Controlled couplings of quinone monoacetals using reusable polystyrene-anchored specific proton catalyst

Article abstract of DOI:10.1016/j.tet.2012.07.089

Controlled couplings of quinone monoacetals 1 with soft nucelophiles have been achieved using a new and reusable perfluorobenzoic acid (PFBA) immobilized on polystyrene beads as an efficient polymer-anchored specific proton. Various advantages regarding the recovery, reusability, and reproducibility as well as the high chemoselectivity toward quinone monoacetals 1 have been determined as the key features of the cleaner systems with newly developed solid acid promoter for the reactions.

Full text of DOI:10.1016/j.tet.2012.07.089

Tetrahedron 68 (2012) 8424e8430
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Controlled couplings of quinone monoacetals using reusable
polystyrene-anchored specific proton catalyst
*
Toshifumi Dohi, Yinjun Hu, Tohru Kamitanaka, Yasuyuki Kita
College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 June 2012
Received in revised form 26 July 2012
Accepted 26 July 2012
Available online 3 August 2012
Controlled couplings of quinone monoacetals 1 with soft nucelophiles have been achieved using a new
and reusable perfluorobenzoic acid (PFBA) immobilized on polystyrene beads as an efficient polymer-
anchored specific proton. Various advantages regarding the recovery, reusability, and reproducibility
as well as the high chemoselectivity toward quinone monoacetals 1 have been determined as the key
features of the cleaner systems with newly developed solid acid promoter for the reactions.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Brønsted acid
Heterogeneous catalysis
Recycling
Quinones
Heterocyclic compd
Fluoroalcohol
1. Introduction
very rare case that can successfully control the formation of car-
bonecarbon bonds to the quinone architecture under acidic con-
Quinone monoacetals, which possess not only an unsaturated
carbonyl, but also allyl acetal moieties in one skeleton, have
attracted considerable interest due to their broad utilities in organic
synthesis as intermediates for natural products and related com-
pounds.1 Due to their bifunctional structures, varied reactivities
during nucleophilic attack on quinone monoacetals can be pro-
duced, for instance, the conjugated addition to an enone moiety,2
addition to a carbonyl carbon,3 etc. In contrast to the established
addition chemistry of quinone monoacetals regarding the re-
ditions, while the used stoichiometric amount of the PFBA is usually
considered to be a waste material after the reactions.8
Therefore, we have become interested in designing a new het-
erogeneous catalyst carrying the specific PFBA functions as our
continued effort in developing more attractive strategies for ap-
plying the quinone compounds. In this paper, we report the prep-
aration and reactivity of a reusable solid-type PFBA alternative, that
is, extremely valuable for the coupling of quinone acetals 1 with
alkene nucleophiles 2, in which the former electrophiles 1 can be
exclusively activated by the solid acid to exclude the formation of
alkene-derived byproducts and deactivation of the acid catalyst
(Eq. 1).
activities of the
a,b-unsaturated carbonyl moieties, methods for
utilizing the allyl acetal functionality for the construction of sub-
stitution reactions have rarely been reported.4,5
Recently, we have succeeded in performing new controlled
couplings of quinone monoacetals with a series of carbon
p-nu-
Reusable catalyst
cleophiles using specific acid promoters.6,7 Thus, penta-
fluorobenzoic acid (PFBA) only served as a good promoter for the
controlled coupling of quinone monoacetals with alkenes, other-
wise other Brønsted acids having different pH values, such as sul-
fonic acids and Nafion resins, showed poorer controls during the
reactions. Hence, the method triggered by the specific acid is the
F
F
O
N
H
COOH
PS
TMS
F
F
O
O
PS-PFBA
TMS
+
(1)
[3+2] coupling
by exclusive activation of 1a
2a
MeO OMe
OMe
3aa
1a
* Corresponding author. Tel./fax: þ81 77 561 5829; e-mail address: kita@ph.rit-
sumei.ac.jp (Y. Kita).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.089

T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
8425
2. Result and discussion
sites in the polymers (ca. 25%) was also checked by elemental
analyses of the corresponding ammonium salt after titration of the
prepared PS-PFBA using hydrogen chloride.
Polymer-supported reagents and catalysts, which have emerged
from solid-phase organic synthesis (SPOS),9 have already become
a promising tool in modern synthetic research in developing
cleaner methodologies.10 Generally, the advantages of reagents and
catalysts that are immobilized on polymer backbones include en-
hanced stabilities, such as robustness, high tolerance to air and
moisture, as well as their convenient handling and recovery, the
benefits, of which have made them useful alternatives to conven-
tional reagents and catalysts.11 Many research studies have
revealed that the immobilization of conventional reagents and
catalysts is one of the promising ways not only to control their
stability, but also to maintain their activity for reuse and recycling.12
For easy access to the preparative polymer containing PFBA, we
envisioned the following one-pot protocol in Scheme 1 starting
from the commercial perfluoroterephthalic acid. Relying on well-
established procedures in Merrifield’s solid-phase peptide syn-
thesis (SPPS),13 the activated ester A was first generated in situ in
a flask by treatment of the PFBA with diisopropylcarbodiimide
(DIC) and hydroxybenzotriazole (HOBt).14 To a stirred solution, of
which aminomethyl functionalized cross-linked polystyrene beads
(SigmaeAldrich Co. LLC, poly(4-vinyl benzylamine), 2% divinyl
benzene (DVB), 200e400 mesh, active NH2 sites: approx. 2.0 mmol/g
measured by elemental analysis of nitrogen contents)15 were suc-
cessively added in one portion at room temperature for immobili-
zation of the PFBA to the polymer by amide bond formation. The
desired polystyrene-anchored PFBA (PS-PFBA) was produced in
good efficiency (75% introduction to the initial NH2 sites de-
termined by elemental analysis of PS-PFBA, see Supplementary
data) as white microbeads by a simple work-up procedure of
rinsing the resins with several solvents. The loading of the PFBA
sites in the obtained polymer was almost constant, and the in-
troduction yield was reproducible in our two preparative trials
(first: 75%, and second: 74%).
To validate the reactivity of the prepared PS-PFBA, the catalyst
ratio, substrate concentration, effects of the solvent and tempera-
ture, were reevaluated in Table 1 during the reaction of the quinone
monoacetal 1a with allyltrimethylsilane 2a16 (Eq. 1). As in our
previous report,7 the fluoroalcohol, i.e., hexafluoroisopropanol
(HFIP),17 still remained as an indispensable polar medium and co-
activator for the PS-PFBA (entries 1e3). A considerable decrease
in the yield of a product 3aa was observed by reducing the HFIP
ratio relative to dichloromethane (DCM). However, the use of DCM
as a co-solvent of HFIP for dissolving the substrates was plausible to
obtain the reproducible results. Indeed, the reactions sometimes
failed in the absence of DCM due to the low solubility of the sub-
strates to HFIP. On the other hand, a change in the concentration of
the substrates in the range of 0.1e0.3 M of the substrate 1a only had
a slight effect on the product yields (entries 3e5). Notably, the re-
action could even proceed with a catalytic amount of the PS-PFBA
(0.5 equiv) under the same conditions, in which the yield was
sufficiently comparable to that of its stoichiometric case to reach an
82% product formation (entry 6). Although the reaction at room
temperature successfully afforded the coupling product 3aa, a fur-
ther approx. 10% increase in the yield was obtained at 0 ꢁC (entry 7)
probably because the reactivity of the charged quinone species can
be better controlled at that lower temperature. Nonetheless, the
used PS-PFBA beads could be quantitatively recovered by filtration
of the reaction mixture, and were then repeatedly used (vide infra).
Based on the optimizations,18,19 the newly prepared PS-anchored
PFBA seems to be a potent environmentally benign promoter that
can effectively replace the homogenous counterpart used in the
previous study.
Table 1
Screening of the conditions for [3þ2] coupling of quinone acetal 1a with allyl-
trimethylsilane 2a using polystyrene-anchored perfluorobenzoic acid (PS-PFBA) as
catalyst (Eq. 1)a
Entry
Conc. of 1a
HFIP/DCM ratio
Temp.
Yield 3aab
N
C N
F
F
F
F
F
F
F
F
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
61%
82%
81%
80%
79%
82%
91%
O
C
1
2
3
4
5
6c
7
0.2 M
0.2 M
0.2 M
0.1 M
0.3 M
0.2 M
0.2 M
1:2
2:1
1:1
1:1
1:1
1:1
1:1
NH
N
(DIC)
HOOC
COOH
O
COOH
DMF
r.t.
PFTA
ꢁC
OH
0
N
N
a
N
(HOBt)
Unless otherwise stated, reactions were examined using 1 equiv of quinone
monoacetal 1a and the acid catalyst (PS-PFBA, 1 equiv) in the presence of 2 equiv of
allyltrimethylsilane 2a in HFIP/CH2Cl2 at room temperature for 6 h.
F
F
O
F
F
F
b
PS
NH2
O
C
Isolated yield.
0.5 equiv of PS-PFBA was used.
PS
N
H
COOH
c
COOH
2 % cross-linked
2.0 mmol/g loading
O
F
F
N
N
F
N
PS-PFBA
1.06 mmol/g
We subsequently tested the extensive ranges of quinone acetals
1bei having different ring substituent patterns under the opti-
mized conditions in order to ascertain the versatility of the PS-PFBA
as a heterogeneous catalyst (Table 2). Using styrene 2b as the
unified coupling partner, all the known derivatives 1bei for the
reactions6,7 were smoothly converted into the expected cyclized
products 3bbeib in good to excellent yields. The reactions typically
finished within several hours, and the yields in most cases were
comparable and sometimes even higher than those for the per-
fluorobenzoic acid itself (Fig. 1) except for the less reactive
methoxy-substituted substrate 1d. The new polymer acid, PS-PFBA,
thus behaved as a powerful and clean promoter with a broad
generality for the quinone monoacetals 1.
A
Scheme 1. Immobilization of PFBA to polystyrene beads.
The prepared PS-PFBA is stable under ambient conditions at
least for several months without special storage conditions. Its
characterization for ascertaining the introduction and loading of
the PFBA in the polymer backbones was determined by IR and el-
emental analyses. The IR spectrum exhibited strong band absorp-
tions at 1698 and 1723 cmꢀ1 corresponding to the vibration peaks
of the amide linkage and carboxylic acid functionality of the PFBA
along with a broad but weak absorption band ranging from 2914 to
3290 cmꢀ1 for the NH and COOH groups. Theoretical loading of the
PFBA based on the elemental analysis of the nitrogen contents
(found: N, 2.20) averaged 1.06 mmol/g in comparison to the
starting aminomethyl polystyrenes (N, 2.88 for 2.0 mmol/g of the
free amine sites). The degree of unreacted and remaining free NH2
For expanding the versatility of the PS-PFBA and the reaction
scope, various alkenes 2bej in Table 3 were similarly evaluated as
the carbon p-nucleophiles for the quinone acetal 1a. As a result, the

8426
T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
Table 2
Table 3
Scope of the reactions in terms of quinone acetals 1beia
Various alkenes 2bej for the coupling with quinone acetal 1aa
Entry
Quinone monoacetal (1)
Product (3), yieldb
Entry
Alkene (2)
Product (3), yieldb
O
R1
R2
R2
Ph
R(1)
R3
O
O
R(1)
R3
R(2)
R1
MeO OMe
R(2)
(2b-g)
(1b-f)
OMe
OMe
(3bb-fb)
(3ab-aj)
1
R1¼H, R2¼Me (1b)
R1¼H, R2¼t-Bu (1c)
R1¼H, R2¼OMe (1d)
R1¼Cl, R2¼H (1e)
R1¼t-Bu, R2¼H (1f)
R1¼H, R2¼Me (3bb), 81%
R1¼H, R2¼t-Bu (3cb), 73%
R1¼H, R2¼OMe (3db), 54%
R1¼Cl, R2¼H (3eb), 91%
R1¼t-Bu, R2¼H (3fb), quant.
1
2
3
4
5
6
R1¼R2¼R3¼H (2b)
R1¼R2¼R3¼H (3ab), 91%
2
R1¼Me, R2¼R3¼H (2c)
R1¼t-Bu, R2¼R3¼H (2d)
R1¼Cl, R2¼R3¼H (2e)
R1¼Me, R2¼R3¼H (3ac), 95%
R1¼t-Bu, R2¼R3¼H (3ad), 96%
R1¼Cl, R2¼R3¼H (3ae), 85%
R1¼R3¼H, R2¼Me (3af), 99%
R1¼OMe, R2¼H, R3¼Me (3ag), 97%
3c
4
5
R1¼R3¼H, R2¼Me (2f)
R1¼OMe, R2¼H, R3¼Me (2g)
Ph
O
O
6
7
O
MeO OMe
OMe
7
(1g)
(3gb), 98%
(2h)
Ph
O
O
OMe
(3ah), 73%
OMe
AcOMeO
SPh
O
AcO
OMe
(1h)
(3hb), 99%
SPh
Ph
8
NTs
(2i)
TsN
OMe
8
(3ai), 88%
MeO OMe
OMe
(1i)
(3ib), 83%
O
a
Reactions were carried out with 1 equiv of PS-PFBA, 2 equiv of styrene 2b in the
mixed solvents of HFIP/CH2Cl2 (1:1, 0.2 M) at 0 ꢁC for 4e6 h. In general, recovery of
the used PS-PFBA was nearly quantitative.
9
(2j) c
b
Isolated yield after purification.
OMe
c
Reaction was performed for 12 h.
(3aj), 78%
a
All reactions were conducted with 1 equiv of the PS-PFBA, 2 equiv of the alkenes
2bej in HFIP/CH2Cl2 at 0 ꢁC for 4e6 h. Recovery of the used PS-PFBA was nearly
quantitative.
PS-PFBA also served as an efficient reusable acid promoter for the
reactions to succinctly provide a series of dihydrobenzofuran
products 3abeaj. The yields were somewhat improved in many
cases when compared to the results of the reported homogeneous
conditions (see Fig. 1).7 One possible explanation for the increased
yields of the products is the excellent chemoselectivity of the PS-
PFBA toward the quinone acetals 1 over the alkenes 2 as a milder
acid. This conclusion was made by our observation that we already
confirmed formation of some byproducts derived from the back-
ground polymerization of the used alkenes20 as a serious problem
of previous homogeneous conditions caused by the acid. In marked
b
Isolated yield after purification.
5 equiv of 2j and 2 equiv of the PS-PFBA were used.
c
contrast, such byproduct formation was not detected at all based on
the NMR detection level for the newly developed PS-PFBA. The
attenuated activity of the PS-PFBA compared with its soluble al-
ternative is mainly due to the heterogeneity of the polymer
catalyst.21
Another merit of the polymer acid has been determined espe-
cially for the acid-sensitive alkene nucleophiles 2. Fig. 2 shows the
Fig. 1. Comparisons of the coupling yields for the newly developed PS-PFBA and soluble PFBA itself. Yields using C6F5CO2H in Ref. 7 are as follows: 83% (for 3bb), 64% (3cb), 78%
(3db), 86% (3eb), quant. (3fb), quant. (3gb), 98% (3hb), 82% (3ib), 90% (3aa), 93% (3ab), 83% (3ac), 92% (3ad), 94% (3ae), 81% (3af), 93% (3ag), 83% (3ah), 80% (3ai), 78% (3aj).

T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
8427
Table 4
Yields of the [3þ2] coupling product 3aa (Eq. 1) using reused PS-PFBAs
Fresh First reuse Second reuse Third reuse Fourth reuse
Yield 3aa 91%
90%
90%
91%
89%
Other Potential Nucleophiles
TMSO
OH
CO2Me
SPh
OTMS
TMSSPh
4d
OMe
4a
Fig. 2. PS-PFBA promoted coupling of quinone monoacetal 1a with varied stoichi-
ometries of several alkene nucleophiles 2.
OMe
OMe
5aa
5ad
(90%)
(75%)
[a]
[b]
[a]
O
influence of the stoichiometry of the representative alkenes 2 used
in the reactions. The results clarified the success of the reactions
using only 1.2 equiv of the alkenes for the same reaction times
(4e6 h). All the tested cases produced products only with a few
percent decrease in the yields, thus enabling an improvement in
terms of the stoichiometry of the alkenes 2.
MeO OMe
1a
[c]
O
OTMS
OH
O
Since the polymer acid was almost inert to the alkenes 2, the
reactions well proceeded even with a catalytic amount of the PS-
PFBA. For example, only 30 mol % of the PS-PFBA was necessary
to promote the described reaction in Eq. 1 (Scheme 2, see also
entries 3 and 6 in Table 1) with similar efficiencies (6 h, 78% for-
mation of 3aa at room temperature). This is an important advan-
tage of the newly developed polymer-anchored acid. In fact, the
reaction was quite sluggish with the same catalytic amount of
pentafluorobenzoic acid7; this observation for the previous acid
strongly suggests deactivation of the catalyst due to the side re-
actions to the alkenes 2. More noteworthy, the recovered PS-PFBA
was not degraded by several repeated uses due to its high stabil-
ity toward the alkenes. Thus, the activity of the recycled PS-PFBAs
for the coupling reaction of Eq. 1 was further investigated. As
shown in Table 4, the used PS-PFBAs retained their initial activities
for the reactions, accordingly being capable of at least three time
reuses. These advantages have sufficiently proved the remarkable
characteristics regarding the reusability of the new PS-PFBA as
a specific solid acid catalyst for the controlled couplings of the
quinone acetals 1.
OTMS
4b
O
OTMS
4c
O
OMe
5ab
OMe
5ac
(57%)
(73% after HCl workup)
Scheme 3. Other potential nucleophiles 4aed for the controlled couplings of quinone
monoacetal 1a promoted by the PS-PFBA. Reaction conditions: [a] PS-PFBA (1 equiv),
nucleophiles 4a or 4d (2 equiv) in HFIP/CH2Cl2¼1:1 (0.2 M) at 0 ꢁC [b] PS-PFBA
(0.25 equiv), nucleophile 4b (5 equiv) in HFIP/CH2Cl2¼10:1 (0.2 M) at 0 ꢁC [c] PS-
PFBA (0.1 equiv), nucleophile 4c (3 equiv) in HFIP/CH2Cl2¼10:1 (0.1 M) at 0 ꢁC-rt.
3. Conclusion
In conclusion, we have succeeded in developing a unique solid
acid catalyst (PS-PFBA) including immobilized perfluorobenzoic
acid sites in the polystyrene backbones that can act as a specific
promoter for the controlled activations of quinone monoacetals 1.
Thepolystyrene-anchored protonsin thePS-PFBAcouldsuccessfully
induce many coupling reactions with a similar efficiency to the PFBA
itself. The prepared catalyst is highly stable, suitable for ambient
storage, and the recovered catalyst beads after being easily sepa-
rated from the reaction mixtures by filtration could be repeatedly
used for additional multiple runs without any loss of activity. Fur-
thermore, the use of the PS-PFBA catalyst sometimes led to the
improvement of the substrate and catalyst stoichiometries for the
reactions as well as the scope of the nucelophiles. Hence, the cou-
pling protocols utilizing the new solid acid catalyst should promise
clean routes to the dihydrobenzofuran molecules and other func-
tionalized phenols starting from the quinone monoacetals.
TMS
O
O
PS-PFBA
(30 mol%)
TMS
+
HFIP/DCM
r.t., 6 h
2a
MeO OMe
1a
OMe
3aa
(78%)
Scheme 2. Successful catalytic use of the PFBA.
3.1. Experimental
3.2. General
As the efficient protocol for the [3þ2] type couplings has been
realized with the newly developed PS-PFBA, we finally attempted
to broaden the scope of nucleophiles in a brief extension of this
study. In evaluating high selectivity of the polymer acid to the
Melting point (mp) was measured by StuartÒ melting point
apparatus SMP3 AC input 100 V. 1H NMR (and 13C NMR) spectra
were recorded by a JEOL JMN-400 spectrometer operating at
400 MHz (100 MHz for 13C NMR) in CDCl3 at 25 ꢁC with tetrame-
thylsilane as an internal standard. The data are reported as follows:
quinone monoacetals 1, other potential carbon p-nucleophiles and
others were further tested for the reactions using the PS-PFBA
(Scheme 3). Toward this objective, the enol silylethers 4a and 4b,
furanyl silylether 4c, and sulfur nucleophile 4d all reacted with the
quinoid 1a to produce different types of coupling products 5aaead
in moderate to good yields without any optimization. Interestingly,
the enol silylethers 4a and 4b could produce the non-cyclized or-
tho-substituted phenols 5aa and 5ab with silyl protection22 instead
of the cyclized products 3 from the alkenes 2.23
chemical shift in parts per million (
(s¼singlet, d¼doublet, t¼triplet,
d
), integration, multiplicity
q¼quartet, m¼multi
plet), and coupling constant (Hz). The infrared spectra (IR) were
obtained using a Hitachi 270-50 spectrometer. The high resolution
mass spectra was performed by the Analysis Section of Osaka
University of Pharmaceutical Sciences.

8428
T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
Unless otherwise stated, all experiments were carried out at
860, 750, 699.1H NMR (400 MHz, CDCl3)
d 7.19e7.34 (m, 5H), 6.65 (s,
room temperature in open flask. Tetrafluoroterephthalic acid
(purchased from TCI) and polystyrene (from SigmaeAldrich) were
used as they stand. Quinone monoacetals 1 were prepared from the
corresponding para-alkoxyphenols or phenols by the conventional
oxidation procedures using phenyliodine diacetate (PhI(OAc)2) in
suitable alcohol solvents.24 Iminoquinone acetal 1i was prepared
from the corresponding aniline derivative, i.e., p-methoxy-N-tosyl
aniline.25 Commercial nucleophiles 2 and solvents, such as hexa-
fluoroisopropanol (HFIP), were used without purification. All other
chemicals were obtained from commercial suppliers and used as
received. Column chromatography was carried out on Merk Sillica
Gel 60 (230e400 mesh) eluting with ethyl acetate and hexane.
Analytical thin-layer chromatography (TLC) was performed on
MERCK silica gel, grade 60 F254. The spots and bands were detected
by UV light of irradiation (254, 365 nm).
1H), 6.61 (s, 1H), 5.65 (t, 1H, J¼9.2 Hz), 3.71 (s, 3H), 3.53 (dd, 1H,
J¼12.7, 7.1 Hz), 3.11 (dd,1H, J¼15.5, 8.1 Hz), 2.13 (s, 3H) ppm 13C NMR
(100 MHz, CDCl3)
d 153.3, 152.3, 142.2, 128.6, 127.9, 126.5, 125.7,
123.6, 111.3, 107.8, 84.1, 56.2, 39.0, 16.6 ppm. HRMS (EI) calcd for
C16H16O2 [M]þ: 240.1150, found: 240.1149.
3.4.3. 6-(1,1-Dimethylethyl)-2,3-dihydro-5-methoxy-2-phenylbenzo-
furan (3cb). Colorless solid, mp 47e49 ꢁC. IR (KBr) cmꢀ1: 2959, 2904,
2866,1767,1736,1604,1490,1458,1362,1325,1199,1180,1110,1092,
948, 828, 759, 699. 1H NMR (400 MHz, CDCl3)
d 7.20e7.39 (m, 5H),
6.78 (d, 2H, J¼8.0 Hz), 5.73 (t,1H, J¼9.0 Hz), 3.86 (s, 3H), 3.56 (dd,1H,
J¼15.4, 9.3 Hz), 3.18 (dd,1H, J¼15.4, 8.7 Hz),1.26 (s, 9H) ppm 13C NMR
(100 MHz, CDCl3)
d 145. 7, 144.9, 143.4, 141.8, 128.5, 127.9, 127.2,
126.0, 113.9, 109.4, 84.9, 56.2, 39.1, 34.6, 31.7 ppm. HRMS (EI) calcd
for C19H22O2 [M]þ: 282.1620, found: 282.1621.
3.3. Preparation of the polystyrene-supported perfluorobenzoic
acid (PS-PFBA)
3.4.4. 2,3-Dihydro-5,6-dimethoxy-2-phenylbenzofuran (3db). Co-
lorless sticky oil. IR (KBr) cmꢀ1: 3027, 2996, 2935, 2832, 1752, 1618,
1504, 1454, 1334, 1217, 1188, 1168, 1104, 996, 856, 762, 700. 1H NMR
To a 100 mL round-bottom flask, aminomethyl functionalized
cross-linked polystyrene resins (1.25 g, 2.0 mmol/g loading, 2% DVB;
from SigmaeAldrich Co. LLC) was added in DMF (25 mL) under
ambient conditions. To the heterogeneous mixture, tetra-
fluoroterephthalic acid (1.0 g, 4.0 mmol) in DMF (6 mL), 1-hydroxy-
benzotriazole (HOBt, 551 mg, 3.6 mmol) in DMF (5 mL), and solid 1,3-
diisopropylcarbodiimide (DIC, 0.6 mL, 3.6 mmol) were successively
and quickly added. The resulting suspension was vigorously stirred
for 16 h at room temperature. The off-white dispersion turned
slightly yellow during the stirring. After the reaction, the mixture
was filtered, then the solid on the filter was washed with DMF, THF,
and DCM, each for three times. After drying under vacuum for
overnight, the desired polystyrene-anchored PFBA (PS-PFBA) at
a 1.06 mmol loading of the PFBA sites was obtained as off-white
beads (calcd 75% introduction for the starting amino resin).
(400 MHz, CDCl3) d 7.23e7.34 (m, 5H), 6.70 (s, 1H), 6.47 (s, 1H), 5.68
(t, 1H, J¼9.0 Hz), 3.79 (s, 3H), 3.77 (s, 3H), 3.52 (dd, 1H, J¼15.2,
9.5 Hz), 3.10 (dd, 1H, J¼15.1, 8.0 Hz) ppm 13C NMR (100 MHz, CDCl3)
d
153.8, 149.4, 143.5, 142.0, 128.6, 128.0, 125.7, 116.0, 119.0, 94.8,
84.6, 56.9, 56.0, 38.6 ppm. HRMS (EI) calcd for C16H16O3 [M]þ:
256.1099, found: 256.1117.
3.4.5. 7-Chloro-2,3-dihydro-5-methoxy-2-phenylbenzofuran (3eb).
Colorless solid, mp 65e66 ꢁC. IR (KBr) cmꢀ1: 3063, 3031, 3001, 2937,
2834, 1595, 1479, 1439, 1365, 1257, 1210, 1115, 1039, 983, 928, 845,
760, 700. 1H NMR (400 MHz, CDCl3)
d 7.16e7.33 (m, 5H), 6.58e6.64
(m, 2H), 5.72 (t, 1H, J¼8.5 Hz), 3.66 (s, 3H), 3.57 (dd, 1H, J¼15.8,
9.2 Hz), 3.16 (dd,1H, J¼15.8, 8.0 Hz) ppm 13C NMR (100 MHz, CDCl3)
d
154.3, 149.6, 141.0, 128.5, 128.4, 127.9, 125.5, 114.1, 112.9, 109.9,
84.4, 55.9, 39.2 ppm. HRMS (EI) calcd for C15H13ClO2 [M]þ:
260.0604, found: 260.0606.
3.4. General procedure for the PS-PFBA induced coupling of
quinone monoacetals 1 with alkenes 2
3.4.6. 7-(1,1-Dimethylethyl)-2,3-dihydro-5-methoxy-2-phenylbenzo-
furan (3fb). Slightly yellow oil. IR (KBr) cmꢀ1: 3028, 2954, 2907,
2869, 2832, 1599, 1481, 1427, 1361, 1314, 1264, 1223, 1195, 1125,
To a stirred solution of the quinone monoacetal 1 (0.20 mmol)
and alkenes 2 (0.40 mmol) in dichloromethane (0.5 mL) was suc-
cessively added 1,1,1,3,3,3-hexafluoroisopropanol (HFIP, 0.5 mL)
and the polystyrene-anchored PFBA (0.20 mmol) under ambient
conditions. The reaction mixture was then stirred at 0 ꢁC for 4e6 h.
After confirming consumption of the quinone acetal 1 by TLC, the
PS-PFBA was separated by filtration, washed with Et2O, and dried
under vacuum, then reused for the next run. The residue from the
concentrated filtrate including the product was purified by column
chromatography on SiO2 (hexane/EtOAc) to give the pure dihy-
drobenzofuran 3.
1053, 931, 812, 758, 699. 1H NMR (400 MHz, CDCl3)
d 7.24e7.43 (m,
5H), 6.73 (d, 1H, J¼2.4 Hz), 6.64 (d, 1H, J¼2.6 Hz), 5.76 (t, 1H,
J¼9.0 Hz), 3.78 (s, 3H), 3.58 (dd, 1H, J¼15.4, 9.5 Hz), 3.13 (dd, 1H,
J¼15.6, 8.5 Hz), 1.42 (s, 9H) ppm 13C NMR (100 MHz, CDCl3)
d 153.9,
151.6, 142.9, 133.5, 128.5, 127.6, 127.2, 125.4, 111.6, 107.2, 83.4, 55.9,
39.0, 34.2, 29.2 ppm. HRMS (EI) calcd for C19H22O2 [M]þ: 282.1620,
found: 282.1622.
3.4.7. 2,3-Dihydro-5-methoxy-2-phenylnaphtho[1,2-b]furan (3gb).
Green solid, mp 82e84 ꢁC. IR (KBr) cmꢀ1: 3062, 3027, 2936, 2854,
1640, 1595, 1459, 1402, 1376, 1259, 1235, 1200, 1113, 1081, 1032, 979,
The catalytic use of the PS-PFBA (0.3 equiv) could also provide
the cycloadducts 3 in comparable yields under the stated condi-
tions (Scheme 2).
816, 763, 698.1H NMR (400 MHz, CDCl3)
d
8.24 (d,1H, J¼8.1 Hz), 8.00
(d, 1H, J¼8.0 Hz), 7.46e7.53 (m, 4H), 7.32e7.40 (m, 3H), 6.72 (s, 1H),
5.94 (t, 1H, J¼9.5 Hz), 3.96 (s, 3H), 3.80 (dd, 1H, J¼15.4, 9.7 Hz), 3.36
3.4.1. 2,3-Dihydro-5-methoxy-2-[(trimethylsilyl)methyl]benzofuran
(3aa).16c Colorless oil. IR (KBr) cmꢀ1: 2905, 2903, 2831, 1603, 1487,
1433, 1362, 1249, 1213, 1138, 1034, 954, 840, 761, 693. 1H NMR
(dd, 1H, J¼15.4, 7.8 Hz) ppm 13C NMR (100 MHz, CDCl3)
d 150.2,
148.4, 142.6, 128.6, 128.5, 127.9, 126.0, 125.7, 125.4, 125.0, 122.5,
121.2, 120.8, 117.9, 101.5, 84.1, 56.0, 40.2 ppm. HRMS (EI) calcd for
C19H16O2 [M]þ: 276.1150, found: 276.1147.
(400 MHz, CDCl3)
d 6.65 (s, 1H), 6.53e6.56 (m, 2H), 4.76e4.84 (m,
1H), 3.65 (s, 3H), 3.14 (dd, 1H, J¼15.4, 8.3 Hz), 2.69 (dd, 1H, J¼15.4,
8.3 Hz), 1.22 (dd, 1H, J¼14.2, 6.1 Hz), 1.01 (dd, 1H, J¼14.2, 8.8 Hz),
3.4.8. 6-Acetoxy-2,3-dihydro-5-methoxy-2-phenylnaphtho[1,2-b]fu-
ran (3hb). Pink solid, mp 150e152 ꢁC. IR (KBr) cmꢀ1: 3061, 3030,
2993, 2938, 2838, 1761, 1602, 1461, 1355, 1249, 1213, 1122, 1061,
0.02 (s, 9H) ppm 13C NMR (100 MHz, CDCl3)
d 154.6, 154.5, 129.3,
113.4, 112.2, 109.8, 83.3, 56.9, 39.5, 26.0, 0.0 ppm.
985, 862, 815, 755, 700. 1H NMR (400 MHz, CDCl3)
d 7.81 (d, 1H,
3.4.2. 2,3-Dihydro-5-methoxy-6-methyl-2-phenylbenzofuran (3bb).
Yellow sticky oil. IR (KBr) cmꢀ1: 3062, 3028, 2934, 2855, 2831, 1748,
1602, 1496, 1465, 1415, 1354, 1285, 1256, 1201, 1161, 1096, 1011, 927,
J¼8.3 Hz), 7.15e7.35 (m, 6H), 6. 96 (d, 1H, J¼8.0 Hz), 6.67 (s, 1H),
5.83 (t, 3H, J¼8.8 Hz), 3.78 (s, 3H), 3.68 (dd, 1H, J¼15.4, 9.7 Hz),
3.23 (dd, 1H, J¼15.4, 7.8 Hz), 2.28 (s, 3H) ppm 13C NMR (100 MHz,

T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
8429
CDCl3)
d
170.1, 149.8, 149.0, 146.7, 142.3, 128.6, 127.9, 125.8, 125.7,
772, 741, 710. 1H NMR (400 MHz, CDCl3)
d
6.86 (d, 2H, J¼8.0 Hz),
122.7, 120.1, 119.2, 119.1, 118.6, 104.3, 84.2, 56.8, 40.0, 20.9 ppm.
6.40e6.45 (m, 2H), 6.18e6.30 (m, 3H), 4.58 (d, 1H, J¼8.0 Hz), 3.31 (s,
HRMS (EI) calcd for C21H18O4 [M]þ: 334.1205, found: 334.1198.
3H), 3.29 (s, 3H), 2.90e2.93 (m, 1H), 0.88 (d, 3H, J¼8.0 Hz) ppm 13C
NMR (100 MHz, CDCl3)
d 159.6, 154.4, 153.2, 133.0, 132.6, 127.6,
3.4.9. 2,3-Dihydro-5-methoxy-1-[(4-methylphenyl)sulfonyl]-2-
phenylindole (3ib). Slightly brown solid, mp 57e60 ꢁC. IR (KBr)
cmꢀ1: 3061, 3027, 2924, 2837, 1739, 1598, 1492, 1454, 1352, 1326,
1256, 1228, 1164, 1090, 1030, 955, 814, 753, 700. 1H NMR (400 MHz,
113.9, 112.8, 110.0, 109.3, 92.5, 56.0, 55.3, 45.6, 17.5 ppm.
3.4.16. 5,6,6a,11a-Tetrahydro-8-methoxybenzo[b]naphtho[2,1-d]fu-
ran (3ah). Slightly yellow solid, mp 81e84 ꢁC. IR (KBr) cmꢀ1: 3063,
3023, 2933, 2832, 1603, 1486, 1434, 1360, 1201, 1137, 1032, 928, 818,
CDCl3)
d
¼7.56 (d, 1H, J¼8.3 Hz), 7.46 (d, 2H, J¼8.8 Hz), 7.10e7.26 (m,
7H), 6.72 (dd,1H, J¼8.8, 3.2 Hz), 6.52 (s, 1H), 5.19e5.23 (m, 1H), 3.69
749. 1H NMR (400 MHz, CDCl3)
(m, 2H),7.10e7.14 (m, 1H), 6.80 (s, 1H), 6.64e6.68 (m, 2H), 5.61 (d,
1H, J¼8.3 Hz), 3.74 (s, 3H), 3.60e3.62 (m, 1H), 2.61e2.69 (m, 2H),
1.98e2.05 (m, 1H), 1.77e1.81 (m, 1H) ppm 13C NMR (100 MHz,
d
7.50 (d, 1H, J¼8.0 Hz), 7.19e7.30
(s, 3H), 3.02 (dd, 1H, J¼16.0, 9.7 Hz), 2.72 (dd, 1H, J¼15.8, 8.7 Hz),
2.30 (s, 3H) ppm 13C NMR (100 MHz, CDCl3)
d 157.5, 143.8, 142.5,
135.2, 134.9, 133.5, 129.5, 128.6, 127.6, 127.2, 125.9, 118.2, 112.9,
110.8, 64.9, 55.6, 37.8, 21.6 ppm. HRMS (EI) calcd for C22H21NO3S
[M]þ: 379.1242, found: 379.1243.
CDCl3)
d 154.2, 153.4, 138.7, 133.5, 132.4, 130.1, 128.4, 128.2, 126.6,
112.9, 110.7, 109.4, 81.9, 56.0, 41.6, 27.8, 27.6 ppm. HRMS (EI) calcd
for C17H16O2 [M]þ: 252.1150, found: 252.1159.
3.4.10. 2,3-Dihydro-5-methoxy-2-phenylbenzofuran (3ab).26a Color-
less oil, IR (KBr) cmꢀ1: 3062, 3030, 2937, 2831,1604,1487,1433,1231,
1203, 1136, 1032, 975, 808, 756, 669. 1H NMR (400 MHz, CDCl3)
3.4.17. 2,3-Dihydro-5-methoxy-2-(phenylthio)benzofuran (3ai).26c
Colorless solid, mp 65e66 ꢁC. IR (KBr) cmꢀ1: 3057, 2995, 2950,
2909, 2831, 1583, 1485, 1436, 1254, 1222, 1194, 1030, 923, 810, 746,
d
7.28e7.39 (m, 5H), 6.75e6.76 (m, 2H), 6.66e6.74 (m, 1H), 5.70 (t,
1H, J¼8.8 Hz), 3.73 (s, 3H), 3.57 (dd, 1H, J¼15.6, 9.2 Hz), 3.16 (dd, 1H,
692. 1H NMR (400 MHz, CDCl3)
d 7.47e7.49 (m, 2H), 7.16e7.27 (m,
J¼15.6, 8.3 Hz) ppm 13C NMR (100 MHz, CDCl3)
d
153.9, 153.4, 141.6,
3H), 6.68e6.70 (m, 2H), 6.60e6.63 (m, 1H), 6.09 (dd, 1H, J¼8.8,
128.2, 127.6, 127.1, 125.4, 112.6, 110.8, 108.8, 83.8, 55.6, 38.5 ppm.
4.9 Hz), 3.67 (s, 3H), 3.57 (dd, 1H, J¼16.6, 8.8 Hz), 3.07 (dd, 1H,
J¼17.1, 4.9 Hz) ppm 13C NMR (100 MHz, CDCl3)
d 155.0, 152.4, 134.4,
132.1, 129.4, 127.9, 127.3, 113.6, 111.2, 110.7, 89.8, 56.4, 37.6 ppm.
3.4.11. 2,3-Dihydro-5-methoxy-2-(4-methylphenyl)benzofuran(3ac).
Colorless solid, mp 62e63 ꢁC. IR (KBr) cmꢀ1: 3009, 2948, 2916, 2833,
1609, 1488, 1470, 1428, 1363, 1320, 1296, 1265, 1211, 1138, 1111, 1026,
3.4.18. 5-Methoxy-spiro[benzofuran-2(3H),10-cyclopentane]
(3aj). Colorless oil. IR (KBr) cmꢀ1: 2956, 2871, 2830, 1603, 1487,
1433, 1337, 1257, 1231, 1169, 1137, 1034, 974, 834, 730. 1H NMR
969, 924, 813, 738, 707. 1H NMR (400 MHz, CDCl3)
d 7.09e7.23 (m,
4H), 6.67e6.70 (m, 2H), 6.62 (d, 1H, J¼8.8 Hz), 5.63 (t, 1H, J¼8.8 Hz),
3.69 (s, 3H), 3.49 (dd,1H, J¼15.7, 9.5 Hz), 3.11 (dd,1H, J¼15.7, 8.4 Hz),
(400 MHz, CDCl3)
d 6.67 (s,1H), 6.56 (s, 2H), 3.67 (s, 3H), 3.10 (s, 2H),
2.28 (s, 3H) ppm 13C NMR (100 MHz, CDCl3)
d 154.2, 153. 8, 138.9,
1.98e2.03 (m, 2H), 1.79e1.83 (m, 2H), 1.58e1.69 (m, 4H) ppm 13C
137.8, 129.3, 127.6, 125.8, 112.9, 111.1, 109.1, 84.2, 56.0, 38.8, 21.1 ppm.
NMR (100 MHz, CDCl3) d 153.8, 153.2, 128.4, 112.7, 111.4, 109.2, 97.1,
HRMS (EI) calcd for C16H16O2 [M]þ: 240.1150, found: 240.1153.
56.1, 40.6, 39.4, 23.9 ppm. HRMS (EI) calcd for C13H16O2 [M]þ:
204.1150, found: 204.1147.
3.4.12. 2-[4-(1,1-Dimethylethyl)phenyl]-2,3-dihydro-5-methoxybeno
furan (3ad). Colorless solid, mp 46e47 ꢁC. IR (KBr) cmꢀ1: 2961, 2905,
2867, 2830, 1604, 1485, 1433, 1362, 1303, 1230, 1203, 1136, 1033, 977,
Detailed information about the spectroscopic data of the pre-
pared PFBA resin and experimental procedures for the coupling
reactions in Scheme 3 are included in Supplementary data.
808, 748, 708. 1H NMR (400 MHz, CDCl3)
d 7.33e7.40 (m, 4H),
6.68e6.78 (m, 3H), 5.71 (t, 1H, J¼8.8 Hz), 3.76 (s, 3H), 3.56 (dd, 1H,
3.4.19. 5-Methoxy-2-silyloxy-a,a-dimethylbenzeneacetic acid methyl
J¼15.6, 9.3 Hz), 3.22 (dd,1H, J¼15.6, 8.3 Hz),1.31 (s, 9H) ppm 13C NMR
ester (5aa). Colorless oil. IR (KBr) cmꢀ1: 2950, 2833, 1737, 1497,
(100 MHz, CDCl3)
d
155.0,154.6,151.9,139.6,128.5,126.5,126.4,113.7,
1424, 1255, 1234, 1215, 1145, 1078, 1049, 915, 883, 843, 763. 1H NMR
112.0, 110.0, 85.0, 56.8, 39.4, 35.4, 32.1 ppm. HRMS (EI) calcd for
(400 MHz, CDCl3)
d
6.41e6.62 (m, 3H), 3.61 (s, 3H), 3.36 (s, 3H), 1.23
177.4, 153.0,
C19H22O2 [M]þ: 282.1620, found: 282. 1622.
(s, 6H), 0.02 (s, 9H) ppm 13C NMR (100 MHz, CDCl3)
d
146.4, 136.3, 116.8, 112.8, 110.6, 55.2, 51.5, 43.9, 25.3, 0.0 ppm. HRMS
(EI) calcd for C15H24O4Si [M]þ: 296.1444, found: 296.1446.
3.4.13. 2-(4-Chlorophenyl)-2,3-dihydro-5-methoxybenzofuran
(3ae). Slightly yellow solid, mp 60e61 ꢁC. IR (KBr) cmꢀ1: 2995,
2940, 2909, 2831,1601,1487,1434,1231,1202,1136,1090,1032, 924,
3.4.20. 2-(5-Methoxy-2-silyloxyphenyl)cyclopentanone (5ab). Color-
less oil. IR (KBr) cmꢀ1: 2959, 2834, 1743, 1499, 1465, 1426, 1250,
1225, 1160, 1142, 1040, 937, 904, 889, 845, 757. 1H NMR (400 MHz,
813, 738, 706. 1H NMR (400 MHz, CDCl3)
d 7.32 (s, 4H), 6.68e6.77
(m, 3H), 6.69 (t, 1H, J¼9.3 Hz), 3.75 (s, 3H), 3.58 (dd, 1H, J¼15.8,
9.5 Hz), 3.12 (dd, 1H, J¼15.6, 8.1 Hz) ppm 13C NMR (100 MHz, CDCl3)
CDCl3)
2.05e2.16 (m, 3H), 1.84e1.90 (m, 2H), 1.57e1.67 (m, 1H, J¼14.2,
8.8 Hz), 0.02 (s, 9H) ppm 13C NMR (100 MHz, CDCl3)
218.0, 158.2,
d
6.31e6.47 (m, 3H), 3.47 (s, 3H), 3.04 (dd, 1H, J¼10.9, 8.3 Hz),
d
155.1, 154.3, 141.3, 134.4, 129.5, 127.9, 127.8, 113.8, 111.9, 110.0, 84.1,
56.7, 39.6 ppm. HRMS (EI) calcd for C15H13ClO2 [M]þ: 260.0604,
found: 260.0608.
d
146.6, 130.2, 118.1, 116.0, 112.2, 55.1, 52.5, 37.8, 30.7, 20.9, 0.0 ppm.
HRMS (EI) calcd for C15H22O3Si [M]þ: 278.1388, found: 278.1368.
3.4.14. 2,3-Dihydro-5-methoxy-2-methyl-2-phenylbenzofuran
(3af). Colorless solid, mp 53e54 ꢁC. IR (KBr) cmꢀ1: 3059, 3027,
2973, 2830, 1603, 1487, 1446, 1373, 1270, 1148, 1030, 921, 862, 765,
3.4.21. 5-(2-Hydroxy-5-methoxyphenyl)-2(5H)-furanone (5ac).
Slightly yellow oil. IR (KBr) cmꢀ1: 3362, 3110, 2956, 2837, 1790,
1739, 1596, 1502, 1460, 1278, 1214, 1176, 1081, 1028, 832, 797. 1H
700. 1H NMR (400 MHz, CDCl3)
d
7.14e7.40 (m, 5H), 6.71 (d, 1H,
J¼8.5 Hz), 6.58e6.65 (m, 2H), 3.65 (s, 3H), 3.23e3.36 (m, 2H), 1.68
(s, 3H) ppm 13C NMR (100 MHz, CDCl3)
153.6, 152.5, 146.4, 127.9,
NMR (400 MHz, CDCl3)
6.10 (s, 1H), 5.88e5.96 (m, 2H), 3.61 (s, 3H) ppm 13C NMR
(100 MHz, CDCl3) 174.2, 156.7, 149.9, 149.6, 122.8, 119.9, 115.9,
d 7.41e7.46 (m, 1H), 6.50e6.60 (m, 3H),
d
127.0, 126.5, 124.0, 112.5, 110.9, 108.9, 88.7, 55.5, 44.7, 28.7 ppm.
HRMS (EI) calcd for C16H16O2 [M]þ: 240.1150, found: 240.1153.
d
112.4, 111.6, 80.0, 55.7 ppm. HRMS (EI) calcd for C11H11O4
[MþH]þ: 207.0657, found: 207.0654.
3.4.15. 2,3-Dihydro-5-methoxy-2-(4-methoxyphenyl)-3-methylben-
zofuran (3ag).26b Colorless oil. IR (KBr) cmꢀ1: 2996, 2959, 2933,
2833, 1613, 1513, 1484, 1375, 1249, 1202, 1175, 1146, 1034, 970, 829,
3.4.22. 4-Methoxy-2-(phenylthio)phenol (5ad).26d Slightly brownoil.
IR (KBr) cmꢀ1: 3435, 3058, 3001, 2938, 2832, 1581, 1486, 1438, 1336,

8430
T. Dohi et al. / Tetrahedron 68 (2012) 8424e8430
1276, 1253, 1212, 1181, 1051, 1034, 768. 1H NMR (400 MHz, CDCl3)
6.89e7.18 (m, 8H), 6.06 (s,1H), 3.68 (s, 3H) ppm 13C NMR (100 MHz,
CDCl3) 153.3,151.2, 135.5, 129.1, 126.7, 126.0, 120.1, 118.7, 116.1, 115.9,
Rev. 2002, 102, 3275; (d) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. Rev. 2003, 103,
3401; (e) Lu, J.; Toy, P. H. Chem. Rev. 2009, 109, 815; (f) Chang, Y.; Bae, C. Curr.
Org. Synth. 2011, 8, 208.
d
d
12. An extreme number of polymer-supported reagents and catalysts are now
readily available from commercial suppliers.
55.7 ppm.
13. (a) Barany, G.; Merrifield, R. B. In Solid Phase Peptide Synthesis; Gross, E.,
Meinhofer, J., Eds.; The Peptide: Analysis, Synthesis, Biology; Academic: New
York, NY, 1980; vol. 2, pp 1e284; (b) Lloyd-Williams, P.; Albericio, F.; Giralt, E.
Tetrahedron 1993, 49, 11065; (c) Songster, M. F.; Barany, G. Methods Enzymol.
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Jammalamadaka, V.; Lyttle, M. H.; Songster, M. F. J. Org. Chem. 1998, 63, 3706;
(d) Lee, T.-K.; Ryoo, S.-J.; Byun, J.-W.; Lee, S.-M.; Lee, Y.-S. J. Comb. Chem. 2005, 7,
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search (A) and Encouragement of Young Scientists (A) from JSPS,
a Grant-in-Aid for Scientific Research on Innovative Areas ‘Ad-
vanced Molecular Transformations by Organocatalysts’ from MEXT,
and Ritsumeikan Global Innovation Research Organization (R-
GIRO) project. T.D. is grateful to financial support from the Asahi
Glass Foundation and the Industrial Technology Research Grant
Program from NEDO of Japan.
Supplementary data
16. For allylsilane in other type cyclizations, see the examples: (a) Schmidt, A. W.;
Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.tet.2012.07.089.
€
€
Knoelker, H.-J. Synlett 2010, 2207; (b) Knoelker, H.-J. J. Prakt. Chem. 1997, 339,
ꢀ
304; (c) Berard, D.; Giroux, M. A.; Racicot, L.; Sabot, C.; Canesi, S. Tetrahedron
2008, 64, 7537.
References and notes
17. For characteristics of the fluoroalcohols, see the following accounts and re-
views: (a) Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem. 1996, 68, 627; (b)
Eberson, L.; Hartshorn, M. P.; Persson, O.; Radner, F. Chem. Commun. 1996, 2105;
1. Reviews on preparation and synthetic utility of quinone acetals: (a) Magdziak,
D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 138; (b) Liao, C.-C.; Peddinti,
R. K. Acc. Chem. Res. 2002, 35, 856.
ꢀ
(c) Begue, J.; Bonnet-delpon, D.; Crousse, B. Synlett 2004, 18; (d) Dohi, T.; Ya-
maoka, N.; Kita, Y. Tetrahedron 2010, 66, 5775.
18. Other aminomethyl polystyrene-supported C6F4COOH having different load-
ings and DVB content as well as aminopropyl silica gel-supported PFBA were
also tested for this [3þ2] coupling, which showed inferior results. See
Supplementary data.
19. It should be noted that Montmorillonite clays (see Ref. 6) required longer re-
action times of several days to consume all of the starting materials. Their use
usually resulted in lower product yields for the same substrates.
20. Polymerization of styrenes can occur in the presence of strong Brønsted acids,
such as perhalocarboxylic acids. See: (a) Hamaya, T. Makromol. Chem., Rapid
Commun. 1982, 3, 953; (b) Higashimura, T.; Hiza, M.; Hasegawa, H. s Macro-
molecules 1979, 12, 1058.
21. Some of soluble para-substituted PFBA were already screened in the reaction of
Eq. 1, which can conclude that the presence of the carboxamide group as
substituent at the para-position is less influential in the reactivity of the
catalyst.
22. For reports of intramolecular silyl transfer from enol silylethers to phenolic and
carbonyl oxygens, see: (a) Kita, Y.; Haruta, J.; Segawa, J.; Tamura, Y. Tetrahedron
Lett. 1979, 20, 4311; (b) Kita, Y.; Haruta, J.; Fujii, T.; Segawa, J.; Tamura, Y.
Synthesis 1981, 451; For review on the silyl and acyl transfer reagents, see; (c)
Kita, Y.; Akai, S. Chem. Rec. 2004, 4, 363; Silyl transfer from other atom in this
type of reaction is under investigation, and the reason for the formation of the
desilylated product 5ad will be explained in future study.
2. For selected examples, see: (a) Foster, C. H.; Payne, D. A. J. Am. Chem. Soc. 1978,
100, 2834; (b) Parker, K. A.; Kang, S.-K. J. Org. Chem. 1980, 45, 1218; (c) Ciufolini,
M. A.; Dong, Q.; Yates, M. H.; Schunk, S. Tetrahedron Lett. 1996, 37, 2881; (d)
Stern, A. J.; Rohde, J. J.; Swenton, J. S. J. Org. Chem. 1989, 54, 4413; (e) Imbos, R.;
Brilman, M. H. G.; Pineschi, M.; Feringa, B. L. Org. Lett. 1999, 1, 623; (f) Grecian,
€
S.; Wrobleski, A. D.; Aube, J. Org. Lett. 2005, 7, 3167; (g) Giroux, M.-A.; Guerard,
K. C.; Beaulieu, M.-A.; Sabot, C.; Canesi, S. Eur. J. Org. Chem. 2009, 3871.
3. Early examples: (a) Evans, D. A.; Cain, P. A.; Wong, R. Y. J. Am. Chem. Soc. 1977,
99, 7083; (b) Stern, A. J.; Swenton, J. S. J. Org. Chem. 1988, 53, 2465; (c) Imamoto,
T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. J. Am. Chem. Soc. 1989,
111, 4392; (d) Parker, K. A.; Coburn, C. A. J. Am. Chem. Soc. 1991, 113, 8516.
4. Reactions using organometallic reagents: (a) Coutts, I. G. C.; Hamblin, M. J.
Chem. Soc., Chem. Commun. 1976, 58; (b) Sartori, G.; Maggi, R.; Bigi, F.; Giaco-
melli, S.; Porta, C.; Arienti, A.; Bocelli, G. J. Chem. Soc., Perkin Trans. 1 1995, 2177.
5. Formal substitution via 1,2-addition of nucleophile to the carbonyls followed by
rearrangement: (a) Henton, D. R.; Anderson, K.; Manning, M. J.; Swenton, J. S. J.
Org. Chem. 1980, 45, 3422; (b) Mal, D.; Pahari, P.; Bidyut, B. K. Tetrahedron Lett.
2005, 46, 2097.
6. Dohi, T.; Washimi, N.; Kamitanaka, T.; Fukushima, K.; Kita, Y. Angew. Chem., Int.
Ed. 2011, 50, 6142.
7. Dohi, T.; Hu, Y.; Kamitanaka, T.; Washimi, N.; Kita, Y. Org. Lett. 2011, 13, 4814.
8. Aqueous base extraction followed by acidification could afford partial recovery
of the used PFBA.
9. Comprehensive reviews on SPOS: (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
Chem. Rev. 2003, 103, 893; (b) Blaney, P.; Grigg, R.; Sridharan, V. Chem. Rev.
2002, 102, 2607; (c) Brown, R. D. J. Chem. Soc., Perkin Trans. 1 1998, 3293; (d)
Czarnik, A. W. Solid-Phase Organic Synthesis; Wiley: New York, NY, 2001; vol. 1;
See also, Ref. 11e.
10. (a) Clark, J. H. Chemistry of Waste Minimisation; Chapman and Hall: Glasgow,
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2007, 138, 363.
11. Recent reviews and book dealing with polymer-supported reagents and cata-
lysts: (a) Frenzel, T.; Solodenko, W.; Kirschning, A. In Polymeric Materials in
Organic Synthesis and Catalysis; Buchmeiser, M. R., Ed.; Wiley-VCH: Weinheim,
2003; pp 201e240; (b) Kirschning, A.; Monenschein, H.; Wittenberg, R. Angew.
Chem., Int. Ed. 2001, 40, 650; (c) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem.
23. The formation of the product 5ac is probably caused as a result of the formation
and ring-opening of acid-labile [3þ2] type coupling product (see
Supplementary data).
24. (a) Moriarty, R. M.; Prakash, O. Org. React. 2001, 57, 327; (b) Tamura, T.; Yakura,
T.; Haruta, J.; Kita, Y. J. Org. Chem. 1987, 52, 3927; (c) Fleck, A. E.; Hobart, J. A.;
Morrow, G. W. Synth. Commun. 1992, 22, 179; (d) Mitchell, A. S.; Russell, R. A.
ꢀ
~
Tetrahedron 1997, 53, 4387; (e) Camps, P.; Gonzalez, A.; Munoz-Torrero, D.;
ꢀ~
Simon, M.; Zuniga, A.; Martins, M. A.; Font-Bardia, M.; Solans, X. Tetrahedron
2000, 56, 8141; (f) Pelter, A.; Elgendy, M. A. J. Chem. Soc., Perkin Trans. 1 1993, 1,
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25. Banfield, S. C.; Kerr, M. A. Can. J. Chem. 2004, 82, 131.
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