1,n-rearrangement of allylic alcohols promoted by hot water: Application to the synthesis of navenone B, a polyene natural product

Article abstract of DOI:10.1021/jo5004086

It was reported for the first time that hot water as a mildly acidic catalyst efficiently promoted 1,n-rearrangement (n = 3, 5, 7, 9) of allylic alcohols. In some cases, the rearrangement reactions joined isolated C-C double or triple bonds to generate conjugated polyene or enyne structure motifs. We used the 1,3-rearrangement reaction of an allylic alcohol in hot water as part of an attractive new strategy for construction of the polyene natural product navenone B by iterative use of a Grignard reaction, a 1,3-rearrangement of the resulting allylic alcohol, and subsequent oxidation of the rearranged product.

Full text of DOI:10.1021/jo5004086

Article
pubs.acs.org/joc
1,n‑Rearrangement of Allylic Alcohols Promoted by Hot Water:
Application to the Synthesis of Navenone B, a Polyene Natural
Product
Pei-Fang Li, Heng-Lu Wang, and Jin Qu*
State Key Laboratory and Institute of Elemento-organic Chemistry, Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Nankai University, Tianjin 300071, China
S
* Supporting Information
ABSTRACT: It was reported for the first time that hot water as a mildly acidic
catalyst efficiently promoted 1,n-rearrangement (n = 3, 5, 7, 9) of allylic alcohols.
In some cases, the rearrangement reactions joined isolated C−C double or triple
bonds to generate conjugated polyene or enyne structure motifs. We used the 1,3-
rearrangement reaction of an allylic alcohol in hot water as part of an attractive
new strategy for construction of the polyene natural product navenone B by iterative use of a Grignard reaction, a 1,3-
rearrangement of the resulting allylic alcohol, and subsequent oxidation of the rearranged product.
play important roles in the construction of conjugated polyenes
and enynes, which are common structural motifs in a great
variety of natural products, including retinoids, rapamycin,
amphotericin B, cicutoxin, and fumagillin.1,2
INTRODUCTION
■
Rearrangement reactions are useful for the preparation of
synthetically challenging products from readily accessible
precursors. The two regioisomers of an asymmetrically
substituted allylic alcohol generally have different thermody-
namic stabilities as a result of differences in the extent of
conjugation or substitution. If the less synthetically accessible
isomer happens to be the more thermodynamically stable one,
it can be readily obtained through a 1,3-rearrangement reaction
of the more synthetically accessible isomer. Furthermore, if the
carbon atom bearing the hydroxyl group is substituted with an
additional C−C double bond or a triple bond, the 1,3-
rearrangement reaction can bring the isolated unsaturated
bonds together to form a system with extended conjugation
(Scheme 1a). Therefore, these rearrangement reactions may
Some catalysts, including Brønsted acids,3 Lewis acids,4
transition metal complexes,5 and transition metal oxo
complexes,6 can mediate 1,3-rearrangement of allylic alcohols.
In addition to 1,3-rearrangements of allylic alcohols, 1,n-
rearrangements (n = 5, 7, 9) of conjugated polyenols was
synthetically useful and can also generate polyenes with
extended conjugation. However, most of the literature reports
have focused on 1,3-rearrangements, and 1,n-rearrangements (n
= 5, 7, 9) of conjugated polyenols (Scheme 1b) have rarely
been studied,7 perhaps because conjugated polyenols are readily
oxidized and undergo polymerization or cycloaddition reac-
tions. Thus, it is highly desirable to develop an efficient and
widely applicable method for 1,n-rearrangements of allylic
alcohols.
Scheme 1. Rearrangements of Allylic Alcohols
Water, the most abundant liquid on the Earth and solvent in
which most of the chemistry of biological processes occurs, is
cheaper, safer, and cleaner than organic solvents. In addition to
being a green reaction medium, it has unique chemical and
physical properties that allow it to catalyze organic reactions.8
One particularly striking example, reported by Jamison and co-
workers, is a water-promoted cascade epoxide-opening via 6-
endo mode, yielding a trans-fused ladder-type polyether
(Scheme 2).8i This finding suggests that water might catalyze
the biosynthesis of ladder-type polyether natural products.
Water is only weakly self-ionizing at 25 °C (pKw = 14).9
However, as temperature is increased, the extent of self-
ionization increases substantially; the pKw of water reaches its
highest value (11.2) at 250 °C, at which both the strong acid
H3O+ and the strong base OH− are more abundant than that at
Received: February 21, 2014
Published: April 9, 2014
© 2014 American Chemical Society
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Scheme 2. Epoxide-Opening Cascades Promoted by Water
Table 1. Hot Water-Promoted 1,3-Rearrangements of Cyclic
Allylic Alcohols
a
25 °C.9 Increasing the temperature also decreases the dielectric
constant of water, making it a better solvent for organic
compounds. Studies of organic reactions in high-temperature or
near-critical water (200−374 °C) have shown that organic
reactions traditionally catalyzed by Brønsted acids can take
place in high-temperature water in the absence of an additional
catalyst, and extensive mechanistic studies have suggested that
at high temperature, water acts as a mildly acidic catalyst in
these reactions.10 Unlike high-temperature water under
pressure, hot water (60−100 °C) is more accessible both in
the laboratory and in nature. In previous studies, we found that
hot water can act as a mildly acidic catalyst, which is similar to
high-temperature water.11 Recently, we found that the SN1
hydrolysis of allylic and benzylic alcohols occurs in hot water,
and we systematically studied the effects of various reaction
parameters on the outcome of this reaction.11d Our findings
inspired us to explore further the applications of hot water
chemistry to organic synthesis. Herein, we report that hot water
efficiently promoted 1,n-rearrangements of allylic alcohols, in
many cases forming conjugated polyenes or enynes that would
be difficult to synthesize by other means. We also describe the
iterative use of a Grignard reaction of an aldehyde, a 1,3-
rearrangement of the resulting allylic alcohol in hot water, and
subsequent oxidation of the rearranged allylic alcohol to
efficiently construct a conjugated polyene natural product via a
modular approach.
a
Reaction conditions: 1 mmol of allylic alcohol in water (25 mL),
b
vigorously stirring. Isolated yield.
RESULTS AND DISCUSSION
■
We began with investigating whether the 1,3-rearrangement of
1-phenyl-2-cyclohexen-1-ol (1a) occurred in water in the
absence of an additional catalyst. We found that no reaction
occurred when 1a was heated in an aprotic organic solvent such
as THF, 1,4-dioxane, toluene, acetonitrile, or DMF or in a
protic organic solvent such as methanol or isopropanol, even
after prolonged reaction times. However, at 80 °C in water, the
reaction was complete after 9 h and afforded the
thermodynamically more stable isomer 2a almost quantitatively
(1 mmol of 1a did not dissolve completely in 25 mL of water;
the reaction mixture was a slightly hazy solution even at 80 °C).
The fact that 1a remained inert in methanol or isopropanol at
their refluxing temperature indicated that the rearrangement
did not initiate at raised temperature in a polar solvent that is
capable of forming hydrogen bond and confirmed that water
played a catalytic role in the reaction.
We then carried out 1,3-rearrangements of various other
cyclic allylic alcohols in hot water (Table 1). Reactions of 1a−
1f, which have six-membered rings bearing various phenyl,
vinyl, alkynyl, and alkyl groups, afforded good to excellent
yields of products 2a−2f (entries 1−6), and some of them are
conjugated diene or enyne (2b−2d). It is noteworthy that even
at 80 °C, allylic alcohol 1g gave the desired rearrangement
product (2g) in 93% yield and none of the elimination product
(entry 7). Five-membered-ring allylic alcohol 1h gave a 90%
yield of 2h after 0.5 h at 40 °C (entry 8). We attributed the
high activity of these cyclic allylic alcohols to the effects of
“allylic strain”,12 which favors the production of less-strained,
more thermodynamically stable isomers.
Compared to cyclic allylic alcohols, acyclic allylic alcohol 1i
underwent the 1,3-rearrangement very slowly in water even
when the temperature was raised to 100 °C (Table 2, entries 1,
2). However, to our delight, the reaction was markedly
accelerated when a small amount of organic solvent was
introduced to disperse the substrate, and the effect of 1,4-
dioxane was more pronounced than that of THF (Table 1,
entries 3, 8). The addition of 10 vol % 1,4-dioxane considerably
sped up the reaction by improving the solubility of organic
reactant in the aqueous solution (entry 9). The more
effectiveness of water/1,4-dioxane mixed solvent than water/
THF mixed solvent may be due to the higher boiling point of
water/1,4-dioxane binary system. However, when the volume
percentage of the organic solvent was further increased, the
reaction rate decreased drastically (entries 4−7, 10−13). It may
be partly because of a reduction in the extent of ionization of
water,13 a decrease in the dielectric constant, or both.
The reactions of acyclic allylic alcohol substrates were
explored under the optimal conditions (Table 3). Phenyl-,
naphthyl-, and thienyl-substituted substrates 1i−1l (entries 1−
4) all gave the desired products with E selectivity. Notably, 1j,
which has an acid-sensitive phenolic silyl group, tolerated the
reaction conditions (entry 2). Tertiary substituted alcohols 1m
and 1n afforded allylic alcohols with trisubstituted alkene
moieties (entries 5, 6). Substrates 1o−1r with alkyl substituents
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Table 2. Effects of Solvent and Temperature on the 1,3-
Rearrangement of Allylic Alcohol 1i
Table 3. Hot Water-Promoted 1,3-Rearrangements of
a
a
Acyclic Allylic Alcohols
b
entry
solvent
temp (°C) time (h) yield/conv (%)
1
H2O
H2O
80
48
48
48
48
48
48
48
48
12
16
48
48
48
2/5
2
100
80
7/10
18/24
7/10
NR
3
H2O:THF = 9:1
4
H2O:THF = 4:1
80
5
H2O:THF = 1:1
80
6
H2O:THF = 1:4
80
NR
7
H2O:THF = 1:9
80
NR
8
H20:1,4-dioxane = 9:1
H2O:1,4-dioxane = 9:1
H2O:1,4-dioxane = 4:1
H2O:1,4-dioxane = 1:1
H2O:1,4-dioxane = 1:4
H2O:1,4-dioxane = 1:9
80
78/96
98/100
96/100
43/64
NR
9
100
100
100
100
100
10
11
12
13
NR
a
Reaction conditions: 1 mmol of 1i in solvent (25 mL), vigorously
b
stirring. Isolated yield.
on alkene afforded very high yields of products 2o−2r (entries
7−10). Allylic alcohols 1s and 1t, which are substituted with
styryl and phenylethynyl groups, respectively, reacted smoothly
to afford diene 2s and enyne 2t in high yield (entries 11, 12).
The hydroxy group of 1s could have rearranged either to the
benzylic position or to the end of the alkyl chain, but only diene
2s, which has more-extended conjugation, was formed (entry
11). When the reaction of adamantyl-substituted allylic alcohol
1u reached equilibrium after 4 h, we obtained about 70% of
isomer 2u, which is less sterically congested and has a more
highly substituted olefin bond. In the meantime, 23% of isomer
2u was transformed to the Z-configuration isomer 1u (entry
13). Secondary alcohol substrates with an aliphatic side chain
are unreactive in the presence of polyfluorinated arylboronic
acids in toluene at room temperature.4b However, we found
that heating aliphatic substrate 1v in aqueous solvent system at
100 °C for 24 h afforded a 56% yield of isomer 2v, which has
similar thermodynamic stability to that of 1v. In addition, (S)-
1p with 92% optical purity rearranged within 2 h in water at
100 °C, but racemic 2p was obtained (Scheme 3). This
evidence is consistent with a mechanism involving an allylic
cation, the stability of which strongly influences the rate of the
dehydration step. We observed no reaction when we attempted
Meyer−Schuster rearrangements of propargylic alcohols in hot
water.
a
Reaction conditions: 1 mmol substrate in solvent (25 mL, H2O:1,4-
b
c
dioxane = 9:1), vigorously stirring. Isolated yield. H2O:1,4-dioxane =
4:1. Under a N2 atmosphere. The E/Z ratio was determined by H
NMR spectroscopy. H2O:1,4-dioxane = 4:1, 80 °C. 23% cis-1u was
obtained. 39% of 1v was recovered.
d
e
1
f
g
h
Encouraged by the high efficiency of the catalyst-free 1,3-
rearrangements of allylic alcohols in hot water, we further
investigated 1,5-, 1,7-, and 1,9-rearrangements of allylic alcohols
in water without an additional catalyst (Table 4). The 1,5-
rearrangement of dienol 3a in hot water readily afforded a 98%
yield of the more conjugated isomer 4a in which all the double
bonds are in the E configurations (entry 1). Polyenol 3b, which
has an electron-donating substituent on the phenyl ring, was
converted to the desired product at a lower temperature (entry
2), and substrate 3c, which has an electron-withdrawing
substituent, reacted slower than 3a (entry 3). Phenylethynyl
dienol 3d rearranged to conjugated enyne 4d (entry 4). Allylic
alcohol 3e could be controlled to undergo the 1,5-rearrange-
ment giving secondary trienol 4e at 50 °C, because at higher
temperature, the reaction produced a mixture of 4e and a more
Scheme 3. Stereochemical Study of the 1,3-Rearrangement
of (S)-1p
thermodynamically stable product with the hydroxyl group at
the end of the alkyl chain. Similarly, substrate 3f rearranged to
conjugated trienol 4f at 50 °C (the quaternary center in the
molecule underwent a 1,5-rearrangement during the reaction);
both 3f and 4f accumulate in apple skin and are produced by
the oxidation of the sesquiterpene α-farnesene.14 The 1,7-
rearrangement of polyenol 3g was complete after 1 h at 100 °C,
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Table 4. Hot Water-Promoted 1,5-, 1,7-, and 1,9-
Rearrangements of Allylic Alcohols
Scheme 4. New Strategy for the Synthesis of Conjugated
Polyenes (a) and the Synthesis of Navenone B (b)
a
a
Reaction conditions: 1 mmol of substrate in solvent (25 mL),
inexpensive starting material (cinnamaldehyde) and only two
reagents (the Grignard reagent and MnO2), both of which are
commercially available and inexpensive. The rearrangement
reaction was carried out in neutral water and gave high E
selectivity. The chemical yield of the reactions in the third
iteration was comparable to that of the first two iterations.
b
c
vigorously stirring. Isolated yield. The E/Z ratio was determined by
d
e
1H NMR spectroscopy. H2O:THF = 9:1. 0.5 mmol scale, H2O:1,4-
dioxane = 1:1.
and polyenol 3h (entry 8) underwent 1,9-rearrangement in 1 h
at 80 °C. A 1:1 (v/v) mixture of water and 1,4-dioxane was
used for the reaction of 3h, which is very hydrophobic. As the
extent of conjugation was increased, the energy barrier for the
isomerization decreased, and the reaction became fast even at a
temperature below 100 °C.
CONCLUSION
■
Here, we report for the first time that hot water promotes the
1,n-rearrangement of allylic alcohols under neutral conditions.
Because no additional catalyst is required, no waste salts are
generated, as is the case for reactions catalyzed by Brønsted
acids, Lewis acids, or transition metal complexes. The
rearranged products were obtained in high to excellent
chemical yields and with high E:Z selectivities in most cases,
making this method a valuable addition to the synthetic
chemist’s toolbox. We incorporated this method into an
attractive new strategy for the construction of a polyene
natural product using simple, inexpensive reagents. In addition,
the unique catalytic effects of water demonstrated here add to
our understanding of the behavior of water as a medium for
organic reactions and can be expected to facilitate its use in
organic synthesis.
Because polyene structures are quite stable in hot water, we
hypothesized that a polyene natural product could be
synthesized through the iteration of a sequence of the three
reactions shown in Scheme 4a. This novel synthetic strategy
starts with the addition of a vinyl Grignard reagent to an α,β-
unsaturated aldehyde to afford an allylic alcohol with two
alkenyl substituents. Treatment of this allylic alcohol with hot
water provides an allylic alcohol in which the hydroxy group is
rearranged to the end of the polyene. Oxidation of this more-
conjugated allylic alcohol affords an α,β-unsaturated aldehyde,
which can then be used as the substrate for the next iteration of
the sequence. We demonstrated the efficacy of this strategy by
synthesizing navenone B, an alarm pheromone produced under
duress by the blind pacific carnivorous opisthobranch mollusk
Navanax inermis (Scheme 4b). The previously reported
syntheses of navenone B have been based on a Wittig-type
reaction, the reduction of an alkyne, or transition metal-
mediated coupling reactions.15 In contrast, our synthesis started
with a Grignard reaction between cinnamaldehyde and
vinylmagnesium bromide. The resulting allylic alcohol was
rearranged and then oxidized to give the corresponding α,β-
unsaturated aldehyde, which was subjected to two additional
iterations of the reaction sequence to afford navenone B in 30%
overall yield. This synthesis has the advantage of using an
EXPERIMENTAL SECTION
■
General Methods. Unless otherwise mentioned, all reactions were
carried out in aerial atmosphere. 1,4-dioxane (HPLC grade) was used
as received from Alfa Aesar, and other organic solvents were purified
prior to use. Water was purchased from Watson’s or from Milli-Q
Ultrapure Water Purification System. Substrates were synthesized
according to the known procedures. Flash column chromatography
was performed using the indicated solvent system on Qingdao-
Haiyang silica gel (200−300 mesh). All of the compounds were
1
characterized by H NMR and 13C NMR. Peaks recorded are relative
to the internal standards: TMS (δ = 0.00) for 1H NMR and CDCl3 (δ
= 77.00) for 13C NMR spectra. Mass spectral analyses were performed
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for low-resolution MS with EI ionization and for high-resolution MS
(HRMS) on a QFT-ESI mass spectrometer.
6.02 (m, 2H), 5.83 (dd, J = 15.2, 6.8 Hz, 1H), 5.79−5.68 (m, 1H),
5.26 (dd, J = 6.8, 3.6 Hz, 1H), 1.92 (d, J = 3.2 Hz, 1H), 1.77 (d, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 142.9, 134.1, 134.0, 131.5,
131.2, 130.6, 129.2, 128.6, 127.7, 126.2, 74.9, 18.3; HRMS (ESI) for
C14H16O calcd for [M + Na]+ m/z 223.1099, found 223.1095.
(2E,4E,6E,8E)-1-Phenyldeca-2,4,6,8-tetraen-1-ol (3h). To a sol-
ution of (2E,4E,6E,8E)-deca-2,4,6,8-tetraenal (917 mg, 6.2 mmol) in
THF (30 mL) was added phenylmagnesium bromide (1.0 M in THF,
7.4 mL, 7.4 mmol) dropwise at 0 °C. The reaction mixture was stirred
at 0 °C for 30 min. Then the reaction mixture was allowed to warm to
room temperature and further stirred at room temperature for 2 h.
Diluted aqueous NH4Cl solution (20 mL) was added to quench the
reaction, and the reaction mixture was extracted with EtOAc (2 × 50
mL). The combined organic layers were washed with brine, dried over
MgSO4, filtered, and evaporated under reduced pressure. The residue
was purified by silica gel column chromatography (EtOAc/hexanes =
1:10) to afford the title allylic alcohol 3h (1.172 g, 99%). Yellow solid:
Preparation of Allylic Alcohols 1a−1v. Allylic alcohols 1a−1v
were prepared according to previously reported procedures.16
1
1-(Hex-1-ynyl)cyclohex-2-enol (1d). Colorless oil: H NMR (400
MHz, CDCl3) δ 5.80 (dt, J = 9.6, 3.2 Hz, 1H), 5.73 (d, J = 9.6 Hz,
1H), 2.21 (t, J = 6.8 Hz, 2H), 2.06−1.96 (m, 3H), 1.94 (d, J = 2.4 Hz,
1H), 1.93−1.85 (m, 1H), 1.80−1.71 (m, 2H), 1.53−1.34 (m, 4H),
0.91 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 131.1, 128.9,
84.2, 83.8, 65.1, 38.1, 30.6, 24.6, 21.8, 19.1, 18.3, 13.5; MS (EI, 70 eV)
m/z (%) 177 (M+−1, 9), 150 (45), 135 (100), 79 (98), 55 (65),
41(54); HRMS (ESI) for C12H18O calcd for [M + Na]+ m/z 201.1255,
found 201.1251.
2-((E)-Prop-1-en-1-yl)adamantan-2-ol (1u). White solid: mp =
1
36.5−38 °C; H NMR (400 MHz, CDCl3) δ 5.74 (dq, J = 12.0, 1.6
Hz, 1H), 5.56 (dq, J = 11.7, 7.2 Hz, 1H), 2.24 (d, J = 12.1 Hz, 2H),
1.95 (s, 2H), 1.86 (dd, J = 7.2, 1.8 Hz, 3H), 1.85−1.66 (m, 8H), 1.56
(br s, 1H), 1.53 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 136.7, 127.4,
75.4, 38.4, 37.9, 34.9, 32.6, 27.0, 26.8, 14.8; HRMS (ESI) for C13H20O
calcd for [M − OH]+ m/z 175.1487, found 175.1481.
1
mp = 103−106 °C; H NMR (400 MHz, CDCl3) δ 7.42−7.24 (m,
5H), 6.34 (dd, J = 14.8, 10.4 Hz, 1H), 6.27−6.05 (m, 5H), 5.85 (dd, J
= 15.2, 6.8 Hz, 1H), 5.74 (m, 1H), 5.26 (dd, J = 6.8, 2.8 Hz, 1H), 1.98
(d, J = 3.6 Hz, 1H), 1.78 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 142.8, 134.5, 134.0, 133.8, 131.8, 131.1, 130.9, 130.6, 130.1,
128.6, 127.7, 126.2, 74.9, 18.4; HRMS (ESI) for C16H18O calcd for [M
+ Na]+ m/z 249.1255, found 249.1248.
Preparation of Allylic Alcohols 3a−3h. Allylic alcohols 3a−
3c,17 3e,17 3f18 were prepared according to previously reported
procedures.
(2E,4E)-1-(4-Chlorophenyl)hexa-2,4-dien-1-ol (3c). Colorless oil:
1H NMR (400 MHz, CDCl3) δ 7.33−7.26 (m, 4H), 6.22 (dd, J = 15.2,
10.4 Hz, 1H), 6.03 (ddd, J = 14.8, 10.4, 1.3 Hz, 1H), 5.80−5.61 (m,
2H), 5.17 (d, J = 5.3 Hz, 1H), 2.15 (s, 1H), 1.75 (d, J = 6.7 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 141.4, 133.2, 131.8, 131.6, 131.1,
130.4, 128.5, 127.6, 74.2, 18.1.
General Procedure for Rearrangements of Allylic Alcohols
in Table 1. 3-(Hex-1-ynyl)cyclohex-2-enol (2d). To a round-bottom
flask (50 mL) containing the allylic alcohol 1d (178 mg, 1.0 mmol)
was added H2O (25 mL). The flask was fitted with a condenser, stirred
vigorously at the indicated temperature, and monitored by TLC. After
completion, the resulting solution was cooled to room temperature.
The mixture was extracted with EtOAc (3 × 50 mL), washed with
brine, dried over MgSO4, and evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (EtOAc/
hexanes = 1:10) to afford the desired product 2d (153 mg, 86%).
(4E,6E)-1-Phenylocta-4,6-dien-1-yn-3-ol (3d). To a solution of
phenylacetylene (1.53 g, 15.0 mmol,) in THF (25 mL) at −78 °C was
added n-BuLi solution (2.4 M in hexanes, 2.9 mL, 7.0 mmol). The
solution was allowed to warm to 0 °C over 1 h and stirred at 0 °C for
30 min. Then the solution was cooled to −78 °C, and (2E,4E)-hexa-
2,4-dienal (505 mg, 5.0 mmol, 95% purity) in THF (10 mL) was
added. The reaction mixture was allowed to warm to room
temperature over 1 h and stirred at room temperature for 3 h.
Diluted aqueous NH4Cl solution (20 mL) was added to quench the
reaction, and the reaction mixture was extracted with EtOAc (2 × 60
mL). The combined organic layers were washed with brine, dried over
MgSO4, filtered, and concentrated. The residue was purified by silica
gel column chromatography (EtOAc/hexanes = 1:10) to afford the
1
Colorless oil: H NMR (400 MHz, CDCl3) δ 6.00 (m, 1H), 4.23 (s,
1H), 2.30 (t, J = 6.8 Hz, 2H), 2.18−2.00 (m, 2H), 1.88−1.80 (m, 1H),
1.80−1.70 (m, 1H), 1.63−1.55 (m, 2H), 1.53−1.46 (m, 3H), 1.45−
1.36 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 134.0, 124.7, 90.0, 81.1, 65.5, 31.1, 30.8, 29.8, 21.9, 18.9, 18.8, 13.6;
HRMS (ESI) for C12H18O calcd for [M + Na]+ m/z 201.1255, found
201.1251.
General Procedure for Rearrangements of Allylic Alcohols
in Table 3. 1-(Adamantan-2-ylidene)propan-2-ol (2u). To a round-
bottom flask (50 mL) containing the substrate 1u (192 mg, 1.0 mmol)
was added 1,4-dioxane (5.0 mL), and then to the solution was added
H2O (20 mL). The flask was fitted with a condenser, stirred vigorously
at the indicated temperature, and monitored by TLC. After
completion, the resulting solution was cooled to room temperature.
The mixture was extracted with EtOAc (3 × 50 mL), washed with
brine, dried over MgSO4, and evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (EtOAc/
hexanes = 1:10) to afford the desired product 2u (134 mg, 70%).
1
desired product 3d (978 mg, 99%). Yellow oil: H NMR (400 MHz,
CDCl3) δ 7.48−7.42 (m, 2H), 7.35−7.28 (m, 3H), 6.44 (dd, J = 15.2,
10.4 Hz, 1H), 6.15−6.05 (m, 1H), 5.88−5.70 (m, 2H), 5.12 (d, J = 6.0
Hz, 1H), 2.00 (br s, 1H), 1.78 (dd, J = 6.4, 1.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 132.5, 131.8, 131.7, 130.1, 128.6, 128.5, 128.3,
122.4, 88.1, 86.0, 63.2, 18.2; HRMS (ESI) for C14H14O calcd for [M +
Na]+ m/z 221.0942, found 221.0936.
(4E,6E)-Octa-1,4,6-trien-3-ol (3e). Colorless oil: 1H NMR (400
MHz, CDCl3) δ 6.21 (dd, J = 15.2, 10.4 Hz, 1H), 6.05 (dd, J = 15.2,
11.2 Hz, 1H), 5.90 (ddd, J = 17.2, 10.4, 6.0 Hz, 1H), 5.78−5.68 (m,
1H), 5.58 (dd, J = 15.2, 6.8 Hz, 1H), 5.26 (d, J = 17.2 Hz, 1H), 5.14
(d, J = 10.4 Hz, 1H), 4.64 (m, 1H), 1.76 (d, J = 6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 139.4, 131.4, 131.0, 130.6, 130.5, 115.0,
73.6, 18.1.
1
White solid (70%, 134 mg): mp = 35.5−37 °C; H NMR (400 MHz,
CDCl3) δ 5.13 (d, J = 8.4 Hz, 1H), 4.62 (m, 1H), 2.87 (s, 1H), 2.32 (s,
1H), 1.98−1.65 (m, 12H), 1.30 (d, J = 2.8 Hz, 1H), 1.24 (d, 6.4 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 150.3, 121.4, 63.6, 40.2, 39.8,
39.5, 39.1, 37.1, 32.8, 28.4, 24.2; MS (EI, 70 eV) m/z (%) 192 (M+,
50), 177 (100), 135 (70), 43 (98), 27 (18); HRMS (ESI) for C13H20O
calcd for [M + Na]+ m/z 215.1412, found 215.1405.
(2E,4E,6E)-1-Phenylocta-2,4,6-trien-1-ol (3g). To a solution of
(2E,4E,6E)-octa-2,4,6-trienal (622 mg, 5.0 mmol) in THF (25 mL)
was added phenylmagnesium bromide (1.0 M in THF, 6.0 mL, 6.0
mmol) dropwise at 0 °C. The reaction mixture was stirred at 0 °C for
30 min. Then the reaction mixture was allowed to warm to room
temperature and further stirred at room temperature for 2 h. Diluted
aqueous NH4Cl solution (20 mL) was added to quench the reaction,
and the reaction mixture was extracted with EtOAc (2 × 50 mL). The
combined organic layers were washed with brine, dried over MgSO4,
filtered, and evaporated under reduced pressure. The residue was
purified by silica gel column chromatography (EtOAc/hexanes = 1:10)
to afford the title allylic alcohol 3g (987 mg, 99%). White solid: mp =
Z isomer of 1u: white solid; mp = 93−95 °C; 1H NMR (400 MHz,
CDCl3) δ 5.87−5.72 (m, 2H), 2.26 (s, 1H), 2.22 (s, 1 H), 1.86 (d, J =
12.5 Hz, 2H), 1.80 (m, 4H), 1.73 (d, J = 4.8 Hz, 3H), 1.72−1.66 (m,
4H), 1.58 (s, 1H), 1.55 (s, 1H), 1.34 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 138.0, 124.5, 74.4, 38.0, 38.0, 34.7, 32.8, 27.4, 27.2, 18.2;
MS (EI, 70 eV) m/z (%) 192 (M+, 100), 177 (42), 149 (95), 135
(58), 93 (26), 69 (75), 41 (38); HRMS (ESI) for C13H20O calcd for
[M − OH]+ m/z 175.1487, found 175.1479.
Stereochemical Study of the 1,3-Rearrangement of Allylic
73−75 °C; H NMR (400 MHz, CDCl3) δ 7.40−7.27 (m, 5H), 6.31
Alcohol (S)-1p. Preparation of (S)-1p.19 [α]D +33.4 (c = 1.2,
1
20
(dd, J = 15.2, 11.2 Hz, 1H), 6.22 (dd, J = 14.8, 10.4 Hz, 1H), 6.14−
chloroform); HPLC (Chiralcel OD−H) 5:95 i-PrOH/Hexane, 1.0
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Article
mL/minute, λ = 220 nm, tminor = 6.9 min, tmajor = 8.4 min, ee = 92.4%.
The characterization data for compound (S)-1p are comparable with
that of a previous report.20
at 0 °C. The reaction mixture was stirred at 0 °C for 30 min. Then the
reaction mixture was allowed to warm to room temperature and
further stirred at room temperature for 2 h. Diluted aqueous NH4Cl
solution was added to quench the reaction, and the reaction mixture
was extracted with EtOAc (3 × 50 mL). The combined organic layers
were washed with brine, dried over MgSO4, filtered and evaporated
under reduced pressure. The residue was purified by silica gel column
chromatography (EtOAc/hexanes = 1:10) to afford the desired
product 1s (1.237 g, 96%): 1H NMR (400 MHz, CDCl3) δ 7.41−7.35
(m, 2H), 7.34−7.28 (m, 2H), 7.27−7.21 (m, 1H), 6.61 (d, J = 15.6
Hz, 1H), 6.23 (dd, J = 16.0, 6.4 Hz, 1H), 5.97 (ddd, J = 17.2, 10.4, 6.0
Hz, 1H), 5.34 (dt, J = 17.2, 1.2 Hz, 1H), 5.19 (d, J = 10.4, 1.2 Hz, 1H),
4.81 (br s, 1H), 1.89 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 139.2,
136.5, 130.8, 130.3, 128.5, 127.7, 126.5, 115.4, 73.8. The character-
ization data for this compound matched that of a previous report.21
To a solution of (E)-1-phenylpenta-1,4-dien-3-ol 1s (480 mg, 3.0
mmol) in 1,4-dioxane (7.5 mL) was added H2O (67.5 mL). The flask
was fitted with a condenser and stirred vigorously at 100 °C under N2
atmosphere for 1 h. After completion, the resulting solution was
cooled to room temperature. Brine (25 mL) was added, and the
mixture was extracted with EtOAc (2 × 100 mL), washed with brine,
dried over MgSO4, and evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (EtOAc/
hexanes = 1:6) to afford the desired product 2s (434 mg, 90%) as a
1,3-Rearrangement of (S)-1p. To a round-bottom flask (50 mL)
containing the substrate (S)-1p (190 mg, 1 mmol, 92.4% ee) was
added 1,4-dioxane (2.5 mL), and then to the solution was added H2O
(22.5 mL). The flask was fitted with a condenser, stirred vigorously at
100 °C, and monitored by TLC. After completion, the resulting
solution was cooled to room temperature. The mixture was extracted
with EtOAc (3 × 50 mL), washed with brine, dried over MgSO4, and
evaporated under reduced pressure. The residue was purified by silica
gel column chromatography (EtOAc/hexanes = 1:10) to afford the
product 2p (180 mg, 95% yield, 0% ee indicated by chiral HPLC).
General Procedure for Rearrangements of Allylic Alcohols
in Table 4. (3E,5E)-6-(4-Chlorophenyl)hexa-3,5-dien-2-ol (4c). To a
50 mL round-bottom flask containing the substrate 3c (208 mg, 1.0
mmol) was added 1,4-dioxane (2.5 mL), and then to the solution was
added H2O (22.5 mL). The flask was fitted with a condenser and
stirred vigorously for 15 min at the indicated temperature under N2
atmosphere. The resulting solution was cooled to room temperature.
The mixture was extracted with EtOAc (3 × 50 mL), washed with
brine, dried over MgSO4, and evaporated under reduced pressure. The
residue was purified by silica gel column chromatography (EtOAc/
hexanes = 1:6) to afford the desired product 4c (201 mg, 97%). White
solid: mp = 94−96 °C; 1H NMR (400 MHz, CDCl3) δ 7.37−7.26 (m,
4H), 6.72 (dd, J = 15.6, 10.5 Hz, 1H), 6.49 (d, J = 15.7 Hz, 1H), 6.36
(dd, J = 15.2, 10.5 Hz, 1H), 5.88 (dd, J = 15.2, 6.3 Hz, 1H), 4.50−4.35
(m, 1H), 1.57 (br s, 1H), 1.33 (d, J = 6.4 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 138.3, 135.7, 133.1, 131.3, 129.4, 128.8, 128.8, 127.5,
68.5, 23.3; MS (EI, 70 eV) m/z (%) 208 (M+, 24), 190 (20), 151 (20),
125 (70), 77 (11), 43 (100); HRMS (EI) for C12H13ClO calcd for
[M]+ m/z 208.0655, found 208.0648.
1
white solid: H NMR (400 MHz, CDCl3) δ 7.4−7.2 (m, 5H). 6.79
(dd, J = 15.6 Hz, 10.4 Hz, 1H), 6.56 (d, J = 15.6, 1H), 6.43 (dd, J =
15.2 Hz, 10.8 Hz, 1H), 5.97 (dt, J = 15.2 Hz, 6.0 Hz, 1H), 4.25 (d, J =
5.6 Hz, 2H), 1.43 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 137.1,
132.8, 132.5, 131.6, 128.6, 128.1, 127.6, 126.4, 63.4. The character-
ization data for this compound matched that of a previous report.22
To a solution of the alcohol 2s (660 mg, 4.1 mmol) in THF (40
mL) was added MnO2 (3.56 g, 41.0 mmol). The reaction mixture was
stirred for 1 h before being filtered through a pad of celite to remove
inorganic compound. The filtrate was concentrated, and the residue
was purified by silica gel column chromatography (EtOAc/hexanes =
(3E,5Z)-8-Phenylocta-3,5-dien-7-yn-2-ol (4d-1). Slight yellow oil:
1H NMR (400 MHz, CDCl3) δ 7.50−7.43 (m, 2H), 7.35−7.29 (m,
3H), 6.84 (dd, J = 15.2 Hz, 11.2 Hz, 1H), 6.42 (t, J = 10.8 Hz, 1H),
5.95 (dd, J = 15.2 Hz, 6.4 Hz, 1H), 5.67 (d, J = 10.8 Hz, 1H), 4.45 (m,
1H), 1.75 (br s, 1H), 1.33 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 140.6, 139.1, 131.4, 128.3, 128.2, 126.6, 123.3, 109.5, 95.8,
86.4, 68.4, 23.1; MS (EI, 70 eV) m/z (%) 198 (M+, 8), 197 (14), 183
(45), 153 (47), 105 (92), 77 (58), 43 (100); HRMS (ESI) for
C14H14O calcd for [M + Na]+ m/z 221.0942, found 221.0934.
(3E,5E)-8-Phenylocta-3,5-dien-7-yn-2-ol (4d-2). Slight yellow oil:
1H NMR (400 MHz, CDCl3) δ 7.47−7.40 (m, 2H), 7.35−7.28 (m,
3H), 6.66 (dd, J = 15.6 Hz, 10.8 Hz, 1H), 6.31 (dd, J = 15.2, 10.8 Hz,
1H), 5.87 (dd, J = 15.6 Hz, 6.4 Hz, 1H), 5.83 (d, J = 15.6 Hz, 1H),
4.40 (m, 1H), 1.62 (br s, 1H), 1.31 (d, J = 6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 140.9, 139.7, 131.4, 128.6, 128.3, 128.1, 123.3,
111.4, 92.1, 88.7, 68.2, 23.2; HRMS (ESI) for C14H14O calcd for [M +
Na]+ m/z 221.0942, found 221.0934.
1
1:10) to give the aldehyde 5 (544 mg, 83%): H NMR (400 MHz,
CDCl3) δ 9.62 (d, J = 8.0 Hz, 1H), 7.53−7.48 (m, 2H), 7.42−7.34 (m,
3H), 7.27 (ddd, J = 14.8, 7.2, 2.8 Hz 1H), 7.04−6.99 (m, 2H), 6.27
(dd, J = 15.2, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 193.6,
152.0, 142.4, 135.5, 131.6, 129.7, 128.9, 127.5, 126.1. The character-
ization data for this compound matched that of a previous report.23
To a solution of aldehyde 5 (901 mg, 5.7 mmol) in THF (30 mL)
was added vinylmagnesium bromide (1.0 M in THF, 6.8 mL, 6.8
mmol) dropwise at 0 °C. The reaction mixture was stirred at 0 °C for
30 min. Then the reaction mixture was allowed to warm to room
temperature and further stirred at room temperature for 2 h. Diluted
aqueous NH4Cl solution was added to quench the reaction, and the
reaction mixture was extracted with EtOAc (3 × 50 mL). The
combined organic layers were washed with brine, dried over MgSO4,
filtered, and evaporated under reduced pressure. The residue was
purified by silica gel column chromatography (EtOAc/hexanes = 1:6)
to afford the desired product 6 (960 mg, 91%). Slight yellow solid: mp
(3E,5E)-Octa-3,5,7-trien-2-ol (4e). Colorless oil (89%, 110 mg): 1H
NMR (400 MHz, CDCl3) δ 6.41−6.30 (m, 1H), 6.27−6.17 (m, 3H),
5.80−5.72 (m, 1H), 5.22 (dd, J = 16.4, 1.6 Hz, 1H), 5.10 (dd, J = 10.0,
1.6 Hz, 1H), 4.35 (m, 1H), 1.82 (s, 1H), 1.28 (d, J = 6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 137.8, 136.8, 133.5, 132.3, 129.3, 117.5,
68.4, 23.2; MS (EI, 70 eV) m/z (%) 124 (M+, 13), 91 (10), 81 (31),
55 (16), 43 (100); HRMS (EI) for C8H12O calcd for [M]+ m/z
124.0888, found 124.0890.
(3E,5E,7E)-8-Phenylocta-3,5,7-trien-2-ol (4g). A slight yellow solid
(83%, 166 mg): mp =104.5−106.5 °C; 1H NMR (400 MHz, CDCl3) δ
7.40 (d, J = 7.2 Hz, 2H), 7.31 (d, J = 7.6 Hz, 2H), 7.22 (t, J = 7.6
Hz,1H), 6.82 (dd, J = 15.6 Hz, 10.0 Hz, 1H), 6.56 (d, J = 15.6 Hz,
1H), 6.44−6.26 (m, 3H), 5.80 (dd, J = 13.6, 6.8 Hz, 1H), 4.40 (m,
1H), 1.52 (br s, 1H), 1.32 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 137.5, 137.2, 133.4, 132.7, 132.4, 129.7, 128.8, 128.6, 127.6,
126.3, 68.6, 23.3; MS (EI, 70 eV) m/z (%) 200 (M+, 63), 128 (80), 91
(100), 77 (24), 43 (63); HRMS (ESI) for C14H16O calcd for [M +
Na]+ m/z 223.1099, found 223.1092.
1
= 70.5−72 °C; H NMR (400 MHz, CDCl3) δ 7.42−7.37 (m, 2H),
7.35−7.28 (m, 2H), 7.25−7.20 (m, 1H), 6.78 (dd, J = 15.6, 10.4 Hz,
1H), 6.57 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.2, 10.4 Hz, 1H), 5.94
(ddd, J = 17.2, 10.4, 6.0 Hz, 1H), 5.84 (dd, J = 15.2, 6.4 Hz, 1H), 5.34
(dt, J = 17.2, 1.6 Hz, 1H), 5.18 (dt, J = 10.4, 1.6 Hz, 1H), 4.78−4.70
(m, 1H), 1.66 (d, J = 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
139.1, 137.0, 134.2, 133.1, 131.1, 128.6, 128.0, 127.6, 126.4, 115.3,
73.5; MS (EI, 70 eV) m/z (%) 186 (M+, 17), 167 (8), 141 (13), 115
(51), 91 (100), 82 (33), 55 (77); HRMS (ESI) for C13H14O calcd for
[M − H]− m/z 185.0966, found 185.0977.
To a solution of allylic alcohol 6 (558 mg, 3.0 mmol) in THF (15
mL) was added H2O (135 mL). The flask was fitted with a condenser
and stirred vigorously at 80 °C under N2 atmosphere for 4 h. The
resulting solution was cooled to room temperature. Brine (50 mL) was
added. Then the mixture was extracted with EtOAc (2 × 150 mL),
washed with brine, dried over MgSO4, and evaporated under reduced
pressure. The residue was purified by silica gel column chromatog-
raphy (EtOAc/hexanes = 1:5) to afford the desired product 7 (479
Synthesis of Navenone B. To a solution of cinnamaldehyde
(1.078 g, 8.0 mmol, 98% purity) in THF (25 mL) was added
vinylmagnesium bromide (1.0 M in THF, 9.6 mL, 9.6 mmol) dropwise
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Article
1
mg, 86%). White solid: mp = 93.5−96 °C; H NMR (400 MHz,
CDCl3) δ 7.40 (d, J = 7.6 Hz, 2H), 7.32 (t, J = 7.2 Hz, 2H), 7.22 (t, J =
7.2 Hz, 1H), 6.82 (dd, J = 15.6, 9.6 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H),
6.45−6.29 (m, 3H), 5.95−5.85 (m, 1H), 4.23 (m, 2H), 1.52 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 137.2, 133.4, 132.8, 132.4, 132.3,
131.5, 128.8, 128.6, 127.6, 126.3, 63.4 (CH2).
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: qujin@nankai.edu.cn.
Notes
The authors declare no competing financial interest.
To a solution of the alcohol 7 (372 mg, 2.0 mmol) in THF (50 mL)
was added MnO2 (1.74 g, 20 mmol). The reaction mixture was stirred
for 1 h before being filtered through a pad of celite to remove
inorganic compound. The filtrate was concentrated, and the residue
was purified by silica gel column chromatography (EtOAc/hexanes =
ACKNOWLEDGMENTS
■
This work was financially supported by the NSFC (21072098,
21372119). We thank Professor Chi Zhang at Nankai
University for helpful discussions.
1
1:10) to give the aldehyde 8 (303 mg, 82%) as a yellow solid: H
NMR (400 MHz, CDCl3) δ 9.58 (d, J = 8.0 Hz, 1H), 7.47−7.42 (m,
2H), 7.38−7.32 (m, 2H), 7.32−7.24 (m, 1H), 7.17 (dd, J = 15.2, 11.2
Hz, 1H), 6.94−6.76 (m, 3H), 6.55 (dd, J = 14.0, 11.2 Hz, 1H), 6.18
(dd, J = 15.2, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 193.4,
151.7, 142.7, 138.3, 136.2, 131.1, 130.1, 128.8, 127.6, 126.9. The
characterization data for this compound matched that of a previous
report.24
To a solution of aldehyde 8 (253 mg, 1.3 mmol) in THF (10 mL)
was added prop-1-enylmagnesium bromide (0.5 M in THF, 3.2 mL,
1.6 mmol) dropwise at 0 °C. The reaction mixture was stirred at 0 °C
for 30 min. Then the reaction mixture was allowed to warm to room
temperature and further stirred at room temperature for 2 h. Diluted
aqueous NH4Cl solution was added to quench the reaction, and the
reaction mixture was extracted with EtOAc (3 × 20 mL). The
combined organic layers were washed with brine, dried over MgSO4,
filtered, and evaporated under reduced pressure. The residue was
purified by passing it through a short silica gel column chromatog-
raphy (EtOAc/hexanes = 1:4) to afford a yellow solid (1.17 mmol, 266
mg), which was directly used in the next step.
To a solution of the yellow solid (1.17 mmol, 266 mg) in THF (11
mL) was added H2O (44 mL). The flask was fitted with a condenser
and stirred vigorously at 80 °C under N2 atmosphere for 1 h. The
resulting solution was cooled to room temperature. Brine (20 mL) was
added. Then the mixture was extracted with EtOAc (2 × 80 mL),
washed with brine, dried over MgSO4, and evaporated under reduced
pressure. The residue was purified by silica gel column chromatog-
raphy (EtOAc/hexanes = 1:3) to afford the desired product 4h (196
mg, 75%) as a yellow solid: mp = 124−125.5 °C; 1H NMR (400 MHz,
CDCl3) δ 7.40 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 7.6 Hz, 2H), 7.22 (t, J
= 7.2 Hz,1H), 6.84 (dd, J = 15.6 Hz, 9.6 Hz, 1H), 6.57 (d, J = 15.6 Hz,
1H), 6.46−6.22 (m, 5H), 5.79 (dd, J = 13.6, 6.8 Hz, 1H), 4.39 (m,
1H), 1.47 (d, J = 4.0 Hz, 1H), 1.31 (d, J = 6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 137.5, 137.3, 133.5, 133.3, 133.2, 132.7, 132.3,
129.8, 129.0, 128.6, 127.5, 126.3, 68.6, 23.3. The characterization data
for this compound matched that of a previous report.25
To a solution of the alcohol 4h (113 mg, 0.5 mmol) in THF (10
mL) was added MnO2 (435 mg, 5 mmol). The reaction mixture was
stirred for 1 h before being filtered through a pad of celite to remove
inorganic compound. The filtrate was concentrated, and the residue
was purified by silica gel column chromatography (EtOAc/hexanes =
1:5) to give the desired product navenone B (99 mg, 87%). Yellow
solid: mp =136−138 °C; 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J =
7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.28−7.26 (m, 1H), 7.19 (dd, J =
15.2, 11.2 Hz, 1H), 6.88 (dd, J = 15.6, 10.8 Hz, 1H), 6.75−6.65 (m,
2H), 6.60 (dd, J = 14.8, 10.8 Hz, 1H), 6.49−6.33 (m, 2H), 6.16 (d, J =
15.6 Hz, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3,
143.2, 141.6, 137.7, 136.9, 135.3, 132.2, 130.5, 129.9, 128.7, 128.5,
128.2, 126.6, 27.4.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of products in Table 1, Table 3, Table
4, and Scheme 4. This material is available free of charge via the
Internet at http://pubs.acs.org.
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