Understanding the reactivity of enol ether radical cations: Investigation of anodic four-membered carbon ring formation

Article abstract of DOI:10.1021/jo3028246

The reactivity of enol ether radical cations was investigated in anodic four-membered carbon ring formations, advancing the mechanistic understanding of these reactions. The mono-ring-containing aromatic cations were reduced through inter- or intramolecular electron transfer to give mono- or bis-ring-containing compounds, respectively. Small structural changes in the hydrocarbon linkers tethering two aromatic rings exerted a powerful effect on the efficiency of such electron transfer events.

Full text of DOI:10.1021/jo3028246

Article
pubs.acs.org/joc
Understanding the Reactivity of Enol Ether Radical Cations:
Investigation of Anodic Four-Membered Carbon Ring Formation
Yusuke Yamaguchi, Yohei Okada, and Kazuhiro Chiba*
Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo
183-8509, Japan
S
* Supporting Information
ABSTRACT: The reactivity of enol ether radical cations was investigated in anodic
four-membered carbon ring formations, advancing the mechanistic understanding of
these reactions. The mono-ring-containing aromatic cations were reduced through
inter- or intramolecular electron transfer to give mono- or bis-ring-containing
compounds, respectively. Small structural changes in the hydrocarbon linkers tethering
two aromatic rings exerted a powerful effect on the efficiency of such electron transfer
events.
methods using alcohols and sulfonamides as trapping groups,
which has provided clear-cut mechanistic insights.5
INTRODUCTION
■
In the field of organic chemistry, a remarkable array of powerful
reactions and transformations has been added to the growing
toolbox. The modern synthetic landscape has been dominated
largely by the use of conventional intermediates, including
carbanions, carbocations, radicals, and carbenes, and the
chemoselectivity of such reactive species is well established.
Electron-transfer-induced reactions that involve transient
radical ions, typically generated using photochemical ap-
proaches, one-electron-redox reagents, and electrochemical
processes, are also potential candidates for the design of
sophisticated new synthetic sequences based on the distinctive
reactivity unique to them.1 A mechanistic understanding of the
behavior of such radical ions would be a great aid for their
installation into the framework of existing organic synthesis.
Enol ether radical cations can be produced readily via either
oxidative or nonoxidative reactions and constitute one of the
simplest members of the radical cation family. The non-
oxidative generation of enol ether radical cations involves
heterolytic fragmentation of an α-alkoxy radical containing a β-
leaving group, and such an entry to enol ether radical cations
has been introduced creatively into ribose scaffolds, affording
studies of electron transfer in DNA that are implicated in its
degradation.2 In addition, the nonoxidative access to enol ether
radical cations has been well-combined with radical clock
methods, leading to an accurate kinetic understanding.3
In this context, we have been developing four-membered
carbon ring formation reactions initiated via the anodic
umpolung process of enol ethers, which generate radical
cations that are then trapped by several unactivated olefin
nucleophiles.6 For example, the anodic oxidation of 1-(prop-1-
en-1-yloxy)-4-propylbenzene (1) in the presence of 3-
methylenepentane (2) gave the four-membered carbon ring
containing compound 3 (Scheme 1).7 Our previous studies
Scheme 1. Anodic Four-Membered Carbon Ring
a
Formation
a
Reagents and conditions: (a) LiClO4, MeNO2, carbon felt electrodes
1.2 V vs Ag/AgCl, room temperature.
have indicated that the aromatic radical cation (3•+)
constructed through intermolecular carbon−carbon bond
formation between the enol ether radical cation (1•+) and 3-
methylenepentane (2) was reduced to give the ring-containing
compound 3 (Scheme 2). For the aromatic radical cation (3•+)
to be reduced, there are two possible pathways, including the
oxidation of 1-(prop-1-en-1-yloxy)-4-propylbenzene (1) and
On the other hand, the oxidative generation of enol ether
radical cations is an umpolung process in which the polarity of
nucleophilic enol ethers is reversed such that they function as
electrophilic radical cations.4 In particular, the chemoselectivity
of electrochemically generated enol ether radical cations has
been investigated directly on the basis of competition study
Received: December 30, 2012
Published: February 26, 2013
© 2013 American Chemical Society
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between (4-methoxyphenyl)magnesium bromide and 1,3-
dibromopropane followed by deprotection of the phenolic
methyl ethers provided the corresponding bis-phenol precursor
5, which was then allylated. Isomerization of the allyl groups
gave 1,3-bis(4-(prop-1-en-1-yloxy)phenyl)propane (4).
Scheme 2. Proposed Reaction Mechanism for Anodic Four-
Membered Carbon Ring Formation
The anodic oxidation of 1,3-bis(4-(prop-1-en-1-yloxy)-
phenyl)propane (4) in the presence of 3-methylenepentane
(2) as an unactivated olefinic nucleophile was expected to
provide the mono-ring-containing compound 6 or the bis-ring-
containing compound 7 (Scheme 6). In particular, the
formation of the bis-ring-containing compound (7) should
involve the transformation from the aromatic radical cation
(6a•+) to the enol ether radical cation (6e•+) via intramolecular
electron transfer, such that the reaction would be completed
with a catalytic amount of electricity. When the reaction at 0.5
F (i.e., 0.5 F for every one enol ether) was monitored using
GC-MS, however, 28% of 1,3-bis(4-(prop-1-en-1-yloxy)-
phenyl)propane (4) was recovered, and the peak associated
with the mono-ring-containing compound 6 was predominant,
with only a small peak associated with the bis-ring-containing
compound 7 observed (Figure S1, Supporting Information).
Intramolecular four-membered carbon ring formation via the
trapping of the enol ether radical cation by the additional enol
ether group in the molecule was not observed, apparently
because of the conformational restriction. At 1.0 F, the 1,3-
bis(4-(prop-1-en-1-yloxy)phenyl)propane (4) was almost com-
pletely consumed, and the peak associated with the mono-ring-
containing compound 6 remained the major product (Figure
S1, Supporting Information). At 2.0 F, however, both 1,3-bis(4-
(prop-1-en-1-yloxy)phenyl)propane (4) and the peak associ-
ated with the mono-ring-containing compound 6 finally
disappeared, and that associated with the bis-ring-containing
compound 7 was observed as the predominant product (Figure
S1, Supporting Information). These results suggested that the
transformation from the aromatic radical cation 6a•+ to the enol
ether radical cation 6e•+ via intramolecular electron transfer
barely took place and that the aromatic radical cation 6a•+ was
reduced once via intermolecular electron transfer to give the
mono-ring-containing compound 6, which then underwent
further anodic oxidation, leading to construction of the bis-ring-
containing compound 7.
the electrode process. While the oxidation of 1-(prop-1-en-1-
yloxy)-4-propylbenzene (1) can lead to the generation of the
further enol ether radical cation 1•+ in order to drive the overall
reaction cycle with a catalytic amount of electricity, the
electrode process was not effective unless an anodic backward
discharge took place. Because both of these reductions are
intermolecular electron transfer events, a higher concentration
of 1-(prop-1-en-1-yloxy)-4-propylbenzene (1) is effective for
preferentially driving the electrocatalytic route over the
electrode process; however, undesired dimerization also
competes under such reaction conditions.8
With respect to kinetic aspects, intramolecular electron
transfer generally has an advantage over intermolecular variants.
Indeed, our previous studies clearly demonstrated that
intramolecular electron donors completed the formation of
four-membered carbon rings, while intermolecular variants did
not (Scheme 3).9 On the basis of these observations, we
Scheme 3. Comparison of the Reactivity of Intra- and
Intermolecular Electron Donors for Anodic Four-Membered
Carbon Ring Formation
Although the bis-ring-containing compound 7 was selectively
obtained with an excess amount of electricity, enabling the
confirmation of the structural identity, the mono-ring-
containing compound 6 was not readily separable. Therefore,
the mono-ring-containing compound 6 was synthesized
alternatively to confirm the structural identity of the compound
produced in the reaction (Scheme 7). The monoallylation of
bis-phenol precursor 5 followed by isomerization of the allyl
group provided a monoenol ether, which was then further
allylated. Subsequent anodic oxidation constructed a mono-
ring-containing intermediate bearing an allyl group, which was
then isomerized to give the mono-ring-containing compound 6.
The synthesized compound 6 was then coinjected with the
reaction mixture obtained from the anodic oxidation of 1,3-
bis(4-(prop-1-en-1-yloxy)phenyl)propane (4) in the presence
of 3-methylenepentane (2), confirming the postulated structure
(Figure S2, Supporting Information).
envisioned that an intramolecular, tethered enol ether should
be an efficient electron donor that could lead to the
regeneration of an enol ether radical cation, affording bis
four-membered carbon ring containing compounds using a
catalytic amount of electricity (Scheme 4). Described herein is
the further investigation of the reactivity of enol ether radical
cations toward anodic four-membered carbon ring formation.
RESULTS AND DISCUSSION
■
With the fully characterized four-membered carbon ring
containing compounds 6 and 7 in hand, the anodic oxidation of
1,3-bis(4-(prop-1-en-1-yloxy)phenyl)propane (4) in the pres-
ence of 3-methylenepentane (2) was carefully remonitored
using GC-MS (Figure 1). These results clearly illustrated that
The present study began with the synthesis of 1,3-bis(4-(prop-
1-en-1-yloxy)phenyl)propane (4) as a model bis-enol ether,
which was prepared via the simple addition of a second enol
ether moiety at the end of the propyl group of 1-(prop-1-en-1-
yloxy)-4-propylbenzene (1) (Scheme 5). A Grignard reaction
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Scheme 4. General Strategy of This Study
a
Scheme 5. Synthesis of 1,3-Bis(4-(prop-1-en-1-yloxy)phenyl)propane (4)
a
Reagents and conditions: (a) 1,3-Dibromopropane, Li2CuCl4, THF, 0 °C to room temperature, 99%; (b) BBr3, CH2Cl2, 0 °C to room temperature,
t
90%; (c) allyl bromide, K2CO3, DMF, 60 °C; (d) BuOK, DMSO, room temperature.
the formation of the four-membered carbon rings took place in
a stepwise manner. Thus, the mono-ring-containing compound
6 was initially accumulated in the early stages of the reaction
and was then reoxidized at the anode to complete the
formation of the bis-ring-containing compound 7. Moreover,
cyclic voltammograms of 1,3-bis(4-(prop-1-en-1-yloxy)phenyl)-
propane (4) and the mono-ring-containing compound 6 were
recorded, and the peak oxidation potentials were determined to
be 1.22 and 1.14 V vs Ag/AgCl, respectively, clearly indicating
that the reactivities toward anodic oxidation of the enol ether
moieties in both 1,3-bis(4-(prop-1-en-1-yloxy)phenyl)propane
(4) and the mono-ring-containing compound 6 were similar
(Figure S3, Supporting Information). This similarity ruled out
the possibility that the mono-ring-containing compound 6 was
accumulated because of its low reactivity. Indeed, the anodic
oxidation of the mono-ring-containing compound 6 in the
presence of 3-methylenepentane (2) at 1.0 F also gave the bis-
ring-containing compound 7 in 72% yield, and no mono-ring-
containing compound 6 was recovered. Therefore, in this case,
intermolecular electron transfer has some advantage over the
intramolecular variant for the reduction of the aromatic radical
aromatic radical cation (6a•+) was unclear in the reaction
mixture, the contraction of the propylene linker that tethered
the two aromatic rings would affect the intramolecular electron
transfer significantly. For this reason, additional bis-enol ethers
(8 and 9) were designed and synthesized from the
corresponding bis-phenol precursors (Schemes 8 and 9).
The anodic oxidation of 1,2-bis(4-(prop-1-en-1-yloxy)-
phenyl)ethane (8) in the presence of 3-methylenepentane
(2) was then monitored using GC-MS. Although the yields of
the mono- and bis-ring-containing compounds 12 and 13,
respectively, were both moderately decreased in comparison to
those obtained from 1,3-bis(4-(prop-1-en-1-yloxy)phenyl)-
propane (4), their ratios changed significantly (Figure 2).
The bis-/mono-ring-containing compound values were 0.09 at
0.5 F and 0.24 at 1.0 F, respectively, when 1,3-bis(4-(prop-1-en-
1-yloxy)phenyl)propane (4) was used and increased to 0.15
and 0.63, respectively, in the case of 1,2-bis(4-(prop-1-en-1-
yloxy)phenyl)ethane (8). (The structural identity of the mono-
ring-containing compound 12 was confirmed through its
alternative synthesis (Scheme 10)). Notably, the anodic
oxidation of mono-ring-containing compound 12 in the
presence of 3-methylenepentane (2) at 1.0 F gave the bis-
ring-containing compound 13 in only 4% yield, and 64% of the
mono-ring-containing compound 12 was recovered (Scheme
11). Apparently, the bis-ring-containing compound 13 was
cation 6a•+
.
In general, the efficiency of electron transfer events depends
to a large extent on the orientation of the electron donor and
the electron acceptor. Although the conformation of the
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Scheme 6. Proposed Reaction Mechanism for the Anodic Four-Membered Carbon Ring Formation Starting from 1,3-Bis(4-
(prop-1-en-1-yloxy)phenyl)propane (4)
a
Scheme 7. Synthesis of the Mono-Ring-Containing Compound 6
a
Reagents and conditions: (a) allyl bromide, K2CO3, DMF, 60 °C; (b) tBuOK, DMSO, room temperature; (c) allyl bromide, K2CO3, DMF, 60 °C;
t
(d) 3-methylenepentane, LiClO4, MeNO2, carbon felt electrodes, 1.2 V vs Ag/AgCl, room temperature; (e) BuOK, DMSO, room temperature.
formed mainly from 1,2-bis(4-(prop-1-en-1-yloxy)phenyl)-
ethane (8) in a direct manner, not via formation of the
mono-ring-containing compound 12, which would involve
transformation from the aromatic radical cation 12a•+ to the
enol ether radical cation 12e•+ via intramolecular electron
transfer (Scheme 12).
The synthesis of enol ether bis(4-(prop-1-en-1-yloxy)-
phenyl)methane (9) was not as straightforward as that of 4
and 8. The standard synthetic scheme for the enol ethers,
including allylation and basic isomerization, had to be modified.
Because of the relatively high acidity of the benzylic protons of
bis(4-(allyloxy)phenyl)methane (11), its treatment with base
resulted in a messy mixture. To address this issue, a ruthenium
catalyst was used to isomerize the allyl groups of bis(4-
(allyloxy)phenyl)methane (11). This method has proven to be
a highly versatile and successful approach for obtaining bis(4-
(prop-1-en-1-yloxy)phenyl)methane (9). Reaction monitoring
of the anodic oxidation of bis(4-(prop-1-en-1-yloxy)phenyl)-
methane (9) in the presence of 3-methylenepentane (2) using
GC-MS was disappointing, because the mono-ring-containing
compound 14 was the predominant product, even at 2 F, with
only a small amount of the bis-ring-containing compound 15
observed (Figure 3). (The mono-ring-containing compound 14
was also synthesized alternatively to confirm its structural
identity; see Scheme 13.). These results were presumably due
to the stability of the corresponding diarylcarbenium ion, which
can be generated and accumulated by the low-temperature
anodic oxidation of diarylmethanes.10 There was the possibility
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Figure 1. Monitoring of the reaction of 4 via GC-MS: (black line) 1,3-bis(4-(prop-1-en-1-yloxy)phenyl)propane (4); (purple line) mono-ring-
containing compound 6; (pink line) bis-ring-containing compound 7.
a
Scheme 8. Synthesis of 1,2-Bis(4-(prop-1-en-1-yloxy)phenyl)ethane (8)
a
Reagents and conditions: (a) Grubbs second-generation catalyst, CH2Cl2, 40 °C, 93%; (b) H2, Pd/C, THF, room temperature, 84%; (c) BF3SMe2,
t
CH2Cl2, room temperature, 96%; (d) allyl bromide, K2CO3, DMF, 60 °C; (e) BuOK, DMSO, room temperature.
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that both the aromatic radical cation 14a•+ and the mono-ring-
containing compound 14 could undergo transformation to the
diarylcarbenium ion 14+ via anodic oxidation accompanied by
deprotonation, which seemed not to afford the bis-ring-
containing compound 15 even on reaction with 3-methyl-
enepentane (2) (Scheme 14). Therefore, 4,4′-(propane-2,2-
diyl)bis((prop-1-en-1-yloxy)benzene) (16), in which the acidic
benzylic protons were preliminarily abstracted, was finally
designed and synthesized (Scheme 15).
Scheme 9. Synthesis of Bis(4-(prop-1-en-1-
yloxy)phenyl)methane (9)
a
This structural change had the desired effect on the synthetic
outcome and confirmed our suspicions about the previous
failed synthetic effort with bis(4-(prop-1-en-1-yloxy)phenyl)-
methane (9). Reaction monitoring of the anodic oxidation of
4,4′-(propane-2,2-diyl)bis((prop-1-en-1-yloxy)benzene) (16)
in the presence of 3-methylenepentane (2) using GC-MS
a
Reagents and conditions: (a) allyl bromide, K2CO3, DMF, 60 °C; (b)
(Ph3P)3RuCl2, toluene, reflux, 90%.
Figure 2. Monitoring of the reaction of 8 via GC-MS: (black line) 1,2-bis(4-(prop-1-en-1-yloxy)phenyl)ethane (8); (purple line) mono-ring-
containing compound 12; (pink line) bis-ring-containing compound 13.
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a
Scheme 10. Synthesis of the Mono-Ring-Containing Compound 12
a
Reagents and conditions: (a) allyl bromide, K2CO3, DMF, 60 °C; (b) tBuOK, DMSO, room temperature; (c) allyl bromide, K2CO3, DMF, 60 °C;
t
(d) 3-methylenepentane, LiClO4, MeNO2, carbon felt electrodes, 1.2 V vs Ag/AgCl, room temperature; (e) BuOK, DMSO, room temperature.
Scheme 11. Anodic Four-Membered Carbon Ring
Formation of the Mono-Ring-Containing Compound 12
direct manner (Scheme 17). In this case, a hopping mechanism
using a second aromatic ring as relay station was also possible
for the intramolecular electron transfer.11 The peak oxidation
potentials of 4,4′-(propane-2,2-diyl)bis((prop-1-en-1-yloxy)-
benzene) (16) and the mono-ring-containing compound 17
are 1.25 and 1.27 V vs Ag/AgCl, respectively, clearly indicating
that the selective anodic oxidation of the mono-ring-containing
compound 17 in the presence of 4,4′-(propane-2,2-diyl)bis-
((prop-1-en-1-yloxy)benzene) (16) was barely achieved
(Figure S4, Supporting Information). In this case, intra-
molecular electron transfer was strongly preferred over the
intermolecular variant for reduction of the aromatic radical
a
a
Reagents and conditions: 3-methylenepentane, LiClO4, MeNO2,
carbon felt electrodes, 1.2 V vs Ag/AgCl, 1.0 F/mol, room
temperature.
showed that the bis-ring-containing compound 18 was
predominantly observed, even at 0.5 F, with generation of
only a minor amount of the mono-ring-containing compound
17. At 1.0 F, the ratio of the bis- and mono-ring-containing
compounds 18 and 17, respectively, was 8.4, and almost no
mono-ring-containing compound 17 was detected (Figure 4).
The structural identity of the mono-ring-containing compound
17 was confirmed through its alternative synthesis (Scheme
16). On the basis of these observations, it can be rationalized
that transformation from the aromatic radical cation 17a•+ to
cation 17a•+
.
CONCLUSION
■
The experimental results presented herein successfully
advanced the mechanistic understanding of the reactivity of
enol ether radical cations for anodic four-membered carbon
ring formation (Scheme 18). The anodically generated enol
ether radical cations were trapped by olefinic nucleophiles in
order to afford the corresponding mono-ring-containing
aromatic radical cations. There are two possible pathways for
such aromatic radical cations to be reduced, inter- and
intramolecular electron transfers, and both were directly
investigated through the synthetic outcomes. The intermolec-
•+
the enol ether radical cation 17e occurred rapidly via
intramolecular electron transfer, and the resulting enol ether
radical cation 17e•+ was then trapped by 3-methylenepentane
(2) to construct the bis-ring-containing compound 18 in a
Scheme 12. Proposed Electron Transfer in the Mono-Ring-Containing Compound 12
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Figure 3. Monitoring of the reaction of 9 via GC-MS: (black line) bis(4-(prop-1-en-1-yloxy)phenyl)methane (9); (purple line) mono-ring-
containing compound 14; (pink line) bis-ring-containing compound 15.
a
Scheme 13. Synthesis of the Mono-Ring-Containing Compound 14
a
Reagents and conditions: (a) allyl bromide, K2CO3, DMF, 60 °C; (b) (Ph3P)3RuCl2, toluene, reflux; (c) allyl bromide, K2CO3, DMF, 60 °C,; (d) 3-
methylenepentane, LiClO4, MeNO2, carbon felt electrodes, 1.2 V vs Ag/AgCl, room temperature; (e) (Ph3P)3RuCl2, toluene, reflux.
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Scheme 14. Possible Formation of the Diarylcarbenium Ion 14+
reaction (determined by TLC), followed by dilution with EtOAc. The
organic layer was washed with brine, dried over MgSO4, and
concentrated in vacuo. Purification by silica gel column chromatog-
raphy (EtOAc/hexanes) gave the desired bis-allylated compounds. To
Scheme 15. Synthesis of 4,4′-(Propane-2,2-diyl)bis((prop-1-
a
en-1-yloxy)benzene) (16)
t
a solution of the resulting bis-allylated compound in DMSO, BuOK
(8.0 equiv for every one phenol) was added. The resulting reaction
mixture was stirred at room temperature for 6 h, followed by dilution
with hexane. The layers were separated, the DMSO layer was extracted
several times with hexane, and the combined hexane phases were
washed with brine, dried over MgSO4, and concentrated in vacuo.
Purification by silica gel column chromatography (EtOAc/hexanes)
gave the desired bis-enol ethers.
General Procedure for the Anodic Four-Membered Carbon
Ring Formations. To a solution of lithium perchlorate (1.0 M) in
MeNO2, the enol ether substrate (0.10 mmol) and 3-methylenepen-
tane (2; 0.50 M) were added. Carbon felt electrodes (20 mm × 20
mm) were inserted into the solution, and electrolysis was performed
using an undivided cell with stirring at a constant potential of 1.2 V vs
Ag/AgCl under room-temperature conditions. The reaction progress
was monitored by TLC and GC-MS. If it was desired to obtain the bis-
ring-containing compounds selectively, an excess amount of electric
charge (5−10 F) was passed through the solution to consume the
mono-ring-containing compounds, followed by dilution with EtOAc.
The organic layer was washed with brine, dried over MgSO4, and
concentrated in vacuo. Purification by silica gel column chromatog-
raphy (EtOAc/hexanes) gave the desired bis-ring-containing com-
pounds.
a
Reagents and conditions: (a) allyl bromide, K2CO3, DMF, 60 °C; (b)
tBuOK, DMSO, room temperature.
ular reduction simply gave the mono-ring-containing com-
pound that could be further oxidized. The intramolecular
reduction triggered the regeneration of the enol ether radical
cations, affording the bis-ring-containing compounds. The
information gained about the tether between the aromatic
rings influencing the relative rates of inter- and intramolecular
electron transfer will be critical for the design of new synthetic
sequences that aim to capitalize on the distinctive reactivity
unique to enol ether radical cations in combination with the use
of more conventional reactive intermediates.
General Procedure for the Preparation of the Mono-Ring-
Containing Compounds. All mono-ring-containing compounds
were synthesized from the corresponding bis-phenol precursors
through the combined procedures described above. To a solution of
the bis-phenol precursor in DMF were added allyl bromide (1.1 equiv)
and K2CO3 (4.5 equiv). The resulting reaction mixture was stirred at
60 °C until completion of the reaction (determined by TLC), followed
by dilution with EtOAc. The organic layer was washed with brine,
dried over MgSO4, and concentrated in vacuo. Purification by silica gel
column chromatography (EtOAc/hexanes) gave the desired mono-
allylated compounds. To a solution of the resulting monoallylated
EXPERIMENTAL SECTION
■
All solvents and reagents were from commercial source and were used
without further purification. 1H NMR spectra were collected on a 600
MHz NMR spectrometer using the deuterated solvent as an internal
deuterium reference. Chemical shift data are given in δ units calibrated
with residual protic solvent. The multiplicity of a signal is indicated as
follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. 13C
NMR spectra were collected on a 150 MHz spectrometer with proton
decoupling using the deuterated solvent as an internal carbon
reference. Chemical shift data are given in δ units calibrated with
residual solvent. Only selected absorbances are reported in the IR
spectra. HRMS analysis was performed in DARTTOF mode.12 The
reaction yields were determined by NMR or GC-MS.
General Procedure for the Preparation of Bis Enol Ethers.
Unless otherwise stated, all enol ether substrates were prepared from
the corresponding bis-phenol precursors through a previously
described procedure in the literature.13 To a solution of the bis-
phenol precursor in DMF, allyl bromide (3.0 equiv for every one
phenol) and K2CO3 (4.5 equiv for every one phenol) were added. The
resulting reaction mixture was stirred at 60 °C until completion of the
t
compound in DMSO was added BuOK (8.0 equiv). The resulting
reaction mixture was stirred at room temperature for 6 h, followed by
dilution with EtOAc. The organic layer was washed with brine, dried
over MgSO4, and concentrated in vacuo. Purification by silica gel
column chromatography (EtOAc/hexanes) gave the desired mono
enol ethers. The remaining phenol was similarly allylated, followed by
the anodic four-membered carbon ring formation, and the remaining
allyl group was isomerized. Purification by silica gel column
chromatography (EtOAc/hexanes) gave the desired mono-ring-
containing compounds.
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Figure 4. Monitoring of the reaction of 16 via GC-MS: (black line) 4,4′-(propane-2,2-diyl)bis((prop-1-en-1-yloxy)benzene) (16); (purple line)
mono-ring-containing compound 17; (pink line) bis-ring-containing compound 18.
Preparation of 4,4′-(Propane-1,3-diyl)diphenol (5). To a
solution of 1,3-dibromopropane (2.04 mL, 20.0 mmol) in THF (20
mL) was added lithium tetrachlorocuprate(II) (0.10 M in THF, 1.20
mL, 0.120 mmol), and the mixture was cooled with an ice bath. (4-
Methoxyphenyl)magnesium bromide (1.0 M in THF, 70.0 mL, 70.0
mmol) was added dropwise, and the resulting reaction mixture was
stirred at room temperature for 16 h, followed by dilution with cold
water and Et2O. The layers were separated, the aqueous layer was
extracted several times with Et2O, and the combined organic phases
were washed with brine, dried over MgSO4, and concentrated in vacuo
to give 5.08 g of 1,3-bis(4-methoxyphenyl)propane (99% yield). This
compound was finally purified by recrystallization from EtOH. 1,3-
Bis(4-methoxyphenyl)propane was then dissolved in CH2Cl2 (100
mL) and cooled with an ice bath. BBr3 (1.0 M in CH2Cl2, 3.0 equiv.)
was added dropwise, and the resulting reaction mixture was stirred at
room temperature for 16 h. The reaction mixture was poured into
water, and the layers were separated. The aqueous layer was extracted
several times with CH2Cl2, and the combined organic phases were
washed with brine, dried over MgSO4, and concentrated in vacuo to
give 4.07 g of 4,4′-(propane-1,3-diyl)diphenol (5) (90% yield). This
compound was finally purified by silica gel column chromatography
(EtOAc/hexanes).
Preparation of 4,4′-(Ethane-1,2-diyl)diphenol (10). 1,2-Bis(4-
methoxyphenyl)ethane was prepared from 1-methoxy-4-vinylbenzene
through a procedure previously described in the literature.14 To a
solution of 1-methoxy-4-vinylbenzene (2.68 mL, 20 mmol) in CH2Cl2
(40 mL) was added Grubbs’ second-generation catalyst (5 mol %).
The resulting reaction mixture was stirred at 40 °C for 2 h and
concentrated in vacuo to give 2.23 g of 1,2-bis(4-methoxyphenyl)-
ethane (93% yield). This compound was finally purified by silica gel
column chromatography (EtOAc/hexanes). 1,2-Bis(4-
methoxyphenyl)ethane was then dissolved in THF (40 mL). 5%
Pd/C (112 mg) was added and the mixture purged with hydrogen gas.
The resulting reaction mixture was vigorously stirred under a hydrogen
atmosphere for 6 h at room temperature. The reaction mixture was
then filtered and concentrated in vacuo to give 1.89 g of 1,2-bis(4-
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a
Scheme 16. Synthesis of the Mono-Ring-Containing Compound 16
a
t
Reagents and condition: (a) Allylbromide, K2CO3, DMF, 60 °C. (b) BuOK, DMSO, room temperature. (c) Allylbromide, K2CO3, DMF, 60 °C,
t
(d) 3-Methylenepentane, LiClO4, MeNO2, carbon felt electrodes, 1.2 V vs Ag/AgCl, room temperature. (e) BuOK, DMSO, room temperature.
Scheme 17. Proposed Reaction Mechanism for Anodic Four-
Membered Carbon Ring Formation Starting from 4,4′-
(Propane-2,2-diyl)bis((prop-1-en-1-yloxy)benzene) (16)
Scheme 18. Mechanistic Understanding of the Behavior of
Enol Ether Radical Cations during Anodic Four-Membered
Carbon Ring Formation
Preparation of Bis(4-(prop-1-en-1-yloxy)phenyl)methane
(9). To a solution of bis(4-(allyloxy)phenyl)methane (11; 2.80 g,
10.0 mmol) in toluene (10 mL) was added tris(triphenylphosphine)-
ruthenium(II) dichloride (10 mol %). The resulting reaction mixture
was stirred under reflux conditions for 12 h. The reaction mixture was
concentrated in vacuo to give 2.52 g of bis(4-(prop-1-en-1-yloxy)-
phenyl)methane (9) (90% yield). This compound was finally purified
by silica gel column chromatography (EtOAc/hexanes).
1,3-Bis(4-(prop-1-en-1-yloxy)phenyl)propane (4), mixture of
1
methoxyphenyl)ethane (84% yield). This compound was finally
purified by silica gel column chromatography (EtOAc/hexanes).
4,4′-(Ethane-1,2-diyl)diphenol (10) was prepared from 1,2-bis(4-
methoxyphenyl)ethane through a procedure previously described in
the literature.15 To a solution of 1,2-bis(4-methoxyphenyl)ethane in
CH2Cl2 (40 mL) was added boron trifluoride−dimethyl sulfide
complex (5.0 equiv for every one methoxy group) dropwise, and the
resulting reaction mixture was stirred at room temperature for 12 h,
followed by dilution with CH2Cl2 and 2.0 M HCl. The layers were
separated, the aqueous layer was extracted several times with CH2Cl2,
and the combined organic phases were washed with brine, dried over
MgSO4, and concentrated in vacuo to give 1.61 g of 4,4′-(ethane-1,2-
diyl)diphenol (10) (96% yield). This compound was finally purified by
silica gel column chromatography (EtOAc/hexanes).
diastereomers (oil): H NMR (CDCl3, 600 MHz) δ 7.11−7.08 (4H,
m), 6.92−6.86 (4H, m), 6.41−6.36 (0.2H, m) 6.36−6.33 (1.8H, m),
5.30 (0.2H, dq, J = 12.4, 6.9 Hz), 4.83 (1.8H, dq, J = 6.9, 6.5 Hz), 2.58
(4H, t, J = 7.6 Hz), 1.92−1.86 (2H, m), 1.70 (5.4H, dd, J = 6.9, 2.1
Hz), 1.65 (0.6H, dd, J = 6.8, 1.7 Hz); 13C NMR (CDCl3, 150 MHz) δ
155.8, 141.3, 136.3, 129.5, 128.0, 116.3, 116.2, 107.8, 107.0, 34.6, 33.4,
12.3, 9.4; IR (NaCl, cm−1) 3036, 2921, 2857, 1668, 1607, 1509, 1234,
1021; HRMS [M + H]+ calcd for C21H25O2 309.1855, found 309.1854.
1-(2,2-Diethyl-4-methylcyclobutoxy)-4-(3-(4-(prop-1-en-1-yloxy)-
phenyl)propyl)benzene (6), mixture of diastereomers (oil): 1H NMR
(CDCl3, 600 MHz) δ 7.12−6.99 (4H, m), 6.94−6.86 (2H, m), 6.81−
6.77 (1H, m), 6.75−6.71 (1H, m), 6.43−6.28 (1H, m), 5.36−5.28
(0.2H, m), 4.87−4.79 (0.8H, m), 4.31 (0.6H, d, J = 6.9 Hz), 3.96
(0.4H, d, J = 6.9 Hz), 2.71−2.64 (0.6H, m), 2.60−2.51 (4H, m), 2.43−
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2.32 (0.4H, m), 1.91−1.83 (2H, m), 1.81−1.72 (2H, m), 1.70 (2.6H,
dd, J = 6.9, 2.1 Hz), 1.65 (0.4H, dd, J = 6.9, 1.4 Hz), 1.64−1.54 (1H,
m), 1.52−1.43 (2H, m), 1.39 (0.6H, dd, J = 11.7, 6.2 Hz), 1.15 (1.2H,
d, J = 6.2 Hz), 1.01 (1.8H, d, J = 7.6 Hz), 0.99−0.90 (0.4H, m), 0.84−
0.76 (6H, m); 13C NMR (CDCl3, 150 MHz) δ 157.5, 157.2, 155.7,
141.3, 136.5, 134.3, 133.8, 129.5, 129.2, 129.1, 116.3, 116.1, 115.8,
114.5, 107.0, 85.2, 79.6, 45.4, 45.2, 41.0, 35.5, 34.6, 33.7, 33.4, 31.8,
31.0, 30.1, 30.0, 24.8, 24.0, 20.0, 19.9, 15.8, 13.9, 12.3, 9.4, 8.5, 8.4, 8.3,
7.8; IR (NaCl, cm−1) 3029, 2960, 2929, 2858, 1672, 1607, 1509, 1238,
1021; HRMS [M + H]+ calcd for C27H37O2 393.2794, found 393.2793.
1,3-Bis(4-(2,2-diethyl-4-methylcyclobutoxy)phenyl)propane (7),
mixture of diastereomers (oil): 1H NMR (CDCl3, 600 MHz) δ
7.08−7.01 (4H, m), 6.86−6.77 (2H, m), 6.76−6.72 (2H, m), 4.32
(1.6H, d, J = 7.3 Hz), 3.96 (0.4H, d, J = 7.3 Hz), 2.74−2.62 (1.6H, m),
2.55 (4H, t, J = 7.3 Hz), 2.42−2.32 (0.4H, m), 1.91−1.83 (2H, m),
1.80−1.68 (4H,m), 1.65−1.55 (2H, m), 1.50−1.44 (4H, m), 1.40
(1.6H, dd, J = 11.5, 6.0 Hz), 1.15 (1.2H, d, J = 6.9 Hz), 1.01 (4.8H,
m), 0.99−0.90 (0.4H, m), 0.85−0.76 (12H, m); 13C NMR (CDCl3,
150 MHz) δ 157.5, 157.1, 134.5, 134.0, 129.3, 129.2, 129.1, 115.9,
114.8, 85.2, 79.8, 45.4, 45.2, 35.5, 34.6, 33.8, 33.5, 31.8, 31.0, 30.6,
30.1, 24.8, 24.0, 20.0, 15.8, 8.5, 8.4, 8.3, 7.8; IR (NaCl, cm−1) 2964,
2929, 2873, 1607, 1509, 1458, 1241, 826; HRMS [M + H]+ calcd for
C33H49O2 477.3733, found 477.3731.
Bis(4-(prop-1-en-1-yloxy)phenyl)methane (9), mixture of diaster-
eomers (oil): 1H NMR (CDCl3, 600 MHz) δ 7.11 (4H, d, J = 8.4 Hz),
6.95−6.89 (4H, m), 6.43−6.39 (1.7H, m) 6.38−6.34 (0.3H, m), 5.36
(1.7H, dq, J = 12.4, 6.9 Hz), 4.89 (0.3H, dq, J = 6.9, 6.5 Hz), 3.90 (2H,
s), 1.73 (0.9H, dd, J = 6.9, 2.1 Hz), 1.67 (5.1H, dd, J = 6.8, 1.7 Hz);
13C NMR (CDCl3, 150 MHz) δ 155.9, 142.3, 141.2, 135.4, 130.0,
116.5, 116.3, 108.0, 107.3, 40.4, 12.4, 9.5; IR (NaCl, cm−1) 3036, 2918,
2857, 1672, 1607, 1509, 1234, 1173; HRMS [M + H]+ calcd for
C19H21O2 281.1542, found 281.1540.
1-(2,2-Diethyl-4-methylcyclobutoxy)-4-(4-(prop-1-en-1-yloxy)-
benzyl)benzene (14), mixture of diastereomers (oil): 1H NMR
(CDCl3, 600 MHz) δ 7.14−6.99 (4H, m), 6.92−6.70 (4H, m), 6.39−
6.36 (0.8H, m), 6.35−6.31 (0.2H, m), 5.36−5.29 (0.8H, m), 4.86−
4.80 (0.2H, m), 4.30 (0.7H, d, J = 6.9 Hz), 3.95 (0.3H, d, J = 6.9 Hz),
3.85 (2H, m), 2.71−2.62 (0.7H, m), 2.39−2.32 (0.3H, m), 1.82 −1.71
(2H, m), 1.70 (0.6H, dd, J = 6.9, 2.1 Hz), 1.64 (2.4H, m), 1.62−1.55
(1H, m), 1.52−1.44 (2H, m), 1.39 (0.7H, dd, J = 11.7, 6.2 Hz), 1.14
(0.9H, d, J = 6.2 Hz), 1.01 (2.1H, d, J = 7.6 Hz), 0.99−0.94 (0.3H, m),
0.83−0.76 (6H, m); 13C NMR (CDCl3, 150 MHz) δ 157.6, 157.4,
155.9, 155.8, 142.5, 141.2, 135.8, 133.4, 132.9, 129.9, 129.7, 129.6,
116.4, 116.3, 116.2, 115.9, 115.0, 107.9, 107.1, 85.1, 79.6, 45.4, 45.1,
40.3, 35.5, 33.7, 31.7, 31.0, 30.0, 29.9, 24.8, 24.0, 20.0, 15.8, 12.3, 9.4,
8.5, 8.4, 8.3, 7.7; IR (NaCl, cm−1) 3029, 2955, 2929, 2863, 1672, 1608,
1504, 1229, 1021; HRMS [M + H]+ calcd for C25H33O2 365.2481,
found 365.2483.
Bis(4-(2,2-diethyl-4-methylcyclobutoxy)phenyl)methane (15),
mixture of diastereomers (oil): 1H NMR (CDCl3, 600 MHz) δ
7.07−6.99 (4H, m), 6.81−6.70 (4H, m), 4.30 (1.5H, d, J = 7.6 Hz),
3.94 (0.5H, d, J = 7.6 Hz), 3.82 (2H, s), 2.71−2.62 (1.5H, m), 2.38−
2.31 (0.5H, m), 1.80−1.69 (4H, m), 1.64−1.57 (2H, m), 1.52−1.41
(4H, m), 1.39 (1.5H, dd, J = 11.7, 6.2 Hz), 1.13 (1.5H, d, J = 6.2 Hz),
1.03−0.93 (5H, m), 0.83−0.75 (12H, m); 13C NMR (CDCl3, 150
MHz) δ 157.7, 157.3, 133.7, 133.3, 129.7, 129.6, 115.8, 115.0, 85.1,
79.6, 45.3, 45.1, 40.2, 35.5, 33.7, 31.7, 31.0, 30.0, 29.9, 24.8, 24.0, 19.9,
15.8, 8.5, 8.4, 8.2, 7.7; IR (NaCl, cm−1) 2964, 2929, 2872, 1610, 1510,
1452, 1241, 824; HRMS [M + H]+ calcd for C31H45O2 449.3420,
found 449.3423.
1,2-Bis(4-(prop-1-en-1-yloxy)phenyl)ethane (8), mixture of dia-
stereomers (amorphous solid): 1H NMR (CDCl3, 600 MHz) δ 7.09−
7.05 (4H, m), 6.91−6.80 (4H, m), 6.40−6.37 (0.2H, m) 6.35−6.33
(1.8H, m), 5.33 (0.2H, dq, J = 12.4, 6.9 Hz), 4.84 (1.8H, dq, J = 6.9,
6.5 Hz), 2.84 (4H, s), 1.71 (5.4H, dd, J = 6.9, 2.1 Hz), 1.65 (0.6H, dd,
J = 6.8, 1.7 Hz); 13C NMR (CDCl3, 150 MHz) δ 155.9, 142.4, 141.3,
135.7, 129.6, 116.3, 116.1, 107.9, 107.1, 37.3, 12.3, 9.4; IR (NaCl,
cm−1) 3044, 2929, 2849, 1671, 1607, 1509, 1234, 1024; HRMS [M +
H]+ calcd for C20H23O2 295.1698, found 295,1695; mp 71−76 °C.
1-(2,2-Diethyl-4-methylcyclobutoxy)-4-(4-(prop-1-en-1-yloxy)-
1
phenethyl)benzene (12), mixture of diastereomers (oil): H NMR
(CDCl3, 600 MHz) δ 7.12−7.06 (2H, m), 7.02 (2H, d, J = 8.7 Hz),
6.92−6.86 (2H, m), 6.82−6.76 (1H, m), 6.74 (1H, d, J = 8.7 Hz),
6.43−6.31 (1H, m), 5.38−5.28 (0.1H, m), 4.88−4.78 (0.9H, m), 4.32
(0.6H, d, J = 6.9 Hz), 3.96 (0.4H, d, J = 6.9 Hz), 2.81 (4H, m), 2.74−
2.62 (0.6H, m), 2.43−2.30 (0.4H, m), 1.83 −1.73 (2H, m), 1.70
(2.7H, dd, J = 6.9, 2.1 Hz), 1.67−1.57 (1.3H, m), 1.52−1.43 (2H, m),
1.40 (0.6H, dd, J = 11.7, 6.2 Hz), 1.15 (1.2H, d, J = 6.2 Hz), 1.01
(1.8H, d, J = 7.6 Hz), 0.99−0.90 (0.4H, m), 0.85−0.75 (6H, m); 13C
NMR (CDCl3, 150 MHz) δ 157.6, 157.3, 155.9, 155.7, 141.3, 136.0,
135.9, 133.8, 133.3, 129.5, 129.3, 129.2, 116.1, 115.9, 114.9, 107.0,
85.2, 79.6, 45.4, 45.2, 37.5, 37.4, 37.3, 35.5, 33.7, 31.8, 31.0, 30.1, 29.9,
24.8, 24.0, 19.9, 15.8, 12.3, 9.5, 8.5, 8.4, 8.3, 7.8; IR (NaCl, cm−1)
3030, 2954, 2929, 2863, 1672, 1608, 1509, 1234, 1021; HRMS [M +
H]+ calcd for C26H35O2 379.2637, found 379.2637.
4,4′-(Propane-2,2-diyl)bis((prop-1-en-1-yloxy)benzene) (16), mix-
ture of diastereomers (oil): 1H NMR (CDCl3, 600 MHz) δ 7.16 (4H,
m), 6.90−6.83 (4H, m), 6.40−6.37 (0.2H, m) 6.36−6.31 (1.8H, m),
5.33 (0.2H, dq, J = 12.4, 6.9 Hz), 4.84 (1.8H, dq, J = 6.9, 6.5 Hz), 1.69
(5.4H, dd, J = 6.9, 2.1 Hz), 1.67 −1.59 (6.6H, m); 13C NMR (CDCl3,
150 MHz) δ 155.5, 144.8, 142.2, 141.1 127.9, 115.8, 115.6, 108.0,
107.2, 42.0, 31.3, 12.4, 9.5; IR (NaCl, cm−1) 3043, 2970, 2863, 1672,
1607, 1505, 1253, 1231; HRMS [M + H]+ calcd for C21H25O2
309.1855, found 309.1856.
1-(2,2-Diethyl-4-methylcyclobutoxy)-4-(2-(4-(prop-1-en-1-yloxy)-
phenyl)propan-2-yl)benzene (17), mixture of diastereomers (oil):
1H NMR (CDCl3, 600 MHz) δ 7.19−7.05 (4H, m), 6.91−6.84 (2H,
1,2-Bis(4-(2,2-diethyl-4-methylcyclobutoxy)phenyl)ethane (13),
1
one diastereomer (oil): H NMR (CDCl3, 600 MHz) δ 7.03 (4H,
m), 6.801−6.75 (1H, m), 6.72 (1H, d, J = 8.9 Hz), 6.42−6.38 (0.2H,
m),6.37−6.34 (0.8H, m) 5.37−5.28 (0.2H, m), 4.84 (0.8H, dq, J = 6.9,
6.5 Hz), 4.31 (0.6H, d, J = 6.9 Hz), 3.97 (0.4H, d, J = 7.6 Hz), 2.72−
2.62 (0.6H, m), 2.41−2.32 (0.4H, m), 1.81−1.72 (2H, m), 1.70 (2.4H,
dd, J = 6.9, 2.1 Hz), 1.65−1.60 (6.6H, m), 1.61−1.45(3H, m), 1.40
(0.6H, dd, J = 11.7, 6.2 Hz), 1.16 (1.2H, d, J = 6.2 Hz), 1.02 (1.8H, d, J
= 7.6 Hz), 0.99−0.90 (0.4H, m), 0.85−0.76 (6H, m); 13C NMR
(CDCl3, 150 MHz) δ 157.2, 156.9, 155.4, 145.2, 145.1, 142.8, 142.4,
142.3, 141.4, 127.9, 127.7, 127.6, 127.5, 115.7, 115.6, 115.2, 114.5,
114.0, 107.9, 107.1, 85.0, 79.6, 45.3, 45.2, 41.9, 41.8, 41.0, 35.5, 33.7,
31.7, 31.5, 31.1, 31.0, 30.1, 30.0, 24.8, 24.1, 20.0, 15.9, 13.1, 12.9, 12.4,
9.4, 8.5, 8.4, 8.3, 7.8; IR (NaCl, cm−1) 3036, 2964, 2929, 2872, 1668,
1607, 1509, 1254, 1179; HRMS [M + H]+ calcd for C27H37O2
393.2794, found 393.2791.
4,4′-(Propane-2,2-diyl)bis((2,2-diethyl-4-methylcyclobutoxy)-
benzene) (18), one diastereomer (oil): 1H NMR (CDCl3, 600 MHz)
δ 7.10−7.03 (4H, m), 6.72−6.65 (4H, m), 4.30 (2H, d, J = 7.6 Hz),
2.70−2.65 (2H, m), 1.79−1.70 (4H, m), 1.65−1.56 (8H, m), 1.48
(4H, q, J = 7.6 Hz), 1.38 (2H, dd, J = 11.7, 5.6 Hz), 1.01 6H, d, J = 6.9
Hz), 0.79 (12H, dt, J = 11.0, 7.6 Hz); 13C NMR (CDCl3, 150 MHz) δ
157.1, 142.7, 127.6, 114.4, 79.6, 45.2, 41.7, 35.4, 31.2, 30.1, 30.0, 24.9,
dd, J = 8.3, 2.1 Hz), 6.73 (4H, d, J = 7.6 Hz), 4.31 (2H, d, J = 7.6 Hz),
2.79 (4H, s), 2.72−2.63 (2H, m), 1.79−1.72 (4H, m), 1.65−1.57
(2H,m), 1.52−1.46 (4H, m), 1.39 (2H, dd, J = 11.7, 5.6 Hz), 1.01
(6H, d, J = 6.9 Hz), 0.79 (12H, dt, J = 11.0, 7.6 Hz); 13C NMR
(CDCl3, 150 MHz) δ 157.6, 133.6, 129.2, 114.9, 79.6, 45.2, 37.4, 35.5,
30.0, 29.9, 24.8, 15.8, 8.2, 7.7; IR (NaCl, cm−1) 2961, 2931, 2870,
1607, 1516, 1448, 1241, 825; HRMS [M + H]+ calcd for C32H47O2
463.3576, found 463.3575.
1,2-Bis(4-(2,2-diethyl-4-methylcyclobutoxy)phenyl)ethane (13),
1
mixture of other diastereomers (oil): H NMR (CDCl3, 600 MHz)
δ 7.09−6.99 (4H, m), 6.85−6.69 (4H, m), 4.31 (1H, d, J = 7.6 Hz),
3.96 (1H, d, J = 7.6 Hz), 2.79 (4H, s), 2.71−2.64 (1H, m), 2.39−2.29
(1H, m), 1.82−1.68 (4H, m), 1.65−1.56 (2H, m), 1.52−1.44 (4H, m),
1.40 (1H, dd, J = 11.7, 6.2 Hz), 1.14 (3H, d, J = 6.2 Hz), 1.01 (3H, d, J
= 6.9 Hz), 0.99−0.95 (1H, m), 0.83−0.76 (12H, m); 13C NMR
(CDCl3, 150 MHz) δ 157.6, 157.2, 134.1, 133.6, 129.4, 129.2, 115.8,
114.9, 85.2, 79.6, 45.4, 45.1, 37.5, 37.4, 35.5, 33.7, 31.8, 30.9, 30.0,
29.9, 24.8, 24.0, 19.9, 15.8, 8.5, 8.4, 8.3, 7.7; IR (NaCl, cm−1) 2964,
2930, 2872, 1607, 1509, 1457, 1241, 826; HRMS [M + H]+ calcd for
C32H47O2 463.3576, found 463.3575.
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15.9, 8.3, 7.8; IR (NaCl, cm−1) 2958, 2932, 2870, 1609, 1512, 1448,
1240, 826; HRMS [M + H]+ calcd for C33H49O2 477.3733, found
477.3731.
Am. Chem. Soc. 2010, 132, 2839−2844. (e) Xu, H.-C.; Moeller, K. D. J.
Am. Chem. Soc. 2008, 130, 13542−13543.
(5) (a) Campbell, J. M.; Xu, H.-C.; Moeller, K. D. J. Am. Chem. Soc.
2012, 134, 18338−18344. (b) Xu, H.-C.; Moeller, K. D. Org. Lett.
2010, 12, 1720−1723.
4,4′-(Propane-2,2-diyl)bis((2,2-diethyl-4-methylcyclobutoxy)-
benzene) (18), mixture of other diastereomers (oil): 1H NMR
(CDCl3, 600 MHz) δ 7.13−7.05 (4H, m), 6.79−6.67 (4H, m), 4.30
(1.2H, d, J = 7.6 Hz), 3.95 (0.8H, d, J = 7.6 Hz), 2.70−2.61 (1.2H, m),
2.40−2.29 (0.8H, m), 1.79−1.70 (4H, m), 1.65−1.56 (8H, m), 1.51−
1.46 (4H, m), 1.38 (1.2H, dd, J = 11.7, 5.6 Hz), 1.14 (2.4H, d, J = 6.2
Hz), 1.01 (3.6H, d, J = 6.9 Hz), 0.99−0.95 (0.8H, m), 0.79 (12H, dt, J
= 11.0, 7.6 Hz); 13C NMR (CDCl3, 150 MHz) δ 157.6, 156.8, 143.1,
142.6, 127.7, 127.6, 115.1, 114.4, 84.9, 79.6, 45.3, 45.1, 41.7, 35.5, 33.7,
31.7, 31.2, 30.9, 30.1, 30.0, 24.8, 24.1, 20.0, 15.9, 8.5, 8.4, 8.3, 7.8; IR
(NaCl, cm−1) 2961, 2931, 2870, 1607, 1516, 1448, 1241, 825; HRMS
[M + H]+ calcd for C33H49O2 477.3733, found 477.3731.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving additional data and H and 13C NMR spectra.
1
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*K.C.: tel, (+81)-42-367-5667; fax, (+81)-42-367-5667; e-mail:
chiba@cc.tuat.ac.jp.
(12) Cody, R. B.; Laramee
2297−2302.
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, J. A.; Durst, H. D. Anal. Chem. 2005, 77,
(13) Mamouni, R.; Soukri, M.; Lazar, S.; Akssira, M.; Guillaumet, G.
Tetrahedron Lett. 2004, 45, 2631−2633.
Notes
The authors declare no competing financial interest.
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Lett. 2002, 43, 7445−7448.
ACKNOWLEDGMENTS
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(15) Hickenboth, C. R.; Rule, J. D.; Moore, J. S. Tetrahedron Lett.
2008, 64, 8435−8448.
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
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