Direct synthesis of protected arylacetaldehydes by tetrakis(phosphane)- palladium-catalyzed arylation of ethyleneglycol vinyl ether

Article abstract of DOI:10.1002/ejoc.200500540

A range of aryl bromides undergo Heck reaction with ethylene glycol vinyl ether, in the presence of [PdCl(C₃H₅)]₂/ cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphanyl)methyl]cyclopentane as catalyst, to give regioselectively protected arylacetaldehydes in good yields. The β-arylation products were obtained in with 93-100 % selectivity with electron-poor aryl bromides or heteroaryl bromides. Furthermore, this catalyst can be used at low loading, even for reactions with sterically hindered aryl bromides. The aryl vinyl ether intermediates undergo subsequent ketalisation to give the corresponding 2-benzyl-1,3-dioxolane derivatives. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500540

FULL PAPER
DOI: 10.1002/ejoc.200500540
Direct Synthesis of Protected Arylacetaldehydes by Tetrakis(phosphane)-
palladium-Catalyzed Arylation of Ethyleneglycol Vinyl Ether
Isabelle Kondolff,[a] Henri Doucet,*[a] and Maurice Santelli*[a]
Keywords: Aryl halides / Arylacetaldehydes / Homogeneous catalysis / Palladium / Phosphane ligands
A range of aryl bromides undergo Heck reaction with ethyl-
ene glycol vinyl ether, in the presence of [PdCl(C3H5)]2/
can be used at low loading, even for reactions with sterically
hindered aryl bromides. The aryl vinyl ether intermediates
cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphanyl)methyl]cyclo- undergo subsequent ketalisation to give the corresponding
pentane as catalyst, to give regioselectively protected aryl-
acetaldehydes in good yields. The β-arylation products were
obtained in with 93–100% selectivity with electron-poor aryl
bromides or heteroaryl bromides. Furthermore, this catalyst
2-benzyl-1,3-dioxolane derivatives.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
selectively the isomer e shown in Scheme 1.[24] Surprisingly,
to the best of our knowledge, selective β-arylation in the
presence of ethylene glycol vinyl ether has never been de-
scribed.
Introduction
The palladium-catalysed functionalisation of aromatic
halides with alkenes has become an important method in
preparative organic chemistry.[1–6] As a C–C bond-forming
process, the Heck arylation of alkenes inherently holds
powerful synthetic potential if its regio- and stereoselectiv-
ity can be controlled.[7] Nevertheless, the arylation of elec-
tron-rich olefins such as enol ethers is often limited by poor
α/β regioselectivity.[8–12] Highly α-regioselective arylations
in the presence of n-butyl vinyl ether have been reported by
Cabri et al. and Hallberg et al. in the presence of Pd(OAc)2/
dppp.[13–16] In some procedures, TlOAc was added in order
to improve the regioselectivity of the reaction. The reaction
performed in ionic liquids as solvent also leads selectively to
α-arylation.[17] On the other hand, the use of poly(ethylene
glycol) as solvent with Pd(OAc)2 as catalyst leads selectively
to the β-arylated products.[18] It has been demonstrated that
the regioselectivity of the addition of organopalladium in-
termediates can be influenced by coordinating groups adja-
cent to the substrate double bond.[19–24] For example,
Hallberg et al. have described that the nitrogen-containing
vinyl ether [2-(dimethylamino)ethoxy]ethene undergoes re-
gioselective β-arylation with several aryl halides in the pres-
ence of palladium acetate.[19,21] On the other hand, in the
presence of ethylene glycol vinyl ether with Pd(OAc)2/dppp
as catalyst, they obtained selective α-arylations to give aryl
vinyl ethers, which undergo subsequent ketalisation to form
Scheme 1.
In order to obtain stable and efficient palladium cata-
lysts, we have prepared the tetrakis(phosphane) ligand
cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphanyl)methyl]cyclo-
pentane (Tedicyp;[25] Figure 1) in which four diphenylphos-
phanyl groups are stereospecifically bound to the same face
of a cyclopentane ring. We have already reported the results
obtained in allylic substitutions,[25] Suzuki cross-coup-
lings[26] and Sonogashira alkynylations[27] with this ligand.
We have also reported several results obtained for the Heck
vinylation reaction:[28–39] we observed that n-butyl vinyl
ether, in the presence of the tetrakis(phosphane) and
[Pd(C3H5)Cl]2, gave high reaction rates and moderate to
good regioselectivities in favour of β-arylation,[30] although
in many cases these selectivities were not high enough to
provide a useful process for the preparation of arylacetal-
dehydes. The control of regioselectivity with the aid of in-
teractions between substrate and catalyst is a continuing
challenge in catalysis. In order to improve the selectivity of
the reaction with vinyl ethers in favour of the β-addition
with our catalyst, we decided to investigate arylation reac-
tions with enol ethers containing a coordinating substitu-
[a] UMR 6180 CNRS and Université d’Aix-Marseille III: “Chiro-
technologies: catalyse et biocatalyse”, Laboratoire de Synthèse
Organique, Faculté des Sciences de Saint Jérôme,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex
20, France
Fax: +33-4-91983865
E-mail: henri.doucet@univ.u-3mrs.fr
m.santelli@univ.u-3mrs.fr
Eur. J. Org. Chem. 2006, 765–774
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
765

I. Kondolff, H. Doucet, M. Santelli
FULL PAPER
ent. We have already reported preliminary results with eth- The reaction also proceeds in diglyme or xylene, but lower
ylene glycol vinyl ether and aryl bromides.[39] Here, we wish selectivities were observed. No reaction was observed when
to describe the results obtained with alcohol-containing ethylene glycol was used. We then studied the selectivity
substrates derived from ethyl vinyl ether with a variety of using K2CO3 or Cs2CO3 as base and DMF, NMP or
aryl and heteroaryl halides using 1 as ligand.
DMAC as solvent for the reaction with 1-bromo-4-fluoro-
benzene (Table 1, Entries 12–15). With this substrate, the
best selectivity in favour of isomer 2d (57%) was obtained
with DMF and K2CO3 (Table 1, Entry 12).
Figure 1. Structure of Tedicyp.
In the presence of ethylene glycol vinyl ether and 4-bro-
mobenzophenone with Pd(OAc)2 (3%) and dppp (6%) as
catalyst and NEt3 and TlOAc in DMF, Hallberg et al. ob-
tained selective α-arylation.[24] Under our reactions condi-
tions {[Pd(C3H5)Cl]2/Tedicyp (0.01%) with K2CO3 in
DMF} we selectively obtained the β-arylation of ethylene
glycol vinyl ether. Cabri has rationalised the regiochemical
outcome dictated by bidentate ligands in terms of genera-
tion of cationic organopalladium complexes.[23] The differ-
ence or regioselectivity between these two catalysts might
come from different (aryl)Pd(enol) intermediates
(Scheme 2). The Pd(OAc)2/dppp catalyst in the presence of
TlOAc probably generates a cationic organopalladium com-
plex by halide abstraction, which promotes the α-arylation.
Our [Pd(C3H5)Cl]2/Tedicyp system probably stabilizes a
neutral Pd complex, which favours the formation of the β-
arylated products.
Results and Discussion
The Heck reaction between ethylene glycol vinyl ether
and aryl bromides should lead to the three products a, b
and c (Scheme 1). Attack on the substituted carbon atom
of the vinyl ether would give product a, and attack on the
terminal carbon atom products b and c. However, in the
course of this reaction, we also observed the intramolecular
cyclisation of these arylalkenols a–c (Scheme 1) to give the
corresponding derivatives 2-benzyl-1,3-dioxolane (d) and 2-
methyl-2-phenyl-1,3-dioxolane (e). This ketal formation is
probably not palladium-catalysed, but arises through in-
ternal nucleophilic attack of the hydroxy group.[40,41]
First, we investigated the Heck reaction of 4-bromoace-
tophenone and 1-bromo-4-fluorobenzene with ethylene
glycol vinyl ether in the presence of the system Pd/Tedicyp
(Scheme 1, Table 1). The results show a strong influence of
the reaction conditions on the regioselectivity and on the
rate of the reaction. 4-Bromoacetophenone and ethylene
glycol vinyl ether, with K2CO3 or Cs2CO3 as base, in DMF,
give the isomer 1d with high selectivity (93%; Table 1, En-
tries 1 and 2). Mixtures of isomers were obtained in the
presence of NaOAc, Na2CO3, NaHCO3 or KF (Table 1,
Entries 3–6). Next, we studied the influence of the solvent
(Table 1, Entries 7–11). High selectivities in favour of the
Scheme 2.
In order to determine the scope and limitations of this
formation of isomer 1d were observed in NMP or DMAC. reaction under the operating conditions {[Pd(C3H5)Cl]2/
Table 1. Tedicyp/palladium-catalysed selective synthesis of protected arylacetaldehydes from ethylene glycol vinyl ether. Influence of the
base and solvent on the selectivity (Scheme 1).
Entry[a]
ArBr
Substrate/catalyst
ratio
Base
Solvent
Ratio of isomers
Product
Yield
[%]
a/b/c/d/e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
10000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
250
K2CO3
Cs2CO3
NaOAc
Na2CO3
NaHCO3
KF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOAc
Cs2CO3
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
NMP
0:0:0:93:7
0:0:0:93:7
0:14:39:29:18
17:1:2:79:1
15:29:30:21:5
14:29:29:25:3
0:0:0:93:7
0:0:0:93:7
10:1:1:87:1
–
16:14:14:54:2
0:0:0:57:43
0:15:42:8:35
36:2:1:57:4
12:19:40:25:4
1d,e
1d,e
1b–e
1a–e
1a–e
1a–e
1d,e
1d,e
1a–e
–
1a–e
2d,e
2b–e
2a–e
2a–e
87[b]
100
100
100
100
100
55
100
100
0
DMAC
xylene
ethylene glycol
diglyme
DMF
57
52[b]
100
100
72
250
250
250
DMF
DMF
DMAC
[a] Conditions: catalyst see ref.[25], aryl halide (1 equiv.), ethylene glycol vinyl ether (1.2 equiv.), base (2 equiv.), 130 °C, 20 h. GC yields
1
of the mixture of isomers. Ratio of isomers determined by GC and H NMR spectroscopy of the crude mixtures. [b] Isolated yields of
isomer d.
766
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 765–774

Direct Synthesis of Protected Arylacetaldehydes
FULL PAPER
Tedicyp, DMF, K2CO3, 130 °C}, the coupling with ethylene
With para-substituted aryl bromides, we obtained good
glycol vinyl ether was applied to several para-substituted regioselectivities in favour of β-arylation with electron-poor
aryl bromides (Table 2), meta- and ortho-substituted aryl aryl bromides such as 4-bromobenzophenone, methyl 4-
bromides (Table 3) and also to heteroaryl bromides bromobenzoate, 4-bromobenzonitrile, 1-bromo-4-nitroben-
(Table 4).
zene or 1-bromo-4-(trifluoromethyl)benzene (Table 2, En-
Table 2. Tedicyp/palladium-catalysed selective synthesis of protected arylacetaldehydes from ethylene glycol vinyl ether and para-substi-
tuted aryl halides (Scheme 1).
Entry[a]
ArX
Substrate/catalyst
ratio
Ratio of isomers
Product
Yield of d
a/b/c/d/e
[%]
1
2
3
4
5
6
7
8
9
4-bromobenzaldehyde
4-bromobenzophenone
methyl 4-bromobenzoate
4-bromopropiophenone
4-bromobenzonitrile
10000
10000
10000
10000
10000
1000
10000
100
0:0:0:97:3
0:0:0:94:6
0:0:0:97:3
5:0:0:95:0
0:0:0:98:2
0:0:0:98:2
0:0:0:94:6
0:13:41:13:33
0:10:11:57:22
0:26:44:8:22
0:10:29:27:34
3d,e
4d,e
91
89
88
93
92
5d,e
6a,d
7d,e
1-bromo-4-nitrobenzene
1-bromo-4-(trifluoromethyl)benzene
bromobenzene
8d,e
87
9d,e
90
10b–e
10b–e
10b–e
11b–e
89[b]
52
iodobenzene
iodobenzene
1-bromo-4-tert-butylbenzene
100
100
250
10
11
100[c,d]
87[b]
[a] Conditions: catalyst see ref.[25], aryl halide (1 equiv.), ethylene glycol vinyl ether (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h.
Isolated yields of isomer d. Ratio of isomers determined by GC and 1H NMR spectroscopy of the crude mixtures. [b] Yield of the mixture
containing all the isomers a–e. [c] GC and NMR conversions. [d] NaOAc was used as base.
Table 3. Tedicyp–palladium catalysed selective synthesis of protected aryl acetaldehydes from ethylene glycol vinyl ether and meta- and
ortho-substituted aryl bromides (Scheme 1 and Scheme 3).
Entry[a]
ArX
Substrate/catalyst
ratio
Ratio of isomers
Product
Yield of d
a/b/c/d/e
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1-bromo-3,5-bis(trifluoromethyl)benzene
1-bromo-4-nitro-3-(trifluoromethyl)benzene
3-bromoacetophenone
10000
10000
10000
10000
250
10000
1000
250
1000
10000
100
250
1000
250
0:0:0:97:3
0:0:0:97:3
0:0:0:96:4
0:0:0:93:7
5:0:0:95:0
0:0:0:94:6
29:6:17:48:0
0:0:0:96:4
3:0:0:97:0
0:0:0:94:6
12d,e
13d,e
14d,e
15d,e
16a,d
17d,e
18a–d
19d,e
20a,d
21d,e
22d,e
23d
24d,e
25d,e
26a–d
27d,e
28d,e
29dd
90
89
90
91
84
89
44
77
91
88
77
79
74
61
57
74
79
51
3-bromobenzaldehyde
1-bromo-3-nitrobenzene
1-bromo-3-(trifluoromethyl)benzene
2-bromo-6-methoxynaphthalene
2-bromobenzaldehyde
2-bromobenzonitrile
1-bromo-2-(trifluoromethyl)benzene
methyl 2-bromobenzoate
0:0:0:97:3
1-bromo-3,4-difluorobenzene
1-bromo-2,4-difluorobenzene
1-bromo-2-fluorobenzene
1-bromo-2-methylbenzene
1-bromonaphthalene
0:0:0:85:15
0:0:0:80:20
0:0:0:74:26
17:6:15:62:0
0:0:0:78:22
0:0:0:90:10
not determined
100
1000
1000
100
9-bromoanthracene
1,2-dibromobenzene
[a] Conditions: catalyst see ref.[25], aryl bromide (1 equiv.), ethylene glycol vinyl ether (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h.
1
Isolated yields of isomer d. Ratio of isomers determined by GC and H NMR spectroscopy of the crude mixtures.
Table 4. Tedicyp/palladium-catalysed selective synthesis of protected arylacetaldehydes from ethylene glycol vinyl ether and heteroaryl
bromides (Scheme 1 and Scheme 3).
Entry[a]
ArX
Substrate/catalyst
ratio
Ratio of isomers
Product
Yield of d
a/b/c/d/e
[%]
1
2
3
4
5
6
7
3-bromopyridine
4-bromopyridine
3-bromoquinoline
4-bromoisoquinoline
5-bromopyrimidine
3,5-dibromopyridine
5-bromo-2-furaldehyde
1000
1000
10000
1000
1000
250
12:0:0:88:0
3:0:0:97:0
10:0:0:90:0
12:0:0:88:0
0:0:0:100:0
not determined
0:1:0:99:0
30a,d
31a,d
32a,d
33a,d
34d
35dd
36b,d
83
88
85
81
76
78
78
250
[a] Conditions: catalyst see ref.[25], aryl halide (1 equiv.), ethylene glycol vinyl ether (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h.
1
Isolated yields of isomer d. Ratio of isomers determined by GC and H NMR spectroscopy of the crude mixtures.
Eur. J. Org. Chem. 2006, 765–774
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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767

I. Kondolff, H. Doucet, M. Santelli
FULL PAPER
tries 1–7). The β-selectivities observed were in the range 94–
98%. Moreover, most of these reactions were performed
with high substrate/catalyst ratios (up to 10000). On the
other hand, the reaction performed with the electron-rich
aryl bromide 1-bromo-4-tert-butylbenzene led to a lower se-
lectivity. With this substrate, a larger amount of α-arylated
product was obtained (34%; Table 2, Entry 11). Bromoben-
zene or iodobenzene also led to mixtures of α- and β-aryl-
ated products (Table 2, Entries 8–10), thus indicating that
the lower regioselectivities observed with electron-rich aryl
bromides are not due to a slower oxidative addition of the
aryl halide, but more likely to the electronic properties of
the Ar(X)Pd(CH2=CHOCH2CH2OH) intermediates. With
electron-deficient aryl bromides, the complete intramolecu-
lar cyclisation of the arylalkenes a, b and c (Scheme 1) was
generally observed to give the corresponding ketal products
2-benzyl-1,3-dioxolane (d) and 2-methyl-2-phenyl-1,3-diox-
olane (e). On the other hand, when 1-bromo-4-tert-butyl-
benzene was used, mixtures of cyclised and linear products
were obtained.
We then studied the influence of the presence of meta
and ortho substituents of the aryl bromides on the regiose-
lectivity of the addition and on the reaction rates. As ex-
pected, similar selectivities and reaction rates were obtained
with the meta-substituted aryl bromides. 3-Bromoaceto-
phenone, 3-bromobenzaldehyde and 1-bromo-3-(trifluoro-
methyl)benzene with ethylene glycol vinyl ether gave iso-
mers d in 93–96% selectivities in the presence of 0.01%
catalyst (Table 3, Entries 3, 4 and 6). 1-Bromo-3,5-bis(tri-
fluoromethyl)benzene and 1-bromo-4-nitro-3-(trifluoro-
methyl)benzene also gave isomers d in high selectivities
(97%) and high TONs (9000 and 8900; Table 3, Entries 1
and 2, respectively); ortho substituents on the aryl bromides
have a more important effect on the regioselectivities of the
addition and on the reaction rates. With electron-poor 2-
bromobenzaldehyde, 2-bromobenzonitrile, 1-bromo-2-(tri-
fluoromethyl)benzene or methyl 2-bromobenzoate high
selectivities in favour of isomer d were obtained in all cases
(94–97%) but the TONs were low in some cases (77–8800;
Table 3, Entries 8–11). In order to determine the relative in-
Scheme 3.
bromoquinolines as with electron-poor aryl bromides. With
3-bromopyridine, 3-bromoquinoline and 4-bromoisoquinol-
ine selectivities of 88, 90 and 88% in favour of β-arylation
were obtained, respectively (Table 4, Entries 1, 3 and 4).
The highest selectivities with heteroaromatic substrates
were observed with 4-bromopyridine, 5-bromopyrimidine
and 5-bromo-2-furaldehyde (97, 100 and 99% respectively;
Table 4, Entries 2, 5 and 7). Even 3,5-dibromopyridine gave
a satisfactory yield of the corresponding protected dialde-
hyde 35dd (Table 4, Scheme 3, Entry 6).
In order to determine if an ether function instead of an
alcohol on the vinyl ether would have an effect on the con-
trol of the regioselectivity of the addition, we performed
the reaction in the presence of ethylene glycol n-butyl vinyl
diether and n-butyl vinyl ether with 1-bromo-4-(trifluoro-
methyl)benzene (substrate/catalyst ratio 1000; Scheme 4).
We observed that very similar mixtures of isomers were ob-
tained and in both cases large amounts of α-arylated prod-
ucts were formed (24 and 25%, respectively). With this aryl
bromide, the formation of only 6% of α-arylated product e
was observed in the presence of ethylene glycol vinyl ether
(Table 2, Entry 7).
fluence of electronic and steric factors on the regioselectiv- Scheme 4.
ity of this reaction, we also performed the coupling with 1-
We also studied the selectivity of this reaction with 4-
bromo-3,4-difluorobenzene, 1-bromo-2,4-difluorobenzene,
1-bromo-2-fluorobenzene and 1-bromo-2-methylbenzene
(Table 3, Entries 12–15). With these four substrates selec-
tivities of 85, 80, 74 and 83% in favour of β-addition prod-
ucts were obtained, respectively. The sterically hindered
substrates 1-bromonaphthalene and 9-bromoanthracene
gave the β-arylated products in 78 and 90% selectivities,
respectively (Table 3, Entries 16 and 17). These results indi-
cate that the regioselectivity of the addition is partially con-
trolled by steric factors. The reaction using 1,2-dibro-
mobenzene led to the corresponding protected 1,2-bis(2-
oxoethyl)benzene 29dd in satisfactory yield [Table 3 (En-
try 18) and Scheme 3].
(vinyloxy)butan-1-ol (Scheme 5). Two aryl bromides were
used, but in both cases mixtures of isomers were obtained.
4-Bromoacetophenone gave the intramolecularly ketalized
Next, we studied the reaction with heteroaryl bromides
(Table 4). Pyridines or quinolines are π-electron-deficient,
so we should expect similar results with bromopyridines or Scheme 5.
768
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Eur. J. Org. Chem. 2006, 765–774

Direct Synthesis of Protected Arylacetaldehydes
FULL PAPER
Table 5. Palladium-catalysed synthesis of protected arylacetaldehydes from ethylene glycol vinyl ether and aryl bromides using dppb as
ligand.
Entry[a]
ArX
[Pd(C3H5)Cl]2/dppb
ratio
Substrate/catalyst
ratio
Ratio of isomers
Product
Yield
a/b/c/d/e
1
2
3
4
5
6
7
8
9
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
9-bromoanthracene
1:2
1:2
1:4
1:2
1:2
1:4
1:2
1:2
1:4
1000
10000
1000
100
250
250
100
250
250
8:0:0:92:0
8:0:0:92:0
7:0:0:93:0
23:13:19:42:3
26:14:24:27:9
16:3:12:42:27
37:0:0:55:8
0:0:0:78:22
14:0:0:78:8
1a,d
1a,d
100
17
100
100
69
1a,d
2a–e
2a–e
2a–e
33[b]
27[b,c]
34[b,c]
26[b,d]
28a,d,e
28d,e
28a,d,e
9-bromoanthracene
9-bromoanthracene
[a] Conditions: catalyst: [Pd(C3H5)Cl]2/dppb, aryl halide (1 equiv.), ethylene glycol vinyl ether (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C,
20 h. GC yields of the mixture of isomers. Ratio of isomers determined by GC and 1H NMR spectroscopy of the crude mixtures.
[b] Isolated yields of isomer d. [c] The formation of 35% of anthracene was also observed. [d] The formation of 46% of anthracene was
also observed.
isomer 39d in 15% selectivity. The linear (Z) and (E) iso- function probably imposes a conformational change in the
mers 39b and 39c were obtained in 19 and 48% selectivity, structure of the (aryl)Pd(enol) intermediate and stabilizes a
respectively, together with 18% of the branched isomer 39a. neutral Pd complex, thus favouring the formation of the β-
1-Bromonaphthalene gave a larger amount of the branched arylated products. Therefore, the reaction with ethylene
isomer 40a (42%). These results indicate that the position glycol vinyl ether is one of the Heck substrate directed reac-
of the alcohol function on the (vinyloxy)alkanol has a large tions. Both the steric hindrance and the electronic proper-
effect on the control of the regioselectivity of this reaction. ties of the aryl bromide have an effect on the reaction rates
Finally, we compared our catalyst with the system PPh3 and the selectivities. The best selectivities in favour of β-
(4 equiv.)/[Pd(C3H5)Cl]2 (1 equiv.) for the reaction of ethyl- arylations were observed with electron-poor or sterically
ene glycol vinyl ether with 9-bromoanthracene. In the pres- congested aryl bromides. With bromobenzene or electron-
ence of 0.4% catalyst, the ratio of products b+c+d/a+e was rich aryl bromides, mixtures or regioisomers were observed.
72:28 instead of 90:10 with Tedicyp/[Pd(C3H5)Cl]2. More- In all cases, only traces (Ͻ1%) of homocoupling products
over, using PPh3 as ligand, compound 28d was isolated in were observed with this catalyst. Apart from achieving ex-
a very low yield (21%), and a very important debromina- cellent regiocontrol, another advantage is the remarkable
tion of 9-bromoanthracene was observed. The major prod- functional group tolerance: substituents such as fluoro, tri-
uct of this reaction was anthracene. We also studied the fluoromethyl, acetyl, formyl, benzoyl, carboxylate, nitro or
reactivity and selectivity of this reaction using the bidentate nitrile on the aryl bromide have been used successfully. Eth-
ligand dppb. With the system dppb (2 or 4 equiv.)/ ylene glycol vinyl ether is commercially available, and the
[Pd(C3H5)Cl]2 (1 equiv.) as catalyst, satisfactory results in reaction can be performed with as little as 0.01% catalyst
terms of substrate/catalyst ratio and also of selectivity were with several substrates, so this catalyst appears to be the
obtained with 4-bromoacetophenone (Table 5, Entries 1–3). most active and stable one reported so far for this reaction.
On the other hand with 1-bromo-4-fluorobenzene or 9-bro- Due to the high price of palladium, the practical advantage
moanthracene low yields of isomers 2d or 28d were ob- of such low catalyst loadings can become increasingly im-
tained due to the formation of mixtures of isomers or de- portant for industrial processes.
bromination of 9-bromoanthracene (Table 5, Entries 4–9).
The difference of reactivity and selectivity between PPh3,
dppb and our tetradentate ligand probably arises from the
stability of the catalysts.
Experimental Section
General Remarks: All reactions were run under argon in Schlenk
tubes using vacuum lines. DMF, DMAC, NMP, xylene, diglyme
and ethylene glycol (analytical grade) were not distilled before use.
K2CO3 (99+%), Cs2CO3 (97%), Na2CO3 (99%), NaHCO3 (99%),
Conclusions
NaOAc (99%), ethylene glycol vinyl ether (97%) and commercial
aryl halides were used without purification. The reactions were
monitored by GC and NMR spectroscopy for high-boiling-point
substrates and by GC for low-boiling-point substrates. GC MS
In summary, we have established that the Tedicyp/palla-
dium system provides a convenient catalyst for the synthesis
of protected arylacetaldehyde derivatives by coupling of
aryl bromides with ethylene glycol vinyl ether followed by
intramolecular ketalisation. The electronic control of the re-
gioselectivity of the addition encountered with n-butyl vinyl
ether appears to be partially suppressed by an adjacent
alcohol function on the vinyl ether. This alcohol function
appears to be capable of coordinating to the palladium cat-
1
data were recorded with a Varian Saturn 2100T spectrometer. H
and 13C NMR spectra were recorded with a Bruker 300 MHz spec-
trometer in CDCl3 solutions. Chemical shifts are reported in ppm
relative to CDCl3 (1H: δ = 7.25 ppm; 13C: δ = 77.0 ppm). Flash
chromatography was performed on silica gel (230–400 mesh). GC
and NMR conversions in the tables are conversions of the aryl
alyst. Anchoring the enol to the metal atom by an alcohol halides into the mixture of products calculated from the GC and
Eur. J. Org. Chem. 2006, 765–774
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
769

I. Kondolff, H. Doucet, M. Santelli
FULL PAPER
1H NMR spectrum of the crude mixtures. Ratios of isomers were
determined by GC and NMR spectroscopy.
2-(4-Formylbenzyl)-1,3-dioxolane (3d): Isomer 3d was obtained in
91% (0.175 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
1
= 9.98 (s, 1 H, CHO), 7.81 (d, J = 8.3 Hz, 2 H, Ar), 7.43 (d, J =
8.3 Hz, 2 H, Ar), 5.08 (t, J = 4.8 Hz, 1 H, CH2CH), 3.96–3.82 (m,
4 H, CH2CH2), 3.04 (d, J = 4.8 Hz, 2 H, CH2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 192.0, 143.3, 134.9, 130.4, 129.7, 103.8, 65.0,
40.8 ppm. C11H12O3 (192): calcd. C 68.74, H 6.29; found C 68.52,
H 6.12. MS (EI, 70 eV): m/z (%) = 192 (100) [M+]. Before purifica-
tion, traces of 2-(4-formylphenyl)-2-methyl-1,3-dioxolane (3e) were
also observed. 1H NMR (300 MHz, CDCl3): δ = 4.04 (m, 2 H,
CH2CH2), 3.75 (m, 2 H, CH2CH2), 1.63 (s, 3 H, Me) ppm. The
other peaks were hidden by those of compound 3d.
Preparation of the Pd/Tedicyp Catalyst:[25] An oven-dried 40-mL
Schlenk tube, equipped with a magnetic stirring bar, was charged
with [Pd(C3H5)Cl]2 (4.2 mg, 11.6 µmol) and Tedicyp (20 mg,
23.2 µmol) under argon. Anhydrous DMF (2.5 mL) was then
added and the solution was stirred at room temperature for 10 min.
The appropriate amount of catalyst (see tables) was transferred into
the mixture of aryl halide, alkene and base.
General Procedure for the Coupling of Enol Ethers with Aryl Ha-
lides: The reaction of the aryl halide (1 mmol), K2CO3 (0.276 g,
2 mmol) and the enol ether (1.2 mmol) in DMF (5 mL) in the pres-
ence of the Tedicyp/palladium complex (see tables for substrate/
catalyst ratio) under argon at 130 °C during 20 h afforded the cor-
responding mixture of products after addition of water, extraction
with dichloromethane or diethyl ether, drying (MgSO4) and con-
centration. The major isomer was purified by chromatography on
silica gel.
2-(4-Benzoylbenzyl)-1,3-dioxolane (4d): Isomer 4d was obtained in
1
89% (0.239 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
= 7.78 (d, J = 7.2 Hz, 2 H, Ar), 7.76 (d, J = 8.2 Hz, 2 H, Ar), 7.56
(t, J = 7.2 Hz, 1 H, Ar), 7.45 (t, J = 7.2 Hz, 2 H, Ar), 7.37 (d, J =
8.2 Hz, 2 H, Ar), 5.10 (t, J = 4.8 Hz, 1 H, CH2CH), 3.97–3.82 (m,
4 H, CH2CH2), 3.04 (d, J = 4.8 Hz, 2 H, CH2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 196.4, 141.1, 137.7, 135.8, 132.2, 130.1,
129.9, 129.6, 128.2, 104.0, 65.0, 40.7 ppm. C17H16O3 (268): calcd.
C 76.10, H 6.01; found C 75.99, H 5.89. MS (EI, 70 eV): m/z (%)
= 268 (100) [M+]. Before purification, traces of 2-(4-benzo-
ylphenyl)-2-methyl-1,3-dioxolane (4e) were also observed. 1H
NMR (300 MHz, CDCl3): δ = 4.06 (m, 2 H, CH2CH2), 3.79 (m, 2
H, CH2CH2), 1.67 (s, 3 H, Me) ppm. The other peaks were hidden
by those of compound 4d.
2-(4-Acetylbenzyl)-1,3-dioxolane (1d): The reaction of 4-bromoace-
tophenone (0.199 g, 1 mmol), K2CO3 (0.276 g, 2 mmol) and ethyl-
ene glycol vinyl ether (0.106 g, 1.2 mmol) in DMF (5 mL) in the
presence of the Tedicyp/palladium complex (0.1 µmol) under argon
at 130 °C for 20 h afforded the corresponding coupling product 1d
after extraction with diethyl ether, drying (MgSO4), concentration
and filtration through silica gel (diethyl ether/pentane, 1:4) in 87%
(0.179 g) isolated yield. White solid. M.p. 55 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.90 (d, J = 8.1 Hz, 2 H, Ar), 7.36 (d, J =
8.1 Hz, 2 H, Ar), 5.08 (t, J = 5.1 Hz, 1 H, CH2CH), 3.95–3.80 (m,
4 H, CH2CH2), 3.02 (d, J = 5.1 Hz, 2 H, CH2CH), 2.56 (s, 3 H,
Me) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.8, 141.7, 135.6,
129.9, 128.3, 103.9, 65.0, 40.6, 26.5 ppm. C12H14O3 (206): calcd. C
69.88, H 6.84; found C 69.62, H 6.63. MS (EI, 70 eV): m/z (%) =
206 (19) [M+]. Before purification, traces of 2-(4-acetylphenyl)-2-
methyl-1,3-dioxolane (1e) were present along with 1a–c. 1e: 1H
NMR (300 MHz, CDCl3): δ = 7.91 (d, J = 8.3 Hz, 2 H, Ar), 7.55
(d, J = 8.3 Hz, 2 H, Ar), 4.03 (m, 2 H, CH2CH2), 3.75 (m, 2 H,
Methyl 4-[(1,3-Dioxolan-2-yl)methyl]benzoate (5d): Isomer 5d was
1
obtained in 88% (0.195 g) isolated yield. Oil. H NMR (300 MHz,
CDCl3): δ = 7.94 (d, J = 8.2 Hz, 2 H, Ar), 7.31 (d, J = 8.2 Hz, 2
H, Ar), 5.06 (t, J = 4.3 Hz, 1 H, CH2CH), 3.95–3.75 (m, 4 H,
CH2CH2), 3.88 (s, 3 H, OMe), 2.99 (d, J = 4.3 Hz, 2 H, CH2CH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 166.9, 141.6, 129.7, 129.6,
128.3, 103.9, 64.9, 51.9, 40.6 ppm. C12H14O4 (222): calcd. C 64.85,
H 6.35; found C 64.99, H 6.14. Before purification, traces of methyl
4-(2-methyl-1,3-dioxolan-2-yl)benzoate (5e) were also observed. 1H
NMR (300 MHz, CDCl3): δ = 1.62 (s, 3 H, Me) ppm. The other
peaks were hidden by those of compound 5d.
1
2-(4-Propionylbenzyl)-1,3-dioxolane (6d): Isomer 6d was obtained in
CH2CH2), 2.57 (s, 3 H, Me), 1.62 (s, 3 H, Me) ppm. 1a: H NMR
1
93% (0.205 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
(300 MHz, CDCl3): δ = 4.80 (d, J = 3.2 Hz, 1 H, C=CH2), 4.36 (d,
J = 3.2 Hz, 1 H, C=CH2) ppm. (Z)-1b: 1H NMR (300 MHz,
CDCl3): δ = 6.31 (d, J = 7.1 Hz, 1 H, C=CH), 5.18 (d, J = 7.1 Hz,
= 7.86 (d, J = 8.1 Hz, 2 H, Ar), 7.31 (d, J = 8.1 Hz, 2 H, Ar), 5.04
(t, J = 4.3 Hz, 1 H, CH2CH), 3.95–3.75 (m, 4 H, CH2CH2), 2.98
(d, J = 4.3 Hz, 2 H, CH2CH), 2.93 (q, J = 7.2 Hz, 2 H), 1.17 (t, J
= 7.2 Hz, 3 H, Me) ppm. 13C NMR (75 MHz, CDCl3): δ = 200.4,
141.4, 135.2, 129.8, 127.9, 103.9, 64.9, 40.5, 31.5, 8.1 ppm.
C13H16O3 (220): calcd. C 70.89, H 7.32; found C 70.98, H 7.15.
Before purification, traces of 1-(2-hydroxyethoxy)-1-(4-propi-
onylphenyl)ethene (6a) were also observed. 1H NMR (300 MHz,
CDCl3): δ = 4.75 (d, J = 3.2 Hz, 1 H, C=CH2), 4.31 (d, J = 3.2 Hz,
1 H, C=CH2) ppm. The other peaks were hidden by those of com-
pound 6d.
1
1 H, C=CH) ppm. (E)-1c: H NMR (300 MHz, CDCl3): δ = 7.09
(d, J = 13.0 Hz, 1 H, C=CH), 5.78 (d, J = 13.0 Hz, 1 H, C=CH)
ppm.
2-(4-Fluorobenzyl)-1,3-dioxolane (2d): Isomer 2d was obtained in
52% (0.095 g) isolated yield. Oil. 1H NMR (300 MHz, CDCl3): δ
= 7.20 (dd, J = 8.5 and 5.5 Hz, 2 H, Ar), 6.97 (dd, J = 8.5 and
8.5 Hz, 2 H, Ar), 5.01 (t, J = 4.7 Hz, 1 H, CH2CH), 3.95–3.80 (m,
4 H, CH2CH2), 2.92 (d, J = 4.7 Hz, 2 H, CH2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 161.8 (d, J = 244.4 Hz), 131.7 (d, J =
2.9 Hz), 131.1 (d, J = 8.0 Hz), 115.1 (d, J = 21.2 Hz), 104.4, 65.0,
39.9 ppm. C10H11FO2 (182): calcd. C 65.92, H 6.09; found C 65.73,
H 6.17. MS (EI, 70 eV): m/z (%) = 182 (1) [M+]. Before purifica-
tion, 2-(4-fluorophenyl)-2-methyl-1,3-dioxolane (2e) and 2a–c were
also present. 2e: 1H NMR (300 MHz, CDCl3): δ = 7.43 (dd, J =
8.5 and 5.5 Hz, 2 H, Ar), 7.00 (dd, J = 8.5 and 8.5 Hz, 2 H, Ar),
4.03 (m, 2 H, CH2CH2), 3.76 (m, 2 H, CH2CH2), 1.63 (s, 3 H, Me)
[42]
2-(4-Cyanobenzyl)-1,3-dioxolane (7d):
Isomer 7d was obtained
1
in 92% (0.174 g) isolated yield. H NMR (300 MHz, CDCl3): δ =
7.57 (d, J = 8.3 Hz, 2 H, Ar), 7.38 (d, J = 8.3 Hz, 2 H, Ar), 5.07
(t, J = 4.5 Hz, 1 H, CH2CH), 3.93–3.80 (m, 4 H, CH2CH2), 3.02
(d, J = 4.5 Hz, 2 H, CH2CH). Before purification, traces of 2-(4-
cyanophenyl)-2-methyl-1,3-dioxolane (7e) were also observed. 1H
NMR (300 MHz, CDCl3): δ = 1.59 (s, 3 H, Me) ppm. The other
peaks were hidden by those of compound 7d.
1
ppm. 2a: H NMR (300 MHz, CDCl3): δ = 4.56 (d, J = 2.9 Hz, 1
[43]
H, C=CH2), 4.17 (d, J = 2.9 Hz, 1 H, C=CH2) ppm. (Z)-2b: 1H 2-(4-Nitrobenzyl)-1,3-dioxolane (8d):
Isomer 8d was obtained in
NMR (300 MHz, CDCl3): δ = 6.17 (d, J = 7.1 Hz, 1 H, C=CH),
5.13 (d, J = 7.1 Hz, 1 H, C=CH). (E)-2c: 1H NMR (300 MHz, (d, J = 8.7 Hz, 2 H, Ar), 7.42 (d, J = 8.7 Hz, 2 H, Ar), 5.09 (t, J
CDCl3): δ = 5.77 (d, J = 13.0 Hz, 1 H, C=CH) ppm. = 4.4 Hz, 1 H, CH2CH), 3.95–3.80 (m, 4 H, CH2CH2), 3.06 (d, J
87% (0.182 g) isolated yield. 1H NMR (300 MHz, CDCl3): δ = 8.15
770
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 765–774

Direct Synthesis of Protected Arylacetaldehydes
FULL PAPER
= 4.4 Hz, 2 H, CH2CH). Before purification, traces of 2-methyl-
2-(4-nitrophenyl)-1,3-dioxolane (8e) were also observed. H NMR
(m, 2 H, CH2CH2), 1.65 (s, 3 H, Me) ppm. The other peaks were
hidden by those of compound 13d.
1
(300 MHz, CDCl3): δ = 1.62 (s, 3 H, Me) ppm. The other peaks
were hidden by those of compound 8d.
2-(3-Acetylbenzyl)-1,3-dioxolane (14d): Isomer 14d was obtained in
90% (0.186 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
= 7.84 (s, 1 H, Ar), 7.80 (d, J = 7.8 Hz, 1 H, Ar), 7.46 (d, J =
7.8 Hz, 1 H, Ar), 7.38 (t, J = 7.8 Hz, 1 H, Ar), 5.06 (t, J = 4.8 Hz,
1 H, CH2CH), 3.94–3.78 (m, 4 H, CH2CH2), 3.00 (d, J = 4.8 Hz,
1
[44]
2-[4-(Trifluoromethyl)benzyl]-1,3-dioxolane (9d):
Isomer 9d was
obtained in 90% (0.209 g) isolated yield. 1H NMR (300 MHz,
CDCl3): δ = 7.55 (d, J = 8.2 Hz, 2 H, Ar), 7.38 (d, J = 8.2 Hz, 2
H, Ar), 5.07 (t, J = 4.8 Hz, 1 H, CH2CH), 3.95–3.80 (m, 4 H, 2 H, CH2CH), 2.57 (s, 3 H, Me) ppm. 13C NMR (75 MHz, CDCl3):
CH2CH2), 3.02 (d, J = 4.8 Hz, 2 H, CH2CH). Before purification, δ = 198.1, 137.1, 136.6, 134.5, 129.5, 128.4, 126.6, 104.1, 64.9, 40.3,
traces of 2-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-dioxolane (9e)
were also observed. H NMR (300 MHz, CDCl3): δ = 4.05 (m, 2
26.6 ppm. C12H14O3 (206): calcd. C 69.88, H 6.84; found C 69.69,
1
H 6.61. MS (EI, 70 eV): m/z (%) = 206 (3) [M+]. Before purifica-
H, CH2CH2), 3.75 (m, 2 H, CH2CH2), 1.64 (s, 3 H, Me) ppm. The tion, traces of 2-(3-acetylphenyl)-2-methyl-1,3-dioxolane (14e) were
other peaks were hidden by those of compound 9d.
also observed. 1H NMR (300 MHz, CDCl3): δ = 8.08 (s, 1 H, Ar),
7.89 (d, J = 7.8 Hz, 1 H, Ar), 7.69 (d, J = 7.8 Hz, 1 H, Ar), 7.44
(t, J = 7.8 Hz, 1 H, Ar), 4.06 (m, 2 H, CH2CH2), 3.77 (m, 2 H,
CH2CH2), 2.61 (s, 3 H, Me), 1.64 (s, 3 H, Me) ppm.
[24]
2-Benzyl-1,3-dioxolane (10d):
Isomer 10d was obtained in 52%
(0.85 g) isolated yield. 1H NMR (300 MHz, CDCl3): δ = 7.30–7.10
(m, 5 H, Ar), 5.04 (t, J = 4.8 Hz, 1 H, CH2CH), 3.95–3.75 (m, 4
H, CH2CH2), 2.95 (d, J = 4.8 Hz, 2 H, CH2CH). Before purifica-
tion, the presence of (Z)-2-(2-phenylvinyloxy)ethanol (10b), (E)-2-
(2-phenylvinyloxy)ethanol (10c) and 2-methyl-2-phenyl-1,3-dioxol-
2-(3-Formylbenzyl)-1,3-dioxolane (15d): Isomer 15d was obtained in
1
91% (0.175 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
= 9.96 (s, 1 H, CHO), 7.75 (s, 1 H, Ar), 7.71 (d, J = 7.3 Hz, 1 H,
Ar), 7.52 (d, J = 7.3 Hz, 1 H, Ar), 7.42 (t, J = 7.3 Hz, 1 H, Ar),
1
ane (10e) was also observed. 10b: H NMR (300 MHz, CDCl3): δ
= 6.23 (d, J = 7.1 Hz, 1 H, C=CH), 5.25 (d, J = 7.1 Hz, 1 H, 5.06 (t, J = 4.8 Hz, 1 H, CH2CH), 3.92–3.76 (m, 4 H, CH2CH2),
1
C=CH) ppm. 10c: H NMR (300 MHz, CDCl3): δ = 7.01 (d, J = 3.01 (d, J = 4.8 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz,
13.0 Hz, 1 H, C=CH), 5.87 (d, J = 13.0 Hz, 1 H, C=CH) ppm. CDCl3): δ = 192.3, 137.1, 136.3, 135.9, 131.0, 128.8, 127.9, 103.9,
10e: 1H NMR (300 MHz, CDCl3): δ = 7.47 (d, J = 8.3 Hz, 2 H, 64.9, 40.2 ppm. C11H12O3 (192): calcd. C 68.74, H 6.29; found C
Ar), 7.35–7.25 (m, 3 H, Ar), 4.03 (m, 2 H, CH2CH2), 3.75 (m, 2
H, CH2CH2), 1.64 (s, 3 H, Me) ppm. The other peaks were hidden.
68.45, H 6.09. MS (EI, 70 eV): m/z (%) = 192 (3) [M+]. Before
purification, traces of 2-(3-formylphenyl)-2-methyl-1,3-dioxolane
1
(15e) were also observed. H NMR (300 MHz, CDCl3): δ = 10.02
2-(4-tert-Butylbenzyl)-1,3-dioxolane (11d)[42] and Products 11b, 11c
and 11e: A mixture of isomers 11b–e was obtained in 87% (0.191 g)
(s, 1 H, CHO), 4.06 (m, 2 H, CH2CH2), 3.77 (m, 2 H, CH2CH2),
1.65 (s, 3 H, Me) ppm. The other peaks were hidden by those of
compound 15d.
1
isolated yield. 11d: H NMR (300 MHz, CDCl3): δ = 7.32 (d, J =
8.1 Hz, 2 H, Ar), 7.19 (d, J = 8.1 Hz, 2 H, Ar), 5.03 (t, J = 4.9 Hz,
1 H, CH2CH), 3.95–3.82 (m, 4 H, CH2CH2), 2.92 (d, J = 4.9 Hz,
2-(3-Nitrobenzyl)-1,3-dioxolane (16d): Isomer 16d was obtained in
1
1
2 H, CH2CH), 1.28 (s, 9 H, tBu) ppm. 11b: H NMR (300 MHz,
84% (0.176 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
CDCl3): δ = 6.20 (d, J = 7.0 Hz, 1 H, C=CH), 5.26 (d, J = 7.0 Hz, = 8.14 (s, 1 H, Ar), 8.09 (d, J = 7.6 Hz, 1 H, Ar), 7.60 (d, J =
1
1 H, C=CH) ppm. 11c: H NMR (300 MHz, CDCl3): δ = 7.27 (d, 7.6 Hz, 1 H, Ar), 7.45 (t, J = 7.6 Hz, 1 H, Ar), 5.09 (t, J = 4.4 Hz,
J = 8.3 Hz, 2 H, Ar), 7.15 (d, J = 8.3 Hz, 2 H, Ar), 6.97 (d, J =
13.0 Hz, 1 H, C=CH), 5.87 (d, J = 13.0 Hz, 1 H, C=CH), 1.29 (s,
9 H, tBu) ppm. 11e: H NMR (300 MHz, CDCl3): δ = 1.68 (s, 3
1 H, CH2CH), 3.94–3.80 (m, 4 H, CH2CH2), 3.06 (d, J = 4.4 Hz,
2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.1, 138.0,
136.1, 129.0, 124.7, 121.7, 103.5, 65.1, 40.1 ppm. C10H11NO4 (209):
calcd. C 57.41, H 5.30; found C 57.11, H 5.12. Before purification,
traces of 2-[1-(3-nitrophenyl)vinyloxy]ethanol (16a) were also ob-
served. 1H NMR (300 MHz, CDCl3): δ = 4.79 (d, J = 3.2 Hz, 1 H,
C=CH2), 4.38 (d, J = 3.2 Hz, 1 H, C=CH2) ppm. The other peaks
were hidden by those of compound 16d.
1
H, Me) ppm. The other peaks were hidden.
2-[3,5-Bis(trifluoromethyl)benzyl]-1,3-dioxolane (12d): Isomer 12d
was obtained in 90% (0.270 g) isolated yield. Oil. 1H NMR
(300 MHz, CDCl3): δ = 7.72 (s, 1 H, Ar), 7.71 (s, 2 H, Ar), 5.09 (t,
J = 4.4 Hz, 1 H, CH2CH), 3.90–3.80 (m, 4 H, CH2CH2), 3.08 (d,
J = 4.4 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 2-[3-(Trifluoromethyl)benzyl]-1,3-dioxolane (17d):[25] Isomer 17d
1
138.4, 131.3 (q, J = 32.3 Hz), 130.1, 123.2 (q, J = 273.1 Hz), 120.6
(q, J = 4.0 Hz), 103.2, 65.1, 40.1 ppm. C12H10F6O2 (300): calcd. C
was obtained in 89% (0.207 g) isolated yield. H NMR (300 MHz,
CDCl3): δ = 7.55–7.35 (m, 4 H, Ar), 5.08 (t, J = 4.5 Hz, 1 H,
48.01, H 3.36; found C 47.89, H 3.42. MS (EI, 70 eV): m/z (%) = CH2CH), 3.95–3.75 (m, 4 H, CH2CH2), 3.01 (d, J = 4.5 Hz, 2 H,
299 (6) [M+]. Before purification, traces of 2-methyl-2-[3,5-bis(tri-
CH2CH). Before purification, traces of 2-[3-(trifluoromethyl)
fluoromethyl)phenyl]-1,3-dioxolane (12e) were also observed. 1H
phenyl]-2-methyl-1,3-dioxolane (17e) were also observed. 1H NMR
NMR (300 MHz, CDCl3): δ = 1.65 (s, 3 H, Me) ppm. The other (300 MHz, CDCl3): δ = 4.05 (m, 2 H, CH2CH2), 3.76 (m, 2 H,
peaks were hidden by those of compound 12d.
CH2CH2), 1.65 (s, 3 H, Me) ppm. The other peaks were hidden by
those of compound 17d.
2-[4-Nitro-3-(trifluoromethyl)benzyl]-1,3-dioxolane (13d): Isomer
13d was obtained in 89% (0.247 g) isolated yield. Oil. 1H NMR
(300 MHz, CDCl3): δ = 7.82 (d, J = 8.3 Hz, 1 H, Ar), 7.72 (s, 1 H,
Ar), 7.61 (d, J = 8.3 Hz, 1 H, Ar), 5.10 (t, J = 4.1 Hz, 1 H,
2-(6-Methoxynaphthalen-2-ylmethyl)-1,3-dioxolane (18d): Isomer
18d was obtained in 44% (0.107 g) isolated yield. White solid. M.p.
1
57 °C. H NMR (300 MHz, CDCl3): δ = 7.73–7.63 (m, 3 H, Ar),
CH2CH), 3.85 (m, 4 H, CH2CH2), 3.09 (d, J = 4.1 Hz, 2 H, 7.38 (dd, J = 8.3, 1.7 Hz, 1 H, Ar), 7.15–7.09 (m, 2 H, Ar), 5.14
CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.7, 141.9,
134.4, 129.4 (q, J = 5.2 Hz), 124.9, 123.4 (q, J = 33.9 Hz), 121.8 (q,
J = 273.6 Hz), 102.8, 65.1, 39.9 ppm. C11H10F3NO4 (277): calcd. C
(t, J = 4.3 Hz, 1 H, CH2CH), 3.97–3.82 (m, 4 H, CH2CH2), 3.90
(s, 3 H, MeO), 3.09 (d, J = 4.3 Hz, 2 H, CH2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 157.3, 133.4, 131.3, 129.1, 129.0, 128.6,
47.66, H 3.64; found C 47.36, H 3.51. MS (EI, 70 eV): m/z (%) = 128.0, 126.7, 118.7, 105.6, 104.7, 65.0, 55.2, 40.7 ppm. C15H16O3
277 (3) [M+]. Before purification, traces of 2-methyl-2-[4-nitro-3-
(244): calcd. C 73.75, H 6.60; found C 73.89, H 6.41. Before purifi-
(trifluoromethyl)phenyl]-1,3-dioxolane (13e) were also observed.
cation, traces of 18a–c were also observed. 18a: 1H NMR
1H NMR (300 MHz, CDCl3): δ = 4.06 (m, 2 H, CH2CH2), 3.76 (300 MHz, CDCl3): δ = 4.75 (d, J = 3.2 Hz, 1 H, C=CH2), 4.28 (d,
Eur. J. Org. Chem. 2006, 765–774
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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771

I. Kondolff, H. Doucet, M. Santelli
FULL PAPER
J = 3.2 Hz, 1 H, C=CH2) ppm. 18b: 1H NMR (300 MHz, CDCl3):
70 eV): m/z (%) = 200 (3) [M+]. Before purification, traces of 2-
(3,4-difluorophenyl)-2-methyl-1,3-dioxolane (23e) were also ob-
δ = 6.26 (d, J = 7.2 Hz, 1 H, C=CH), 5.34 (d, J = 7.2 Hz, 1 H,
1
C=CH) ppm. 18c: H NMR (300 MHz, CDCl3): δ = 5.98 (d, J = served. 1H NMR (300 MHz, CDCl3): δ = 4.03 (m, 2 H, CH2CH2),
12.6 Hz, 1 H, C=CH) ppm. The other peaks were hidden by those
of compound 18d.
3.74 (m, 2 H, CH2CH2), 1.60 (s, 3 H, Me) ppm. The other peaks
were hidden by those of compound 23d.
2-(2-Formylbenzyl)-1,3-dioxolane (19d):[44] Isomer 19d was obtained
2-(2,4-Difluorobenzyl)-1,3-dioxolane (24d): Isomer 24d was ob-
1
in 77% (0.148 g) isolated yield. H NMR (300 MHz, CDCl3): δ = tained in 74% (0.148 g) isolated yield. Oil. 1H NMR (300 MHz,
10.27 (s, 1 H, CHO), 7.86 (dd, J = 7.5 and 1.3 Hz, 1 H, Ar), 7.52
(td, J = 7.5 and 1.6 Hz, 1 H, Ar), 7.41 (td, J = 7.5 and 1.3 Hz, 1
H, Ar), 7.86 (d, J = 7.5 Hz, 1 H, Ar), 5.12 (t, J = 4.6 Hz, 1 H,
CH2CH), 3.85–3.76 (m, 4 H, CH2CH2), 3.41 (d, J = 4.6 Hz, 2 H,
CH2CH). Before purification, traces of 2-(2-formylphenyl)-2-
methyl-1,3-dioxolane (19e) were also observed. 1H NMR
(300 MHz, CDCl3): δ = 1.55 (s, 3 H, Me) ppm. The other peaks
were hidden by those of compound 19d.
CDCl3): δ = 7.29 (m, 1 H, Ar), 6.81 (m, 2 H, Ar), 5.10 (t, J =
4.7 Hz, 1 H, CH2CH), 3.98–3.84 (m, 4 H, CH2CH2), 2.99 (d, J =
4.7 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.6
(dd, J = 246.7 and 11.5 Hz), 161.2 (dd, J = 247.9 and 12.0 Hz),
132.6 (dd, J = 9.8 and 5.3 Hz), 118.8 (dd, J = 16.1 and 4.0 Hz),
110.9 (dd, J = 10.7 and 3.5 Hz), 103.6 (t, J = 25.2 Hz), 103.3, 65.0,
33.1 ppm. C10H10F2O2 (200): calcd. C 60.00, H 5.04; found C
59.76, H 5.09. MS (EI, 70 eV): m/z (%) = 200 (3) [M+]. Before
purification, traces of 2-(2,4-difluorophenyl)-2-methyl-1,3-dioxol-
ane (24e) were also observed. 1H NMR (300 MHz, CDCl3): 4.04
(m, 2 H, CH2CH2), 1.71 (s, 3 H, Me) ppm. The other peaks were
hidden by those of compound 24d.
2-(2-Cyanobenzyl)-1,3-dioxolane (20d): Isomer 20d was obtained in
91% (0.172 g) isolated yield. Oil. 1H NMR (300 MHz, CDCl3): δ
= 7.60 (d, J = 7.8 Hz, 1 H, Ar), 7.51 (t, J = 7.5 Hz, 1 H, Ar), 7.42
(d, J = 7.5 Hz, 1 H, Ar), 7.31 (t, J = 7.6 Hz, 1 H, Ar), 5.16 (t, J =
4.8 Hz, 1 H, CH2CH), 3.95–3.80 (m, 4 H, CH2CH2), 3.17 (d, J =
4.8 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ =
2-(2-Fluorobenzyl)-1,3-dioxolane (25d): Isomer 25d was obtained in
1
61% (0.111 g) isolated yield. Oil. H NMR (300 MHz, CDCl3): δ
139.7, 132.6, 132.4, 131.0, 127.1, 118.1, 113.6, 103.3, 65.0, = 7.28 (td, J = 7.3 and 1.7 Hz, 1 H, Ar), 7.20 (t, J = 7.6 Hz, 1 H,
39.1 ppm. C11H11NO2 (189): calcd. C 69.83, H 5.86; found C 69.56,
H 5.90. MS (EI, 70 eV): m/z (%) = 190 (15) [M+]. Before purifica-
tion, traces of 2-[1-(2-cyanophenyl)vinyloxy]ethanol (20a) were also
Ar), 7.10–6.97 (m, 2 H, Ar), 5.11 (t, J = 4.7 Hz, 1 H, CH2CH),
3.95–3.80 (m, 4 H, CH2CH2), 3.00 (d, J = 4.7 Hz, 2 H, CH2CH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 161.3 (d, J = 245.5 Hz),
131.9 (d, J = 4.6 Hz), 128.4 (d, J = 8.6 Hz), 123.9 (d, J = 4.0 Hz),
1
observed. H NMR (300 MHz, CDCl3): δ = 4.65 (d, J = 3.2 Hz, 1
H, C=CH2), 4.43 (d, J = 3.2 Hz, 1 H, C=CH2) ppm. The other 123.1 (d, J = 15.5 Hz), 115.1 (d, J = 22.4 Hz), 103.5, 65.0,
peaks were hidden by those of compound 20d.
33.8 ppm. C10H11FO2 (182): calcd. C 65.92, H 6.09; found C 65.64,
H 6.07. Before purification, 2-(2-fluorophenyl)-2-methyl-1,3-diox-
olane (25e) was also observed. H NMR (300 MHz, CDCl3): δ =
1.59 (s, 3 H, Me) ppm. The other peaks were hidden by those of
compound 25d.
2-[2-(Trifluoromethyl)benzyl]-1,3-dioxolane (21d): Isomer 21d was
1
1
obtained in 88% (0.204 g) isolated yield. Oil. H NMR (300 MHz,
CDCl3): δ = 7.63 (d, J = 8.0 Hz, 1 H, Ar), 7.49 (m, 2 H, Ar), 7.32
(t, J = 8.0 Hz, 1 H, Ar), 5.07 (t, J = 4.9 Hz, 1 H, CH2CH), 4.00
(m, 2 H, CH2CH2), 3.86 (m, 2 H, CH2CH2), 3.14 (d, J = 4.9 Hz,
2-(2-Methylbenzyl)-1,3-dioxolane (26d):[45] Isomer 26d was obtained
2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.7, 132.5, in 57% (0.102 g) isolated yield. H NMR (300 MHz, CDCl3): δ =
1
131.6, 129.1 (q, J = 29.6 Hz), 126.7, 125.9 (q, J = 5.5 Hz), 124.8
(q, J = 274.3 Hz), 103.9, 64.9, 37.4 ppm. C11H11F3O2 (232): calcd.
C 56.90, H 4.77; found C 57.05, H 4.65. MS (EI, 70 eV): m/z (%)
= 231 (6) [M+]. Before purification, traces of 2-methyl-2-[2-(trifluo-
romethyl)phenyl]-1,3-dioxolane (21e) were also observed. 1H NMR
(300 MHz, CDCl3): δ = 1.74 (s, 3 H, Me) ppm. The other peaks
were hidden by those of compound 21d.
7.25–7.00 (m, 4 H, Ph), 5.04 (t, J = 4.9 Hz, 1 H, CH2CH), 3.97–
3.80 (m, 4 H, CH2CH2), 2.98 (d, J = 4.9 Hz, 2 H, CH2CH), 2.34
(s, 3 H, Me). Before purification, the presence of 26a–c was also
observed. 26a: 1H NMR (300 MHz, CDCl3): δ = 4.35 (d, J =
2.1 Hz, 1 H, C=CH2), 4.21 (d, J = 2.1 Hz, 1 H, C=CH2) ppm. 26b:
1H NMR (300 MHz, CDCl3): δ = 6.29 (d, J = 7.2 Hz, 1 H, C=CH),
1
5.38 (d, J = 7.2 Hz, 1 H, C=CH) ppm. 26c: H NMR (300 MHz,
CDCl3): δ = 6.84 (d, J = 12.6 Hz, 1 H, C=CH), 6.01 (d, J =
12.6 Hz, 1 H, C=CH) ppm. The other peaks were hidden by those
of compound 26d.
Methyl 2-(1,3-Dioxolan-2-ylmethyl)benzoate (22): Isomer 22d was
obtained in 77% (0.171 g) isolated yield. Oil. H NMR (300 MHz,
CDCl3): δ = 7.86 (d, J = 7.5 Hz, 1 H, Ar), 7.44 (t, J = 7.5 Hz, 1
H, Ar), 7.33 (d, J = 8.2 Hz, 1 H, Ar), 7.29 (t, J = 7.5 Hz, 1 H, Ar),
5.12 (t, J = 4.9 Hz, 1 H, CH2CH), 3.88 (s, 3 H, Me), 3.87–3.77 (m,
4 H, CH2CH2), 3.37 (d, J = 4.9 Hz, 2 H, CH2CH) ppm. 13C NMR
1
2-(Naphthalen-1-yl)methyl-1,3-dioxolane (27d): Isomer 27d was ob-
tained in 74% (0.159 g) isolated yield. Oil. 1H NMR (300 MHz,
CDCl3): δ = 8.11 (d, J = 8.3 Hz, 1 H, Ar), 7.87 (d, J = 8.0 Hz, 1
(75 MHz, CDCl3): δ = 168.2, 137.4, 132.5, 131.7, 130.6, 130.4, H, Ar), 7.78 (d, J = 7.0 Hz, 1 H, Ar), 7.57–7.42 (m, 4 H, Ar), 5.25
126.7, 104.3, 64.9, 51.9, 38.3 ppm. C12H14O4 (222): calcd. C 64.85,
H 6.35; found C 64.74, H 6.18. Before purification, traces of methyl
2-(2-methyl-1,3-dioxolan-2-yl)benzoate (22e) were also observed.
1H NMR (300 MHz, CDCl3): δ = 1.77 (s, 3 H, Me) ppm. The other
peaks were hidden by those of compound 22d.
(t, J = 4.9 Hz, 1 H, CH2CH), 3.99 (m, 2 H, CH2CH2), 3.84 (m, 2
H, CH2CH2), 3.47 (d, J = 4.9 Hz, 2 H, CH2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 133.8, 132.4, 132.3, 128.6, 127.8, 127.4,
125.8, 125.4 (2C), 123.9, 104.2, 64.9, 37.7 ppm. C14H14O2 (214):
calcd. C 78.48, H 6.59; found C 78.56, H 6.71. MS (EI, 70 eV):
m/z (%) = 214 (63) [M+]. Before purification, traces of 2-methyl-2-
(naphthalen-1-yl)-1,3-dioxolane (27e) were also observed. 1H NMR
(300 MHz, CDCl3): δ = 4.10 (m, 2 H, CH2CH2), 1.90 (s, 3 H, Me)
ppm. The other peaks were hidden by those of compound 27d.
2-(3,4-Difluorobenzyl)-1,3-dioxolane (23d): Isomer 23d was ob-
tained in 79% (0.158 g) isolated yield. Oil. 1H NMR (300 MHz,
CDCl3): δ = 7.15–6.90 (m, 3 H, Ar), 5.02 (t, J = 4.7 Hz, 1 H,
CH2CH), 3.95–3.80 (m, 4 H, CH2CH2), 2.90 (d, J = 4.7 Hz, 2 H,
CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.1 (dd, J =
247.5 and 12.6 Hz), 149.2 (dd, J = 246.4 and 12.6 Hz), 132.9 (dd,
J = 6.1 and 3.9 Hz), 125.7 (dd, J = 6.1 and 3.9 Hz), 118.6 (d, J =
17.0 Hz), 116.8 (d, J = 17.0 Hz), 103.9, 65.0, 39.8 ppm. C10H10F2O2
(200): calcd. C 60.00, H 5.04; found C 59.84, H 4.79. MS (EI,
2-(Anthracen-9-yl)methyl-1,3-dioxolane (28d): Isomer 28d was ob-
1
tained in 79% (0.209 g) isolated yield. White solid. M.p. 93 °C. H
NMR (300 MHz, CDCl3): δ = 8.39 (s, 1 H, Ar), 8.37 (d, J = 8.3 Hz,
2 H, Ar), 8.01 (d, J = 8.3 Hz, 2 H, Ar), 7.56–7.43 (m, 4 H, Ar),
5.32 (t, J = 4.8 Hz, 1 H, CH2CH), 4.04 (d, J = 4.8 Hz, 2 H,
772
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Eur. J. Org. Chem. 2006, 765–774

Direct Synthesis of Protected Arylacetaldehydes
FULL PAPER
CH2CH), 4.01 (m, 2 H, CH2CH2), 3.81 (m, 2 H, CH2CH2) ppm. 70 eV): m/z (%) = 215 (90) [M+]. Before purification, traces of 2-[(1-
13C NMR (75 MHz, CDCl3): δ = 131.5, 130.7, 129.0, 128.3, 126.8, isoquinol-4-yl)vinyloxy]ethanol (33a) were also observed. 1H NMR
125.6, 125.9, 124.8, 104.2, 65.0, 32.7 ppm. C18H16O2 (264): calcd.
C 81.79, H 6.10; found C 81.89, H 6.19. MS (EI, 70 eV): m/z (%)
= 264 (31) [M+]. Before purification, traces of 2-(anthracen-9-yl)-
2-methyl-1,3-dioxolane (28e) were also observed. 1H NMR
(300 MHz, CDCl3): δ = 4.10 (m, 2 H, CH2CH2), 2.25 (s, 3 H, Me)
ppm. The other peaks were hidden by those of compound 28d.
(300 MHz, CDCl3): δ = 4.56 (d, J = 3.2 Hz, 1 H, C=CH2), 4.47 (d,
J = 3.2 Hz, 1 H, C=CH2) ppm. The other peaks were hidden by
those of compound 33d.
2-(Pyrimid-5-ylmethyl)-1,3-dioxolane (34d): Isomer 34d was ob-
tained in 76% (0.126 g) isolated yield. Oil. 1H NMR (300 MHz,
CDCl3): δ = 9.09 (s, 1 H, Ar), 8.65 (s, 2 H, Ar), 5.09 (t, J = 4.0 Hz,
1 H, CH2CH), 3.82 (m, 4 H, CH2CH2), 2.95 (d, J = 4.0 Hz, 2 H,
CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.0 (2C), 157.0,
129.2, 102.5, 65.2, 35.0 ppm. C8H10N2O2 (166): calcd. C 57.82, H
6.07; found C 57.92, H 5.88. MS (EI, 70 eV): m/z (%) = 166 (71)
[M+].
1,2-Bis(1,3-dioxolan-2-ylmethyl)benzene (29dd): Isomer 29dd was
1
obtained in 51% (0.228 g) isolated yield. Oil. H NMR (300 MHz,
CDCl3): δ = 7.30–7.15 (m, 4 H, Ar), 5.06 (t, J = 4.3 Hz, 2 H,
CH2CH), 3.97–3.77 (m, 8 H, CH2CH2), 3.08 (d, J = 4.3 Hz, 4 H,
CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 135.0, 130.8,
126.7, 104.7, 64.9, 37.5 ppm. C14H18O4 (250): calcd. C 67.18, H
7.25; found C 67.30, H 7.35.
3,5-Bis(1,3-dioxolan-2-ylmethyl)pyridine (35dd): Isomer 35dd was
1
obtained in 78% (0.196 g) isolated yield. Oil. H NMR (300 MHz,
2-(Pyrid-3-ylmethyl)-1,3-dioxolane (30d): Isomer 30d was obtained
CDCl3): δ = 8.28 (s, 2 H, Ar), 7.45 (s, 1 H, Ar), 4.98 (t, J = 4.3 Hz,
2 H, CH2CH), 3.85–3.65 (m, 8 H, CH2CH2), 2.85 (d, J = 4.3 Hz,
4 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.8, 138.7,
130.8, 103.5, 64.8, 37.4 ppm. C13H17NO4 (251): calcd. C 62.14, H
6.82; found C 62.31, H 6.70.
1
in 83% (0.137 g) isolated yield. Oil. H NMR (300 MHz, CDCl3):
δ = 8.48 (d, J = 2.1 Hz, 1 H, Ar), 8.76 (dd, J = 5.0 and 1.7 Hz, 1
H, Ar), 7.57 (dt, J = 7.9 and 1.7 Hz, 1 H, Ar), 7.19 (dd, J = 7.9
and 5.0 Hz, 1 H, Ar), 5.05 (t, J = 4.3 Hz, 1 H, CH2CH), 3.90–3.75
(m, 4 H, CH2CH2), 2.94 (d, J = 4.3 Hz, 2 H, CH2CH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 150.8, 147.8, 137.5, 131.5, 123.1,
103.6, 65.0, 37.7 ppm. C9H11NO2 (165): calcd. C 65.44, H 6.71;
found C 65.21, H 6.82. MS (EI, 70 eV): m/z (%) = 165 (17) [M+].
Before purification, traces of 2-[1-(pyrid-3-yl)vinyloxy]ethanol
(30a) were also observed. 1H NMR (300 MHz, CDCl3): δ = 4.70
(d, J = 3.2 Hz, 1 H, C=CH2), 4.31 (d, J = 3.2 Hz, 1 H, C=CH2)
ppm. The other peaks were hidden by those of compound 30d.
5-(1,3-Dioxolan-2-ylmethyl)furan-2-carbaldehyde (36d): Isomer 36d
was obtained in 78% (0.142 g) isolated yield. Oil. 1H NMR
(300 MHz, CDCl3): δ = 9.54 (s, 1 H, CHO), 7.17 (d, J = 3.4 Hz, 1
H, Ar), 6.39 (d, J = 3.4 Hz, 1 H, Ar), 5.19 (t, J = 4.3 Hz, 1 H,
CH2CH), 4.00–3.80 (m, 4 H, CH2CH2), 3.08 (d, J = 4.3 Hz, 2 H,
CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 177.2, 157.7,
152.2, 122.8, 110.8, 101.7, 65.1, 33.9 ppm. C9H10O4 (182): calcd. C
59.34, H 5.53; found C 59.14, H 5.71. Before purification, traces
of (Z)-5-[2-(2-hydroxyethoxy)vinyl]furan-2-carbaldehyde (36b)
2-(Pyrid-4-ylmethyl)-1,3-dioxolane (31d): Isomer 31d was obtained
1
in 88% (0.145 g) isolated yield. Oil. H NMR (300 MHz, CDCl3):
1
were also observed. H NMR (300 MHz, CDCl3): δ = 5.44 (d, J =
δ = 8.28 (d, J = 6.1 Hz, 2 H, Ar), 7.01 (d, J = 6.1 Hz, 2 H, Ar),
4.88 (t, J = 4.5 Hz, 1 H, CH2CH), 3.60–3.75 (m, 4 H, CH2CH2),
2.78 (d, J = 4.5 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 149.4, 144.9, 125.0, 103.3, 64.9, 39.8 ppm. C9H11NO2
(165): calcd. C 65.44, H 6.71; found C 65.18, H 6.60. Before purifi-
cation, traces of 2-[1-(pyrid-4-yl)vinyloxy]ethanol (31a) were also
7.2 Hz, 1 H, C=CH) ppm. The other peaks were hidden by those
of compound 36d.
1
37a–c: 37a: H NMR (300 MHz, CDCl3): δ = 4.70 (d, J = 1.9 Hz,
1 H, =CH2), 4.28 (d, J = 1.9 Hz, 1 H, =CH2) ppm. 37b: δ = 6.29
(d, J = 7.0 Hz, 1 H, =CH), 5.21 (d, J = 7.0 Hz, 1 H, =CH) ppm.
37c: δ = 7.07 (d, J = 12.8 Hz, 1 H, =CH), 5.82 (d, J = 12.8 Hz, 1
H, =CH) ppm.
1
observed. H NMR (300 MHz, CDCl3): δ = 4.84 (d, J = 3.2 Hz, 1
H, C=CH2), 4.38 (d, J = 3.2 Hz, 1 H, C=CH2) ppm. The other
peaks were hidden by those of compound 31d.
1
38a–c: 38a: H NMR (300 MHz, CDCl3): δ = 4.75 (d, J = 1.5 Hz,
2-(Quinol-3-ylmethyl)-1,3-dioxolane (32d): Isomer 32d was obtained
in 85% (0.183 g) isolated yield. Oil. H NMR (300 MHz, CDCl3):
1
1 H, =CH2), 4.31 (d, J = 1.5 Hz, 1 H, =CH2) ppm. 38b: δ = 6.35
(d, J = 7.0 Hz, 1 H, =CH), 5.24 (d, J = 7.0 Hz, 1 H, =CH) ppm.
38c: δ = 7.11 (d, J = 13.0 Hz, 1 H, =CH), 5.85 (d, J = 13.0 Hz, 1
H, =CH) ppm.
δ = 8.82 (d, J = 2.1 Hz, 1 H, Ar), 8.07 (d, J = 8.1 Hz, 1 H, Ar),
8.04 (d, J = 2.1 Hz, 1 H, Ar), 7.77 (d, J = 8.1 Hz, 1 H, Ar), 7.65
(t, J = 8.1 Hz, 1 H, Ar), 7.50 (t, J = 8.1 Hz, 1 H, Ar), 5.15 (t, J =
4.1 Hz, 1 H, CH2CH), 3.90–3.75 (m, 4 H, CH2CH2), 3.13 (d, J =
4.1 Hz, 2 H, CH2CH) ppm. 13C NMR (75 MHz, CDCl3): δ =
152.4, 146.9, 136.3, 129.0, 128.9, 128.7, 127.6, 127.4, 126.4, 103.6,
65.0, 37.8 ppm. C13H13NO2 (215): calcd. C 72.54, H 6.09; found C
72.72, H 6.00. MS (EI, 70 eV): m/z (%) = 215 (52) [M+]. Before
purification, traces of 2-(1-quinol-3-yl-vinyloxy)ethanol (32a) were
also observed. 1H NMR (300 MHz, CDCl3): δ = 4.88 (d, J =
3.2 Hz, 1 H, C=CH2), 4.42 (d, J = 3.2 Hz, 1 H, C=CH2) ppm. The
other peaks were hidden by those of compound 32d.
1
39a–d: 39a: H NMR (300 MHz, CDCl3): δ = 4.74 (d, J = 1.5 Hz,
1 H, =CH2), 4.19 (d, J = 1.5 Hz, 1 H, =CH2) ppm. 39b: δ = 6.30
(d, J = 7.0 Hz, 1 H, =CH), 5.23 (d, J = 7.0 Hz, 1 H, =CH) ppm.
39c: δ = 7.10 (d, J = 12.0 Hz, 1 H, =CH), 5.83 (d, J = 12.0 Hz, 1
H, =CH) ppm. 39d: δ = 4.83 (t, J = 5.5 Hz, 1 H, CH2CH) ppm.
39e was not detected.
1
40a–d: 40a: H NMR (300 MHz, CDCl3): δ = 4.47 (d, J = 1.5 Hz,
1 H, =CH2), 4.34 (d, J = 1.5 Hz, 1 H, =CH2) ppm. 40b: δ = 5.84
(d, J = 7.0 Hz, 1 H, =CH) ppm. 40c: δ = 6.89 (d, J = 12.0 Hz, 1
H, =CH), 6.45 (d, J = 12.0 Hz, 1 H, =CH) ppm. 40d: δ = 5.01 (t,
J = 5.5 Hz, 1 H, CH2CH) ppm. 40e was not detected.
2-(Isoquinol-4-ylmethyl)-1,3-dioxolane (33d): Isomer 33d was ob-
tained in 81% (0.174 g) isolated yield. Oil. 1H NMR (300 MHz,
CDCl3): δ = 9.12 (s, 1 H, Ar), 8.44 (s, 1 H, Ar), 8.04 (d, J = 8.1 Hz,
1 H, Ar), 7.91 (d, J = 8.1 Hz, 1 H, Ar), 7.69 (t, J = 8.1 Hz, 1 H,
Ar), 7.55 (t, J = 8.1 Hz, 1 H, Ar), 5.18 (t, J = 4.7 Hz, 1 H, CH2CH),
3.92–3.74 (m, 4 H, CH2CH2), 3.33 (d, J = 4.7 Hz, 2 H, CH2CH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 151.7, 144.2, 135.1, 130.1,
Acknowledgments
128.4, 128.0, 126.7, 125.6, 123.3, 103.7, 64.9, 34.7 ppm. C13H13NO2 We thank the CNRS and the “Conseil Général des Bouches-du-
(215): calcd. C 72.54, H 6.09; found C 72.33, H 5.97. MS (EI,
Rhône, France” for providing financial support.
Eur. J. Org. Chem. 2006, 765–774
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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