Palladium-catalyzed arylation of the THP derivative of (Z)-2-butene-1,4- diol with arenediazonium salts and the synthesis of β-aryl-γ- butyrolactones

Article abstract of DOI:10.1055/s-0028-1087959

The reaction of arenediazonium tetrafluoroborates with the THP derivative of (Z)-2-butene-l,4-diol in the presence of Pd(OAc)₂ in MeOH at 35 °C gives 4-aryl-2-mefhoxytetrahydrofurans in good to high yields. The reaction tolerates a variety of u

Full text of DOI:10.1055/s-0028-1087959

LETTER
973
Palladium-Catalyzed Arylation of the THP Derivative of (Z)-2-Butene-1,4-diol
with Arenediazonium Salts and the Synthesis of b-Aryl-g-butyrolactones
A
renediazoniu
a
m
Salts in
n
the
S
ynthesis
d
of Furan
D
e
r
rivativeso Cacchi,* Giancarlo Fabrizi, Antonella Goggiamani, Alessio Sferrazza
Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi ‘La Sapienza’, P. le A. Moro 5, 00185 Rome, Italy
Fax +39(06)49912780; E-mail: sandro.cacchi@uniroma1.it
Received 16 December 2008
carbonyldiazobenzene tetrafluoroborate (2b), models of
Abstract: The reaction of arenediazonium tetrafluoroborates with
electron-rich and electron-poor arenediazonium salts, re-
spectively. Reactions were performed in the presence of 5
mol% of Pd(OAc)2. Disappointing results were obtained
the THP derivative of (Z)-2-butene-1,4-diol in the presence of
Pd(OAc)2 in MeOH at 35 °C gives 4-aryl-2-methoxytetrahydro-
furans in good to high yields. The reaction tolerates a variety of use-
ful functional groups including ester, keto, cyano, nitro, chloro, and with 2a under a number of conditions varying the 2a to
bromo functionalities as well as ortho substituents. Based on this
(Z)-2-butene-1,4-diol molar ratios, using THF, MeCN,
process, g-aryl-b-butyrolactone derivatives can be prepared via a
and MeOH as solvents at temperatures ranging from room
sequential palladium-catalyzed arylation–cyclization–oxidation
temperature to 60 °C. Complex reaction mixtures were
protocol that omits the isolation of 4-aryl-2-methoxytetrahydro-
usually formed that we have not carefully analyzed. No
furan intermediates.
evidence of 2-hydroxytetrahydrofuran formation (1a,
Key words: arenediazonium salts, palladium, Mizoroki–Heck
R = 4-MeOC6H4) was attained. In some cases, variable
reaction, tetrahydrofurans, allylic alcohols
amounts of 1,4-dimethoxybenzene and butyrolactone 3a
(formed via trapping the arenediazonium salt with MeOH
and an oxidation process, respectively, Figure 1) were iso-
After the first palladium-catalyzed arylation of olefins
lated.
with arenediazonium salts reported by Matsuda et al.,1
arenediazonium salts have been used as aryl partners in a
MeO
large number of Mizoroki–Heck reactions,2 including the
palladium-catalyzed arylation of allylic alcohols to afford
saturated carbonyl compounds.1,3 The reaction of arenedi-
azonium salts with 2-butene-1,4-diol, however, has not
been investigated.4 The related reaction with aryl iodides
O
O
or vinyl halides and triflates gives substituted 2-hydroxy-
3a
tetrahydrofurans 15,6 (Scheme 1), which have been used
Figure 1
as precursors of butyrolactone derivatives. Extending this
type of Mizoroki–Heck–cyclization process to arenedia-
A similar behavior was observed when 2b was subjected
to the same arylation–cyclization conditions in THF and
MeCN. Interestingly, treatment of 1 equivalent of 2b with
2 equivalents of (Z)-2-butene-1,4-diol and 5 mol% of
Pd(OAc)2 in MeOH for 5 hours at 35 °C led to the isola-
tion of the 2-methoxytetrahydrofuran derivative 5b as an
approximately trans/cis (60:40) diastereomeric mixture8
in 26% yield (Scheme 2). Very likely, 5b is generated via
trapping of the carbocationic intermediate 4b by MeOH.9
The formation of 4b from the corresponding 2-hydroxy-
tetrahydrofuran is in turn favored by the acidity of the
reaction medium, the increase of which parallels the pro-
ceeding of the vinylic substitution [regeneration of Pd(0)
from HPd, which is generated in the syn-b-elimination
step, leads to the formation of fluoroboric acid].
zonium salts would be a convenient route to tethering an
oxygen-containing five-membered ring to aniline precur-
sors. Therefore, as part of a program devoted to the utili-
zation of arenediazonium salts in palladium-catalyzed
reactions,6,7 we became interested in investigating wheth-
er a reactivity similar to that observed with aryl iodides or
vinyl halides and triflates might be observed using arene-
diazonium tetrafluoroborates. Herein we report the results
of this study.
We started our study by examining the reaction of com-
mercially available (Z)-2-butene-1,4-diol with 4-methoxy-
diazobenzene tetrafluoroborate (2a) and 4-methoxy-
R
R
Pd catalyst
+ RX
OH
O
As 2-methoxytetrahydrofurans can be useful synthetic in-
termediates (e.g., acetals of this type can be converted into
the corresponding lactones via oxidation10), we decided to
investigate this reaction more in detail. However, the 2-
methoxytetrahydrofuran 5b was isolated only in moderate
yields under a variety of conditions. The best result (54%
yield) was obtained when 2 equivalents of 2b were treated
OH
OH
OH
O
H
1
Scheme 1
SYNLETT 2009, No. 6, pp 0973–0977
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1087959; Art ID: G39308ST
© Georg Thieme Verlag Stuttgart · New York

974
S. Cacchi et al.
LETTER
MeO2C
MeO2C
CO2Me
Pd(OAc)2
+
OH
MeOH, 35 °C
OH
OMe
O
O
N2+–BF4
5b
4b
2b
Scheme 2
with 1 equivalent of (Z)-2-butene-1,4-diol and 5 mol% of 4–8) and showed that the same conditions could be suc-
Pd(OAc)2 in MeOH at 35 °C for 45 minutes.
cessfully used even with an electron-poor arenediazonium
salt (Table 1, entry 8).
It is unclear as to exactly what is the reason of the complex
reaction mixtures obtained with 2a and the moderate yield The utilization of a silyl protecting group was also briefly
obtained with 2b. In general, arenediazonium salts are not investigated by treating 2b with 7 (Scheme 3). Although
as stable as other aryl donors such as aryl halides or tri- 5b was isolated in high yield, the THP derivative appears
flates, and their successful utilization in palladium- to be superior.
catalyzed reactions depends on a subtle balance between
their stability and the rate of their involvement in catalytic
cycles. In this case, in the presence of the free hydroxy
groups, it is possible that the vinylic substitution reaction
is relatively slow in comparison to their stability under
reaction conditions and that a number of side reactions
can take place. Therefore, we switched to the utilization of
the THP derivative 6 as the starting olefin. The working
hypothesis was that converting the alcoholic groups into
their THP derivatives might allow for a cleaner and more
efficient vinylic substitution and that the acidic medium
resulting from the vinylic substitution might have its ef-
fect on the acid-labile protecting groups (i.e., regenerating
the free alcoholic groups) at an advanced stage of the
reaction, if not after completion of the vinylic substitution
step. Once the free alcoholic groups are regenerated, the
arylated intermediates should afford the desired 2-meth-
oxytetrahydrofurans.
MeO2C
Pd(OAc)2
MeOH, r.t., 1.5 h
+
2b
OSi(t-Bu)Me2
OSi(t-Bu)Me2
7
OMe
5b (71%)
O
Scheme 3
Using the optimized conditions, the reaction was then ex-
tended to include other arenediazonium salts.11 As shown
in Table 2, the desired products were isolated in good to
high yields and a variety of useful functional groups, in-
cluding ester, keto, cyano, nitro, chloro, and bromo func-
tionalities, are tolerated making this method particularly
appealing for subsequent synthetic manipulations, for ex-
ample, with halogen-containing derivatives (Table 2, en-
tries 11, 12, and 16), via cross-coupling reactions.
Arenediazonium salts bearing ortho substituents can also
be successfully used (Table 1, entries 8, 12, 13, 15, 16).
The low yield observed with 4-iododiazobenzene tetra-
After some experimentations, we were pleased to find that
5a could be isolated in 72% yield upon treatment of 2
equivalents of 2a with 1 equivalent of 6 and 5 mol% of
Pd(OAc)2 in MeOH at 35 °C for 1 hour (Table 1, entry 3).
The screening was then extended to 2b (Table 1, entries
Table 1 Optimization of the Reaction Conditionsa
Ar
Pd(OAc)2 (5 mol%)
MeOH, 35 °C
ArN2+–BF4
+
OTHP
OTHP
OMe
O
6
2
5
Entry
2 (equiv)
THP derivative 3 (equiv) Time (h)
Yield (%) of 5b
1
2
3
2a
(1)
(1.5)
(2)
1
1
1
2
1
1
5a
5a
5a
29
62
72
Ar = 4-MeOC6H4
4
5
6
7
8
2b
(1)
(1)
(1)
(1.2)
(2)
1
2
2
1
1
3
0.75
1
1
0.75
5b
5b
5b
5b
5b
40
67
70
73
83
Ar = 4-MeO2CC6H4
a Reactions were carried out on a 0.5 mmol scale in 4 mL of anhyd MeOH.
b Yields are given for isolated products.
Synlett 2009, No. 6, 973–977 © Thieme Stuttgart · New York

LETTER
Arenediazonium Salts in the Synthesis of Furan Derivatives
975
Ar
Pd
Table 2 Palladium-Catalyzed Reaction of Arenediazonium Salts 2
with the THP derivative of (Z)-2-Butene-1,4-diol 6a
Pd catalyst
MeOH
ArN2+–BF4
+
OTHP
OTHP
Entry
1
Ar of 2
Time (min) Yield (%) of 5b,c
OTHP
OTHP
6
2
8
4-MeOC6H4
4-MeO2CC6H4
3-F3CC6H4
4-NCC6H4
4-O2NC6H4
4-MeCOC6H4
4-MeC6H4
2,4-Me2C6H3
4-FC6H4
60
45
80
90
30
30
30
45
30
30
40
30
45
60
30
40
5a
5b
5c
5d
5e
5f
72
83
67
74
72
72
89
68
72
76
76
64
90d
34
76
77
– HPd
THPO
Ar
2
THP
O
OTHP
Pd
3
9
Hb
4
Ha
Ar
THPO Ha
5
10
– HaPd
6
7
5g
5h
5i
OTHP
Ar
Ar
8
O
OMe
OTHP
Ar
O
OH
H
9
5
12
11
10
11
12
13
14
15
16
Ph
5j
Scheme 4
4-ClC6H4
5k
5l
2-ClC6H4
can undergo several side reactions that we have not inves-
tigated.
2-Me-4-FC6H3
4-IC6H4
5m
5n
5o
5p
Most probably, the success of the reaction is due inter alia
to the high regioselectivity of the elimination step. As
shown in Scheme 4, where a possible rationale for this
reaction is outlined, the carbopalladation adduct 8 is likely
to undergo a selective elimination of HPd, possibly via the
cyclic intermediate 10 generated via oxygen coordination
to palladium. Indeed, as only the hydrogens Ha can fit the
steric requirements needed for the syn-b-elimination of
HPd species, its formation can direct the elimination step
so as to give selectively the enol ether 11. No evidence
was attained of 9 or compounds derived from its decom-
position. The desired product 5 is subsequently formed
from 11 through the intermediacy of the aldol 12.
2-MeOC6H4
2-BrC6H4
a Reactions were carried out on a 0.5 mmol scale using 2 (2 equiv), 6
(1 equiv), Pd(OAc)2 (5 mol%) in MeOH (4 mL) at 35 °C.
b Yields are given for isolated products.
c Compounds 2 were isolated as approximately 60:40 trans/cis dia-
stereomeric mixtures.
d Calculated by GC analysis.
fluoroborate (Table 2, entry 14) is most probably due to
the competing oxidative addition of the C–I bond (in the
starting arenediazonium salt and/or in the final product) to
Pd(0) species. The resulting arylpalladium intermediates
We next turned our attention to the conversion of 2-meth-
oxytetrahydrofurans 5 into the corresponding g-butyro-
lactones 13. The results of our screening with the
Table 3 Oxidation of 5a and 5ba
Ar
Ar
oxidation
OMe
O
O
O
5
13
Entry
Ar
Oxidation system, solvent
Time (h)
Yield (%) of 13b
1
2
3
4
5
4-MeOC6H4
4-MeO2CC6H4
MCPBA, BF3·OEt2, CH2Cl2
MCPBA, BF3·OEt2, CH2Cl2
CrO3, H2SO4–Me2CO–H2O
Jones reagent (0.2 M)–Me2CO
Oxone–1,4-dioxane
12
16
24
21
24
13a
13b
13b
13b
13b
80
88
70c
73
38d
a Unless otherwise stated, reactions were carried out on a 0.5 mmol scale at r.t. using: a) MCPBA (1 equiv), BF3·OEt2 (0.4 equiv) in CH2Cl2 (3
mL); b) CrO3 (1.5 equiv), H2SO4 (0.3 equiv) in Me2CO–H2O (8 mL; 75:25); c) Jones reagent (1.5 equiv, 0.2 M) in Me2CO (5 mL); d) Oxone
(3 equiv) in 1,4-dioxane (5 mL).
b Yields are given for isolated products.
c The starting material was recovered in 18% yield.
d At 80 °C.
Synlett 2009, No. 6, 973–977 © Thieme Stuttgart · New York

976
S. Cacchi et al.
LETTER
Le Cousturier de Courcy, N.; Genêt, J.-P. Synlett 2000, 201.
(b) Cai, M. Z.; Hu, R. H.; Zhou, J. Chin. Chem. Lett. 2001,
12, 861. (c) Darses, S.; Pucheault, M.; Genêt, J.-P. Eur.
J. Org. Chem. 2001, 1121. (d) Sengupta, S.; Bhattacharyya,
S. Tetrahedron Lett. 2001, 42, 2035. (e) Andrus, M. B.;
Song, C.; Zhang, J. Org. Lett. 2002, 4, 2079.
oxidation systems that we have investigated are shown in
Table 2. Best results were obtained using MCPBA and
BF3·OEt210a in CH2Cl2 at room temperature (Table 3, en-
tries 1 and 2).
Table 4 Preparation of b-Aryl-g-butyrolactones 13 Omitting the
Isolation of 4-Aryl-2-methoxytetrahydrofuran Intermediates 5a
(f) Selvakumar, K.; Zapf, A.; Spannenberg, A.; Beller, M.
Chem. Eur. J. 2002, 8, 3901. (g) Andrus, M. B.; Ma, Y.;
Zang, Y.; Song, C. Tetrahedron Lett. 2002, 43, 9137.
(h) Ma, Y.; Song, C.; Chai, Q.; Ma, C.; Andrus, M. B.
Synthesis 2003, 2886. (i) Wang, C.; Tan, L.-S.; He, J.-P.;
Hu, H.-W.; Xu, J.-H. Synth. Commun. 2003, 33, 773.
(j) Masllorens, J.; Moreno-Mañas, M.; Pla-Quintana, A.;
Roglans, A. Org. Lett. 2003, 5, 1559. (k) Schmidt, B.
Chem. Commun. 2003, 1656. (l) Nelson, M. L.; Ismail,
M. Y.; McIntyre, L.; Bhatia, B.; Viski, P.; Hawkins, P.;
Rennie, G.; Andorsky, D.; Messersmith, D.; Stapleton, K.;
Dumornay, J.; Sheahan, P.; Verma, A. K.; Warchol, T.;
Levy, S. B. J. Org. Chem. 2003, 68, 5838. (m) Dai, M.;
Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org. Lett. 2004, 6,
221. (n) Kabalka, G. W.; Dong, G.; Venkataiah, B.
Tetrahedron Lett. 2004, 45, 2775. (o) Xu, L.-H.; Zhang,
Y.-Y.; Wang, X.-L.; Chou, J.-Y. Dyes Pigm. 2004, 62, 283.
(p) Sabino, A. A.; Machado, A. H. L.; Correia, C. R. D.;
Eberlin, M. N. Angew. Chem. Int. Ed. 2004, 43, 2514.
(q) Sabino, A. A.; Machado, A. H. L.; Correia, C. R. D.;
Eberlin, M. N. Angew. Chem. Int. Ed. 2004, 43, 4389.
(r) Garcia, A. L. L.; Carpes, M. J. S.; Montes de Oca, A. C.
B.; dos Santos, M. A. G.; Santana, C. C.; Correia, C. R. D.
J. Org. Chem. 2005, 70, 1050. (s) Artuso, E.; Barbero, M.;
Degani, I.; Dughera, S.; Fochi, R. Tetrahedron 2006, 62,
3146. (t) Pastre, J. C.; Correia, C. R. D. Org. Lett. 2006, 8,
1657. (u) Perez, R.; Veronese, D.; Coelho, F.; Antunes,
O. A. C. Tetrahedron Lett. 2006, 47, 1325.
Ar
1. Pd(OAc)2
MeOH, 35 °C
+
ArN2+–BF4
OTHP
O
2. MCPBA
BF3⋅OEt2
CH2Cl2, r.t.
O
OTHP
6
2
13
Entry
Ar of 2
Yield (%) of 13
1
2
3
4-MeOC6H4
Ph
13a
13j
13b
50
69
74
4-MeO2CC6H4
a Reactions were carried out on a 0.5 mmol scale using: (step 1) 2 (2
equiv), 6 (1 equiv), Pd(OAc)2 (5 mol%) in MeOH (4 mL) at 35 °C;
(step 2) MCPBA (1 equiv), BF3⋅OEt2 (0.4 equiv) in CH2Cl2 (3 mL) at
r.t.
To make this overall approach to b-aryl-g-butyrolactones
more attractive from a synthetic standpoint, the whole
process (palladium-catalyzed arylation–cyclization–
oxidation) was conducted so as to avoid the isolation of 2-
methoxytetrahydrofuran intermediates.12 In practice, oxi-
dations were carried out on the crude reaction mixtures af-
ter extraction and filtration through a short bed of silica
gel. The results obtained are listed in Table 4.
(3) (a) Kikukawa, K.; Nagira, K.; Wada, F.; Matsuda, T.
Tetrahedron 1981, 37, 31. (b) Hu, R.-H.; Liu, X.-L.; Cai,
M.-Z. Jiangxi Shifan Daxue Xuebao, Ziran Kexueban 2001,
25, 246; Chem. Abstr. 2001, 136, 355024. (c) Masllorens,
J.; Bouquillon, S.; Roglans, A.; Hénin, F.; Muzart, J.
J. Organomet. Chem. 2005, 690, 3822. (d) Barbero, M.;
Cadamuro, S.; Dughera, S. Synthesis 2006, 3443.
(4) For an excellent recent review on the palladium chemistry of
arenediazonium salts, see: Roglans, A.; Pla-Quintana, A.;
Moreno-Mañas, M. Chem. Rev. 2006, 106, 4622.
(5) (a) Mandai, T.; Hasegawa, S.-i.; Fujimoto, T.; Kawada, M.;
Nokami, J.; Tsuji, J. Synlett 1989, 85. (b) Arcadi, A.;
Bernocchi, E.; Cacchi, S.; Marinelli, F. Tetrahedron 1991,
47, 1525.
(6) For some recent reviews on the palladium-catalyzed
synthesis of heterocycles from unsaturated alcohols, see:
(a) Muzart, J. Tetrahedron 2005, 61, 4179. (b) Muzart, J.
Tetrahedron 2005, 61, 5955. (c) Wolfe, J. P. Eur. J. Org.
Chem. 2007, 571. (d) Wolfe, J. P. Synlett 2008, 2913.
(7) (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Persiani, D.
Org. Lett. 2008, 10, 1597. (b) Bartoli, G.; Cacchi, S.;
Fabrizi, G.; Goggiamani, A. Synlett 2008, 2508.
(8) The stereochemistry of 5b was assigned by NMR analysis.
That of the other 4-aryl-2-methoxytetrahydrofuran
derivatives has been assigned based on these data.
(9) Alternatively, as suggested by one of the referees, 5b might
arise from 4b via proton loss and addition of MeOH to the
resultant dihydrofuran (although no evidence was attained of
the formation of such an intermediate). The tendency of
furanols 1 to dehydrate upon distillation has been described:
(a) Chalk, A. L.; Magennis, S. A. J. Org. Chem. 1976, 41,
273. In the case of formation of the dihydrofuran
In conclusion, we have shown that arenediazonium tetra-
fluoroborates can be efficiently used as aryl donors in the
palladium-catalyzed arylation–cyclization of the THP de-
rivative of (Z)-2-butene-1,4-diol to give 4-aryl-2-methox-
ytetrahydrofurans usually in good to high yields. The
reaction occurs under mild conditions and tolerates a va-
riety of useful functional groups including ester, keto, cy-
ano, nitro, chloro, and bromo functionalities as well as
ortho substituents. Based on this process, b-aryl-g-butyro-
lactone derivatives can be prepared via a sequential palla-
dium-catalyzed arylation–cyclization–oxidation protocol
that omits the isolation of 4-aryl-2-methoxytetrahydro-
furan intermediates. Further studies on this chemistry are
currently under way.
Acknowledgment
We gratefully acknowledge GlaxoSmithKline for their generous fi-
nancial support and a fellowship position and Dr. Alcide Perboni
and Dr. Paolo Stabile of GlaxoSmithKline for valuable discussions.
We are also indebted to MURST and to the University ‘La Sapien-
za’.
References and Notes
(1) Kikukawa, K.; Matsuda, T. Chem. Lett. 1977, 159.
(2) For some recent selected references, see: (a) Brunner, H.;
intermediate, the addition of MeOH to the carbon–carbon
Synlett 2009, No. 6, 973–977 © Thieme Stuttgart · New York

LETTER
double bond might occur via an acid-catalyzed process:
Arenediazonium Salts in the Synthesis of Furan Derivatives
977
3 H), 3.39–3.32 (m, 1 H), 2.70–2.52 (m, 1 H), 2.00–1.85 (m,
1 H). 13C NMR (100.6 MHz, CDCl3): d = 158.4, 133.2,
128.7, 114.0, 110.8, 105.9, 73.2, 55.3, 55.0, 43.6, 41.2. MS:
m/z (%) = 208 (18) [M+], 177 (22), 147 (68).
(b) Wabnitz, T. C.; Yu, J.-Q.; Spencer, J. B. Chem. Eur. J.
2004, 10, 484. Palladium-catalyzed hydroalkoxylation of
carbon–carbon double bonds has also been reported:
(c) Gligorich, K. M.; Schultz, M. J.; Sigman, M. S. J. Am.
Chem. Soc. 2006, 128, 2794. (d) Matsukawa, Y.; Mizukado,
J.; Quan, H.; Tamura, M.; Sekiya, A. Angew. Chem. Int. Ed.
2005, 44, 1128; see also ref. 6a,b.
(12) Preparation of b-Aryl-g-butyrolactones 13 from
Arenediazonium Tetrafluoroborates 2 and the THP
Derivative of (Z)-2-Buten-1,4-diol (6) via a Sequential
Palladium-Catalyzed Arylation–Cyclization–Oxidation
Protocol – Typical Procedure
(10) For some selected references, see: (a) Grieco, P. A.; Oguri,
T.; Yokoyama, Y. Tetrahedron Lett. 1978, 419. (b) Masaki,
Y.; Nagata, K.; Kaji, K. Chem. Lett. 1983, 1835. (c) Shing,
T. K. M.; Yeung, Y.-Y. Chem.-Eur. J. 2006, 12, 8367.
(d) Geng, Z.; Chen, B.; Chiu, P. Angew. Chem. Int. Ed. 2006,
45, 6197. (e) La Clair, J. J. Angew. Chem. Int. Ed. 2006, 45,
2769. (f) Khoury, C.; Minier, M.; Le Goffic, F.; Rager,
M.-N. J. Carbohydr. Chem. 2007, 26, 395. (g) Prasad, K.
R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18, 2479.
(h) Wan, S.; Gunaydin, H.; Houk, K. N.; Floreancig, P. E.
J. Am. Chem. Soc. 2007, 129, 7915.
To a stirred solution of 6 (128.2 mg, 0.50 mmol) and
Pd(OAc)2 (5.6 mg, 0.025 mmol) in anhyd MeOH (4.0 mL),
2b (250.0 mg, 1.0 mmol) was added at r.t. under argon. The
reaction mixture was warmed at 35 °C and stirred for 45 min
(the reactor was protected from light with aluminium film).
After this time, the reaction mixture was diluted with Et2O,
washed with a sat. NaHCO3 solution, dried over Na2SO4, and
concentrated under reduced pressure. The residue was
filtrated through a short bed of SiO2 and concentrated under
reduced pressure. The crude was dissolved in CH2Cl2 (3 mL)
and MCPBA (123.3 mg, 0.5 mmol; a commercially
available 70% MCPBA was used) and BF3·OEt2 (25 mL, 0.2
mmol) were added. The cloudy reaction mixture was
allowed to stir at r.t. for 24 h and then poured into an
NaHSO3 aq solution. The organic layer was removed, and
the aqueous layer was washed with CH2Cl2. The organic
layer was washed with aq NaHCO3, dried over Na2SO4,
filtered, and concentrated under reduced pressure. The
residue was purified by chromatography on silica gel
[n-hexane–EtOAc, 75:25 (v/v)] to afford 81.4 mg (74%)
of 13b.
(11) Preparation of 4-Aryl-2-methoxytetrahydrofuran (5) via
Palladium-Catalyzed Reaction of Arenediazonium
Tetrafluoroborates 2 with the THP Derivative of (Z)-2-
Buten-1,4-diol (6) – Typical Procedure
To a stirred solution of 6 (128.2 mg, 0.50 mmol) and
Pd(OAc)2 (5.6 mg, 0.025 mmol) in anhyd MeOH (4.0 mL),
2a (221.9 mg, 1.0 mmol) was added at r.t. under argon. The
reaction mixture was warmed at 35 °C and stirred for 1 h (the
reactor was protected from light with aluminium film). After
cooling, the reaction mixture was diluted with Et2O, washed
with a sat. NaHCO3 solution, dried over Na2SO4, and
concentrated under reduced pressure. The residue was
purified by chromatography on silica gel [n-hexane–EtOAc,
75:25 (v/v)] to afford 75.2 mg (72% yield) of 5a as an
approximately 60:40 diastereomeric mixture. The cis-isomer
was isolated and characterized.
Mp 78–80 °C. IR (KBr): 1778, 1714, 1282, 1012 cm–1. 1H
NMR (400 MHz, CDCl3): d = 8.02 (d, J = 8.3 Hz, 2 H), 7.31
(d, J = 8.3 Hz, 2 H), 4.68 (dd, J1 = 8.8 Hz, J2 = 7.9 Hz, 1 H),
4.28 (dd, J1 = 8.9 Hz, J2 = 7.9 Hz, 1 H), 3.90 (s, 3 H), 3.86
(qp, J = 8.3 Hz, 1 H), 2.96 (dd, J1 = 9.1 Hz, J2 = 8.8 Hz, 1 H),
2.68 (dd, J1 = 8.8 Hz, J2 = 17.2 Hz, 1 H). 13C NMR (100.6
MHz, CDCl3): d = 175.9, 166.5, 144.7, 130.4, 129.7, 126.8,
73.6, 52.2, 41.0, 35.5. MS: m/z (%) = 220 (14) [M+], 162
(59), 131 (100), 77 (89).
Oil. IR (neat): 2940, 1606, 1077 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.25 (d, J = 8.6 Hz, 2 H), 6.87 (d, J = 8.6 Hz,
2 H), 5.19–5.15 (dd, J1 = 5.5 Hz, J2 = 3.0 Hz, 1 H), 4.17 (t,
J = 8.0 Hz, 1 H), 3.81 (s, 3 H), 3.76–3.71 (m, 1 H), 3.45 (s,
Synlett 2009, No. 6, 973–977 © Thieme Stuttgart · New York