ligands in asymmetric synthesis. However, to
the best of our knowledge, there are few reports about
trans-9,10-dihydroxy-9,10-dihydrophenanthrene (phen-
diol) as chiral ligand in asymmetric synthesis.3 Possessing
a rigid cyclic vicinal diol structure, trans-phendiol could
serve as a potential diol skeleton in asymmetric synthesis
(Figure 1). Moreover, phendiols are the key structural
units in various important natural products, such as
pradimicinone and related compounds.4 There are many
methods to synthesize the phendiol structure: reduction of
phenanthraquinone;5 combination of enantioselective di-
hydroxylation with intramolecular Ullmann coupling;4b or
intramolecular pinacol coupling.4a,6 Described herein is
the development of a novel (Ph3P)2NiCl2-catalyzed cas-
cade Ullmann–pinacol coupling reaction and its applica-
tion to a highly trans-selective preparation of phendiols.
[Ni]
Zn
[O]
ZnBr2
Zn
O
O
CHO
CHO
Scheme 1
In the homocoupling experiment of 2-bromobenz-
aldehyde with excess zinc powder10 catalyzed by
(Ph3P)2NiCl2,11 an Ullmann coupling was believed to oc-
cur first. As the biphenyl-2,2¢-dialdehyde was formed, an
intramolecular pinacol cyclization was then induced by
the ZnBr2 engendered in the Ullmann coupling step to
produce trans-phendiol. If the reaction was stopped in a
shorter reaction time, the biphenyl-2,2¢-dialdehyde could
be isolated as the main product.12 It should also be noted
that phenanthrenequinone was usually isolated as a
byproduct. We suspected that the phenanthrenequinone
was the oxidation product of the phendiol in the workup
process.13
R
Ph Ph
OH
O
OH
OH
OH
OH
O
OH
Ph Ph
TADDOL
R
BINOL
phendiol
We then investigated this Ullmann–pinacol cascade reac-
tion of various ortho-carbonyl-substituted aryl halides
(Table 1). Replacing the bromide 1a with the less reactive
chloride 1a¢ led to a comparable yield of phendiol though
the reaction time was longer (entries 1 and 2). The product
yield was found to decrease for extensively conjugated
systems (entries 3–5).14 When ketone 1e was tested, the
main product was 2,2¢-diacetylbiphenyl instead of phendi-
ol 2e (entry 6). The yield of 2e was only 19% even the re-
action time was prolonged to 24 hours, presumably
because the lower reactivity of ketone and the increased
steric hinderance of the methyl groups that was an
obstacle to the subsequent pinacol coupling step. The re-
action went smoothly if the substituent on the aromatic
Figure 1
The Ullmann reaction7 can be induced by Cu, Ni, and Pd.
Generally, nickel(0)-mediated Ullmann reaction of aryl
halides can tolerate a broad variety of functional groups.
In addition, the reaction condition is mild and the nickel
reagent is inexpensive. We also noted that zinc halide
produced in situ from the coupling of aryl halides was a
promoter for the pinacol couping.8 Exhilaratingly, the
SYNLETT 2007, No. 13, pp 2101–2105
Advanced online publication: 27.06.2007
DOI: 10.1055/s-2007-984543; Art ID: W07007ST
© Georg Thieme Verlag Stuttgart · New York
1
3
.0
8
.2
0
0
7

2102
S.-z. Lin et al.
LETTER
ring was electron-withdrawing but was retarded in the the fact that phendiol was not obtained when biphenyl-
first step if the substituent was electron-donating (entries 2,2¢-dialdehyde was treated with (Ph3P)2NiCl2. On the
7 and 8). For heterocyclic 1h, the dialdehyde intermediate other hand, when the nickel catalyst was replaced by
was reduced to an unexpected alcohol instead of phendiol ZnCl2, the dialdehyde was smoothly converted into trans-
compound (entry 9).15
phendiol in 4 hours (Scheme 2).
Although Ni-catalyzed pinacol couplings have been re-
ported,24 it seemed that (Ph3P)2NiCl2 did not induce the
pinacol reaction in our experiment. This was supported by
Table 1 Cascade Reaction of Various ortho-Carboxyl Aryl Halides16,17
Entry
1
Substratea
Time (h)
Product
Isolated yieldb (%)
HO
OH
CHO
7
80
Br
1a
2a6b
HO
OH
CHO
Cl
2
3
10
12
76
71
1a¢
2a6b
HO
OH
CHO
Cl
1b18
2b
CHO
Br
OH
OH
4
9
63
1c19
2c6a
HO
OH
Br
CHO
5
9
51
1d20
2d21
HO
OH
COMe
6
7
24
12
19c
Cl
1e
2e22
HO
OH
CHO
Cl
73
F
1f
F
F
2f
Synlett 2007, No. 13, 2101–2105 © Thieme Stuttgart · New York

LETTER
A Novel Nickel(0)-Catalyzed Cascade Ullmann–Pinacol Coupling
2103
Table 1 Cascade Reaction of Various ortho-Carboxyl Aryl Halides16,17 (continued)
Entry
8
Substratea
MeO
Time (h)
Product
MeO
Isolated yieldb (%)
OMe CHO
CHO OMe
CHO
Br
MeO
OMe
OMe
50d
MeO
9
OMe
1g23
323
N
CHO
Cl
OH
9
12
45
N
HO
1h
N
4
a The reagents are commercially available unless otherwise noted.
b Uncorrected.
c The main product is the diketone22 (54% yield).
d 3,4,5-Trimethoxybenzaldehyde is isolated with 30% yield.
HO
OH
trans-selectivity26 in the intramolecular pinacol coupling
is still under investigation. We are trying to expand this
reaction to ortho-halogen-substituted aromatic imines and
to apply these chiral phendiols in asymmetric catalysis.
ZnCl2 (>0.4 equiv)
Zn (2.5 equiv)
DMF, 60 °C, 4 h
CHO CHO
80%
Scheme 2
Acknowledgment
Project supported by the National Natural Science Foundation of
China (No. 20472077). In addition, we thank the referees for very
valuable advice.
Despite its excellent efficiency in the intramolecular pina-
col cyclization above, ZnCl2 was not responsible for the
intermolecular pinacol coupling of benzaldehyde under
similar conditions. Even the substituent on the aromatic
ring was strong electron-withdrawing, such as 4-fluoro-
benzaldehyde, the yield of pinacol was only 28% after
5 hours (Scheme 3).
References and Notes
(1) (a) Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem. Int.
Ed. 2001, 40, 93. (b) Blaser, H. U. Chem. Rev. 1992, 92,
935.
(2) Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103,
3155.
(3) For application of phendiol derivatives in asymmetric
catalysis, Suzuki’s group has reported a valuable work
recently. See: Ohmori, K.; Furuya, S.; Yamanoi, S.; Suzuki,
K. Chem. Lett. 2007, 36, 328.
(4) (a) Kitamura, M.; Ohmori, K.; Kawase, T.; Suzuki, K.
Angew. Chem. Int. Ed. 1999, 38, 1229. (b) Kelly, T. R.; Li,
Q.; Bhushan, V. Tetrahedron Lett. 1990, 31, 161.
(5) (a) Cortex, C.; Harvey, R. G. Org. Synth., Coll. Vol. VI;
Wiley and Sons: New York, 1988, 887. (b) Okajima, M.;
Suga, S.; Itami, K.; Yoshida, J. J. Am. Chem. Soc. 2005, 127,
6930.
ZnCl2 (1 equiv)
Zn (3 equiv)
DMF, 60 °C
4-OH-C6H4CHO
C6H5CHO
no reaction
2-Br-C6H4CHO
ZnCl2 (1 equiv)
Zn (3 equiv)
DMF, 60 °C, 5 h
4-F-C6H4
OH
4-F-C6H4CHO
HO
4-F-C6H4
28%, dl:meso = 2.9:1
Scheme 3
(6) (a) Ohmori, K.; Kitamura, M.; Suzuki, K. Angew. Chem. Int.
Ed. 1999, 38, 1226. (b) Taniguchi, N.; Hata, T.; Uemura, M.
Angew. Chem. Int. Ed. 1999, 38, 1232. (c) Yamamoto, Y.;
Hattori, R.; Itoh, K. Chem. Commun. 1999, 825.
(d) Yamamoto, Y.; Hattori, R.; Miwa, T.; Nakagai, Y.-i.;
Kubota, T.; Yamamoto, C.; Okamoto, Y.; Itoh, K. J. Org.
Chem. 2001, 66, 3865. (e) Li, C.-J.; Meng, Y.; Yi, X.-H.;
Ma, J.-H.; Chan, T.-K. J. Org. Chem. 1998, 63, 7498.
(7) (a) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359. (b) Bringmann, G.;
Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.; Garner, J.;
Breuning, M. Angew. Chem. Int. Ed. 2005, 44, 5384.
Thus, based on the experimental results of the tandem
reactions and of the intermolecular pinacol coupling, it
seemed that an electron-withdrawing substituent on the
aromatic ring would favor this cascade reaction and an
electron-donating substituent would retard the second
step of pinacol coupling.
In conclusion, a highly stereoselective Ullmann–pinacol
reaction to prepare trans-9,10-dihydroxy-9,10-dihydro-
phenanthrene was discovered.25 The reason of the highly
Synlett 2007, No. 13, 2101–2105 © Thieme Stuttgart · New York

2104
S.-z. Lin et al.
LETTER
(16) Typical Procedure for the (Ph3P)2NiCl2-Catalyzed
(8) (a) Chatterjee, A.; Joshi, N. N. Tetrahedron 2006, 62,
12137. (b) Tanaka, K.; Kishigami, S.; Toda, F. J. Org.
Chem. 1990, 55, 2981.
Ullmann–Pinacol Coupling
To a mixture of (Ph3P)2NiCl2 (33 mg, 0.05 mmol) and zinc
powder (196 mg, 3 mmol) in anhyd DMF (0.5 ml) was added
the 2-bromobenzaldehyde (1a, 185 mg, 117 mL, 1 mmol) at
60 °C under a nitrogen atmosphere. This mixture was stirred
for 7 h. After cooling to ambient temperature, 5 mL 1 M HCl
and 10 mL CH2Cl2 were added. The mixture was stirred for
10 min, and then filtered to remove the unreacted zinc
powder. The phases were separated and the aqueous phase
was extracted with CH2Cl2 (3 × 5 mL). The combined
organic extracts were dried over MgSO4 for 1 h and
concentrated. Purification of the residue by chromatography
gave the phendiol 2a (85 mg, 80% yield).
(9) (a) Scherf group reported a similar reaction to cis-phendiol
with excess Ni(COD)2 in 1999: Reisch, H. A.; Enkelmann,
V.; Scherf, U. J. Org. Chem. 1999, 64, 655. (b) The trans-
structure of 2a was determined by the J9,10 = 8.1 Hz and the
singlet for acetate at d = 2.11 ppm of trans-9-acetoxy-10-
hydroxy-9,10-dihydrophenanthrene (Scheme 4). (c) For cis-
9-acetoxy-10-hydroxy-9,10-dihydrophenanthrene,
J9,10 = 3.8 Hz and the singlet for acetate is at d = 1.92 ppm,
see: Jerina, D. M.; Selander, H.; Yagi, H.; Wells, M. C.;
Davey, J. F.; Mahadevan, V.; Gilbson, D. T. J. Am. Chem.
Soc. 1976, 98, 5988.
(17) Selective NMR Data of Products
Compound 2a: 1H NMR (300 MHz, CDCl3): d = 7.76 (dd,
J = 6.2, 2.8 Hz, 2 H), 7.67 (dd, J = 9.4, 3.1 Hz, 2 H), 7.42–
7.36 (m, 4 H), 4.76 (s, 2 H), 1.65 (br, 2 H). 13C NMR (75
MHz, CDCl3): d = 136.2, 132.6, 128.6, 128.5, 125.3, 123.9,
74.2.
Ac2O, Na2CO3
EtOAc, r. t.
20 h
OAc
OAc
OH
OH
9
J
9,10 = 8.1 Hz
+
10
OAc
OH
Compound 2b: 1H NMR (300 MHz, acetone-d6): d = 8.41 (d,
J = 8.4 Hz, 2 H), 8.21 (d, J = 8.7 Hz, 2 H), 8.02 (d, J = 8.7
Hz, 2 H), 7.95 (d, J = 7.8 Hz, 2 H), 7.64–7.51 (m, 4 H), 5.69
(s, 2 H), 3.13 (s, 2 H). 13C NMR (75 MHz, acetone-d6): d =
134.3, 133.9, 132.1, 131.5, 129.8, 129.2, 127.5, 126.6,
124.8, 123.5, 67.9.
17%
79%
Scheme 4
(10) The zinc powder was purchased from SCRC (Sinopharm
Chemical Reagent Co., Ltd). The activation procedure was
conducted as follows: The zinc powder was stirred in 1 M
HCl for a few minutes to remove the oxide, then filtered and
washed successively with H2O, EtOH, and Et2O. The
material was dried in vacuum for 24 h and then stored in a
sealed bottle.
(11) Synthesis of (Ph3P)2NiCl2 from NiCl2·6H2O and PPh3
Nickel(II) chloride hexahydrate and PPh3 were purchased
from SCRC and used as available. Then, PPh3 (10.50 g, 40
mmol) was dissolved in 100 mL of warm AcOH, and then
cooled to r.t. To this solution, NiCl2·6H2O (4.76 g, 20 mmol)
in H2O (4 mL) was added dropwise. The mixture was stirred
at r.t. for 48 h. The dark green solution was filtered, yielding
deep green solid, which was washed successively with
AcOH, EtOH, and Et2O. The material was dried in vacuum
for 24 h and then stored in a sealed bottle.
Compound 2c: 1H NMR (300 MHz, CDCl3): d = 8.00 (d,
J = 8.4 Hz, 2 H), 7.95–7.91 (m, 4 H), 7.56 (d, J = 8.4 Hz, 2
H), 7.46 (t, J = 7.5 Hz, 2 H), 7.27 (t, J = 6.6 Hz, 2 H), 4.73
(s, 2 H), 2.61 (br, 2 H). 13C NMR (75 MHz, CDCl3): d =
136.2, 133.8, 130.2, 129.1, 129.1, 128.5, 127.6, 125.6,
125.4, 121.4, 75.0.
(18) Compound 2e: 1H NMR (300 MHz, acetone-d6): d =
7.78–7.72 (m, 4 H), 7.34–7.29 (m, 4 H), 3.04 (s, 2 H), 1.24
(s, 6 H). 13C NMR (75 MHz, acetone-d6): d = 144.8, 132.7,
128.8, 128.0, 125.1, 124.0, 77.3, 25.0.
Compound 2f: 1H NMR (300 MHz, acetone-d6): d = 7.71
(dd, J = 8.4, 6.0 Hz, 2 H), 7.60 (dd, J = 10.3, 2.5 Hz, 2 H),
7.13 (td, J = 8.6, 2.5 Hz, 2 H), 4.60 (s, 2 H), 3.12 (s, 2 H). 13C
NMR (75 MHz, acetone-d6): d = 163.7 (d, J = 241.0 Hz),
135.1 (d, J = 2.9 Hz), 134.7 (dd, J = 8.0, 2.3 Hz), 129.0 (d,
J = 8.4 Hz), 115.6 (d, J = 21.5 Hz), 111.2 (d, J = 23.1 Hz),
73.416.
(12) Addition of PPh3 seems to accelerate the Ullmann coupling
step. When 28 mol% of PPh3 was added and the reaction was
ceased in 53 min, the biphenyl-2,2¢-dialdehyde can be
isolated with 80% yield. But the second step of pinacol
coupling was not affected by PPh3.
Compound 4: 1H NMR (300 MHz, CDCl3): d = 8.48 (s, 4 H),
7.55 (d, J = 4.5 Hz, 2 H), 4.81 (s, 4 H), 2.96 (br, 2 H). 13
NMR (75 MHz, CDCl3): d = 148.7, 148.1, 147.8, 129.8,
122.08, 61.28.
C
(13) The phendiol 2a is stable in solid. But, in our observation, it
could be oxidized to phenanthrenequinone in solution. The
colorless solution of phendiol 2a changed to yellow in
several hours, indicated that some phenanthrenequinone was
formed. This conversion could be accelerated by silica gel or
light, see: Barbas, J. T.; Sigma, M. E.; Dabestani, R.
Environ. Sci. Technol. 1996, 30, 1776; thus, the diol
products must be separated as quickly as possible after
ceasing the reaction to assure high yields.
(14) In solution, 2b and 2c were oxidized faster than 2a in our
observation. That resulted in lower yield of 2b and 2c.
(15) The coordination of the Zn2+ with both the carbonyls, which
brings the two carbonyls together, is essential to the
intramolecular pinacol coupling. In the reaction of
heterocyclic 1h, this effect may be disturbed by the
competitive coordination of the nitrogen atom on the
heterocycle.
(18) Prepared from b-naphthol according to literature procedure:
(a) Russell, A.; Lockhart, L. B. Org. Synth., Coll. Vol. III;
Wiley & Sons: New York, 1955, 463. (b) Shoesmith, J. B.;
Mackie, A. J. Chem. Soc. 1930, 1584.
(19) Prepared from 2-methylnaphthalene according to literature
procedure: (a) Oi, S.; Matsunaga, K.-i.; Hattori, T.; Miyano,
S. Synthesis 1993, 895. (b) Smith, J. G.; Dibble, P. W.;
Sandborn, R. E. J. Org. Chem. 1986, 51, 3762.
(20) Compound 1d was prepared from 9-bromophenanthrene in
five steps (Scheme 5).
(21) Pure diol product was not obtained. The most polar product
was supposed to be the mixture of cis-diol and trans-diol by
NMR analysis.
(22) Sarobe, M.; van Heerbeek, R.; Jenneskens, L. W.; Zwikker,
J. W. Liebigs Ann./Recl. 1997, 2499.
(23) Prepared from 3,4,5-trimethoxybenzaldehyde according to
literature procedure: Molander, G. A.; George, K. M.;
Monovich, L. G. J. Org. Chem. 2003, 68, 9533.
Synlett 2007, No. 13, 2101–2105 © Thieme Stuttgart · New York

LETTER
A Novel Nickel(0)-Catalyzed Cascade Ullmann–Pinacol Coupling
2105
concentrated. Purification of the residue by chromatography
gave the monoacetate.
Br
Br
Method B (2b): To a solution of 2b (18 mg, 0.058 mmol) in
0.5 mL pyridine, Ac2O (8.9 mg, 8.2 mL, 0.087 mmol) was
added at r.t. The reaction was conducted for 10 h.
Conventional procedures led to the isolation of the
monoacetate (5 mg, 24.5%).
a, b
Br
c, d
e
1d
OH
Selective NMR Data of Phendiol Monoacetates
Monoacetate of 2a: 1H NMR (300 MHz, CDCl3): d = 7.75
(m, 2 H), 7.55 (d, J = 7.2 Hz, 1 H), 7.41–7.22 (m, 5 H), 6.02
(d, J = 8.1 Hz, 1 H), 4.82 (d, J = 8.1 Hz, 1 H), 2.48 (s, 1 H),
2.11 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 171.3, 135.5,
133.1, 132.3, 132.0, 129.2, 128.9, 128.5, 128.1, 127.6,
127.1, 123.9, 123.8, 74.5, 71.1, 21.1.
Scheme 5 Preparation of 1d. Reagents and conditions: (a) n-BuLi
(1.1 equiv), Et2O, r.t., 1 h; then Me2SO4 (2 equiv), Et2O, reflux, 5 h,
99%; (b) NBS (1.1 equiv), MeCN, r.t. in dark, 24 h, 92%; (c) NBS
(1.01 equiv), BPO (0.02 equiv), CCl4, reflux, 7 h; (d) CaCO3 (5
equiv), dioxane–H2O (1:1), reflux, 10 h, 92% (2 steps); (e) PCC (1.3
equiv), CH2Cl2, 2 h, 84%.
Monoacetate of 2b: 1H NMR (300 MHz, acetone-d6): d =
8.38 (d, J = 8.4 Hz, 1 H), 8.28–8.25 (m, 3 H), 8.13–8.06 (m,
2 H), 8.00–7.96 (m, 2 H), 7.67–7.53 (m, 4 H), 7.06 (d,
J = 2.4 Hz, 1 H), 5.66 (d, J = 2.4 Hz, 1 H), 3.07 (br, 1 H),
1.84 (s, 3 H). 13C NMR (75 MHz, acetone-d6): d = 171.0,
134.5, 134.3, 133.6, 133.5, 133.4, 131.4, 131.3, 131.1,
130.3, 129.5, 129.3, 128.2, 127.8, 127.2, 126.9, 124.7,
124.0, 123.5, 123.4, 68.7, 65.1, 20.9.
(24) (a) Shi, L.; Fan, C.-A.; Tu, Y.-Q.; Wang, M.; Zhang, F.-M.
Tetrahedron 2004, 60, 2851. (b) Ogoshi, S.; Kamada, H.;
Kurosawa, H. Tetrahedron 2006, 62, 7583.
(25) Preparation in multigram scale is feasible, the dosage of
nickel catalyst can be reduced to 0.03 equiv: To a mixture of
(Ph3P)2NiCl2 (392 mg, 0.60 mmol) and zinc powder (3.930
g, 60.1 mmol) in anhyd DMF (10 mL) was added the 2-
bromobenzaldehyde (1a, 3.70 g, 2.34 mL, 20 mmol) at 60 °C
under nitrogen atmosphere. After stirring for 7 h, the mixture
was poured into ice water (50 mL) and filtered. The filtrate
was discarded. The filter residue was dissolved in hot EtOAc
and filtered again. Concentration of the filtrate gave crude
phendiol 2a, which is easily recrystallized in EtOAc or
EtOH to afford pure product (1.683 g, 79% yield).
Monoacetate of 2c: 1H NMR (300 MHz, CDCl3): d = 8.00–
7.90 (m, 5 H), 7.57–7.43 (m, 5 H), 7.29–7.24 (m, 2 H), 6.06
(d, J = 11.1 Hz, 1 H), 4.92 (d, J = 11.1 Hz, 1 H), 2.65 (br, 1
H), 2.38 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 172.0,
136.1, 133.9, 133.8, 132.8, 130.2, 130.0, 129.3, 129.0,
128.8, 128.44, 128.39, 127.6, 127.5, 125.8, 125.7, 126.5,
125.4, 121.6, 121.0, 76.6, 73.4, 21.1.
(26) The trans-structures of the phendiols in Table 1 were
confirmed based on NMR analysis of the diols and the
corresponding monoacetates (see ref. 9).
Monoacetate of 2f: 1H NMR (300 MHz, acetone-d6): d =
7.73–7.63 (m, 3 H), 7.45 (dd, J = 8.4, 5.7 Hz, 1 H), 7.19–
7.07 (m, 2 H), 5.96 (d, J = 7.2 Hz, 1 H), 4.84 (d, J = 7.2 Hz,
1 H), 3.03 (s, 1 H), 2.09 (s, 3 H). 13C NMR (75 MHz,
acetone-d6): d = 170.9, 165.8 (d, J = 17.1 Hz), 162.6 (d, J =
16.2 Hz), 135.8 (dd, J = 8.2, 2.4 Hz), 134.7 (dd, J = 8.0, 2.2
Hz), 133.6 (d, J = 2.9 Hz), 131.3 (d, J = 8.6 Hz), 130.9 (d,
J = 8.5 Hz), 130.0 (d, J = 3.0 Hz), 116.2 (d, J = 14.3 Hz),
115.8 (d, J = 14.5 Hz), 112.0 (d, J = 15.9 Hz), 111.6 (d,
J = 15.9 Hz), 74.2, 70.1, 21.0.
Typical Procedure for Phendiol Monoacetate
Method A (2a, 2c, 2f): To a suspension of phendiol (0.05
mmol) and Na2CO3 (16 mg, 0.15 mmol) in anhyd EtOAc
(0.5 mL), Ac2O (15 mg, 14 mL, 0.15 mmol) was added at r.t.
After the reaction was complete (monitored by TLC), the
mixture was poured into 2 mL of cold H2O and the phases
were separated. The aqueous phase was extracted with
EtOAc (3 × 1 mL). The combined organic extracts were
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