Oxidation with a photolabile carbonyl protecting group

Article abstract of DOI:10.1021/jo201671v

A novel oxidation approach utilizing a robust photolabile carbonyl protecting group reagent (1) as the oxidizing reagent has been developed. Different from existing methods, this approach oxidizes primary alcohols to the photosensitive acetals (e.g., 3), providing another unique approach to the protected aldehydes. Thus, for the first time, oxidation and protection are achieved in one reaction. Secondary alcohols are oxidized to the corresponding ketones. Moreover, the photolabile protecting group (PPG) also oxidizes ethers and esters. The oxidation is presumably via hydride abstraction by the tritylium ion generated from 1 under acidic conditions. However, the mechanisms for primary alcohols and secondary alcohols are slightly different.

Full text of DOI:10.1021/jo201671v

Article
pubs.acs.org/joc
Oxidation with a Photolabile Carbonyl Protecting Group
Haishen Yang, Feng Mu, and Pengfei Wang*
Department of Chemistry, University of Alabama at Birmingham, 901 14th Street South, Birmingham, Alabama 35294, United States
S
* Supporting Information
ABSTRACT: A novel oxidation approach utilizing a robust
photolabile carbonyl protecting group reagent (1) as the oxidizing
reagent has been developed. Different from existing methods, this
approach oxidizes primary alcohols to the photosensitive acetals
(e.g., 3), providing another unique approach to the protected
aldehydes. Thus, for the first time, oxidation and protection are
achieved in one reaction. Secondary alcohols are oxidized to the
corresponding ketones. Moreover, the photolabile protecting
group (PPG) also oxidizes ethers and esters. The oxidation is presumably via hydride abstraction by the tritylium ion
generated from 1 under acidic conditions. However, the mechanisms for primary alcohols and secondary alcohols are slightly
different.
available materials; they have high protection/deprotection
efficiencies and remarkable dark stability. In particular, mindful
of the unique structural features of these PPGs, we have
developed a neutral protecting protocol and demonstrated for
the first time that both protection and deprotection reactions
can be conducted under neutral conditions without using any
other chemical reagents.7d−f These PPGs have potential applica-
tions in controlled drug release7e and synthesis.8 Interestingly, we
found that salicyl alcohol 1 is also a unique oxidizing reagent.
INTRODUCTION
■
It has long been known that the tritylium ion can oxidize ethers
through hydride abstraction.1−5 Triphenylcarbenium tetrafluoro-
borate (TrBF4) is the source of the tritylium ion in these
applications. However, oxidizing ethers of primary alcohols
with TrBF4 is not as successful as oxidizing ethers of secondary
alcohols, due to the different stabilities of the involved
carbenium ion intermediates.4 Despite the success of oxidizing
ethers with TrBF4, a practical method of directly oxidizing
alcohols with a tritylium ion is not known.6 Herein we report a
unique and effective oxidation method oxidizing both primary
and secondary alcohols. This method utilizes α,α-diphenyl-5-
methoxysalicyl alcohol (1), a robust photolabile carbonyl
protecting group reagent,7a as the oxidizing reagent. Presum-
ably, under acidic conditions, the salicyl alcohol is converted to
a triarylcarbenium ion which is capable of hydride abstraction,
similar in function to TrBF4.
RESULTS AND DISCUSSION
■
The reaction of 3-phenyl-1-propanol (4a) with the PPG
reagent 1 under acidic conditions led to the corresponding
acetal 3a along with the reduction product 5 (eq 1). The
We have demonstrated that the reaction of the carbonyl
compound 2 with the protecting group reagent 1 under mild
acidic or neutral conditions generates the UV-sensitive acetal 3
(Scheme 1). Upon irradiation, the carbonyl compound will be
reaction provided better results at temperatures of 45 °C or
above (up to 90 °C). Although the reactions did not require a
solvent, a few drops of dichloromethane aided in mixing the
reactants and the acid catalyst and improved the reaction
outcome. The reaction slowed down with more solvent present.
Toluene could also be used for this mixing purpose, but the
reaction would be slower. A catalytic amount of concentrated
H2SO4 is used. As expected, the amount of acid was positively
correlated with the reaction rate. With a similar amount of
catalyst, the reaction outcome with p-TsOH was similar to that
with H2SO4. TfOH seemed to be more robust in catalyzing the
Scheme 1. Photolabile Carbonyl Protecting Group
released efficiently in high yields.7a,f The PPG in 3 and other
salicyl alcohol based PPGs recently developed in our laboratory
have some advantageous features.7 For example, the PPG
reagents are easily prepared from inexpensive, commercially
Received: August 10, 2011
Published: September 27, 2011
© 2011 American Chemical Society
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reaction and much smaller amounts of TfOH were needed to
produce similar results. TFA failed to promote a perceptible
oxidation reaction under the same conditions.
With H2SO4 as the catalyst, we compared the oxidation
capacities of salicyl alcohols 1 and 6−8 (Figure 1). Under the
50 °C. Under the same conditions with H2SO4 as the catalyst, a
series of primary alcohols (4b−e) were oxidized and produced
the corresponding acetals (3b−e) in good yields (Table 1,
entries 2−5). Surprisingly, the alcohol 4f was difficult to
oxidize, and the conversion to 3f was slow. Increasing the
reaction temperature to 70 °C did not improve the reaction
outcome. Eventually, the desired 3f was obtained in 56% yield
after using 1 equiv of H2SO4 and excess of 1 for 4 days. The
significantly different reactivity of 4f in comparison to that of
other primary alcohols was confirmed in a control experiment.
A mixture of 4a and 4f (1/1) was treated with 2.2 equiv of 1
and 0.6 equiv of H2SO4. After 9 h at 50 °C, the acetals 3a
(78%) and 3f (8%) were obtained along with the recovered 4a
(19%) and 4f (80%).
Figure 1. Salicyl alcohols as oxidizing reagents.
The oxidation protocol is also applicable to simple secondary
alcohols. Different from oxidizing primary alcohols, the
oxidation reaction led to a ketone product instead of a ketal
(Table 2). For instance, the reaction of 9a with 1.2 equiv of 1 in
same conditions, the salicyl alcohols 1 and 6 demonstrated
similar oxidation reactivity toward 3-phenyl-1-propanol (4a),
resulting in a higher conversion of 4a and cleaner reaction
mixtures. Given the excellent PPG properties of the α,α-
diphenyl-5-methoxysalicyl group,7a we focused on studying
oxidation with 1.
Table 2. Oxidation of Secondary Alcohols with PPG 1
In a typical run, the oxidation of 4a with 2.2 equiv of 1
catalyzed by a 0.2 equiv of H2SO4 generated the acetal 3a in
83% yield along with about an equal amount of the reduction
product 5 (Table 1, entry 1). The reaction took about 15 h.
Table 1. Oxidation of Primary Alcohols with PPG 1
a
Reactions were carried out with 0.1 equiv of H2SO4 in a DCM slurry.
Isolated yields. Reaction at 50 °C. Reaction at 70 °C.
b
c
d
the presence of 0.1 equiv of concentrated H2SO4 resulted in an
80% yield of the ketone 10a in 30.5 h at 50 °C. A similar yield
(e.g. 81%) was obtained from the reaction at 70 °C, and the
reaction time became noticeably shorter (Table 2, entry 1). For
another alcohol 9b, the yield of the product ketone 10b was
86% after 4.5 h of heating at 70 °C (Table 2, entry 2). A control
experiment showed that, under the reaction conditions, it was
not efficient to convert the ketone product to the corresponding
ketal, even with an excess of more than 1 equiv of 1. This
oxidation process could compete with E1 elimination when the
secondary alcohols are capable of forming stabilized secondary
cationic intermediates under acidic conditions. For example,
the oxidation of sec-phenethyl alcohol with 1 mainly produced
the desired product, acetophenone; however, the reaction
mixture was less clean and styrene was identified among the
byproducts.
a
Reactions were carried out with 0.2 equiv of H2SO4 (conc) in a DCM
b
c
slurry at 50 °C. Isolated yields. With 0.05 equiv of TfOH in a DCM
slurry at 50 °C. With 1 equiv of H2SO4 and 4.5 equiv of 1.
d
To our surprise, the primary and secondary alcohols showed
similar reactivity toward oxidation with 1 under the same
reaction conditions. For example, after a mixture of 4a and 9b
(1/1) was treated with 1.2 equiv of 1 and 0.6 equiv of H2SO4
for 9 h, the oxidation products 3a and 10b were obtained in
With less than 2 equiv of the salicyl alcohol 1, the unreacted
alcohol was observed in the reaction mixture after 1 was
completely consumed. Similar results were obtained when 0.05
equiv of TfOH was used as the catalyst. The acetal 3a was
isolated in 81% yield with a 3a/5 ratio of 1/1.01 after 17.5 h at
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32% and 33% yields, respectively, along with recovered 4a
(50%), 9b (66%), and an unknown derivative of 4a.
direct hydride abstraction from the alcohol 9 is feasible, owing
to the increased stability of the secondary carbenium inter-
mediate, compared with a primary carbenium intermediate
from a primary alcohol. This alternative pathway avoids for-
mation of an oxocarbenium intermediate such as 14, and, as a
result, leads to the ketone 10 instead of a ketal product. The
activation energies of generating a carbenium intermediate from
9 and generating 14 from 13 appear to be comparable.
We then synthesized the ether of 3-phenyl-1-propanol: i.e.,
13a.7f Treatment of 13a with 0.2 equiv of H2SO4 at 50 °C for
30 min led to a clean conversion to a mixture of 3a, 5, and the
alcohol 4a in a 1/1/1 ratio (Scheme 3). Given that the
This result was seemingly inconsistent with our initial mecha-
nistic hypothesis. We assumed that the oxidation of an alcohol
with PPG 1 was similar to the oxidation of ethers with TrBF4
via hydride abstraction. With TrBF4, the TMS, t-Bu, and Tr
ethers of primary alcohols were oxidized more slowly than
those of secondary alcohols, presumably due to the stability
difference between the tertiary and secondary carbenium
intermediates obtained from hydride abstraction by the
tritylium ion.4 The comparable rates of the oxidation of
primary and secondary alcohols in our case suggest that
different mechanisms are probably involved. In addition,
aldehydes were not observed in oxidizing primary alcohols.
Although aldehydes could be converted to the corresponding
acetals 3 under the reaction conditions, control experiments
achieved 90% conversion of 3-phenylpropanal to 3a after
70 min.
Scheme 3. Redox Reaction of the Ether 13a
To rationalize the experimental observations, we postulated
that the tritylium ion 11 could be generated from the salicyl
alcohol upon acid treatment (Scheme 2). It would be in
Scheme 2. Proposed Mechanism of Oxidation with PPG 1
oxidation of 4a with 1 took more than 15 h (Table 1, entry 1),
it seemed that the ether formation step in the pathway to 3
(Scheme 2) could be a rate-limiting step.9 Under the same
conditions, the reaction of 13f became slow, and the reaction
mixture was complex. For example, after 6 h, the reaction
mixture contained 13f, 1, 3f, 5, and 4f in a ratio of 14/33/14/
1
24/72, along with other minor products on the basis of H
NMR analysis. We speculate that increasing steric hindrance
slowed down the transformation from 13f to 14f. As a result,
side reactions of the short-lived cationic intermediate 11 increased.
Again, aldehydes were not observed in the reaction mixtures,
consistent with the proposed mechanism in Scheme 2.
Owing to its unique structure, the carbonyl PPG 1 seemed to
be particularly suitable for oxidizing primary alcohols to the
stable acetals. The phenolic hydroxyl group not only helped to
stabilize the benzylic cationic center of 11 through conjugation
(i.e. 11 → 12 in Scheme 2) but also trapped the reactive
carbenium intermediate intramolecularly (e.g. 14) to afford
the chemically stable oxidation product of a primary alcohol
(i.e. the acetal 3). For comparison, control experiments under the
same conditions as for 13a (Scheme 3) showed that the trityl
ether (15), 4-methoxytrityl ether (16), and 2,5-dimethoxytrityl
ether (17) of 3-phenyl-1-propanol all led to a complex reaction
mixture containing various amounts of 3-phenyl-1-propanol, the
corresponding reduced triarylmethane, and the oxidation product-
(s), including 3-phenylpropanal and its condensation product(s).
In addition to oxidizing alcohols, the PPG reagent 1 oxidizes
ethers as well. For example, a diethyl ether solution of 1 was
treated with 0.5 equiv of H2SO4 and heated at 50 °C in a sealed
tube (eq 2). After 10.5 h, the acetal 18 was isolated in 40% yield
(calculated on the basis of 1) and the ratio of the obtained 18/5
equilibrium with the o-quinone methide 12. In the presence of
the primary alcohol 4, the ether 13 would probably form.
Subsequent hydride abstraction from the ether 133 rather than
from the alcohol 4 by 11 resulted in the oxocarbenium ion 14,
which cyclized to produce the acetal 3. The preference of
hydride abstraction from the ether can be rationalized as a
result of the different stabilities of the intermediates involved:
i.e., hydride abstraction from 4 would lead to a simple primary
carbenium ion while the primary carbenium ion generated from
13 could be stabilized by hyperconjugation with the PPG
segment. This reaction pathway would not generate the
aldehyde intermediate, which is consistent with our observa-
tions. This mechanistic postulation could also explain the lower
reactivity of the primary alcohol 4f in that hydride abstraction
from the ether of 4f (i.e. 13f) by the bulky cation 11 should
become difficult due to the increased steric hindrance introduced
by the ethyl group in the ether.
For the secondary alcohol 9, the equilibrium between the
alcohol and its ether would also exist. However, hydride
abstraction from the ether of the secondary alcohol by 11
should also encounter increased steric hindrance. Alternatively,
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was 1/1.09. Another example is oxidation of benzyl-protected
3-phenyl-1-propanol (19) (eq 3). Reaction of 19 with 4.5 equiv
It seemed that the ester oxidation went through hydrolysis of
the ester/lactone first. When 3-phenyl-1-propyl benzoate (25)
was prepared and treated with H2SO4 and an excess of 1 at 50
°C (i.e., the same conditions as for 21), no conversion of 25
was observed and the salicyl alcohol 1 gradually decomposed.
In the control experiments, the acetate 21 and the benzoate 25
were treated separately with 1 equiv of H2SO4 at 50 °C for
hydrolysis, and only the acetate 21 showed production of 4a.
The control experiments were repeated in the presence of 2
equiv of water. The hydrolysis product (4a) from 21 increased,
but the benzoate 25 still did not show any sign of reaction. The
different reactivities of hydrolysis under the reaction conditions
might explain the different outcomes from the oxidation of 21
and 25, which is also in agreement with the production of 24 in
the reaction of 22.
of 1 and 1 equiv of the acid at 50 °C for 15.5 h resulted in a
mixture of 3a (68%), 3c (72%), 5, and the unreacted 19 (18%)
1
and 1 on the basis of H NMR analysis. The ratio of the
combined acetals 3a,c to 5 was 1/1.15. In the case of oxidizing
THF (eq 4) under the same conditions, the diacetal 20 was
Since the PPG reagent 1 can oxidize alcohols as well as esters
and ethers, the chemoselectivity of the approach was studied
with the difunctional alcohols (eqs 9 and 10). In oxidizing the
alcohol 26, the acetal 27 was obtained in 78% yield, indicating
that this approach is compatible with a benzoyl group. However,
under the same reaction conditions, the acetyl group underwent
intermolecular acetyl shifting and complicated the reaction
outcome. In the reaction of 28, oxidation of the primary hydroxyl
group led to 29 in 41% yield along with 3c in 10% yield, showing
a rate of oxidizing the hydroxyl group 4 times faster than that of
oxidizing a benzyl group.
isolated in 68% yield and the ratio of the obtained 20 to 5 was
1/2.5. When the reaction was conducted in THF with 1 as the
limiting reagent, multiple products were obtained. In these
reactions, aldehydes were not observed during monitoring the
reaction progress, suggesting aldehydes were not a reaction
intermediate. Formation of the acetals was probably achieved
through interaction of the salicyl alcohol 1 with the
oxocarbenium intermediate generated from hydride abstraction.
Interestingly, the PPG 1 also oxidizes esters. Heating an ethyl
acetate solution of 1 with 0.5 equiv of H2SO4 at 50 °C for 10.5
h led to the acetal 18 in 38% yield (calculated on the basis of 1)
with a 18/5 ratio of 1/1.13 (eq 5). When ethyl acetate was the
In summary, a novel oxidation approach utilizing a robust
photolabile carbonyl protecting group reagent (1) as the oxidizing
reagent has been developed. Different from existing methods, this
approach oxidizes primary alcohols to photosensitive acetals
(e.g. 3), providing another unique approach to the preparation
of the protected aldehydes.7a,d Thus, for the first time, oxidation
and protection are achieved in one reaction. Secondary alcohols
are oxidized to the corresponding ketones. The primary and
secondary alcohols showed unexpected similarities in reactivity,
which was rationalized by the proposed slightly different mecha-
nisms. Moreover, the PPG also oxidizes ethers and esters.
limiting reagent (eq 6), a similar yield (78%) was obtained after
13.9 h with an 18/5 ratio of 1/1.19. In the reaction of 21, the
acetal 3a was obtained in 76% yield after 18 h with a 3a/5 ratio
of 1/1.12 (eq 7). Reaction of 6-hexanolactone led to the two
EXPERIMENTAL SECTION
■
General Considerations. Organic solutions were concentrated
by rotary evaporation at ca. 12 Torr. Flash column chromatography
was performed employing 230−400 mesh silica gel. Thin-layer
chromatography was performed using glass plates precoated to a
depth of 0.25 mm with 230−400 mesh silica gel impregnated with a
fluorescent indicator (254 nm). Infrared (IR) data are presented as
frequency of absorption (cm−1). Proton and carbon-13 nuclear magnetic
resonance (1H NMR or 13C NMR) spectra were recorded on 300 and
400 MHz NMR spectrometers; chemical shifts are expressed in parts per
million (δ scale) downfield from tetramethylsilane and are referenced to
residual protium in the NMR solvent (CHCl3: δ 7.26). Data are
acetals 23 and 24 in a 4/1 ratio along with unreacted 22 (eq 8).
1
The structure of 24 was supported by H NMR and high-
resolution mass spectrometry analysis. Saponification of 24
converted it to 23 cleanly, and the combined yield of 23 was 59%.
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presented as follows: chemical shift, multiplicity (s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet and/or multiple resonances),
coupling constant in Hertz (Hz), integration.
Materials. Tetrahydrofuran was distilled from appropriate drying
reagents under a nitrogen atmosphere at 760 Torr. Other chemicals
were obtained from commercial vendors and used without further
purification.
ether/ethyl acetate from 12/1 to 5/1) provided 3e (64.5 mg, 0.155 mmol,
91%) as a colorless oil and 5 (45.8 mg, 0.158 mmol) as a white solid.
Oxidation to 3f (Known Compound7d). To a suspension of 2-
ethylhexanol (23.2 mg, 0.18 mmol) and 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1; 110 mg, 0.36 mmol) in dichloromethane (75 μL)
was added H2SO4 (10 μL, 0.18 mmol), and the resulting mixture was
stirred at 50 °C. More PPG 1 (55 mg) was added at 18 and 63 h. The
reaction mixture was worked up after 4.3 days to provide 3f in 57%
yield with a 3f/5 ratio of 1/1.7 on the basis of NMR analysis with an
internal standard (pyridinium p-toluenesulfonate as standard).
Oxidation to 10a (Known Compound7a). Method 1. To a sus-
pension of 2-(hydroxydiphenylmethyl)-4-methoxyphenol (1; 66.6 mg,
0.22 mmol) and 4-(4-methoxyphenyl)-2-butanol (25.9 mg, 0.14 mmol) in
dichloromethane (50 μL) was added H2SO4 (1 μL, 0.018 mmol). The
mixture was heated to 50 °C for 30.5 h. The crude product was purified
with flash column chromatography (petroleum ether/ethyl acetate from
9/1 to 5/1) to provide 10a (20.7 mg, 0.116 mmol, 80%) as a colorless oil
and 5 (34.0 mg, 0.117 mmol) as a white solid.
Oxidation to 3a (Known Compound7a). To a suspension of 2-
(hydroxydiphenylmethyl)-4-methoxyphenol (1; 110.2 mg, 0.36 mmol)
and 3-phenyl-1-propanol (20.7 mg, 0.15 mmol) in dichloromethane
(75 μL) was added H2SO4 (2 μL, 0.036 mmol). The mixture was
heated at 50 °C for 15.5 h. The crude reaction mixture was directly
purified with flash column chromatography (petroleum ether/ethyl
acetate from 20/1 to 5/1) to provide 3a (53.8 mg, 0.127 mmol, 83%)
and 5 (39.5 mg, 0.136 mmol), both as white solids. Data for 5: Rf =
0.33 (petroleum ether/ethyl acetate 5/1); mp 112.0−112.5 °C; 1H NMR
(300 MHz, CDCl3) δ 7.28−7.11 (m, 7H), 7.11−7.03 (m, 3H), 6.68
(d, J = 8.7 Hz, 1H), 6.61 (dd, J = 8.7, 3.0 Hz, 1H), 6.31 (d, J = 2.9 Hz,
1H), 5.62 (s, 1H), 4.22 (s, 1H), 3.58 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 153.7, 147.4, 142.3, 131.8, 129.3, 128.6, 126.8, 116.8, 112.1,
55.6, 51.2; IR (neat; cm−1) 3025, 1505, 1449, 1336, 1267, 1078, 700;
MS (−ESI): m/z 212.3 (15%), 290.5 (15%); HRMS (ESI) m/e calcd
for C20H18O2Na 313.1199, found 313.1198.
Method 2. To a suspension of 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1; 56.3 mg, 0.184 mmol) and 4-(4-methoxyphen-
yl)-2-butanol (27.8 mg, 0.154 mmol) in dichloromethane (25 μL) was
added H2SO4 (1 μL, 0.018 mmol). The mixture was heated to 70 °C
for 10.3 h. The same purification procedure provided 10a (22.2 mg,
0.125 mmol, 81%) as a colorless oil and 5 (38.6 mg, 0.133 mmol) as a
white solid.
Oxidation to 3b. To a suspension of 2-(hydroxydiphenylmethyl)-
4-methoxyphenol (1) (110.2 mg, 0.36 mmol) and 2-phenyl-1-ethanol
(18.9 mg, 0.155 mmol) in dichloromethane (50 μL), H2SO4 (2 μL,
0.036 mmol) was added. The mixture was heated at 50 °C for 16.5 h.
The crude product was directly loaded onto a flash column (petroleum
ether/ethyl acetate from 15:1 to 5:1) to provide 3b (51.6 mg, 0.126
mmol, 81%) and 5 (39.7 mg, 0.137 mmol), both as white solids. Data
for 3b: Rf = 0.53 (petroleum ether/ethyl acetate 15/1); 1H NMR (300
MHz, CDCl3) δ 7.25−7.07 (m, 15H), 6.85 (d, J = 8.8 Hz, 1H), 6.74
(dd, J = 8.9, 3.0 Hz, 1H), 6.35 (d, J = 2.9 Hz, 1H), 5.10 (t, J = 5.3 Hz,
1H), 3.63 (s, 3H), 3.15 (d, J = 5.3 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 152.9, 146.4, 145.9, 143.8, 135.6, 130.0, 129.0, 128.07,
128.05, 127.85, 127.81, 127.78, 127.4, 126.4, 126.0, 117.6, 115.0,
114.0, 95.4, 84.3, 55.6, 41.2; IR (neat; cm−1) 2988, 1662, 1643, 1624,
1458, 1207, 1171, 1089, 804, 684, 630; MS (+ESI): m/z 213.2 (25%),
289.4 (100%), 290.4 (25%), 291.4 (5%); HRMS (ESI) m/e calcd for
C28H25O3 409.1798, found 409.1796.
Oxidation to 10b (Known Compound7a). To a suspension of
2-(hydroxydiphenylmethyl)-4-methoxyphenol (1; 56.1 mg, 0.183
mmol) and 2-undecanol (22.7 mg, 0.132 mmol) in dichloromethane
(50 μL) was added H2SO4 (1 μL, 0.018 mmol). The mixture was heated
to 70 °C for 4.5 h. Flash column chromatography (petroleum ether/ethyl
acetate gradually from 6/1 to 3/1) provided 10b (19.5 mg, 0.115 mmol,
86%) as a colorless oil and 5 (34.6 mg, 0.120 mmol) as a white solid.
Preparation of 13a. To a stirred solution of 2-(hydroxydiphe-
nylmethyl)-4-methoxyphenol (1; 380 mg, 1.25 mmol) in dichloro-
methane (2.5 mL) at 0 °C was added AcCl (89 μL, 98 mg), followed
by Et3N (190 μL, 1.38 mmol). The reaction solution was stirred at
room temperature for 12.5 h before 3-phenyl-1-propanol (0.68 g, 5.0
mmol) was added. After 52 h, the solution was concentrated, and the
residue was purified with flash chromatography (petroleum ether/
ethyl acetate 6/1) to provide 13a (432 mg, 81%) as a white solid: Rf =
0.3 (petroleum ether/ethyl acetate 5/1); mp 91.5−91.8 °C; 1H NMR
(300 MHz, CDCl3) δ 8.64 (s, 1H), 7.39−7.08 (m, 15H), 6.80 (dd, J =
0.4, 8.8 Hz, 1H), 6.74 (dd, J = 2.8, 8.8 Hz, 1H), 6.50 (dd, J = 0.4, 2.9
Hz, 1H), 3.63 (s, 3H), 3.30 (t, J = 6.4 Hz, 2H), 2.67 (d, J = 7.8 Hz,
2H), 2.01−1.92 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 151.9, 150.2,
141.2, 140.8, 129.0, 128.9, 128.2, 127.9, 127.7, 125.8, 117.8, 116.3,
113.8, 90.1, 63.8, 55.6, 32.2, 31.4; IR (neat; cm−1) 2234, 2942, 1490,
1236, 1045, 739, 701; HRMS (ESI) m/e calcd for C29H28O3Na
447.1931, found 447.1930.
Oxidation to 3c (Known Compound7a). To a suspension of
2-(hydroxydiphenylmethyl)-4-methoxyphenol (1) (112 mg 0.37 mmol)
and benzyl alcohol (17.2 mg, 0.16 mmol) in dichloromethane (100 μL),
H2SO4 (2 μL, 0.036 mmol) was added. The mixture was heated at
50 °C for 4.7 h. The crude product was directly loaded onto a flash
column chromatography (petroleum ether/ethyl acetate from 12:1 to 5:1)
to provide 3c (56.8 mg, 0.144 mmol, 90%) and 5 (42.9 mg, 0.148 mmol)
as white solids.
Oxidation to 3d. To a suspension of 2-(hydroxydiphenylmethyl)-
4-methoxyphenol (1) (110.6 mg, 0.36 mmol) and 4-penten-1-ol (13.6
mg, 0.16 mmol) in dichloromethane (50 μL), H2SO4 (2 μL, 0.036
mmol) was added. The mixture was heated at 50 °C for 12 h. The
crude product was directly loaded onto a flash column (petroleum
ether/ethyl acetate from 16:1 to 6:1) to provide 3d (47.1 mg, 0.126
mmol, 80%) and 5 (39.8 mg, 0.137 mmol), both as white solids. For
3d, Rf0.47 (petroleum ether/ethyl acetate =16:1); mp 104.0−105.0 °C;
1H NMR (300 MHz, CDCl3) δ 7.44−7.30 (m, 5H), 7.30−7.18 (m,
5H), 6.85 (d, J = 8.9 Hz, 1H), 6.74 (dd, J = 8.9, 2.9 Hz, 1H), 6.37 (d,
J = 2.9 Hz, 1H), 5.75 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 5.00−4.82 (m,
3H), 3.62 (s, 3H), 2.32−2.06 (m, 2H), 2.00−1.82 (m, 2H); 13C NMR
(75 MHz, CDCl3): δ 152.9, 146.6, 146.1, 144.2, 137.7, 129.3, 128.1,
128.03, 127.99, 127.87, 127.5, 125.9, 117.6, 115.0, 114.8, 114.1, 94.6,
84.2, 55.6, 33.7, 27.6; IR (neat; cm−1) 3128, 1493, 1446, 1273, 1230,
757, 701; MS (+ESI) m/z 289.5 (100%), 290.5 (25%); HRMS (ESI)
m/e calcd for C25H25O3 373.1798, found 373.1790.
Preparation of 13f. To a stirred solution of 2-(hydroxydiphenyl-
methyl)-4-methoxyphenol (1; 307 mg, 1.0 mmol) in dichloromethane
(2 mL) at 0 °C was added AcCl (79 μL, 86 mg), followed by Et3N
(153 μL, 1.1 mmol). The obtained solution was stirred at room
temperature for 4.5 h before 3-phenyl-1-propanol (290 mg, 2.2 mmol)
was added. After 3.6 days, the solution was concentrated, and the
residue was directly purified with a flash chromatography column to
provide 13f (343 mg, 82%) as a colorless oil: Rf = 0.5 (petroleum
ether/ethyl acetate 7/1); 1H NMR (300 MHz, CDCl3) δ 8.79 (s, 1H),
7.42−7.30 (m, 10H), 6.79 (d, J = 8.8 Hz, 1H), 6.72 (dd, J = 2.9,
8.8 Hz, 1H), 6.48 (d, J = 2.9 Hz, 1H), 3.62 (s, 3H), 3.11−3.20 (m,
2H), 1.58−1.50 (m, 1H), 1.40−1.07 (m, 8H), 0.84 (t, J = 7.2 Hz, 3H),
0.77 (t, J = 7.4 H, 3H); 13C NMR (75 MHz, CDCl3) δ 151.9, 150.3,
140.8, 140.8, 129.3, 129.2, 127.8, 127.7, 117.8, 116.2, 113.7, 90.2, 66.6,
55.6, 39.9, 30.3, 28.8, 23.8, 22.8, 14.0, 10.8; MS (−-ESI): m/z 417.8
(5%); IR (neat) 2958, 2858, 1491, 1448, 1384, 1236, 1043; HRMS
(ESI) m/e calcd for C28H34O3Na 441.2406, found 441.2403.
Oxidation to 3e (Known Compound7a). To a suspension of
octan-1-ol (22.0 mg, 0.17 mmol) and 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1; 112.1 mg, 0.37 mmol) in dichloromethane (50 μL)
was added H2SO4 (2 μL, 0.036 mmol), and the resulting mixture was
stirred at 50 °C for 13.7 h. Flash column chromatography (petroleum
Competing Oxidation of 2-Undecanol (9b) and 3-Phenyl-1-
propanol (4a). To a suspension of 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1; 66.7 mg, 0.2 mmol), 9b (28.5 mg, 0.165 mmol),
and 4a (25.2 mg, 0.185 mmol) in dichloromethane (50 μL) was added
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Article
H2SO4 (6 μL, 0.108 mmol). The reaction mixture was stirred at 50 °C
for 9 h. The 1H NMR analysis with an internal reference indicated that
the yields of 3a, 10b, 4a, and 9b were 32%, 33%, 50%, and 66%,
respectively.
The crude product was purified with flash column chromatography
(petroleum ether/ethyl acetate from 12/1 to 5/1) to provide 18 (25.9
mg, 0.078 mmol, 78%) and 5 (27.0 mg, 0.093 mmol) as white solids.
Oxidation of 3-Phenylpropyl Acetate (21). To a suspension of
2-(hydroxydiphenylmethyl)-4-methoxyphenol (1; 46.1 mg, 0.15
mmol) and 21 (8.9 mg, 0.05 mmol) in dichloromethane (25 μL)
was added H2SO4 (6 μL, 0.108 mmol). The mixture was heated to 50
°C for 13.9 h. The crude product was purified with flash column
chromatography (petroleum ether/ethyl acetate from 16/1 to 5/1) to
provide 3a (16.1 mg, 0.038 mmol, 76%) and 5 (12.3 mg, 0.042 mmol)
as white solids.
Oxidation of ε-Caprolactone (22). To a suspension of 2-
(hydroxydiphenylmethyl)-4-methoxyphenol (1; 132.1 mg, 0.43 mmol)
and ε-caprolactone (15.3 mg, 0.134 mmol) in dichloromethane (75
μL) was added H2SO4 (8 μL, 0.144 mmol). After 27 h, the reaction
was quenched with Na2CO3 (20 mg, 0.19 mmol), and the solvent was
removed. The obtained residue was treated with a solution of NaOH
(9.6 mg, 0.24 mmol) in methanol (1.2 mL). After the mixture was
stirred at room temperature for 24 h, it was quenched with HCl (6 N,
2 mL) and extracted with dichloromethane (1.3 mL × 5). The
combined organic layers were concentrated, and the and the residue
was purified first with a flash chromatography column (petroleum
ether/ethyl acetate 5/1) to provide 5 (33.0 mg, 0.114 mmol) as a
white solid. The column was then eluted with dichloromethane/ethyl
acetate (4/1) to provide 23 (33.2 mg, 0.079 mmol, 59%) as a colorless
oil. Data for 23: Rf = 0.36 (dichloromethane/ethyl acetate 4/1);
1H NMR (300 MHz, CDCl3) δ 7.37−7.33 (m, 5H), 7.26−7.22 (m,
5H), 6.84 (d, J = 8.9 Hz, 1H), 6.75 (dd, J = 8.9, 3.0 Hz, 1H), 6.36 (d,
J = 2.9 Hz, 1H), 4.94 (t, J = 5.1 Hz, 1H), 3.63 (s, 3H), 2.33 (t, J = 7.3
Hz, 2H), 1.91−1.77 (m, 2H), 1.69−1.40 (m, 4H); 13C NMR (75
MHz, CDCl3) δ 152.2, 147.2, 143.64, 143.62, 132.7, 129.41, 129.37,
128.2, 126.1, 125.1, 115.8, 110.3, 82.2, 68.4, 55.6, 49.9, 33.0, 25.3; IR
(neat; cm−1) 2952, 1708, 1495, 1403, 1233, 1047, 909, 810, 758, 734,
704, 648; HRMS (ESI) m/e calcd for C26H26O5Na 441.1673, found
441.1672.
Competing Oxidation of 2-Ethylhexanol (4f) and 3-Phenyl-
1-propanol (4a). To a suspension of 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1; 121 mg, 0.395 mmol), 4f (23.1 mg, 0.178 mmol),
and 4a (25.1 mg, 0.184 mmol) in dichloromethane (50 μL) was added
H2SO4 (6 μL, 0.108 mmol). The reaction mixture was stirred at 50 °C
for 9 h. The 1H NMR analysis with an internal reference indicated the
yields of 3a,f and 4a,f were 78%, 8%, 19%, and 80%, respectively.
Oxidation of Diethyl Ether. To a solution of 2-(hydroxydiphe-
nylmethyl)-4-methoxyphenol (1; 22.0 mg, 0.072 mmol) in diethyl
ether (35 μL) was added H2SO4 (2 μL, 0.036 mmol). The resulting
mixture was stirred at 50 °C for 10.5 h. The crude product was purified
with flash column chromatography (petroleum ether/ethyl acetate
gradually from 15/1 to 5/1) to provide 18 (9.7 mg, 0.029 mmol, 40%)
and 5 (9.2 mg, 0.0317 mmol), both as white solids. Data for 18: Rf =
1
0.53 (petroleum ether/ethyl acetate 15/1); mp 125.0−126.0 °C; H
NMR (300 MHz, CDCl3) δ 7.43−7.29 (m, 5H), 7.25 (d, J = 3.2 Hz,
5H), 6.85 (d, J = 8.9 Hz, 1H), 6.80−6.69 (m, 1H), 6.36 (d, J = 2.9 Hz,
1H), 5.11 (d, J = 5.1 Hz, 1H), 3.63 (s, 3H), 1.51 (d, J = 5.1 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 152.9, 146.6, 146.0, 144.3, 129.1,
128.13, 128.10, 128.0, 127.9, 127.5, 125.8, 117.5, 115.1, 114.1, 92.5,
84.3, 55.6, 20.8; IR (neat; cm−1) 2994, 1493, 1446, 1400, 1274, 1231,
1098, 756, 701; HRMS (ESI) m/e calcd for C22H21O3 333.1485, found
333.1484.
Oxidation of 3-Phenylpropyl Benzyl Ether (19). To a
suspension of 2-(hydroxydiphenylmethyl)-4-methoxyphenol (1; 41.3
mg, 0.135 mmol) and 3-phenylpropyl benzyl ether (19; 12 mg, 0.053
mmol) in dichloromethane (25 μL) was added H2SO4 (3 μL, 0.054
mmol). The mixture was heated at 50 °C for 5.5 h before more PPG 1
(31.1 mg, 0.1 mmol) was added. The mixture was then heated at 50
°C for 10 h more. The crude product was filtrated through a silica gel
plug (eluted with petroleum ether/ethyl acetate 1/1) to provide a
yellow liquid, and its composition was determined by NMR analysis
with an internal reference (i.e., DMAP). The yields of 3a,c and the
recovered 19 were 68%, 72%, and 18%, respectively. The ratio of the
combined acetals 3a,c to 5 was 1:1.15.
Oxidation of Tetrahydrofuran. To a suspension of 2-(hydroxy-
diphenylmethyl)-4-methoxyphenol (1; 202.9 mg, 0.662 mmol) and
THF (10.6 mg, 0.147 mmol) in dichloromethane (125 μL) was added
H2SO4 (8 μL, 0.144 mmol). The mixture was heated to 50 °C for 6 h.
The crude product was washed with acetonitrile (three times) to
remove 5. The combined acetonitrile solutions were concentrated and
purified with flash column chromatography (benzene/ethyl acetate
100/1) to provide 5 (73.9 mg, 0.254 mmol). The white solid residue
was washed with methanol and dichloromethane to provide
compound 20 as a white solid (0.101 mmol, 68%). Data for 20:
Rf = 0.3 (petroleum ether/ethyl acetate 10/1); mp 263.0−264.0 °C;
1H NMR (700 MHz, CDCl3) δ 7.40−7.34 (m, 5H), 7.28−7.22 (m,
5H), 6.82 (d, J = 8.9 Hz, 1H), 6.76 (dd, J = 9.0, 3.0 Hz, 1H), 5.02 (s,
1H), 3.66 (s, J = 5.1 Hz, 3H), 2.08 (dd, J = 9.9, 3.0 Hz, 1H), 1.97 (dd,
J = 9.9, 3.0 Hz, 1H); 13C NMR (176 MHz, CDCl3) δ 152.8, 146.4,
146.0, 144.1, 129.2, 128.1, 128.0, 127.9, 127.5, 125.8, 117.6, 115.0,
114.0, 94.7, 84.1, 55.6, 28.4; IR (neat; cm−1) 2924, 2852, 1494, 1275,
1042, 729; HRMS (ESI) m/e calcd for C44H38O6Na 685.2563, found
685.2566.
Oxidation of 26. To a suspension of 2-(hydroxydiphenylmethyl)-
4-methoxyphenol (1; 116.5 mg, 0.38 mmol) and the compound 26
(31.6 mg, 0.15 mmol) in dichloromethane (300 μL) was added H2SO4
(2 μL, 0.036 mmol). The mixture was heated to 50 °C for 23.3 h. The
crude product was directly loaded onto a flash column and eluted with
petroleum ether/ethyl acetate from 12/1 to 8/1 to provide 27 (59.1 mg,
0.119 mmol, 78%) as a yellow oil: Rf = 0.38 (petroleum ether/ethyl
1
acetate 8/1); H NMR (300 MHz, CDCl3) δ 8.04−8.01 (m, 2H),
7.56−7.51 (m, 5H), 7.43−7.31 (m, 7H), 7.26−7.21 (m, 5H), 6.84 (d,
J = 8.9 Hz, 1H), 6.74 (dd, J = 8.9, 2.9 Hz, 1H), 6.37 (d, J = 2.9 Hz,
1H), 4.97 (t, J = 5.0 Hz, 1H), 4.29 (t, J = 6.3 Hz, 2H), 3.62 (s, 3H),
1.95−1.87 (m, 2H), 1.79−1.55 (m, 4H); 13C NMR (75 MHz, CDCl3)
δ 166.6, 152.8, 146.5, 146.0, 144.2, 132.8, 130.4, 129.5, 129.2, 128.3,
128.1, 128.0, 127.8, 127.5, 125.8, 117.5, 115.0, 114.1, 94.8, 84.2, 64.8,
55.5, 34.0, 28.4, 20.1; IR (neat; cm−1) 3061, 3034, 2954, 1718, 1602,
1585, 1494, 1464, 1449, 1315, 1275, 1229, 1071, 1027, 758, 712, 703;
HRMS (ESI) m/e calcd for C32H30O5Na 517.1991, found 517.1988.
Oxidation of 28. To a suspension of 2-(hydroxydiphenylmethyl)-
4-methoxyphenol (1; 121.2 mg, 0.40 mmol) and the compound 28
(32.0 mg, 0.18 mmol) in dichloromethane (300 μL) was added H2SO4
(2 μL, 0.036 mmol). The mixture was heated to 50 °C for 19 h. The
crude product was directly loaded onto a flash column and eluted with
petroleum ether/ethyl acetate from 15/1 to 10/1 to provide 3c (7.0 mg,
0.018 mmol, 10%) and 29 (33.7 mg, 41%) as a yellow oil. Data for 29:
Oxidation of Ethyl Acetate (with 1 as the Limiting
Reagent). To a solution of 2-(hydroxydiphenylmethyl)-4-methoxy-
phenol (1; 22.1 mg, 0.072 mmol) in ethyl acetate (35 μL) was added
H2SO4 (2 μL, 0.036 mmol), and the reaction mixture was stirred at 50
°C for 10.5 h. The crude product was purified with flash column
chromatography (petroleum ether/ethyl acetate from 15/1 to 5/1) to
provide 18 (9.2 mg, 0.0277 mmol, 38%) and 5 (9.1 mg, 0.0313 mmol)
as white solids.
Oxidation of Ethyl Acetate. To a suspension of 2-(hydroxy-
diphenylmethyl)-4-methoxyphenol (1; 91.9 mg, 0.3 mmol) and ethyl
acetate (8.5 mg, 0.10 mmol) in dichloromethane (50 μL) was added
H2SO4 (6 μL, 0.108 mmol). The mixture was heated to 50 °C for 13.9 h.
1
Rf = 0.38 (petroleum ether/ethyl acetate 8/1); H NMR (300 MHz,
CDCl3) δ 7.36−7.22 (m, 15H), 6.84 (d, J = 8.9 Hz, 1H), 6.74 (dd, J =
8.9, 2.9 Hz, 1H), 6.36 (d, J = 2.9 Hz, 1H), 4.96 (t, J = 5.0 Hz, 1H),
4.45 (s, 2H), 3.62 (s, 3H), 3.44 (dt, J = 6.4, 0.9 Hz, 2H), 1.97−1.68
(m, 4H); 13C NMR (75 MHz, CDCl3) δ 152.8, 146.5, 146.0, 144.2,
138.5, 129.2, 128.3, 128.1, 128.0, 127.9, 127.8, 127.6, 127.49, 127.48,
125.8, 117.5, 115.0, 114.0, 94.8, 84.1, 72.8, 69.9, 55.5, 31.2, 23.8; IR
(neat; cm−1) 3059, 3031, 2933, 2856, 1494, 1447, 1274, 1231, 757,
700; HRMS (ESI) m/e calcd for C31H30O4Na 489.2042, found
489.2042.
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Isotope Effect Studies. Preparation of Deuterium-Labeled
Octan-1-ol (i.e., H(CH2)7CD2OH (4e(D)). To a stirred solution of
octanoyl choride (0.17 mL, 1.0 mmol) in DMF (1.0 mL) was added
NaBD4 (147.6 mg, 3.5 mmol) at −34 °C. The mixture was stirred at
room temperature overnight. Workup followed by column chromatog-
raphy (eluted with petroleum ether/ethyl acetate 8/1, Rf = 0.2)
afforded 4e(D) (76.3 mg, 57%) as a colorless oil: 1H NMR (300 MHz,
CDCl3) δ 1.55 (t, J = 6.7 Hz, 2H), 1.39−1.28 (m, 10H), 0.88 (t, J =
6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 62.4 (q, JCD = 21.8 Hz),
32.6, 31.8, 29.3, 29.2, 25.6, 22.6, 14.0; IR (neat; cm−1) 3337 (br),
2928, 1466, 968; MS (EI) m/e 56.1 (100%), 61.1, 70.1, 84.1.
(5) Hoye, T. R.; Kurth, M. J. J. Am. Chem. Soc. 1979, 101, 5065.
(6) Reducing triphenylmethyl to triphenylmethane with alcohol
under strongly acidic conditions has been reported: (a) Smith, H. A.;
Smith, R. J. J. Am. Chem. Soc. 1948, 70, 2400. (b) Bartlett, P. D.;
McCollum, J. D. J. Am. Chem. Soc. 1956, 78, 1441.
(7) (a) Wang, P.; Hu, H.; Wang, Y. Org. Lett. 2007, 9, 1533.
(b) Wang, P.; Hu, H.; Wang, Y. Org. Lett. 2007, 9, 2831. (c) Wang, P.;
Wang, Y.; Hu, H.; Spencer, C.; Liang, X.; Pan, L. J. Org. Chem. 2008,
73, 6152. (d) Wang, P.; Wang, Y.; Hu, H.; Liang, X. Eur. J. Org. Chem.
2009, 208. (e) Wang, P.; Mondal, M.; Wang, Y. Eur. J. Org. Chem.
2009, 2055. (f) Yang, H.; Zhang, X.; Zhou, L.; Wang, P. J. Org. Chem.
2011, 76, 2040.
(8) Kim, J.-H.; Huang, F.; Ly, M.; Linhardt, R. J. J. Org. Chem. 2008,
73, 9497.
(9) Isotope effects were studied with 4e and its deuterium-
substituted counterpart 4e(D): i.e., H(CH2)7CD2OH. An inconclusive
KH/KD ratio of 1.7 was obtained for the reactions involving C−H and
C−D bond cleavage.
Reaction of 4e. To a suspension of 2-(hydroxydiphenylmethyl)-4-
methoxyphenol (1;102.0 mg, 0.33 mmol) and 4e (19.6 mg, 0.15
mmol) in dichloromethane (300 μL) was added H2SO4 (2 μL, 0.036
mmol). The mixture was heated to 50 °C for 8.3 h, and 3e was
1
obtained in 75% yield (based on H NMR).
Reaction of 4e(D). To a suspension of 2-(hydroxydiphenylmethyl)-
4-methoxyphenol (1; 102.7 mg, 0.33 mmol) and 4e(D) (19.5 mg, 0.15
mmol) in dichloromethane (300 μL) was added H2SO4 (2 μL, 0.036
mmol). The mixture was heated to 50 °C for 8.3 h, and 3e(D) was
obtained in 42% yield (based on 1H NMR). Data for 3e(D): Rf = 0.50
(petroleum ether/ethyl acetate 20/1); 1H NMR (300 MHz, CDCl3) δ
7.42−7.34 (m, 5H), δ 7.28−7.23 (m, 5H), 6.86 (d, J = 8.9 Hz, 1H),
6.76 (dd, J = 8.9, 3.0 Hz, 1H), 6.38 (d, J = 2.9 Hz, 1H), 3.65 (s, 3H),
1.91−1.75 (m, 2H), 1.51−1.37 (m, 2H), 1.31−1.25 (m, 8H), 0.88 (t,
J = 6.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 152.7, 146.6, 146.1,
144.3, 129.2, 128.1, 128.0, 127.9, 127.8, 127.4, 125.9, 117.5, 115.0,
114.0, 94.8 (t, JCD = 25.5), 84.1, 55.5, 34.3, 31.7, 29.2, 29.1, 23.4, 22.6,
14.0; IR (neat; cm−1) 2953, 2928, 2856, 1493, 1447, 1255, 1177, 1255,
1137, 1042, 970, 756; HRMS (ESI) m/e calcd for C28H32DO3Na
440.2312, found 440.2316.
Reaction of a 4e/4e(D) Mixture (∼1:1). To a suspension of 2-
(hydroxydiphenylmethyl)-4-methoxyphenol (1; 102.0 mg, 0.33
mmol), 4e (9.8 mg, 0.075 mmol), and 4e(D) (9.5 mg, 0.072 mmol)
in dichloromethane (300 μL) was added H2SO4 (2 μL, 0.036 mmol).
The mixture was heated to 50 °C for 8.3 h, and the acetals 3e and
3e(D) were obtained in 54% yield (3e/3e(D) ≈ 2.0/1) (based on 1H
NMR).
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Figures giving H NMR and 13C NMR spectra of 5, 3b,d,
1
3e(D), 4e(D), 13a,f, 18, 20, 23, 27, and 29 and H NMR
spectra of the known compounds 3a,c,e,f and 10a,b. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: wangp@uab.edu.
■
ACKNOWLEDGMENTS
We thank the NSF for its support (No. CHE-0848489).
■
REFERENCES
■
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G.; Zurr, D. Chem. Commun. 1971, 1109. (c) Barton, D. H. R.;
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8961
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