Oxidative nucleophilic substitution of hydrogen in nitroarenes with phenylacetic acid derivatives

Article abstract of DOI:10.1016/j.tet.2005.09.053

Oxidative nucleophilic substitution of hydrogen (ONSH) in nitroarenes with carbanion of isopropyl phenyl acetate gives various products depending on the conditions and oxidant. The reaction carried out in liquid ammonia and KMnO ₄ oxidant gives

Full text of DOI:10.1016/j.tet.2005.09.053

Tetrahedron 61 (2005) 11952–11964
Oxidative nucleophilic substitution of hydrogen in nitroarenes
with phenylacetic acid derivatives
*
´
Mieczysław Ma˛kosza, Krystyna Kamienska-Trela, Maciej Paszewski
and Małgorzata Bechcicka
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PL-01-224 Warsaw, Poland
Received 9 June 2005; revised 1 September 2005; accepted 15 September 2005
Available online 10 October 2005
Dedicated to Professor V. I. Minkin on the occasion of his 70th birthday
Abstract—Oxidative nucleophilic substitution of hydrogen (ONSH) in nitroarenes with carbanion of isopropyl phenyl acetate gives various
products depending on the conditions and oxidant. The reaction carried out in liquid ammonia and KMnO4 oxidant gives iso-propyl
a-hydroxy-a-nitroarylphenylacetates formed via hydroxylation of the initial ONSH products. In some cases additionally dimeric, trimeric
and tetrameric products are formed. In THF and Bu4NCMnO4K or DDQ oxidants simple ONSH products are formed whereas oxidation by
dimethyl dioxirane (DMD) gave iso-propyl hydroxyaryl phenyl acetates. The dimeric and trimeric products are apparently formed via
coupling of nitrobenzylic radicals generated in course of oxidation with nitrobenzylic carbanions of the ONSH products.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
of the sH adducts in a process analogous to the Nef
reaction.15
Oxidative nucleophilic substitution of hydrogen (ONSH), in
nitroarenes and other electron deficient arenes is presently a
well recognized process.1–6 Of particular interest and value
is introduction of carbon substituents into nitroaromatic
rings via oxidation of sH adducts of carbon nucleophiles
such as Grignard reagents7–9 and carbanions10 to nitro-
arenes. In our recent studies we have shown that this
reaction proceeds efficiently between nitroarenes and
tertiary (methinic) carbanions generated from 2-phenyl-
alkanenitriles11 and esters of iso-butyric12 and 2-phenyl-
propionic acids.13 Addition of these carbanions to
Oxidation of sH adducts of secondary (methylenic)
carbanions to nitroarenes is somewhat more complicated
process because the addition can take place at ortho and
para positions so isomeric sH adducts and subsequently
ONSH products can be formed. Moreover the products in
which hydrogen of the methylenic group is replaced with a
nitroaromatic ring are much stronger CH acids than the
carbanion precursors thus in the case the reaction media
contain basis agents, the ONSH products could be
deprotonated and further oxidized. The highly stabilized
nitrobenzylic carbanions of the ONSH products are weak
nucleophiles and do not form sH adducts with nitroarenes so
disubstitution via ONSH is not observed. There are many
reported examples of ONSH process with secondary
carbanions in which atmospheric oxygen acted as the
oxidant, usually in these cases the reaction requires excess
of base.10,16,17 It is therefore supposed that sH adducts of
such carbanions are further deprotonated before being
oxidized with oxygen. The reaction of secondary carbanion
of phenylacetonitrile with nitrobenzene in liquid ammonia
and KMnO4 oxidant gave a mixture of o- and p-nitrobenzo-
phenones.18 It seems that the initial ONSH products formed
by oxidation of the sH adducts ortho and para to the
nitrogroup were deprotonated and the produced carbanions
oxidized to cyanohydrines that dissociated to
benzophenones.
nitroarenes proceeds mainly para to the nitro group and
11–13
the produced sH adducts are oxidized by KMnO4
in
liquid ammonia or DDQ in THF giving products of ONSH
in para positions. It should be noted that oxidation with
KMnO4 is sensitive to steric hindrances, bulky substituents
ortho to the addition site (meta to the nitro group) hinder or
inhibit the oxidation process.11 On the other hand,
oxidation of these sH adducts with dimethyl dioxirane
(DMD) in THF gives para substituted phenols.14,15 This
oxidant reacts directly with negatively charged nitro group
Keywords: Carbanions; Nitroarenes; s-Adducts; Oxidation; Nucleophilic
substitution.
*
Corresponding author. Tel.: C48 22 3432334; fax: C48 22 6326681;
e-mail: icho-s@icho.edu.pl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.053

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11953
Scheme 1.
2. Results and discussion
correlation spectra of the compounds 5e and 6e they were
assigned dimeric and trimeric structures, respectively, as
shown in Scheme 1. Detailed analyses of the NMR spectra
of compounds 5 and 6 are presented at the end of the paper.
Results of the reaction of 2 with nitroarenes and KMnO4
oxidant are given in Table 1
The products of ONSH reaction in nitroarenes by
carbanions of alkyl phenylacetates—esters of nitroaryl
phenylacetic acids—upon deprotonation and further oxi-
dation should form esters of a-hydroxy nitroaryl phenyl-
acetic acids. Since such esters should be stable under these
conditions we have studied ONSH reaction in a series of
substituted nitrobenzenes 1a–o with carbanion of iso-propyl
phenylacetate 2. The reactions were carried out in liquid
ammonia, the carbanions generated by action of NaNH2 and
the intermediate sH adducts oxidized with KMnO4. Since
the expected ONSH products 3a should be strong CH acids
the base was used in excess. The reaction of 2 with
nitrobenzene 1a in ratio 1:1 gave not a simple ONSH
product 3a, but iso-propyl 2-phenyl-2-p-nitrophenyl-2-
hydroxypropionate 4a, in moderate yield 40%. Obviously,
the expected initially formed ONSH product was further
deprotonated and oxidized in form of nitrobenzylic
carbanion to the hydroxy ester. When nitrobenzene was
used in an excess (2 equiv) yield of 4a was much higher:
78%. It seems therefore that in the former case, due to
moderate electrophilicity of 1a, the addition equilibrium
was not sufficiently shifted to the sH adducts, hence in
further experiments nitroarenes were used in excess. It
should be mentioned that under these conditions the ONSH
reaction proceeded only para to the nitro group. Similar
products were formed in the reaction of 2 with a series of
nitroarenes 1b–m.
Table 1. Oxidation of sH adducts of 2K to nitroarenes by KMnO4 in NH3liq
and by Bu4NCMnOK4 in THF (Scheme 1)
ArNO2
No.
Products, No. yields
KMnO4/NH3liqa
X
QCMnOK4
THFb
/
H
2-F
3-F
1a
1b
1c
1d
1e
1f
1g
1h
1j
4a
4b
4c
4d
4e
4f
4g
4h
4j
78
77
39
57
29
60
27
22
29
47
26
40
3b
3c
3d
3e
3f
45
20
30
69
26
73
5c
5e
27
39
6c
6e
5
2-Cl
3-Cl
2-Br
3-Br
3-I
3-MeO
2-CN
2-NTd
1-NNe
15
5g
5h
5j
48
37
19
6g
6h
6j
17
13
3g
23c
1k
1l
1m
4k
4l
4m
a
2
Ratio ArNO : 2Z2.
b
2
Ratio ArNO : 2Z1.2.
c Tetramer 6j0 was also isolated.
d 2-Nitrothiophene.
e 1-Nitronaphthalene.
It should be stressed that compounds 5 and 6 were formed
only when the reacting nitroarene contained a substituent X
located meta to the nitro group. It appears that this
substituent affects the reaction course due to its steric, not
electronic, effects because products 5 and 6 were formed
also in the reaction of 2 with nitrobenzene substituted in
meta position not only with halogens but also with
electrodonating group (XZOMe), m-nitroanisole 1j. It
appears that hydroxy esters 3 and dimeric and trimeric
products 5 and 6 are formed as a result of oxidation of
The reaction of 2 with m-halonitrobenzenes 1c,e,g,h, and j
was more complicated. Besides of the expected a-hydroxy-
esters 4c,e,g,h,j, produced via hydroxylation of the initial
ONSH products, substantial quantities of products of higher
molecular weight were isolated from the reaction mixtures.
For instance the reaction of 2 with m-chloronitrobenzene 1e
gave expected hydroxyester 4e 29% and two other products
5e and 6e. On the basis of detailed MS (EI and ESI
experiments), 1H and 13C NMR analysis including

11954
M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
Scheme 2.
carbanions of initial ONSH products 3. In the oxidation of
the initial products of ONSH in nitroarenes containing
substituents X in meta position formation of dimeric
products 5 competes with the hydroxylation reaction. In
order to confirm that products 4, 5 and 6 are indeed formed
via oxidation of nitrobenzylic carbanions of the initial
ONSH products, 3a and 3e were prepared independently via
SNAr of halogen in 4-fluoro and 3,4-dichloronitrobenzene

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11955
Scheme 3.
with carbanion of 2. These nitroarylated esters 3a and 3e
dissolved in liquid ammonia are deprotonated by the solvent
to a low degree, addition of NaNH2 to such solutions
converts 3a and 3e into carbanions 3aK and 3eK that are
stable and can be recovered upon acidification of the
solution with NH4Cl. Treatment of a solution of carbanion
of 3a in NH3 liquid with KMnO4 gave 4a whereas carbanion
of 3e gave a mixture of 4e, 5e and 6e, respectively.
Composition of the latter mixture was similar to that
obtained in the direct reaction of 2 with 3-chloronitro-
benzene. These results confirm that of 4, 5 and 6 are
produced by further conversion of 3 as shown in Scheme 1.
Formation and oxidation of sH adducts with permanganate
anions can be carried out not only in liquid NH3 but also in
moderately polar solvents, for example, THF, provided a
soluble salt of this anion is used. Indeed, treatment of 2 with
t-BuOK in THF produced carbanions that form sH adducts
upon addition of ArNO2. Oxidation of such system with
tetrabutylammonium permanganate, results in formation of
ONSH products 3 in moderate to good yields. Interestingly
no hydroxylated esters 4 were formed under these
conditions and the reaction proceeded only para to the
nitro group. Results of these reactions are presented in
Table 1.
It appears that compounds 5 and 6 are formed via coupling
of carbanions 3K with free radicals of 3, produced by
oxidation of carbanions of 3 by KMnO4. A speculative
pathway of formation of 4 and 5 is shown in Scheme 2.
Perhaps substituents X hinder conjugation of the carbo-
anionic and free radical centers in 3K and 3% with the
nitroaryl rings, whereas steric hindrances prevent addition
of 3% to the carbanion a- to the alkoxycarbonyl group.
Thanks to the increased electron density on unsubstituted
phenyl ring of 3K it adds electrophilic radical 3% giving
anion-radical, that is subsequently oxidized, deprotonated
and hydroxylated to 5. On the other hand, direct oxidation of
3% with KMnO4 gave 4. Thus competition between
formation of 4 and 5 seems to depend on relation of rates
of direct oxidation 3%/4 and addition of 3% to 3K, that is
affected by steric effects of substituents X. Similar
carbanion coupling under oxidative condition has been
previously observed.19,20
Another oxidant, widely used for oxidation of the anionic
sH adducts, is DDQ. For obvious reasons it cannot be used
in the reactions carried out in liquid ammonia. Oxidation of
sH adducts of 2K to nitroarenes generated in THF with
DDQ gave somewhat different results as compared with
oxidation by QCMnO4K. As it was mentioned earlier,
permanganate anions oxidize efficiently only sH adducts
para to the nitro group so with KMnO4 and QCMnO4K
oxidants the reaction of 2 with nitroarenes 1 gave products
3, 4 (and 5 and 6), in which hydrogen located para to the
nitro group was substituted by the carbanion moiety.
Oxidation of sH adducts with DDQ is less sensitive to
steric hindrances and the reaction of 2K with nitroarenes
and DDQ oxidant always gives mixtures of para and ortho
isomers of the ONSH products 3 and 7, respectively
(Scheme 3, Table 2).
Since oxidation of the sH adducts of 2K and nitroarenes by
DDQ in THF is not accompanied with hydroxylation we
have applied this system for the ONSH in nitrobenzene 1a
and 4-chloronitrobenzene 1o with phenylacetonitrile
carbanion. This reaction proceeded efficiently giving a
mixture of 2-nitrophenyl and 4-nitrophenyl phenylaceto-
nitrile 10a and 11a and 2-nitro-5-chlorophenyl acetonitrile
11o, respectively. Further hydroxylation of the ONSH
products was not observed (Scheme 4).
In order to verify this hypothesis we have done additional
experiments changing ratio and order of mixing of the
reactants. However changes of the procedure, for example,
slow addition of a solution of sH adducts to a solution of
KMnO4 did not change the outcome of the reaction.
Attempts to arrest the reaction of 2K with ArNO2, carried
out in NH3 and KMnO4 oxidant, on the stage of 3 by using
small amounts of the base and oxidant gave negative results.
In such experiments mixtures of starting materials and
products 3, 4 (and 5 and 6) were produced.
Although oxygen is a moderately active oxidant, it can
oxidize sH adducts, particularly those produced by

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M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
Table 2. Oxidation of sH adducts of 2K to nitroarenes by DDQ in THF
(Scheme 3)
o- and p-isomers of substituted phenols usually in good
yields (Table 3).
ArNO2
X
Products
No. yield
No.
2.1. Detailed analysis of the NMR spectra of compounds
5–6
H
2-F
3-F
2-Cl
3-Cl
2-Br
3-Br
1-NNd
3-CN
4-Cl
1a
1b
1c
1d
1e
1f
1g
1m
1n
1o
3a
3b
3cc
3d
3e
16
36
54
44
59
32
56
12
32
7a
7b
30a
17b
The structures of compounds 3, 4, 7, 8 and 9 (see Schemes 1
and 3) could be easily established on the basis of H NMR
7d
7e
7f
7g
7m
7n
7o
23a
10a
24b
9b
1
spectra only, but a special effort has to be made in order to
prove the structures of the products of higher molecular
weight (5 and 6), which were obtained when KMnO4 was
used as the oxidizing agent (see Scheme 1). For all these
3f
3g
3m
3n
75a
53a
78a
1
compounds a meticulous analysis of the H and 13C NMR
a
2
Ratio ArNO : 2Z2.
Ratio ArNO : 2Z1.2.
data including g-HSQC and g-HMQC spectra has to be
performed. A similar analysis has to be made also for
compounds 4c, 4e, 4g, 4h and 4j which served as the model
compounds.
b
2
c Small amount of a mixture containing isomeric products ortho-
substitution was formed but not separated.
d 1-Nitronaphthalene.
Scheme 4.
1
secondary carbanions that under the reaction conditions can
be deprotonated to dianions. We have made a few
experiments in order to oxidize sH adducts of 2K to
nitroarenes in liquid ammonia and in THF bubbling oxygen
through the reaction mixtures. Indeed under these con-
ditions the oxidation proceeded giving mixtures of ONSH
products 3, and hydroxylated products 4 but usually in low
overall yields so this line of experiments was not pursued.
The H and 13C NMR data obtained for compound 5g has
been collected in Table 4, for compounds 4c, 4e, 4g, 4h and
4j in Tables 5 and 6, and for compounds 5 in Tables 7 and 8
(Tables 5–8 are available in Supplementary data). This form
of the presentation of the vast NMR material revealed the
trends occurring in the chemical shifts under the influence of
substituents and provided us with an additional check of the
correctness of the assignments made on the basis of the
correlation spectra.
As it was mentioned earlier oxidation of the sH adducts of
tertiary carbanions to nitroarenes with dimethyldioxirane,
DMD, gave p-substituted phenols—the oxidation proceeded
at the negatively charged nitro group.14,15
An analysis of the spectra has been performed in two steps.
In the first step, the signals in the 1H and 13C NMR spectra
of the 3-substituted a-hydroxyesters, 4c, 4e, 4g, 4h and 4j,
were assigned on the basis of the general knowledge of
substituent effects, and the preliminary assignments have
been confirmed by means of the g-HSBC and g-HMBC
spectra.
In our experiments we have found that oxidation of sH
adducts of secondary carbanions 2K to nitroarenes with
DMD proceeds also along this pathway to give mixtures of
Table 3. Oxidation of sH adducts of 2K to nitroarenes by DMD in THF
1
In the second step the H and 13C NMR spectra of the
(Scheme 3)a
products of the oxidation reaction denoted as 5 have been
compared with the spectra of the corresponding compounds
4. It becomes immediately clear that the spectra of these
new compounds contain two fragments which are very
similar, in some cases almost identical, to the spectra of
compounds 4. The differences observed can be easily
interpreted in terms of the substitution effects. Furthermore,
many of the signals are apparent doublets, the differences
between them being in the range of several Hz at 11.7 T,
which is typical of the pairs of diastereoisomers. A thorough
ArNO2
X
Products
No. yield
No.
2-Cl
3-Cl
2-Br
3-Br
1-NN
4-Cl
1d
1e
1f
1g
1m
1o
8d
8e
8f
8g
8m
49
65
42
76
19
9d
9e
9f
9g
9m
9o
17
12
18
20
42
60
a
2
Ratio ArNO : 2Z1.2.

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11957
Table 4. 1H (in parantheses) and 13C NMR spectra of bromo dimer 5g measured in CDCl3 and acetone-d6 and the relevant g-HMB correlation peaks; all data
are in ppm against TMSa,b,c
In CDCl3
In CD3COCD3
HMBC
C/HNo.
20
In CDCl3
In CD3COCD3
HMBC
2
72.12; 72.11
(5.22)dd
172.31; 172.30
80.73; 80.70
147.67
124.30
129.32
(8.480)
147.57; 147.53
121.63; 121.62
(8.015; 8.008)
131.63; 131.60
(7.037; 7.009)
138.31; 138.28
126.72; 126.67
(7.602)
71.58; 71.56
(5.17)e
172.15; 172.10
81.83; 81.88
149.54; 149.51
124.82
129.70
(8.445)
148.54
122.59
(8.133; 8.128)
132.19; 132.16
(7.287; 7.264)
140.30; 140.27
127.82;1 27.78
(7.657)
130.97; 130.93
(7.448)
142.13; 142.09
70.69
(5.22)d
71.13
(5.17)e
170.98
67.83
151.60
127.35
129.45
(8.470; 8.466)
148.01
122.74
(8.189; 8.187)
133.19
(7.121; 7.119)
141.76; 141.72
130.73
(7.314)
129.21; 129.20
(7.384)g
128.64; 128.63
(7.384)g
30
40
50
60
70
20, CH3
100,120,13
70,90, 100
70,90,100
90
3
4
5
6
7
2, OH, CH3
10,12
7,9,OH
7,9,10
9,10
170.45; 170.41
67.10; 67.08
150.69; 150.65
126.84; 126.81
129.00; 128.98
(8.485)
147.00
121.71
(8.080; 8.076)
132.01
(7.012; 7.009)
141.26; 141.22
129.83
(7.23)
128.52; 128.50
(7.35)f
128.03; 128.00
(7.35)f
(5.8)
80
90
70,90, 100
70,100
8
9
7,9,10
7,10
100
10
110
120
130
130
11
12
12,13,OH
130
140
140
13
130.42; 130.37
(7.41)
140.54; 140.53
120,130
14
12
OH
(4.370; 4.357)
a Signals of the protons 1 and 10 (centred at ca. 1.26 ppm) and carbons 1 and 10 (centred at ca. 21.5 ppm) are strongly overlapped.
b JHH coupling values are almost identical with those observed for the corresponding compounds 4 (see Table 5 in Supplementary data) and therefore are not
shown in this Table.
c g-HSQ correlation peaks are shown in Table 8 (see Supplementary data).
d–g
Signals overlapped.
analysis of the g-HSBC and g-HMBC spectra performed for
compounds 5 indicated that, as a matter of fact, a dimeric
structure should be assigned to them (see Scheme 1). As an
example the spectra obtained for the bromo derivative 5g,
are discussed below more closely.
becomes easy. Further crucial information is provided by
the correlations observed in the CDCl3 solution between the
proton of the OH group and the carbon signals at 172.31;
172.30, 147.67 and 138.31; 138.28 ppm which can be
consequently assigned to carbons C3, C5 and C11,
respectively. The correlations (in acetone-d6) between
carbon C40 and signals at 7.121; 7.119, 7.314 and
7.448 ppm indicate that the latter belong to H100, H120
and H13, respectively.
The measurements of the spectra for this compound have
been performed in CDCl3 and acetone-d6 solutions and at
two magnetic fields, 9.4 and 11.7 T. This allowed us to
clarify the problems when an accidental overlap of the
signals occurred and to discriminate between a genuine
coupling and a splitting of the signals due to the presence of
diastereoisomers.
A similar analysis performed for the compounds with
still higher molecular weights showed that the trimeric
and tetrameric structures should be assigned to them
(see Scheme 1). However, a precise assignment of the
signals to particular hydrogen and carbon atoms in 1H
and 13C NMR spectra, respectively, is rather difficult for
obvious reasons. First of all, the number of diastereo-
isomers increases causing further splitting of the signals
and secondly, a discriminating influence of the OH
group on the shielding of the atoms in more remote
rings is almost negligible. As a result, in many cases a
strong overlap of the signals occurs. Therefore, the
NMR data for compounds 6 have been included in
Out of the two groups of signals corresponding to the
quaternary aliphatic carbons, appearing at about 80 and at
67 ppm, those at the lower field should be assigned to
carbon 4 and those at the higher field to carbon 40. The
correlation signals observed in the g-HMBC spectra
recorded in acetone-d6 between these two carbons and
protons at 7.287; 7.264 and 7.121; 7.119 ppm allow one to
assign the latter to H10 and H100, respectively. Subsequent
assignment of all the remaining signals of rings A and A0

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M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
Section 3, where only tentative assignments have been
proposed.
4.2. Procedures for the oxidative substitution of
hydrogen with carbanion of 2
Procedure A. Oxidation with KMnO4 in liquid ammonia. To
a suspension of sodium amide freshly prepared from sodium
(120 mg, 5.2 mmol) in liquid ammonia (ca 25 ml), at
K70 8C, iso-propyl phenylacetate 2 (360 mg, 2 mmol) in
THF (1.5 ml) was added. After 3 min nitroarene 1 (4 or
2.4 mmol) in THF (1.5 ml) was added dropwise in 1 min.
The reaction mixture was stirred for additional 3 min, and
solid potassium permanganate (632 mg, 4 mmol) was added
in one portion. The reaction mixture was stirred for 4 min
and quenched with solid ammonium chloride (ca. 400 mg,
8 mmol). The cooling bath was removed and ammonia was
evaporated. To the residue a saturated aqueous solution of
oxalic acid was added and the mixture was extracted with
ethyl acetate (3!20 ml). The combined organic layers were
dried over MgSO4. The solvent was evaporated and the
products were purified by column chromatography with
AcOEt/hexane as eluent.
3. Conclusions
Secondary carbanions of isopropyl phenyl acetate 2 add to
nitroarenes in positions of ortho and para to the nitro group.
The produced anionic sH adducts can be oxidized by a
variety of oxidants. Permanganate anions oxidize only sH
adducts para to the nitro group, the final outcome depends
on the conditions. In liquid ammonia the initially formed
ONSH products 3 are oxidized further to esters of
a-hydroxyacids 4 and, in some cases, undergo dimerization
to 5 and trimerization to 6. This unprecedented process is
observed in the reaction of m-substituted nitroarenes and
proceeds apparently via coupling of carbanions with free
radicals, generated during oxidation of the carbanions. On
the other hand, oxidation of the sH adducts with
tetrabutylammonium permanganate carried out in THF
gave ONSH products 3, under these conditions only sH
adducts in para positions are oxidized. DDQ oxidizes both
ortho and para sH adducts thus in the reaction of 2K with
nitroarenes and DDQ oxidant mixtures of isomeric ONSH
products are formed. Oxidation of sH adducts of 2K to
nitroarenes with DMD proceeds at the negatively charged
nitrogroup of the ortho and para sH adducts that results in
formation of isomeric substituted phenols.
Procedure B. Oxidation with DDQ. To a solution of t-BuOK
(112 mg, 1 mmol) in THF (10 ml) at K70 8C, a solution of
iso-propyl phenylacetate 2 (1 mmol) in THF (1.5 ml) was
added. After 3 min nitroarene 1 (1.2 mmol) in THF (1.5 ml)
was added dropwise during 1 min and the mixture was
stirred for 3 min at K70 8C. Then solution of DDQ
(273 mg, 1.2 mmol) in DMF (2 ml) was added and the
reaction mixture was stirred for 5 min, quenched with
saturated aqueous NH4Cl (0.2 ml) and the cooling bath was
removed. The reaction mixture was poured to water
(100 ml) and extracted with ethyl acetate (3!20 ml) and
extracts were washed with brine and dried over MgSO4. The
solvent was evaporated and products were purified by
column chromatography in AcOEt/hexane. With some
cases we were not able to separate the isomeric products 3
and 7 by column chromatography, so compositions of the
mixtures were established by 1H NMR spectroscopy.
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded with a Mercury-
400BB (400 MHz) and Bruker DRX 500 instruments. Mass
spectra were measured on AMD 604 Inectra GmBH
spectrometer using EI or ESI. For analytical TLC Merck
alufolien sheets Kieselgel 60 F254 were used. For column
chromatography silica gel 230–400 mesh Merck was used.
DMF was distilled over calcium hydride and stored over
molecular sieves, THF was distilled over potassium
benzophenone ketyl. Acetone solution of DMD was
prepared according to the literature procedure.21 All
reactions were performed under argon atmosphere.
Procedure C. Oxidation with QCMnO4K. Experiments were
conducted according to procedure B. Instead of DDQ solid
QCMnOK4 was added. After quench 10 ml of saturated
aqueous solution of oxalic acid was added and procedure B
was followed.
Procedure D. Oxidation with DMD. Experiments were
conducted according to procedure B. Instead of DDQ water
(0.02 ml, 1 mmol) and acetone solution of DMD (ca.
1.2 mmol, 20 ml of ca. 0.06 M) was added to the mixture.
The color changed to bright yellow. After 5 min of stirring,
saturated aqueous NH4Cl (0.2 ml) was added the cooling
bath was removed and procedure B was followed.
Nitroarenes, DDQ, phenylacetonitryle and potassium tert-
butoxide were commercial products. Commercially avail-
able potassium permanganate was ground. Isopropyl
phenylacetate was synthesized from phenylacetic acid and
iso-propyl alcohol.13 Tetrabutylamonium permanganate
was prepared as follows: To a stirred solution of
tetrabutylamonium bromide (5.2 mmol) in water (15 ml) a
solution of potassium permanganate 5 mmol in water
(100 ml) was added. The precipitated product was filtered,
washed with water (10 ml) and dried in vacuum until
constant weight. The product can be stored in fridge for no
longer then 1 month. Caution: dry tetrabutylamonium
permanganate is explosive thus it must not be heated during
drying. All usual precautions should be taken. For safety
reason we dried the product in small, 3–4 mmol portions.
4.2.1. iso-Propyl a-(4-nitrophenyl)phenylacetate 3a.
1
Colourless oil. H NMR (400 MHz, CDCl3): dZ1.22 (d,
3H, JZ6.2 Hz), 1.25 (d, 3H, JZ6.2 Hz), 5.06 (s, 1H), 5.06–
5.14 (m, 1H), 7.27–7.38 (m, 5H), 7.47–7.51 (m, 2H), 8.15–
8.19 (m, 2H). 13C NMR (CDCl3): dZ21.54, 21.63, 56.93,
69.27, 123.66, 127.74, 128.39, 128.89, 129.58, 137.42,
146.14, 147.03, 170.8. MS (EI): m/z (%)Z299 (MC, 6), 212
(100), 196 (28), 165 (66), 105 (29), 43 (79). Anal. Calcd for
C17H17NO4: C, 68.22: H, 5.72; N, 4.68. Found: C, 68.17; H,
5.74; N, 4.45.

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11959
4.2.1.1. iso-Propyl a-(2-nitrophenyl)phenylacetate 7a.
Colourless oil. H NMR (400 MHz, CDCl3): dZ1.17 (d,
phenylacetate 7d. Colourless oil. 1H NMR (400 MHz,
CDCl3): dZ1.16–1.24 (m, 3H), 1.26 (d, 3H, JZ6.3 Hz),
4.95 (s, 0.3H), 4.99 (s, 0.7H), 5.04–5.14 (m, 1H), 7.26–7.4
(m, 5H), 7.4–7.44 (m, 0.3H), 7.51 (d, 0.7H, JZ1.9 Hz), 7.84
(d, 0.7H, JZ8.4 Hz). 13C NMR (CDCl3): dZ21.47, 21.52,
21.65, 51.78, 56.46, 69.52, 69.7, 124.99, 125.72, 127.27,
127.87, 127.95, 127.98, 128.32, 128.35, 128.98, 129.05,
129.15, 129.43, 130.72, 132.06, 132.68, 136.27, 136.88,
169.8, 170.4.
1
1.8H, JZ6.2 Hz), 1.23 (d, 1.2H, JZ6.2 Hz), 1.25 (d, 1.2H,
JZ6.2 Hz), 1.28 (d, 1.8H, JZ6.2 Hz), 5.06 (s, 0.4H), 5.06–
5.17 (m, 1H), 5.62 (s, 0.6), 7.08–7.16 (m, 0.6H), 7.15–7.33
(m, 3H), 7.33–7.45 (m, 3H), 7.46–7.51 (m, 1.5H), 8.02 (dd,
0.6H, JZ1.51, 8 Hz), 8.17 (m, 0.6H). 13C NMR (CDCl3):
dZ21.41, 21.55, 21.64, 21.68, 53.41, 56.94, 69.17, 69.28,
123.67, 124.81, 127.77, 128.07, 128.4, 128.9, 128.96,
129.16, 129.58, 131.6, 133.07, 134.14, 136.72, 137.42,
146.14, 148.87, 170.82.
4.2.6. iso-Propyl a-(2-chloro-4-nitrophenyl)phenyl-
acetate 3e. Colourless oil. H NMR (400 MHz, CDCl3):
1
4.2.2. iso-Propyl a-(3-fluoro-4-nitrophenyl)phenyl-
acetate 3b. Colourless oil. H NMR (400 MHz, CDCl3):
dZ1.22 (d, 3H, JZ6.3 Hz), 1.26 (d, 3H, JZ6.3 Hz), 5.0 (s,
1H), 5.03–5.13 (m, 1H), 7.22–7.26 (m, 1H), 7.28–7.31 (m,
4H), 7.32–7.39 (m, 3H), 7.99–8.06 (m, 1H). 13C NMR
dZ1.21 (d, 3H, JZ6.4 Hz), 1.26 (d, 3H, JZ6.2 Hz), 5.05–
5.19 (m, 1H), 5.49 (s, 1H), 7.26–7.3 (m, 1H), 7.32–7.41 (m,
5H), 8.03 (ddd, 1H, JZ0.4, 2.4, 8.6 Hz), 8.27 (d, 1H, JZ
2.4 Hz). 13C NMR (CDCl3): dZ21.45, 21.61, 54.21, 69.48,
121.67, 124.53, 128.01, 128.76, 129.07, 130.94, 135.11,
135.92, 144.08, 147.19, 170.12. MS (EI): m/z (%)Z333
(MC, 1), 273 (9), 246 (100), 230 (22), 165 (59), 43 (74).
Anal. Calcd for C17H16ClNO4: C, 61.18; H, 4.83; N, 4.2; Cl,
10.62. Found: C, 61.07, H, 4.93, N, 4.11, Cl, 10.54.
1
(CDCl3): dZ21.51, 21.64, 56.69, 69.54, 118.69 (d, JCF
Z
21.1 Hz), 124.78 (d, JCFZ5 Hz), 126.12 (d, JCFZ3 Hz),
128.02, 128.33, 129.07, 136.77, 147.83 (d, JCFZ9 Hz),
155.4 (d, JCFZ265 Hz), 170.3 MS (EI): m/z (%)Z317
(MC, 1), 257 (27), 230 (100), 214 (43), 183 (66), 105 (31),
43 (98). Anal. Calcd for C17H16FNO4: C, 64.35: H, 5.08; N,
4.41. Found: C, 64.4; H, 5.1, N, 4.38.
4.2.6.1. iso-Propyl a-(4-chloro-2-nitrophenyl)phenyl-
acetate 7e. Colourless oil. 1H NMR (400 MHz, CDCl3): dZ
1.16 (d, 0.45H, JZ6.3 Hz), 1.21 (d, 2.5H, JZ6.2 Hz), 1.27
(d, 3H, JZ6.3 Hz), 5.08–5.15 (m, 1H), 5.45 (s, 0.85H), 5.57
(s, 0.15H), 7.02–7.05 (d, 0.15H, JZ8.5 Hz), 7.22–7.29 (m,
2H), 7.32–7.42 (m, 5H), 7.44 (dd, 0.15H, JZ2.2, 8.5 Hz),
8.02–8.06 (m, 0.85H), 8.27 (d, 0.85H, JZ2.3 Hz). 13C NMR
(CDCl3): dZ21.46, 21.63, 21.63, 21.67, 53.06, 54.22,
69.04, 69.49, 121.68, 124.56, 128, 128.76, 129.09, 129.12,
130.95, 132.75, 132.9, 133.08, 133.92, 135.13, 135.94,
136.25, 144.09, 147.22, 170.14, 170.47.
4.2.3. iso-Propyl a-(3-fluoro-2-nitrophenyl)phenyl-
acetate 7b. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.2 (d, 0.9H, JZ6.2 Hz), 1.22 (d, 2.1H, JZ6.3 Hz),
1.25–1.28 (dCd, 3H, JZ6.3, 6.2 Hz), 5.0 (s, 0.7H), 5.03–
5.13 (m, 1H), 5.17 (s, 0.3H), 7.06–7.12 (m, 0.3H), 7.12–7.21
(m, 0.3H), 7.21–7.31 (m, w4H), 7.31–7.45 (m, w4H),
7.97–8.06 (m, 0.7H). 13C NMR (CDCl3): dZ21.44, 21.52,
21.57, 21.64, 51.85, 51.86, 56.69, 69.55, 69.63, 115.91,
116.1, 118.58, 118.8, 124.75, 124.8, 126.1, 126.13, 127.97,
128.03, 128.34, 128.64, 128.99, 129.07, 129.16, 131.79,
131.87, 136.21, 136,77, 147.78, 147,86, 152.62, 154.11,
156.75, 169.96, 170.3.
4.2.7. iso-Propyl a-(3-bromo-4-nitrophenyl)phenyl-
acetate 3f. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.23 (d, 3H, JZ6.3 Hz), 1.26 (d, 3H, JZ6.3 Hz), 4.98
(s, 1H), 5.03–5.16 (m, 1H), 7.27–7.39 (m, 5H), 7.40–7.44
(m, 1H), 7.70 (d, 1H, JZ1.8 Hz), 7.80 (d, 1H, JZ8.5 Hz).
13C NMR (CDCl3): dZ21.52, 21.65, 56.36, 69.5, 114.63,
125.71, 127.95, 128.31, 128.53, 129.03, 135.02, 136.92,
144.98, 148.5, 170.4. MS (EI): m/z (%)Z377 (MC, 1), 317
(16), 290 (100), 274 (21), 195 (27), 165 (56), 105 (17), 43
(43). Anal. Calcd for C17H16BrNO4: C, 53.99; H, 4.26; N,
3.7. Found: C, 54.2; H, 4.25; N, 3.57.
4.2.4. iso-Propyl a-(2-fluoro-4-nitrophenyl)phenyl-
acetate 3c. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.21 (d, 3H, JZ6.24 Hz), 1.26 (d, 3H, JZ6.23 Hz), 5.11
(m, 1H), 5.28 (s, 1H), 7.28–7.44 (m, 6H), 7.91–7.99 (m,
2H). 13C NMR (CDCl3): dZ21.46, 21.59, 50.21, 69.5,
111.09 (d, JCFZ27 Hz), 119.2 (d, JCFZ4 Hz), 128.03,
128.63, 129.07, 130.8 (d, JCFZ4 Hz), 134.07 (d, JCF
Z
Z
15 Hz), 135.79, 147.78 (d, JCFZ9 Hz), 159.83 (d, JCF
251.5 Hz), 170.1. MS (EI): m/z (%)Z317 (MC, 2), 230
(100), 214 (18), 183 (44), 105 (9), 43 (71). HRMS (ES)
calcd for C17H16FNO4Na: 340.0956. Found: 340.0976.
4.2.7.1. iso-Propyl a-(3-bromo-2-nitrophenyl)phenyl-
acetate 7f. Colourless oil. 1H NMR (400 MHz, CDCl3): dZ
1.2–1.23 (m, 3H), 1.27 (m, 3H), 4.96 (s, 0.4H), 4.98 (s,
0.6H), 5.03–5.16 (m, 1H), 7.23–7.3 (m, 2H), 7.3–7.43 (m,
4H), 7.57 (dd, 0.4H, JZ1.3, 8.1 Hz), 7.69–7.71 (m, 0.6H),
7.81 (d, 0.6H, JZ8.3 Hz). 13C NMR (CDCl3): dZ21.47,
21.53, 21.65, 51.91, 56.37, 69.5, 69.68, 112.78, 114.63,
125.71, 127.93, 127.95, 128.31, 128.53, 128.97, 129.03,
129.81, 130.95, 132.56, 132.69, 135.2, 136.32, 136.92,
144.98, 148.5, 169.81, 170.4.
4.2.5. iso-Propyl a-(3-chloro-4-nitrophenyl)phenyl-
acetate 3d. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.22 (d, 3H, JZ6.2 Hz), 1.27 (d, 3H, JZ6.2 Hz), 4.99
(s, 1H), 5.04–5.14 (m, 1H), 7.26–7.4 (m, 6H), 7.51 (d, 1H,
JZ1.9 Hz), 7.84 (d, 1H, JZ8.4 Hz). 13C NMR (CDCl3):
dZ21.52, 21.65, 56.46, 69.52, 125.72, 127.27, 127.87,
127.97, 128.32, 129.05, 132.06, 136.89, 145.08, 146.63,
170.39. MS (EI): m/z (%)Z333 (MC, 1), 273 (16), 246
(100), 230 (33), 165 (62), 105 (29), 43 (82). Anal. Calcd for
C17H16ClNO4: C, 61.18; H, 4.83; N, 4.2; Cl, 10.62. Found:
C, 61.25; H, 4.86; N, 4.33; Cl, 10.52.
4.2.8. iso-Propyl a-(2-bromo-4-nitrophenyl)phenyl-
acetate 3g. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.23 (d, 3H, JZ6.3 Hz), 1.27 (d, 3H, JZ6.2 Hz), 5.06–
5.18 (m, 1H), 5.46 (s, 1H), 7.26–7.34 (m, 3H), 7.34–7.42
(m, 3H), 8.08 (ddd, 1H, JZ0.4, 2.4, 8.7 Hz), 8.46 (d, 1H,
JZ2.4 Hz). 13C NMR (CDCl3): dZ21.48, 21.66, 56.67,
4.2.5.1. iso-Propyl a-(3-chloro-2-nitrophenyl)

11960
M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
69.52, 122.24, 125.17, 127.82, 128.02, 128.75, 129.09,
131.06, 136.2, 145.75, 147.13, 170.11. MS (EI): m/z (%)Z
377 (MC, 1), 317 (8), 290 (95), 274 (19), 211 (20), 165
(100), 43 (91). Anal. Calcd for C17H16BrNO4: C, 53.99; H,
4.26; N, 3.7. Found: C, 54.3; H, 4.47; N, 3.58.
4.2.13. a-(4-Nitrophenyl)phenyloacetonitrile 10a.
Colourless oil. H NMR (400 MHz, CDCl3): dZ5.25 (s,
1
1H), 7.3–7.47 (m, 5H), 7.52–7.57 (m, 2H), 8.2–8.28 (m,
2H). 13C NMR (CDCl3): dZ42.27, 118.46, 124.39, 126.61,
127.69, 128.7, 128.91, 129.58, 134.35, 142.7. MS (EI): m/z
(%)Z238 (MC, 100), 221 (17), 192 (37), 165 (58). Anal.
Calcd for C14H10N2O4: C, 70.58; H, 4.23; N, 11.76. Found:
C, 70.72; H, 4.5; N, 11.53.
4.2.8.1. iso-Propyl a-(4-bromo-2-nitrophenyl)phenyl-
acetate 7g. Colourless oil. H NMR (400 MHz, CDCl3):
1
dZ1.2–1.24 (dCd, 3H, JZ6.3, 6.3 Hz), 1.26–1.29 (dCd,
3H, JZ6.2, 6.2 Hz), 5.06–5.18 (m, 1H), 5.46 (s, 0.85H),
5.55 (s, 0.15H), 6.97 (d, 0.15H, JZ8.5 Hz), 7.22–7.3 (m,
w2H), 7.3–7.44 (m, w4H), 7.59 (ddd, 0.15H, JZ0.4, 2.1,
8.5 Hz), 8.08 (ddd, 0.85H, JZ0.4, 2.5, 8.7 Hz), 2.16 (d,
0.15H, JZ2.1 Hz), 8.46 (d, 0.85H, JZ2.5 Hz).
4.2.14. a-(2-Nitrophenyl)phenylacetonitrile 11a. Colour-
less oil. 1H NMR (400 MHz, CDCl3): dZ6.17 (s, 1H), 7.3–
7.4 (m, 5H), 7.53–7.58 (m, 1H), 7.68–7.75 (m, 2H), 8.07
(dd, 1H, JZ1.3, 8.2 Hz). 13C NMR (CDCl3): dZ38.3,
118.61, 125.77, 127.87, 128.51, 129.31, 129.68, 130.53,
130.94, 134.07, 134.14, 147.66. MS (EI): m/z (%)Z238
(MC, 1), 221 (100), 204 (90), 190 (70), 167 (72), 77 (30).
Anal. Calcd for C14H10N2O4: C, 70.58; H, 4.23; N, 11.76.
Found: C, 70.6; H, 4.49; N, 11.74.
4.2.9. iso-Propyl 1-(4-nitronaphthyl)phenylacetate 7m.
Yellow crystals, mp 156–158 8C (hexane/ethyl acetate). 1H
NMR (400 MHz, CDCl3): dZ1.24 (d, 3H, JZ6.4 Hz), 1.26
(d, 3H, JZ6.3 Hz), 5.05–5.19 (m, 1H), 5.21 (s, 1H), 1.29–
1.38 (m, 5H), 7.5 (d, 1H, JZ8.8 Hz), 7.55–7.65 (m, 2H),
7.74–7.76 (m, 1H), 7.84–7.91 (m, 2H). 13C NMR (CDCl3):
dZ21.56, 21.58, 51.83, 69.47, 121.77, 124.21, 126.42,
127.51, 127.71, 127.95, 128.12, 128.42, 128.65, 128.89,
130.51, 132.84, 136.98, 147.63, 170.26. MS (EI) m/zZ303
(13), 262 (37), 261 (48), 218 (52), 105 (100), 77 (22), 43
(29). Anal. Calcd for C21H19NO4: C, 72.19; H, 5.42; N,
4.01. Found: C, 71.47; H, 5.23; N, 3.72.
4.2.15. a-(5-Chloro-2-nitrophenyl)phenylacetonitrile
1
11o. Colourless oil. H NMR (400 MHz, CDCl3): dZ6.19
(s, 1H), 7.29–7.35 (m, 2H), 7.35–7.44 (m, 3H), 7.52 (dd, 1H,
JZ8.8, 2.4 Hz), 7.69 (d, 1H, JZ2.4 Hz), 8.04 (d, 1H, JZ
8.8 Hz). 13C NMR (CDCl3): dZ38.17, 118.08, 127.3,
127.87, 129.01, 129.5, 129.89, 130.93, 132.55, 133.33,
140.85, 145.8. MS (EI): m/z (%)Z271 (MCK 1, 1), 255
(71), 238 (94), 229 (36), 201 (39), 190 (100), 166 (88),
77(57). Anal. Calcd for C14H9ClN2O2: C, 61.66; H, 3.33; N,
10.27; Cl, 13. Found: C, 61.59; H, 3.33; N, 10.06; Cl, 13.04.
4.2.10. iso-Propyl a-(2-cyano-4-nitrophenyl)phenyl-
acetate 3n. Colourless oil, H NMR (400 MHz, CDCl3):
1
4.2.16. iso-Propyl a-hydroxy-a-(4-nitrophenyl)phenyl-
acetate 4a. Colourless oil. H NMR (400 MHz, CDCl3):
dZ1.16 (d, 3H, JZ6.2 Hz), 1.28 (d, 3H, JZ6.2 Hz), 5.05–
5.15 (m, 1H), 5.62 (s, 1H), 7.04 (dd, 1H, JZ2.3 Hz), 7.23–
7.27 (m, 1H), 7.35–7.44 (m, 5H), 8.01 (d, 1H, JZ8.8 Hz).
13C NMR (CDCl3): dZ21.37, 21.68, 53.48, 69.46, 126.34,
128.17, 128.3, 129.18, 129.23, 131.76, 135.88, 136.32,
139.75, 147.07, 170.34. MS (ES, MeOH): m/z (%)Z347
(MCC Na), HRMS (ES) calcd for C18H16N2O4Na:
347.1002. Found: 347.1019.
1
dZ1.23 (d, 3H, JZ6.2 Hz), 1.3 (d, 3H, JZ6.4 Hz), 4.42 (s,
1H), 5.14–5.24 (m, 1H), 7.32–7.39 (m, 5H), 7.68 (m, 2H),
8.18 (m, 2H). 13C NMR (CDCl3): dZ21.46, 21.51, 71.95,
80.37, 123.03, 126.96, 128.47, 128.51, 128.58, 131.74,
132.03, 141.41, 147.48, 148.77, 172.68. MS (EI): m/z (%)Z
315 (MC, 1), 228 (100), 150 (67). Anal. Calcd for
C17H17NO5: C, 64.75; H, 5.43; N, 4.44. Found: C, 64.9;
H, 5.25; N, 4.31.
4.2.11. iso-Propyl a-(4-cyano-2-nitrophenyl)phenyl-
acetate 7n. Colourless oil, H NMR (400 MHz, CDCl3):
1
4.2.17. iso-Propyl a-hydroxy-a-(3-fluoro-4-nitrophenyl)
phenylacetate 4b. White crystals, mp 69–75 8C (hexane/
AcOEt). 1H NMR (400 MHz, CDCl3): dZ1.25 (d, 3H, JZ
6.2 Hz), 1.32 (d, 3H, JZ6.3 Hz), 4.42 (s, 1H), 5.11–5.29 (m,
1H), 7.35–7.38 (m, 5H), 7.44 (ddd, 1H, JZ8.7, 1.9,
0.96 Hz), 7.5 (dd, 1H, JZ12.2, 1.9 Hz), 8.02 (dd, 1H, JZ
8.7, 7.6 Hz) 13C NMR (CDCl3): dZ21.47, 21.52, 72.28,
79.99, 117.76 (d, JCFZ22.1 Hz), 123.75 (d, JCFZ3 Hz),
125.47(d, JCFZ2 Hz), 126.77, 128.62, 128.73, 126.51(d,
dZ1.16 (d, 3H, JZ6.2 Hz), 1.28 (d, 3H, JZ6.2 Hz), 5.05–
5.15 (m, 1H), 5.65 (s, 1H), 7.22–7.27 (m, 2H), 7.25 (d, 1H,
JZ8.1 Hz), 7.38–7.45 (m, 3H), 7.74 (dd, 1H, JZ8.1,
1.6 Hz), 8.31 (d, 1H, JZ1.6 Hz). 13C NMR (CDCl3): dZ
21.6, 21.91, 53.88, 70.1, 112.81, 116.62, 128.56, 128.64,
129.33, 129.63, 133.26, 135.7, 136.02, 139.48, 149.22,
170.1. MS (ES, MeOH): m/z (%)Z347 (MCC Na), HRMS
(ES) calcd for C18H16N2O4Na: 347.1002. Found: 347.1017.
JCFZ8 Hz), 141, 150.44 (d, JCFZ4 Hz), 155.02 (d, JCF
264.5 Hz), 172.09. HRMS (ES) calcd for C17H15FNO5:
Z
4.2.12. iso-Propyl a-(5-chloro-2-nitrophenyl)phenyl-
acetate 7o. White crystals, mp 133–134 8C (heptane). H
1
332.0929. Found: 332.0910.
NMR (400 MHz, CDCl3): dZ1.16 (d, 3H, JZ6.2 Hz), 1.28
(d, 3H, JZ6.2 Hz), 5.05–5.15 (m, 1H), 5.62 (s, 1H), 7.04
(dd, 1H, JZ2.3 Hz), 7.23–7.27 (m, 1H), 7.35–7.44 (m, 5H),
8.01 (d, 1H, JZ8.8 Hz). 13C NMR (CDCl3): dZ21.37,
21.68, 53.48, 69.46, 126.34, 128.17, 128.3, 129.18, 129.23,
131.76, 135.88, 136.32, 139.75, 147.07, 170.34. MS (EI): m/
z (%)Z315 (2), 273 (37), 246 (48), 229 (34), 194 (24), 165
(41), 105 (58), 77 (37), 43 (100). HRMS (EI) calcd for
C17H16N2O4Cl: 333.07679. Found: 333.07717. Anal. Calcd
for C17H16ClNO4: C, 61.16; H, 4.83; N, 4.2; Cl, 10.62.
Found: C, 61.2; H, 4.86; N, 4.03; Cl, 10.55.
4.2.18. iso-Propyl a-hydroxy-a-(2-fluoro-4-nitrophenyl)
phenylacetate 4c. White crystals, mp 73–76 8C (hexane/
AcOEt). 1H NMR Table 4, 13C NMR, Table 5 MS (EI): m/z
(%)Z333 (MC, 2), 246 (MCK 87, 100), 168 (63), 122 (18).
Anal. Calcd for C17H16FNO5: C, 61.26; H, 4.84; N, 4.2.
Found: C, 61.09; H, 4.91; N, 4.21.
4.2.19. iso-Propyl a-hydroxy-a-(3-chloro-4-nitrophenyl)
phenylacetate 4d. White crystals, mp 65–70 8C (hexane/

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11961
AcOEt). 1H NMR (400 MHz, CDCl3): dZ1.25 (d, 3H, JZ
6.2 Hz), 1.32 (d, 3H, JZ6.4 Hz), 4.43 (s, 1H), 5.2 (m, 1H),
7.3–7.4 (m, 5H), 7.53 (dd, 1H, JZ8.6, 2.0 Hz), 7.76 (d, 1H,
JZ2.0 Hz), 7.83 (d, 1H, JZ8.6 Hz). 13C NMR (CDCl3):
dZ21.45, 21.48, 72.21, 79.89, 125.01, 126.69, 126.8,
126.97, 128.58, 128.66, 130.87, 141.04, 147.03, 147.64,
172.17. MS (EI): m/z (%)Z349 (MC, 1), 262 (100), 184
(28), 105 (13). Anal. Calcd for C17H16ClNO5: C, 58.38; H,
4.61; N, 4.0; Cl, 10.14. Found: C, 58.38; H, 4.41; N, 3.97;
Cl, 9.98.
114.96, 124.99, 126.55, 128.9, 129.06, 132.77, 134.73,
144.77, 147.64, 149.05, 171.5. MS (EI): m/z (%)Z340
(MC, 1), 253 (MCK 87, 100), 175 (47). Anal. Calcd for
C18H16N2O5: C, 63.52; H, 4.74; N, 8.23. Found: C, 63.43;
H, 4.96; N, 8.14.
4.2.26. iso-Propyl a-hydroxy-a-[2-(5-nitrothiophen)]
phenylacetate 4l. Colourless oil. 1H NMR (400 MHz,
CDCl3): dZ1.19 (d, 3H, JZ6.2 Hz), 1.28 (d, 3H, JZ
6.2 Hz), 4.65 (s, 1H), 5.14, (m, 1H), 6.38 (d, 1H, JZ5.6 Hz),
7.3 (d, 1H, JZ5.6 Hz), 7.38–7.45 (m, 3H), 7.66–7.69 (m,
2H). 13C NMR (CDCl3): dZ21.47, 21.52, 70.92, 126.09,
128.45, 128.77, 129.48, 131.32, 139.29, 145.56, 147.94,
171.11. MS (EI): m/z (%)Z321 (MC, 1), 234 (MCK 87,
100), 200 (25), 156 (95), 105 (20), 77 (17), 43 (22). Anal.
Calcd for C15H15NO5S: C, 56.07; H, 4.7; N, 4.36. Found: C,
55.84; H, 4.81; N, 4.23.
4.2.20. iso-Propyl a-hydroxy-a-(2-chloro-4-nitrophenyl)
phenylacetate 4e. White crystals, mp 65–75 8C (heptane).
1H NMR Table 4, 13C NMR, Table 5 MS (EI): m/z (%)Z
349 (MC, 2), 262 (100), 184 (41). Anal. Calcd for
C17H16ClNO5: C, 58.38; H, 4.61; N, 4.0; Cl, 10.14.
Found: C, 58.18; H, 4.81; N, 3.98; Cl, 9.94.
4.2.21. iso-Propyl a-hydroxy-a-(3-bromo-4-nitrophenyl)
phenylacetate 4f. White crystals, mp 68–75 8C (heptane).
1H NMR (400 MHz, CDCl3): dZ1.26 (d, 3H, JZ6.3 Hz),
1.32 (d, 3H, JZ6.3 Hz), 4.39 (s, 1H), 5.16–5.24 (m, 1H),
7.3–7.44 (m, 5H), 5.58 (dd, 1H, JZ8.6, 2 Hz), 7.8 (d, 1H,
JZ8.6 Hz), 7.96 (d, 1H, JZ2 Hz). 13C NMR (CDCl3): dZ
21.49, 21.52, 72.24, 79.23, 114.09, 125.01, 126.85, 127.68,
128.6, 128.69, 134.03, 141.09, 147.5, 148.97, 172.24. MS
(EI): m/z (%)Z393 (MC, 2), 306 (100), 228 (30), 105 (20),
77 (15), 43 (21). Anal. Calcd for C17H16BrNO5: C, 51.79; H,
4.09; N, 3.55. Found: C, 51.52; H, 4.28; N, 3.49.
4.2.27. iso-Propyl a-hydroxy-a-[2-(1-nitronaphthyl)]-
phenylacetate 4m. Colourless oil. 1H NMR (400 MHz,
CDCl3): dZ1.23 (d, 3H, JZ6.4 Hz), 1.36 (d, 3H, JZ
6.2 Hz), 4.21 (s, 1H), 5.27 (m, 1H), 7.03 (d, 1H, JZ8.8 Hz),
7.4–7.46 (m, 3H), 7.51–7.55 (m, 2H), 7.56–7.66 (m, 2H),
7.78 (m, 2H), 7.86 (m, 1H). 13C NMR (CDCl3): dZ21.41,
21.59, 71.78, 80.62, 122.06, 124.7, 126.85, 127.05, 127.71,
127.75, 128.59, 128.66, 128.74, 129.34, 130.81, 133.34,
141.23, 146.16, 171.82. MS (EI): m/z (%)Z365 (MC, 2),
278 (MCK 87, 100), 200 (32), 105 (11). Anal. Calcd for
C21H19NO5: C, 69.03; H, 5.24; N, 3.83. Found: C, 69.18; H,
5.44; N, 3.63.
4.2.22. iso-Propyl a-hydroxy-a-(2-bromo-4-nitrophenyl)
1
phenylacetate 4g. Colourless oil. H NMR Table 4, 13C
4.2.28. iso-Propyl 2-(2-fluoro-4-nitrophenyl)-2{4-[1-(2-
fluoro-4-nitrophenyl)-1-hydroxy-2-iso-propoxy-2-oxo-
NMR, Table 5 MS (EI): m/z (%)Z393 (MC, 1), 306 (MCK
87, 100), 262 (42), 228 (43), 184 (25), 105 (27), 77 (21), 43
(27). Anal. Calcd for C17H16BrNO5: C, 51.79; H, 4.09; N,
3.55. Found: C, 51.65; H, 3.91; N, 3.6.
1
ethyl]-phenyl}-2-phenylacetate 5c. H NMR Table 6, 13C
NMR, Table 7. MS (EI): m/z (%)Z561 (MCK 87, 100),
474 (MCK 2!87, 32), 306 (10), 43 (67). Anal. Calcd for
C34H30F2N2O9: C, 62.96; H, 4.66; N, 4.32. Found: C, 63.38;
H, 4.68; N, 3.95.
4.2.23. iso-Propyl a-hydroxy-a-(2-iodo-4-nitrophenyl)
1
phenylacetate 4h. Colourless oil. H NMR Table 4, 13C
NMR, Table 5 MS (EI): m/z (%)Z441 (MC, 2), 354 (100),
276 (39). HRMS (ES) calcd for C17H16INO5Na: 463.9965.
Found: 463.9986. Anal. Calcd for C17H16INO5: C, 46.28; H,
3.66; N, 3.17. Found: C, 47.83; H, 3.95; N, 2.95.
4.2.29. iso-Propyl 2-(2-chloro-4-nitrophenyl)-2{4-[1-(2-
chloro-4-nitrophenyl)-2-hydroxy-2-iso-propoxy-2-oxo-
1
ethyl]-phenyl}-2-phenylacetate 5e. H NMR Table 6, 13C
NMR, Table 7 MS (LSIMSC): m/zZ703 (MCC23). MS
(EI): m/z (%)Z593 (MCK 87, 100), 506 (40), 43 (35).
4.2.24. iso-Propyl a-hydroxy-a-(2-methoxy-4-nitro-
phenyl)phenylacetate 4j. White crystals, mp 104–112 8C
35
HRMS (EI) calcd for (M-87 (COOiPr)) C30H Cl2N2O7:
23
1
593.08823. Found: 593.08804. Anal. Calcd for
C34H30Cl2N2O9: C, 59.92; H, 4.44; N, 4.11; Cl, 10.4.
Found: C, 59.67; H, 4.59; N, 4.27; Cl, 9.51.
(heptane). H NMR (400 MHz, CDCl3): dZ1.19–1.3 (m,
6H), 3.97 (s, 3H), 4.44 (s, 1H), 5.14, (m, 1H), 6.91 (d, 1H,
JZ8.6 Hz), 7.37–7.47 (m, 3H), 7.68 (dd, 1H, JZ8.6,
2.2 Hz), 7.69–7.72 (m, 2H), 7.77 (d, 1H, JZ2.2 Hz). 13C
NMR (CDCl3): dZ21.39, 21.42, 55.92, 70.63, 77.92,
105.71, 115.36, 127.04, 128.2, 128.47, 130.04, 138.21,
138.64, 148.66, 157.59, 173.27. MS (EI): m/z (%)Z345
(MC, 1), 258 (100), 180 (62). Anal. Calcd for C18H19NO6:
C, 62.6; H, 5.55; N, 4.06. Found: C, 62.51; H, 5.68; N, 4.11.
4.2.30. iso-Propyl 2-(2-bromo-4-nitrophenyl)-2{4-[1-(2-
bromo-4-nitrophenyl)-1-hydroxy-2-iso-propoxy-2-oxo-
ethyl]phenyl}-2-phenylacetate 5g. White crystals. 1H
NMR Table 6, 13C NMR, Table 7. MS (ES) (CHCl3):
m/zZ793. MS (EI): m/z (%)Z683 (MCK 87, 100), 639
(32), 596 (40), 552 (15), 43(85). HRMS (ES) calcd for
C34H30Br2N2O9Na: 791.0210. Found: 791.0239. Anal.
Calcd for C34H30Br2N2O9: C, 53.01; H, 3.92; N, 3.64.
Found: C, 54.05; H, 4.45; N, 3.48.
4.2.25. iso-Propyl a-hydroxy-a-(3-cyano-4-nitrophenyl)
phenylacetate 4k. Colourless oil, 1H NMR (400 MHz,
CDCl3): dZ1.25 (d, 3H, JZ6.2 Hz), 1.35 (d, 3H, JZ
6.3 Hz), 4.41 (s, 1H), 5.16–5.24 (m, 1H), 7.3–7.37 (m, 2H),
7.37–7.42 (m, 3H), 7.97 (dd, 1H, JZ8.8, 2.1 Hz), 8.09 (dd,
1H, JZ2.1, 0.3 Hz), 8.27 (dd, 1H, JZ8.8, 0.4 Hz). 13C
NMR (CDCl3): dZ21.5, 21.54, 72.62, 79.88, 107.55,
4.2.31. iso-Propyl 2-(2-iodo-4-nitrophenyl)-2{4-[1-(2-
iodo-4-nitrophenyl)-1-hydroxy-2-iso-propoxy-2-oxoethyl]-
phenyl}-2-phenylacetate 5h. White powder. 1H NMR

11962
M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
Table 6, 13C NMR, Table 7. MS (ES): m/z (%)Z887 (MCC
23).
(8.442, 2H)a,b, H7 (8.463d, 1H) C1, C10, C100 (21.54),
C2(71.59; 71.56), C3(172.11; 172.06), C4 (81.93),
C5(149.52), C6(124.82), C7(129.70), C8(148.54),
C9(122.60), C10 (132.18; 132.16), C11 (140.47), C12
(128.01; 127.98), C13(130.84), C14(141.92), C20,
C200(71.27, 71.13)b, C30, C300(170.99; 170.97, 170.90)b,
C40, C400(67.72; 67.70, 67.53; 67.51)b, C50, C500(151.61,
151.40)b00, C60, C600(127.33), C70, 00C700 (129.45, 129.53)b0,
C80, C8 (148.00, 148.05), C90, C9 (122.74, 122.80), C10 ,
C1000(133.16, 131.10), C110, C1100(141.24, 141.65)b, C120,
C1200(130.53, 130.82)b, C130, C1300(130.71, 129.22)b, C140,
(140.96; 140.91)b, C1400 (128.64). MS (ES, negative ions:
m/zZ1170. Anal. Calcd for C51H44N3Br3O13: C, 53.42, H,
3.87; N, 3.66: Br, 20.64. Found: C, 53.2, H, 4.09; N, 3.86:
Br, 20.51.
4.2.32. iso-Propyl 2-(2-methoxy-4-nitrophenyl)-2{4-[1-
(2-methoxy-4-nitrophenyl)-1-hydroxy-2-iso-propoxy-2-
1
oxoethyl]phenyl}-2-phenylacetate 5j. Colourless oil. H
NMR Table 6, 13C NMR, Table 7. MS (LSIMSC): m/z
(%)Z695 (MCC23), 655, 585 (MCK 87). HRMS (ES)
calcd for C36H36N2O11Na: 695.2211. Found: 695.2231.
Anal. Calcd for C36H36N2O11: C, 64.28; H, 5.39; N, 4.16.
Found: C, 63.98; H, 5.55; N, 3.98.
4.2.33. Fluoro trimer 6c. Colourless oil. 1H NMR
(400 MHz, CDCl3): dZ1.2–1.29 (m, 18H), 4.39 (s, 1H),
5.15–5.25 (m, 3H), 6.97–7.06(m, 2H), 7.1–7.17 (m, 1H),
7.17–7.28 (m), 7.30–7.38 (m, 5H), 7.55–7.59 (m, 2H), 7.88–
8.0 (m, 6H). 13C NMR (CDCl3): dZ21.21, 21.3, 2121.16,
21.36, 21.42, 63.3, 63.54, 70.31, 70.44, 72.14, 111.12 (d,
JZ29.2 Hz), 111.29 (d, JZ28 Hz), 111.65 (d, JZ
27.53 Hz), 118.78 (d, JZ3.4 Hz), 118.85 (d, JZ3 Hz),
118.94 (d, JZ3 Hz), 126.68, 126.72, 127.96, 128.4, 129.36,
129.55, 129.77, 130.57, 130.7, 130.73, 130.84, 137.03–
137.12 (m), 137.9–137.93 (m), 138.9 (d, JZ12.8 Hz),
139.12–139.25 (m), 139.76–139.84 (m), 140.4–140.47 (m),
148.03–148.18 (m), 148.73 (d, JZ9.2 Hz), 159.3, 159.35,
159.37, 161.34, 169.37, 161.39, 170.11, 170.28, 172.3. 19F
NMR (CDCl3): dZK107.6–(K107.8) (m, 1F), K101.2–
(K101) (m, 1F), K100.95–(K101) (m, 1F). MS (EI) m/z
(%)Z876 (MCK87, 24), 789 (5), 149 (68), 43 (100).
4.2.36. Iodo trimer 6h. Yellowish, amorphous powder (1H
and 13C NMR measured in CDCl3).
C(CH3)2 (1.32, 18 H)a, OH (4.336; 4.326; 4.324; 4.322; 1H),
H2, H20, H200 (5.12, 3H)a,b, H10, H100, H1000(6.96, 3H)a,b
,
Ar (7.25, 7.37, 11 H)a, H12 (7.585 2H), H9 (8.055dd, 1H),
H90, H900 (8.155, 2H)a,b, H7 (8.808d, 1H), H70, H700 (8.782,
2H)a,b C1, C10, C100 (21.5)a,b, C2(72.26), C3(172.07), C4
(81.94; 81.91), C5(149.79), C6(96.51), C7(136.56),
C8(147.12), C9(122.33), C10(131.70), C11(139.05;
139.03), C12(127.04; 126.98), C13(130.52; 130.48),
C14(141.06), C20, C200(70.89; 70.86, 71.03; 70.99)b, C30,
C300(170.52, 170.48)b, C40, C400(68.92, 68.70)b, C50,
C500(153.58; 153.55, 153.31; 153.24; 153.19)b, C60,
C600(101.86, 101.80)b, C70, C700 (136.18, 136.04)b, C80,
C800(146.36, 146.28)b, C90, C900(122.25, 122.20)b, C100,
C1000(131.58, 131.02)b), C110, C1100(139.78, 141.06)b, C120,
C1200(129.93, 130.48)b, 0C0 130, C1300(129.89, 128.55)b, C140,
(140.67; 140.63), C14 (128.01). MS (ES) m/zZ1310.1
(C51H44N3I3O13Na).
4.2.34. Chloro trimer 6e. Colourless oil. 1H NMR
(400 MHz, CDCl3): dZ1.2–1.3 (m, 18H), 4.41 (s, 1H),
5.15–5.3 (m, 3H), 6.98–7.06 (m, 3H), 7.15–7.45 (m), 7.58–
7.65 (m, 1H), 7.93–8.08 (m, 3H), 8.25–8.29 (m, 3H). 13C
NMR (400 MHz, CDCl3): dZ21.03, 21.3, 21.36, 21.4,
21.47, 65.32, 65.57, 70.49, 70.63, 72.08, 72.11, 79.55,
79.75, 121.17, 121.24, 121.36, 125.39, 125.41, 125.51,
125.77, 126.73, 126.79, 127.95, 128.43, 129.49, 129.72,
129.99, 130.02, 130.08, 130.14, 131.38, 131.59, 131.73,
135.44, 136.65, 138.18, 139.5, 139.58, 140.02, 140.05,
140.09, 140.18, 140.22, 140.69, 140.75, 146.09, 146.13,
147.19, 147.26, 147.86, 148.78, 148.8, 148.84, 149.05,
149.09, 170.24, 170.37, 170.4, 172.36. MS (ES): m/z (%)Z
1034 (MCNa)C.
4.2.37. Methoxy trimer 6j. Yellowish, amorphous powder
(1H and 13C NMR measured in CDCl3) C(CH3)2 (1.19,
18H)a,b, OCH3 –OCH3 (3.74, 6H)a,b, OCH3, (3.96, 3H),
OH (4.41, 1H), H2, H20, H200 (5.12, 3H)a, H10, H100, H1000
(6.90, 3H)a, Ar (7.25, 11 H)a, H12 (7.58, 2H), H7, H70, H700,
H9, H90, H900 (7.72, 6H)a,b C1, C10, C100 (21.39), C2(70.71;
70.67), C3(173.13), C4 (77.88), C5(138.40; 138.31),
C6(157.62), C7(105.74), C8(148.71), C9(115.51),
C10(129.90), C11(137.16), C12(126.49; 126.42),
C13(129.90), C14(141.14), OCH3 (55.93) C20, C200(69.30,
69.21)b, C30, C300(171.15, 171.05)b, C40, C400(63.41,
63.18)b, C50, C500 (140.28, 140.33)b, C60, C600 00(157.57,
157.51)b, C70, C700 (105.42,105.35)b, C80, C8 (148.16,
148.09)b, C90, C900, (115.44, 115.43)b, C100, C1000
0
00
General remarks concerning spectra of compounds 6g, 6h,
6j and 6j0: (a) denotes approximate average for a group of
slightly non-equivalent protons or carbons; (b) denotes that
no efforts were made to assign chemical shifts to individual
1H00o0 r 13C nuclei within this group; H0 (C0), H00 (C00) and H000
(C ) denotes that the particular pro0tons 0(0or carbons) belong
to subsequent aromatic rings A0(B ), A (B00) or A000 (B000),
for atom numbering see Tables 6 or 7. For additional
comments see also the main body of the text.
(129.90)b,
C110,
C1100(139.83),
C120(129.61),
C1200(129.35),00 C130 (129.53), C1300 (127.79), C140
(140.78), C14 (127.24). MS (LSIMSC) m/z (%))Z
1022(MCC23), 982, 912 (MCK87). Anal. Calcd for
C54H53N3O16: C, 64.68; H, 5.34; N, 4.2. Found C, 64.93;
H, 5.52; N, 3.75.
4.2.35. Bromo trimer 6g. Yellowish, amorphous powder
(1H and 13C NMR spectra measured in acetone-d6).
C(CH3)2 (1.25, 18 H)a, OH (5.700, 1H), H2, H20, H200 (5.12,
3H)a, H100, H1000 (7.152d; 7.150d; 7.143d; 7.140d, 1H,
7.095, 1H)b, H10 (ca. 7.28, a signal hidden under aromatic
signals), Ar (7.30, 7.37, 9H)a, H13 (7.444, 2H), H12 (7.668,
2H), H9 (8.109dd, 1H), H90, H900 (8.179, 2H)a, H70, H700
4.2.38. Methoxy tetramer 6j0. Yellowish, amorphous
powder (1H and 13C NMR measured in CDCl3) C(CH3)2
(1.19, 24 H)a,b, OCH3 –OCH3 (3.74, 9H)a, OCH3, (3.95,
3H), OH (4.396; 4.390; 4.378; 4.376, 1H), H2, H20, H200,
H2000 (5.12, 4H)a, H10-10000 (6.90, 4H)a, Ar (7.17, 10 H)a, Ar
0
000

M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
11963
(7.28 5H)a, H12 (7.58, 2H), H7-7000 and H9-9000 (7.72, 8H)a
C1, C10, C100, C1000 (21.39)a,b, C2(70.70; 70.66), C3(173.10),
C4 (77.94), C5(138.49; 138.40), C6 (157.68), C7 (105.83;
105.81), C8(148.77), C9(115.51), C10(130 vs, broad),
C11(137.28), C12 (126.54; 126.46), C13(129.50)0,
C14(141.22; 141.17; 141.12), OCH3 (05005.96) C20, C2 ,
C2000 (69.31, 69.24; 69.20)b, C30, C300, C3 (171.14, 171.11,
171.03 broad)b, C40, C400, C4000(63.46, 63.24; 63.23, 63.11)b,
C50, C500, C5000(a group of the signals at 140.3)b, C60, C600,
C6000(157.63, 157.59, 157.57)b, C70, C700, C7000 (105.52;
105.49, 105.43; 105.40)b, C80, C800, C8000(148.23, 148.17,
148.010 6)b, C90, C900, C9000(115.45 0 vs, broad signal), C100,
C10 , C10000(130, vs, broad), C11 , C1100, C11000(a group of
the signals at about 140)b, C120, C1200, C12000, C130, C1300
(129.55, 129.38; 129.34, vs, broad signals)b, C13000(127.80),
C140, C1400 (140.86,140.41)b, C14000(127.26). MS (ES)
m/zZ1349.4 (C72H70N4O21Na).
304.08662. Found: 304.08801. Anal. Calcd for C17H17ClO3:
C, 67; H, 5.62; Cl, 11.63. Found: C, 66.77; H, 5.91; Cl,
11.14.
4.2.43. iso-Propyl a-(3-bromo-2-hydroxyphenyl)phenyl-
acetate 8f. Colourless oil. 1H NMR (400 MHz, CDCl3): dZ
1.2–1.25 (m, 6H), 4.87 (s, 1H), 5.01–5.13 (m, 1H), 6.94 (d,
1H, JZ8.4 Hz), 7.16 (dd, 1H, JZ8.4, 2.2 Hz), 7.26–7.36
(m, 5H), 7.42 (d, 1H, JZ2.2 Hz). 13C NMR (CDCl3): dZ
21.6, 21.65, 56.01, 68.82, 110.16, 115.98, 126.4, 127.3,
128.33, 128.65, 129.45, 132, 132.48, 138.5, 151.44, 171.76.
MS (EI): m/z (%)Z348 (MC, 13), 263 (100), 261 (99),182
79
(34), 152 (14), 43 (17). HRMS (EI) calcd for C17H NO3:
348.03611. Found: 348.03671.
17
4.2.44. iso-Propyl a-(3-bromo-4-hydroxyphenyl)phenyl-
acetate 9f. Colourless oil. 1H NMR (400 MHz, CDCl3): dZ
1.22 (d, 3H, JZ6.2 Hz), 1.25 (d, 3H, JZ6.3 Hz), 5.04–5.16
(m, 1H), 5.24 (s, 1H), 6.39 (s, 1H), 6.75 (m, 1H), 7.04 (dd,
1H, JZ7.8, 1.3 Hz), 7.26–7.36 (m, 5H), 7.39 (dd, 1H, JZ8,
1.3 Hz). 13C NMR (CDCl3): dZ21.58, 21.64, 52.5, 69.02,
110.91, 121.35, 126.84, 127.36, 128.32, 128.59, 128.63,
129.33, 131.17, 137.15, 150.24, 172.42. MS (EI): m/z (%)Z
4.2.39. iso-Propyl a-(3-chloro-2-hydroxyphenyl)phenyl-
acetate 8d. Colourless oil. H NMR (500 MHz, CDCl3):
1
dZ1.21 (d, 3H, JZ6.3 Hz), 1.23 (d, 3H, JZ6.3 Hz), 4.87
(s, 1H), 5.07 (m, 1H), 5.66 (s, 1H), 6.94 (d, 1H, JZ8.4 Hz),
7.11 (dd, 1H, JZ8.4, 2.2 Hz), 7.25–7.35 (m, 6H). 13C NMR
(CDCl3): dZ21.59, 21.64, 56.11, 68.82, 116.16, 119.86,
127.3, 128.35, 128.64, 128.69, 129.08, 132.07, 138.48,
150.51, 171.78, MS (EI): m/z (%)Z304 (MC, 13), 217
348 (MC, 16), 288 (36), 261 (100), 182 (47), 152 (21), 43
79
(28). HRMS (EI) calcd for C17H BrO3: 348.03611. Found:
348.03571.
17
(100), 182 (20), 136 (20), 107 (22). HRMS (EI) calcd for
C17H ClO3: 304.08662. Found: 304.08594.
35
17
4.2.45. iso-Propyl a-(2-bromo-4-hydroxyphenyl)phenyl-
acetate 8g. White crystals, mp 127–128 8C (heptane). H
1
4.2.40. iso-Propyl a-(3-chloro-4-hydroxyphenyl)phenyl-
acetate 9d. Colourless oil. H NMR (400 MHz, CDCl3):
1
NMR (400 MHz, CDCl3): dZ1.2 (d, 3H, JZ6.4 Hz), 1.28
(d, 3H, JZ6.3 Hz), 5.13 (m, 1H), 5.31 (s, 1H), 6.15, (s, 1H),
6.54 (dd, 1H, JZ8.5, 2.6 Hz), 6.84 (d, 1H, JZ8.5 Hz), 6.95
(d, 1H, JZ2.6 Hz), 7.21–7.4 (m, 5H). 13C NMR (CDCl3):
dZ215, 21.66, 56.06, 69.28, 114.85, 119.77, 124.9, 127.39,
128.76, 128.8, 129.97, 130.86, 137.86, 137.44, 155.62,
172.83. MS (EI): m/z (%)Z348 (MC, 11), 306 (5), 288 (25),
261 (100), 182 (74), 181 (55). Anal. Calcd for C17H17BrO3:
C, 58.47; H, 4.91. Found: C, 58.6; H, 5.01.
dZ1.22 (d, 3H, JZ6.3 Hz), 1.25 (d, 3H, JZ6.2 Hz), 5.1 (m,
1H), 5.24 (s, 1H), 6.37 (s, 1H), 6.78–6.83 (m, 1H), 6.99–
7.03 (m, 1H), 7.25 (dd, 1H, JZ8.3, 1.7 Hz), 7.27–7.35 (m,
5H). 13C NMR (CDCl3): dZ21.58, 21.64, 52.2, 69, 120.48,
120.76, 126.91, 127.36, 128.11, 128.53, 128.61, 137.16,
149.4, 172.37. MS (EI): m/z (%)Z304 (MC, 18), 244 (29),
217 (100), 182 (32). Anal. Calcd for C17H17ClO3: C, 67; H,
5.62; Cl, 11.63. Found: C, 66.86; H, 5.79; Cl, 11.33.
4.2.46. iso-Propyl a-(4-bromo-2-hydroxyphenyl)phenyl-
acetate 9g. Colourless oil. H NMR (400 MHz, CDCl3):
4.2.41. iso-Propyl a-(2-chloro-4-hydroxyphenyl)phenyl-
acetate 8e. White crystals, mp 133–134 8C (heptane). H
1
1
dZ1.28 (d, 3H, JZ6.2 Hz), 1.31 (d, 3H, JZ6.3 Hz), 5 9s,
1H), 5.14 (m, 1H), 6.96 (d, 1H, JZ8.3 Hz), 7.01 (dd, 1H,
JZ8.6, 1.9 Hz), 7.08 (d, 1H, JZ1.9 Hz), 7.17–7.22 (m,
2H), 7.26–7.34 (m, 3H), 8.13 (s, 1H). 13C NMR (CDCl3):
dZ21.58, 21.61, 55, 70.38, 121.29, 122.46, 123.02, 123.66,
127.56, 128.75, 132.37, 136.39, 155.98, 174.71. MS (EI):
m/z (%)Z348 (MC, 22), 306 (8), 288 (26), 261 (100), 181
(22). Anal. Calcd for C17H17BrO3: C, 58.47; H, 4.91. Found:
C, 58.6; H, 4.92.
NMR (500 MHz, CDCl3): dZ1.2 (d, 3H, JZ6.3 Hz), 1.27
(d, 3H, JZ6.3 Hz), 5.12 (sep, 1H, JZ6.3 Hz), 5.31 (s, 1H),
6.18 (s, 1H), 6.82 (d, 1H, JZ8.6 Hz), 6.48 (dd, 1H, JZ8.6,
2.6 Hz), 6.82 (d, 1H, JZ2.6 Hz), 7.20–7.36 (m, 5H). 13C
NMR (CDCl3): dZ21.48, 21.64, 53.74, 69.34, 114.29,
116.59, 127.42, 128.33, 128.76, 128.84, 130.74, 134.37,
137.2, 155.7, 172.99. MS (EI): m/z (%)Z304 (MC, 14),
244 (25), 217 (100), 182 (19). Anal. Calcd for C17H17ClO3:
C, 67; H, 5.62; Cl, 11.63. Found: C, 66.96; H, 5.7; Cl,
11.66.
4.2.47. iso-Propyl a-(1-4-hydroxynaphthyl)phenyl-
acetate 8m. White crystals. Mp 150–152 8C (hexane/ethyl
acetate) H NMR (500 MHz, CDCl3): dZ1.28 (d, 3H, JZ
4.2.42. iso-Propyl a-(4-chloro-2-hydroxyphenyl)phenyl-
acetate 9e. Colourless oil. 1H NMR (400 MHz, CDCl3): dZ
1.29 (d, 3H, JZ6.2 Hz), 1.31 (d, 3H, JZ6.2 Hz), 5 (s, 1H),
5.14 (sep, 1H, JZ6.2 Hz), 6.86 (dd, 1H, JZ8.2, 2.2 Hz),
6.93 (d, 1H, JZ2.2 Hz), 7.03 (d, 1H, JZ8.2 Hz), 7.16–7.22
(m, 2H), 7.25–7.35 (m, 3H), 8.17 (s, 1H). 13C NMR
(CDCl3): dZ21.59, 21.63, 55.1, 70.42, 118.5, 120.74,
122.41, 127.51, 127.56, 128.76, 132.16, 134.65, 136.46,
1
6.3 Hz), 1.36 (d, 3H, JZ6.2 Hz), 5.12 (s, 1H), 5.17 (m, 1H),
7.2–7.3 (m, 6H), 7.38 (d, 1H, JZ8.4 Hz), 7.45–7.5 (m, 2H),
7.75–7.79 (m, 1H), 8.31–8.36 (m, 1H), 9.21 (s, 1H). 13C
NMR (CDCl3): dZ21.63, 21.73, 56.71, 70.64, 115.93,
120.1, 122.82, 125.31, 126.53, 126.61, 127.18, 127.41,
127.45, 128.72, 129.37, 134.49, 136.91, 151.73, 175.9. MS
(EI): m/z (%)Z320 (MC, 24), 260 (43), 231 (100). HRMS
(EI) calcd for C21H20O3: 320.14124. Found: 320.14188.
155.94, 174.85. MS (EI): m/z (%)Z304 (MC, 18), 244 (32),
35
217 (100), 182 (22). HRMS (EI) calcd for C17H ClO3:
17

11964
M. Ma˛kosza et al. / Tetrahedron 61 (2005) 11952–11964
Nucleophilic Aromatic Substitution of Hydrogen; Academic:
San Diego, 1994.
4.2.48. iso-Propyl a-(2-1-hydroxynaphthyl)phenyl-
acetate 9m. White crystals, mp 134–135 8C (hexane/ethyl
acetate) H NMR (400 MHz, CDCl3): dZ1.16 (d, 3H, JZ
1
2. Ma˛kosza, M. Russ. Chem. Bull. 1996, 45, 491.
3. Terrier, F. Nucleophilic Aromatic Displacement, The Influence
of Nitro Group; VCH: New York, 1991.
6.3 Hz), 1.30 (d, 3H, JZ6.2 Hz), 5.03–12 (m, 1H), 5.12 (s,
1H), 6.53 (s, 1H), 7.28–7.43 (m, 6H), 7.72–7.77 (m, 2H),
8.02–8.08 (m, 1H), 8.08–8.14 (m, 1H). 13C NMR (CDCl3):
dZ21.4, 21.66, 51.59, 69.24, 126.2, 126.79, 128.15, 129,
129.16, 131.93, 131.99, 133.86, 133.96, 134.51, 136.54,
149, 170.14, 184.44, 185.02. MS (EI): m/z (%)Z320 (MC,
18), 260 (47), 231(100). HRMS (EI) calcd for C21H20O3:
320.14124. Found: 320.14076.
4. Rose-Munch, F.; Gagliardini, V.; Renard, C.; Rose, E. Coord.
Chem. Rev. 1998, 178, 249.
´
5. (a) Ma˛kosza, M.; Stalinski, K. Pol. J. Chem. 1999, 73, 151. (b)
Ma˛kosza, M.; Paszewski, M. Pol. J. Chem. 2004, 79, 163.
6. Schmitt, S.; Baumgarten, M.; Simon, J.; Hafner, K. Angew.
Chem., Int. Ed. 1998, 37, 1078.
7. Bartoli, G. Acc. Chem. Res. 1984, 17, 109.
8. Ma˛kosza, M.; Surowiec, M. J. Organomet. Chem. 2001, 624,
167.
4.2.49. iso-Propyl a-(5-chloro-2-hydroxy)phenylacetate
9o. White crystals, mp 97–99 8C (heptane), 1H NMR
(400 MHz, CDCl3): dZ1.29 (d, 3H, JZ6.2 Hz), 1.3 (d,
3H, JZ6.3 Hz), 5.03 (s, 1H), 5.10–5.18 (m, 1H), 6.79, (d,
1H, JZ8.5 Hz), 7.07 (d, 1H, JZ2.5 Hz), 7.13 (dd, 1H, JZ
8.5, 2.5 Hz), 7.24–7.35 (m, 5H), 7.8–8.0 (bs, 1H). 13C NMR
(CDCl3): dZ21.56, 54.42, 70.1, 118.79, 125.05, 125.84,
127.56, 127.82, 128.75, 128.95, 130.48, 153.57, 174.17. MS
(ES, MeOH): m/z (%)Z327 (MCC Na). Anal. Calcd for
C17H17ClO3: C, 67.00; H, 5.62; Cl, 11.63. Found: C, 66.81;
H, 5.73; Cl, 11.87.
9. Gallardo, I.; Guirado, G.; Marquet, J. J. Org. Chem. 2003, 68,
631.
10. Ma˛kosza, M.; Sypniewski, M. Tetrahedron 1994, 50, 4913.
11. Ma˛kosza, M.; Stalinski, K. Chem. Eur. J. 1997, 3, 2025.
12. Ma˛kosza, M.; Surowiec, M. Tetrahedron 2003, 59, 6261.
13. Ma˛kosza, M.; Surowiec, M.; Paszewski, M. Arkivoc 2004, 2,
172.
14. Adam, W.; Ma˛kosza, M.; Stalinski, K.; Zhao, C. G. J. Org.
Chem. 1998, 63, 4390.
15. Adam, W.; Ma˛kosza, M.; Zhao, C. G.; Surowiec, M. J. Org.
Chem. 2000, 65, 1099.
Supplementary data
16. Moskalev, N.; Barbasiewicz, M.; Ma˛kosza, M. Tetrahedron
2004, 60, 374.
Supplementary data associated with this article can be
found, in the online version at 10.1016/j.tet.2005.09.053
17. Ma˛kosza, M.; Paszewski, M. Synthesis 2002, 15, 2203.
18. Stalinski, K. PhD dissertation, Institute of Organic Chemistry
PAS, Warsaw, 1998.
19. Lawrence, N. J.; Lamarche, O.; Thurrab, N. Chem. Commun.
1999, 689.
References and notes
20. Renaud, P.; Fox, M. A. J. Org. Chem. 1988, 53, 3745.
21. Adam, W.; BiaŁas, J.; Hadijarapoglou, L. Chem. Ber. 1991,
124, 2377.
1. Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.