Five- and six-membered nickelacyclic carboxylates as reagents for the facile synthesis of δ-ketocarboxylic acids, isocoumarins, and 1,3-dicarbonyl derivatives of benzoic acid

Article abstract of DOI:10.1055/s-2006-942507

The nickelacyclic carboxylates A and B reacted with α-halo ketones to form α,β-unsaturated δ-ketocarboxylic acids which were easily converted into pyranones or isocoumarins. In addition, reaction of the nickelacyclic acyl derivative C with α-halo ketones

Full text of DOI:10.1055/s-2006-942507

PAPER
2697
Five- and Six-Membered Nickelacyclic Carboxylates as Reagents for the Facile
Synthesis of d-Ketocarboxylic Acids, Isocoumarins, and 1,3-Dicarbonyl
Derivatives of Benzoic Acid
N
ickelacy
e
clic Carbox
n
ylates
a
s
Re
s
a
gents Langer, Martin Gärtner, Helmar Görls, Dirk Walther*
Department of Inorganic and Analytical Chemistry, University of Jena, 07743 Jena, Germany
E-mail: Dirk.Walther@uni-jena.de
Received 6 April 2006; revised 5 May 2006
acyl derivative [Ni{C(O)-o-C6H4COO}(bipy)] C, an in-
Abstract: The nickelacyclic carboxylates A and B reacted with a-
halo ketones to form a,b-unsaturated d-ketocarboxylic acids which
were easily converted into pyranones or isocoumarins. In addition,
reaction of the nickelacyclic acyl derivative C with a-halo ketones
termediate in the formation of B that has been little inves-
tigated as a reagent for organic synthesis, reacted with a-
halo ketones to give substituted 1,3-dicarbonyl com-
resulted in the formation of substituted 1,3-dicarbonyl compounds pounds of benzoic acid 5 in good yields (Scheme 3).
with a benzoic acid substituent in the 1-position. In these reactions,
Reactions of A, B, and C with a-halo ketones were carried
many functional groups were tolerated.
out in tetrahydrofuran under argon. In all cases isolation
Key words: cross coupling, metallacycles, organometallic re-
of the products was achieved in a straightforward fashion
agents, nickel, heterocycles
by evaporation of the solvent, subsequent hydrolysis of
the residue with dilute hydrochloric acid and purification
by extraction with chloroform. After workup the products
The nickelacyclic carboxylates [Ni(CH2CH2COO)(L)2]
were isolated in a pure form. Recrystallization from ace-
and [Ni{C(R)=C(R)COO}(L)2] are interesting building
tone/heptane resulted, in most cases, in single crystals
blocks for the synthesis of carboxylic acid derivatives in
suitable for X-ray diffraction.
organic chemistry.1 Reaction of their Ni–C bond with an
alkyl halide, for example, gives carboxylic acids,2 a reac-
tion which was used to construct functionalized side
chains in steroids,3 while insertion of carbon monoxide
and reductive elimination allows the formation of cyclic
anhydrides,4 and reaction with carbon dioxide results in
the formation of dicarboxylic acids.5 In addition, the syn-
thesis of methylaspartic acids has been achieved by the re-
action of a substituted nickelacycle with isocyanides.6
Furthermore, alkenes or alkynes have been inserted into
the Ni–C bond resulting in saturated or unsaturated car-
Figure 1 Molecular structure of 2a (hydrogen atoms are omitted for
clarity). Selected bond lengths (Å) and angles (°): C1–C10 1.494(2),
boxylic acids and derivatives,7 and transmetalation reac-
tions with ZnR2 to form arylated carboxylic acids or
dicarboxylated derivatives has been described.8 Recently,
we have found that organic disulfides reacted to form car-
boxylic esters with a sulfanyl substituent in the b-position
upon workup. Furthermore, we have observed that 2-bro-
mopropiophenone and [Ni{C(Et)=C(Et)COO}(bipy)] re-
acted to yield a substituted 2H-pyran-2-one.1c
C1–O1 1.220(2), C1–C2 1.517(2), C2–C3 1.509(2), C3–C4 1.350(2),
C4–C9 1.482(2), C9–O2 1.244(2), C9–O3 1.304(2), C10–C1–C2
116.92(13), C1–C2–C3 116.60(14), C2–C3–C4 124.40(14), C3–C4–
C9 121.51(13), C4–C9–O2 123.80(14), C4–C9–O3 115.25(13), O1–
C1–C2 122.19(13).
Compound A is readily accessible in high yield (90%)
by oxidative coupling of hex-3-yne and carbon dioxide
Continuing our efforts to develop synthetic methods
based on nickelacyclic carboxylates, we now report the
reaction of a-halo ketones with the unsaturated five-mem-
bered nickelacycles [Ni{C(Et)=C(Et)COO}(bipy)] A and
[Ni(o-C6H4-COO)(bipy)] B resulting in the formation of
a,b-unsaturated d-ketocarboxylic acids 2 and 3 in good
yields (Schemes 1 and 2) which could be easily trans-
formed into the corresponding pyranones and isocou-
marins 4. In addition, the six-membered nickelacyclic
using
(2,2¢-bipyridyl)(h4-cycloocta-1,5-diene)nickel
[Ni(cod)(bipy)] as precursor.7c As shown in Table 1 the
reaction of A with a variety of a-bromo ketones worked
well (Table 1, entries 1–5). Complete conversion of the
starting material was normally achieved by stirring the re-
action mixture overnight at room temperature. Also a-
bromocamphor 1f (Table 1, entry 6), and even the aliphat-
ic a-chloro ketone 1h (Table 1, entry 7) reacted in good
yields.
Functional groups in the para position of the aryl groups
of aryl a-bromoalkyl ketones were tolerated. However,
the reaction of 1e, in which the bromide is bonded to a
quaternary carbon atom, failed. In the case of the chiral
SYNTHESIS 2006, No. 16, pp 2697–2706
Advanced online publication: 19.07.2006
DOI: 10.1055/s-2006-942507; Art ID: Z07206SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
6

2698
J. Langer et al.
PAPER
1. THF
2. HClaq
O
R2
R1
R2
R1
N
N
R2
Ni
+
R1
O
COOH
O
O
O
O
Br
OH
2'
A
2
Scheme 1
Table 1 Reaction of A with a-Halocarbonyl Compounds
Entry
1
Substrate
Product
Yield (%)
76
Ratio 2/2¢
1a
2a¢
1:1
O
Br
O
O
OH
2
3
4
1b
1c
1d
2b¢
2c¢
2d¢
74
72
67
1:3.7
1:1.8
1:6.8
Cl
O
O
Cl
Br
Cl
O
OH
O
Cl
Br
Br
O
O
OH
Br
O
Br
NC
O
O
OH
NC
5
6
1e
1f
–
0
–
O
Br
2f¢
86
1:4
Br
O
O
O
OH
7
8
1g
1h
2g
87
81
>10:1
<1:10
O
O
Br
O
O
HOOC
2h¢
O
Cl
O
O
OH
substrate 1f, retention at the chiral center was observed The equilibrium between the d-ketocarboxylic acids 2 and
and only one enantiomer was isolated as judged from their lactol forms 2¢ (Scheme 1) strongly depends on the
NMR spectral data.
nature of the substituents (Table 1). Electron-withdrawing
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

PAPER
Nickelacyclic Carboxylates as Reagents
2699
groups at the 5-position of the thus-formed carboxylic
acid 2 favor the lactol form 2¢ in deuterochloroform at
1
room temperature, according to the results of H NMR
measurements (Table 1, entries 1–4). The same effect was
achieved by a higher degree of substitution at 4-position
of the product (Table 1, entries 6, 8). In the case of 2a/2a¢,
where the d-ketocarboxylic acid 2a is more favored in so-
lution than in other cases, the solid product crystallized in
this form. Figure 1 shows the X-ray structure of 2a. In
contrast, the other compounds crystallized in the lactol
form 2¢. The X-ray structure of one example, 2f¢, is given
in Figure 2.
Figure 3 Molecular structure of B (hydrogen atoms are omitted for
clarity, only one of two independent molecules shown). Selected
bond lengths (Å) and angles (°): Ni–O1 1.857(2), Ni–N1 1.939(3),
Ni–N2 1.904(3), Ni–C7 1.897(4), C7–C2 1.404(5), C2–C1 1.497(5),
C1–O1 1.311(4), C1–O2 1.223(4), O1–Ni–C7 86.15(13), C7–Ni–N2
101.36(14), O1–Ni–N1 91.19(11), N1–Ni–N2 83.40(12), Ni–C7–C2
110.5(3), C7–C2–C1 113.9(3).
In the reaction of 1c with the nickelalactone B a crystal-
line nickel containing intermediate D could be isolated as
single crystals. Its X-ray structure (Figure 4) gave evi-
dence for the pathway of the reaction: As expected, the at-
tack of the a-halo ketone on the Ni–C bond resulted in the
splitting of this bond with the formation of a new nickel–
carboxylate complex with a bidentate coordinated carbox-
ylate group, a Ni–Br bond, the chelating 2,2¢-bipyridyl
ligand, and an additional tetrahydrofuran ligand that form
an octahedral environment around the nickel center.
Figure 2 Molecular structure of 2f¢ (hydrogen atoms are omitted for
clarity, only one of two independent molecules shown). Selected
bond lengths (Å) and angles (°): O1–C1 1.332(2), C1–C2 1.477(2),
C2–C3 1.335(3), C3–C4 1.494(3), C4–C9 1.546(2), C9–O1 1.459(2),
C1–O2 1.222(2), C9–O3 1.384(2), O1–C1–C2 120.49(16), C1–C2–
C3 120.57(16), C2–C3–C4 122.19(16), C3–C4–C9 116.09(15), C9–
O1–C1 123.57(13), C4–C9–O3 109.35(15), O1–C9–O3 105.86(14).
Compounds of the type 3 were readily transformed into
the related isocoumarins 4 (Scheme 2) by cyclization with
acetic anhydride or sulfuric acid9 (see experimental sec-
tion). In the case of 3a, two different products were ob-
tained depending on the reaction conditions. If acetic
anhydride was used, the expected product, 3-(2-naphth-
yl)isocoumarin (4a), was obtained, while the use of sulfu-
ric acid resulted in additional sulfonation of the naphthyl
group giving the isocoumarin, 7-(1-oxo-1H-2-benzopyr-
an-3-yl)naphthalene-1-sulfonic acid (4aa).
The nickelalactone B, the molecular structure of which is
shown in Figure 3, was prepared by an oxidative addition/
decarbonylation sequence of phthalic anhydride on (2,2¢-
bipyridyl)(h4-cycloocta-1,5-diene)nickel
[Ni(cod)(bi-
py)].1c The reaction of B was very similar to that of A and
it reacted with a-bromo ketones to give benzoic acids 3
(Scheme 2, Table 2). Compared to A, the reactions of B
with a-bromo ketones proceeded slowly; therefore longer
reaction times were necessary. a-Chloro ketones did not
react under usual reaction conditions, but if 2,9-dimeth-
ylphenanthroline is used as the supporting ligand for B in-
stead of 2,2¢-bipyridyl, conversion was observed (Table 2,
entry 9). The isolated products crystallized in most cases
as the keto acid, only 3h¢ was isolated as the lactol.
Compound C was prepared similar to B, by oxidative ad-
dition of phthalic anhydride to (2,2¢-bipyridyl)(h4-
cycloocta-1,5-diene)nickel [Ni(cod)(bipy)].1c Decarbon-
ylation was prevented by working at lower reaction tem-
peratures. As shown in Scheme 3, the nickelalactone C
with its six-membered ring contains a Ni–C(O) bond. Re-
concd H2SO4
R2
1. THF
2. HClaq
O
N
N
R2
R1
or Ac2O
R2
Ni
+
R1
O
R1
O
O
O
COOH
Br
O
3
B
4
Scheme 2
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

2700
J. Langer et al.
PAPER
Table 2 Reaction of B with a-Halocarbonyl Compounds
Entry
1
Substrate
Product
Conditions
r.t., 48 h
Yield (%)
1a
3a
79
65
72
59
82
O
O
Br
COOH
COOH
COOH
COOH
2
3
4
5
1b
1c
1d
1i
3b
3c
3d
3i
r.t., 24 h
r.t., 24 h
r.t., 96 h
r.t., 72 h
Cl
O
Cl
O
Br
Cl
Cl
O
O
O
Br
Br
Br
Br
O
NC
NC
O
O
Br
COOH
6
7
1e
1f
–
O
Br
3f
50 °C, 24 h
80
COOH
Br
O
O
8
9
1g
1h
3g
r.t., 240 h
r.t., 24 h
63
O
O
43a
Br
O
O
HOOC
3h¢
r.t., 240 h
r.t., 24 h
0
O
69a
Cl
O
O
OH
a 2,9-Dimethylphenanthroline instead of 2,2¢-bipyridyl was used as a ligand in complex B.
action of this bond with a-halo ketones resulted in the for- with the homolytic splitting of the C–Br bond in 1e, fol-
·
mation of the enol forms of 1,3-dicarbonyl compounds lowed by reaction of the Ph–C(O )=Me2 radical with the
(5a, 5c) if aryl-substituted a-bromo ketones are used. In Ni–acyl bond of C.
deuterochloroform solution, an equilibrium was observed
In conclusion, the reaction between the nickelacyclic car-
between 5c and the corresponding benzofuranone deriva-
boxylates A–C and a-halo ketones occurred under mild
tive 5c¢. The use of a-bromo esters instead of a-bromo ke-
conditions and could be used for the synthesis of a,b-un-
tones results in exclusive formation of the cyclic form 5¢
saturated d-ketocarboxylic acids (A and B as building
(Table 3, entries 3 and 4).
blocks) and for the preparation of 1,3-dicarbonyl com-
It is noteworthy that 2-bromo-2-methyl-1-phenylpropan- pounds of benzoic acids (C as building blocks). Many
1-one (1e) reacted very different to form the monoester of substituents such as chloride or cyanide or ester groups
phthalic acid with 2-methyl-1-phenylprop-1-enol (6). were tolerated in these reactions.
This may be the result of a radical reaction which starts
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

PAPER
Nickelacyclic Carboxylates as Reagents
2701
O
1. THF
2. HClaq
OH
O
COOH
O
OH
O
O
N
N
R2
R1
R1
+
Ni
R1
O
R2
R2
5'
Br
O
O
C
5
Scheme 3
Table 3 Reaction of C with a-Halocarbonyl Compounds
Entry
1
Substrate
Product
Conditions
r.t., 2 h
Yield (%)
1a
5a
67
73
67
O
OH
O
COOH
Br
2
3
1c
1g
5c
r.t., 30 min
r.t., 5 min
O
OH
O
COOH
Br
Br
O
Br
O
5g¢
O
O
OH
O
Br
O
4
5
1k
1e
5k¢
r.t., 5 min
r.t., 5 min
69
O
O
OH
O
O
O
O
Br
O
6
n.d.a
O
O
Br
HOOC
a Not determined.
Melting points were measured with a Reichert–Jung apparatus Type
302102 and are uncorrected. 1H and 13C NMR spectra were record-
ed at r.t. on a Bruker AC 200 MHz spectrometer. All spectra were
referenced to deuterated solvent as an internal standard. FAB-MS
were obtained on a Finnigan MAT SSQ 710 system (2,4-dimeth-
oxybenzyl alcohol as matrix), IR measurements were carried out on
a Perkin Elmer System 2000 FT-IR.
Coupling Reactions with Organic Substrates; General Proce-
dure
A red suspension (15 mL) of A, B, or C (1 mmol) and an a-halo ke-
tone (1 mmol) in THF was stirred under an argon atmosphere. In
one case (see Table 2) additional heating was necessary. When the
reaction was complete as indicated by the green color of the suspen-
sion, the solvent was evaporated under reduced pressure. The resi-
due was stirred for 1 h with dil aq HCl (20 mL) and extracted with
CHCl3 (2 × 20 mL). The combined organic phases were extracted
with sat. aq Na2CO3 (2 × 20 mL). Then the combined aqueous solns
were acidified (HCl) and extracted with CHCl3 (3 × 20 mL). These
organic layers were dried (anhyd Na2SO4) and the solvent was re-
moved under vacuum to give the crude product. Further purification
was achieved by recrystallization (in most cases from acetone/hep-
tane).
The coupling reactions with A, B, and C were carried out by using
Schlenk techniques under an atmosphere of argon. Prior to use,
THF was dried (KOH) and distilled (Na/benzophenone). Ac2O was
distilled prior to use. 2-Bromo-2¢-acetonaphthone (1a), 2,4¢-dibro-
moacetophenone (1c), 2-bromoisobutyrophenone (1e), (+)-[(1R)-
endo]-3-bromocamphor (1f) and a-bromo-g-butyrolactone (1g)
were purchased from Aldrich, 3-chlorobutan-2-one (1h) from Lan-
caster, 2-bromo-4¢-cyanoacetophenone (1d) from Acros Organics,
and 2,4-dichlorophenacyl bromide (1b) from Fluorochem. These
compounds were used without further purification. A, B, and C
were prepared according to known procedures.1e,7c
Isocoumarins 4 by Dehydration; General Procedure
A soln (10 mL) of the substituted keto acid 3 (1 mmol) in Ac2O was
refluxed for 2 h, after which time the solvent was evaporated under
reduced pressure to give the crude product as colorless solid. Fur-
ther purification by recrystallization (acetone–heptane) gave iso-
coumarins as colorless crystals.
If analytical data of known products are accessible, these substances
were identified by comparing their mp and NMR spectra with those
reported in the literature. For such substances only melting points
are given.
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2702
J. Langer et al.
PAPER
(COO), 198.5 (C=O); hydroxylactone form: d = 11.7 (CH3), 13.9
(CH3), 19.7 (CH2), 26.6 (CH2), 37.3 (CH2), 99.8 (C-OH), 126.2
(>C=), 126.9 (3-CH phenyl), 128.9 (3-CH phenyl), 131.0 (2-CH
phenyl), 132.8 (4-ClC phenyl), 135.2 (2-ClC phenyl), 137.4 (i-C
phenyl), 152.2 (=C<), 165.3 (COO).
MS (DEI): m/z (%) = 315 (6) [M]+, 297 (33) [M – H2O]+, 269 (9)
[M – H2O – CO]+, 175 (52), 173 [2,4-Cl2C6H3-C≡O]+ (84), 124
(100).
Anal. Calcd for C15H16Cl2O3: C, 57.16; H, 5.12. Found: C, 56.96; H,
5.16.
6-(4-Bromophenyl)-3,4-diethyl-6-hydroxy-5,6-dihydro-2H-py-
ran-2-one (2c¢)
13C NMR (100 MHz, CDCl3, 25 °C): keto acid form: d = 12.1
(CH3), 14.0 (CH3), 22.6 (CH2), 28.7 (CH2), 43.5 (CH2), 128.1 (4-
BrC phenyl), 129.6 (2 × 2-CH phenyl), 131.8 (2 × 3-CH phenyl),
131.7 (>C=), 135.8 (i-C phenyl), 148.8 (=C<), 172.8 (COO), 196.4
(C=O); hydroxylactone form: d = 11.6 (CH3), 13.9 (CH3), 19.7
(CH2), 26.5 (CH2), 40.7 (CH2), 100.5 (C-OH), 122.9 (4-BrC phe-
nyl), 126.8 (>C=), 127.0 (2 × 2-CH phenyl), 131.5 (2 × 3-CH phe-
nyl), 141.8 (i-C phenyl), 151.3 (=C<), 165.4 (COO).
Anal. Calcd for C15H17BrO3: C, 55.40; H ,5.27. Found: C, 55.28; H,
5.23.
6-(4-Cyanophenyl)-3,4-diethyl-6-hydroxy-5,6-dihydro-2H-pyr-
an-2-one (2d¢)
13C NMR (100 MHz, CDCl3, 25 °C): hydroxylactone form:
d = 11.6 (CH3), 13.7 (CH3), 19.6 (CH2), 26.6 (CH2), 40.5 (CH2),
100.3 (C-OH), 112.6 (4-NC-C phenyl), 118.4 (CN), 126.2 (2 × 2-
CH phenyl), 126.7 (>C=), 132.2 (2 × 3-CH phenyl), 147.5 (i-C phe-
nyl), 151.6 (=C<), 165.5 (COO).
MS (DEI): m/z (%) = 272 (10) [M + 1]+, 254 (32) [M – OH]+, 225
(24) [M – H2O – CO]+, 130 (100), 130 (100) [NC-C6H4-C≡O]+, 124
(88), 102 (55) [NC-C6H4]+.
Figure 4 Molecular structure (top) and structural formula (bottom)
of [NiBr(3c-H)(bipy)(thf)] (D) (hydrogen atoms are omitted for clari-
ty). Selected bond lengths (Å) and angles (°): Ni–N1 2.076(4), Ni–N2
2.056(4), Ni–O1 2.069(4), Ni–O2 2.135(3), Ni–O4 2.098(5), Ni–Br1
2.5186, O1–C1 1.267(6), O2–C1 1.260(6), N1–Ni–N2 78.91(16),
O1–Ni–O2 62.82(13), Br1–Ni–O4 90.60(13), Br1–Ni–O2 92.22(9),
Br1–Ni–O1 92.83(10), N1–Ni–O1 93.41(15), N1–Ni–O2 91.76(14),
N1–Ni–O4 83.67(17), O1–C1–O2 120.3(4).
Anal. Calcd for C16H17NO3: C, 70.83; H, 6.32; N 5.16. Found: C,
70.70; H, 6.33; N, 4.92.
(1R,2S,7R,8R)-5,6-Diethyl-2-hydroxy-1,11,11-trimethyl-3-oxa-
tricyclo[6.2.1.02,7]undec-5-en-4-one (2f¢)
13C NMR (50 MHz, CDCl3): hydroxylactone form: d = 9.1 (CH3),
12.3 (CH3), 14.2 (CH3), 19.8 (CH3), 20.1 (CH2), 20.4 (CH2), 20.6
(CH3), 24.8 (CH2), 29.8 (CH2), 45.9 (C), 46.8 (CH), 48.2 (CH), 55.0
(C), 106.7 (C-OH), 127.1 (>C=), 154.1 (=C<), 163.8 (COO).
3,4-Diethyl-6-hydroxy-6-(2-naphthyl)-5,6-dihydro-2H-pyran-
2-one (2a¢)
a
b
13C NMR (100 MHz, CDCl3, 25 °C): d = 11.6 (CH3 ), 12.2 (CH3 ),
MS (DEI): m/z (%) = 279 (62) [M + 1]+, 278 (27) [M]+, 261 (100)
[M – OH]+, 260 (26) [M – H2O]+, 232 (14) [M – H2O – CO]+, 140
(15).
a
b
a
b
a
13.9 (CH3 ), 14.0 (CH3 ), 19.8 (CH2 ), 22.7 (CH2 ), 26.5 (CH2 ),
b
a
b
28.4 (CH2 ), 40.7 (CH2 ), 43.6 (CH2 ), 100.9 (C-OHa), 122.9 (CH),
123.9 (CH), 124.3 (CH), 126.4 (CH), 126.6(0) (CH), 126.6(3) (CH),
126.9 (>C=a), 127.5 (CH), 127.7 (CH), 128.3 (3 × CH), 128.5 (CH),
129.6 (CH), 129.8 (CH), 132.0 (>C=b), 132.5 (C), 132.8 (C), 133.2
(C), 134.3 (C), 135.5 (Cb), 139.8 (Ca), 148.4 (=C<b), 151.2 (=C<a),
165.4 (COOa), 173.0 (COOb), 197.6 (C=Ob); a hydroxylactone form
and b keto acid form are present in nearly equimolar amounts, so it
was not possible to judge to which form a signal belongs in all cases.
Anal. Calcd for C17H26O3: C, 73.34; H, 9.41. Found: C, 73.30; H,
9.43.
(2Z)-2-Ethyl-3-(2-oxotetrahydrofuran-3-yl)pent-2-enoic Acid
(2g)
1H NMR (200 MHz, CDCl3, 25 °C): d = 1.08 (m, 3J = 7.6 Hz, 6 H,
2 × CH3), 2.1–2.5 (m, 6 H, 3 × CH2), 4.03 (dd, 3J = 9.6 Hz, 3J = 11.3
Hz, 1 H, CH), 4.22 (m, 1 H, CHH¢), 4.41 (ddd, 3J = 8.8 Hz, 3J = 8.8
Hz, 2J = 2.6 Hz, 1 H, CHH¢), 10.2–10.6 (br, 1 H, COOH).
MS (DEI): m/z (%) = 296 (15) [M]+, 278 (4) [M – H2O]+, 250 (6)
[M – H2O – CO]+, 155 (100), 127 (48) [naphthyl]+, 124 (40).
Anal. Calcd for C19H20O3: C, 77.00; H, 6.80. Found: C, 76.91; H,
6.80.
13C NMR (50 MHz, CDCl3, 25 °C): d = 13.3 (CH3), 13.6 (CH3),
23.0 (CH2), 26.7 (CH2), 28.9 (CH2), 45.2 (CH), 66.6 (OCH2), 133.1
(>C=), 148.1 (=C<), 173.5 (COO), 176.7 (COO).
6-(2,4-Dichlorophenyl)-3,4-diethyl-6-hydroxy-5,6-dihydro-2H-
pyran-2-one (2b¢)
MS (DEI): m/z (%) = 213 (5) [M + 1]+, 194 (100) [M – H2O]+, 166
(81) [M – H2O – CO]+, 151 (72), 138 (48), 93 (65).
13C NMR (100 MHz, CDCl3, 25 °C): keto acid form: d = 12.0
(CH3), 14.0 (CH3), 22.5(CH2), 29.0 (CH2), 48.0 (CH2), 127.2 (CH
phenyl), 130.1 (CH phenyl), 130.2 (CH phenyl), 131.5 (C phenyl),
131.6 (>C=), 136.9 (C phenyl), 137.9 (4-ClC), 148.9 (=C<), 172.6
Anal. Calcd for C11H16O4: C, 62.25; H, 7.60. Found: C, 62.33; H,
7.58.
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

PAPER
Nickelacyclic Carboxylates as Reagents
2703
3,4-Diethyl-6-hydroxy-5,6-dimethyl-5,6-dihydro-2H-pyran-2-
one (2h¢)
IR (KBr): 3200–2800 (br, OH), 2231 (s, C≡N), 1699 cm–1 (vs,
C=O).
IR (KBr): 3343 (br, OH), 1673 cm–1 (s, C=O).
1H NMR (400 MHz, CDCl3): d = 4.66 (s, 2 H, CH2), 7.26 (d,
3J = 7.2 Hz, 1 H, CH), 7.42 (ddd, 4J = 1.0 Hz, 3J = 7.8 Hz, 3J = 8.0
Hz, 1 H, CH), 7.57 (ddd, 4J = 1.4 Hz, 3J = 7.4 Hz, 3J = 7.6 Hz, 1 H,
CH), 7.78 (AA¢BB¢, 2 H, CH Ph), 8.09 (AA¢BB¢, 2 H, CH Ph), 8.10
(dd, 4J = 1.2 Hz, 3J = 8.0 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 45.2 (CH2), 116.2 (CN), 118.0
(CCN), 127.8 (CH), 127.9 (C), 128.5 (2 × CH), 132.1 (CH), 132.5
(2 × CH), 132.8 (CH), 133.6 (CH), 137.0 (C), 140.3 (C), 170.9
(COO), 196.1 (>C=O).
1H NMR (200 MHz, CDCl3, 25 °C): hydroxylactone form (major
pair of diastereomers): d = 1.02 (t, 3J = 7.4 Hz, 3 H, CH3), 1.09 (d,
3J = 7.1 Hz, 3 H, CH3), 1.11 (t, 3J = 7.6 Hz, 3 H, CH3), 1.55 (s, 3 H,
2
3
CH3), 2.02 (dq, J = 14.2 Hz, J = 7.6 Hz, 1 H, CHH¢), 2.25–2.55
(m, 4 H, CHH¢, CH2, CH), 3.45 (br, 1 H, OH).
13C NMR (50 MHz, CDCl3, 25 °C): hydroxylactone form (major
pair of diastereomers): d = 12.2 (CH3), 14.0 (CH3), 15.8 (CH3), 19.8
(CH2), 24.9 (CH2), 25.7 (CH3), 41.2 (CH), 102.1 (C-OH), 125.9
(>C=), 157.3 (=C<), 164.9 (COO).
MS (DEI): m/z (%) = 266 (1) [M + H]+, 248 (5) [M – OH]+, 130 (89)
[OC-C6H4-CN]+, 118 (100) [C6H4-CH2-CO]+, 102 (39) [C6H4-
CN]+.
Anal. Calcd for C11H18O3: C, 66.64; H, 9.15. Found: C, 66.57; H,
9.25.
Anal. Calcd for C16H11NO3: C, 72.45; N, 5.28; H, 4.18. Found: C,
72.27; N, 5.26; H, 4.30.
2-[2-(2-Naphthyl)-2-oxoethyl]benzoic Acid (3a)
Mp 160–162 °C.
IR (KBr): 3200–2800 (br, OH), 1685 (s, C=O), 1675 cm–1 (s, C=O).
2-[(1R,2R,4R)-4,7,7-Trimethyl-3-oxobicyclo[2.2.1]hept-2-
yl]benzoic Acid (3f)
Mp 125 °C (dec.).
1H NMR (400 MHz, THF-d8): d = 4.92 (s, 2 H, CH2), 7.30 (d,
3J = 7.6 Hz, 1 H, CH), 7.34 (ddd, 4J = 1.2 Hz, 3J = 7.6 Hz, 3J = 7.6
Hz, 1 H, CH), 7.47 (ddd, 4J = 1.2 Hz, 3J = 7.6 Hz, 3J = 7.6 Hz, 1 H,
CH), 7.51–7.61 (m, 2 H, CH Ph), 7.88–7.94 (m, 2 H, CH Ph), 8.03
(d, 3J = 8.0 Hz, 1 H, CH), 8.06–8.11 (m, 2 H, CH Ph), 8.69 (s, 1 H,
CH), 11.21 (br, 1 H, COOH).
13C NMR (100 MHz, THF-d8): d = 45.3 (CH2), 124.9 (CH), 127.2
(CH), 127.3 (CH), 128.4 (CH), 128.7 (2 × CH), 130.2 (2 × CH),
131.2 (C), 131.8 (CH), 132.4 (CH), 133.3 (CH), 133.7 (C), 136.0
(C), 136.4 (C), 138.8 (C), 168.5 (COO), 196.5 (>C=O).
IR (KBr): 3200–2800 (br, OH), 2966 (s), 1724 (vs, C=O), 1687 (s,
C=O), 1447 (m), 1373 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 1.00 (s, 3 H, CH3), 1.03 (s, 3 H,
CH3), 1.05 (s, 3 H, CH3), 1.15 (ddd, 3J = 4.2 Hz, 3J = 9.2 Hz,
3
2J = 11.0 Hz, 1 H, CHH¢), 1.46 (ddd, 3J = 4.6 Hz, J = 9.2 Hz,
2J = 11.2 Hz, 1 H, CHH), 1.58–1.66 (m, 1 H, CHH¢), 1.78 (ddd,
3J = 4.0 Hz, 2J = 12.0 Hz, 1 H, CHH), 2.45 (t, 3J = 4.4 Hz, 1 H, CH),
4.88 (d, 3J = 3.6 Hz, 1 H, CH), 7.10 (d, 3J = 7.4 Hz, 1 H, CH), 7.33
4
3
3
(ddd, J = 0.8 Hz, J = 7.6 Hz, J = 7.6 Hz, 1 H, CH), 7.51 (ddd,
MS (DEI): m/z (%) = 290 (8) [M]+, 273 (3) [M – OH]+, 155 (100)
[C10H7-CO]+, 127 (55) [C10H7]+, 118 (18) [-C6H4-CH2-C(O)-]+, 77
(10).
4J = 1.6 Hz, J = 7.2 Hz, J = 7.6 Hz, 1 H, CH), 8.12 (dd, J = 1.2
3
3
4
Hz, 3J = 7.6 Hz, 1 H, CH), 11.20 (br, 1 H, COOH)
13C NMR (50 MHz, CDCl3): d = 9.7 (CH3), 19.3 (CH3), 19.4 (CH3),
21.0 (CH2), 30.2 (CH2), 46.1 (C), 49.7 (CH), 54.3 (CH), 59.6 (C),
126.8 (CH), 128.7 (C), 129.9 (CH), 132.3 (CH), 133.1 (CH), 140.4
(C), 172.6 (COO), 219.2 (CO).
MS (DEI): m/z (%) = 272 (55) [M]+, 254 (39) [M – H2O]+, 244 (23)
[M – CO]+, 229 (31) [M + 1 –CO2]+, 226 (69) [M – H2O – CO]+, 211
(100) [M + 1 –H2O –CO2]+.
Anal. Calcd for C19H14O3: C, 78.60; H, 4.86. Found: C, 78.47; H,
5.01.
2-[2-(2,4-Dichlorophenyl)-2-oxoethyl]benzoic Acid (3b)
Mp 133–135 °C.
IR (KBr): 3200–2800 (br, OH), 1711 (s, C=O), 1679 (vs, C=O),
1083 cm–1 (m).
Anal. Calcd for C17H20O3: C, 74.97; H, 7.40. Found: C, 74.87; H,
7.38.
1H NMR (400 MHz, CDCl3): d = 4.63 (s, 2 H, CH2), 7.28–7.33 (m,
2 H, CH), 7.43 (ddd, 4J = 1.2 Hz, 3J = 7.6 Hz, 3J = 7.6 Hz, 1 H, CH),
7.43 (d, 4J = 2.0 Hz, 1 H, CH), 7.54 (d, 3J = 8.4 Hz, 1 H, CH), 7.58
(ddd, 4J = 1.2, 3J = 7.4 Hz, 3J = 7.6 Hz, 1 H, CH), 8.14 (dd, 4J = 1.2
Hz, 3J = 7.6 Hz, 1 H, CH), 10.50 (br, 1 H, COOH).
2-(2-Oxotetrahydrofuran-3-yl)benzoic Acid (3g)
Mp 153–155 °C.
IR (KBr): 3200–2800 (br, OH), 2925 (m), 1764 (s, C=O), 1709
cm–1 (vs, C=O).
13C NMR (100 MHz, CDCl3): d = 49.2 (CH2), 127.3 (CH), 127.7
(CH), 128.0 (C), 130.3 (CH), 130.4 (CH), 131.9 (C), 132.0 (CH),
133.0 (CH), 133.6 (CH), 136.9 (C), 137.1 (C), 137.6 (C), 172.3
(COO), 198.5 (>C=O).
MS (DEI): m/z (%) = 308 (0.5) [M(35Cl,35Cl)]+, 294 (0.5)
[M(37Cl,37Cl) – H2O]+, 292 (1) [M(37Cl,35Cl) – H2O]+, 290 (1)
[M(35Cl,35Cl) – H2O]+, 177 (6) [OC-C6H337Cl2]+, 175 (55) [OC-
C6H337Cl35Cl]+, 173 (100) [OC-C6H335Cl2]+, 149 (3) [C6H337Cl2]+,
147 (9) [C6H337Cl35Cl]+, 145 (19) [C6H335Cl2]+, 118 (82) [C4H6-
CH2-CO]+.
1H NMR (200 MHz, CDCl3): d = 2.30–2.55 (m, 1 H, CHH¢), 2.69–
2.87 (m, 1 H, CHH¢), 4.31–4.57 (m, 2 H, CHH¢-O), 4.70 (dd,
3J = 9.2 Hz, 3J = 11.0 Hz, 1 H, CH), 7.33 (dd, 4J = 1.2 Hz, 3J = 7.6
Hz, 1 H, CH), 7.41 (ddd, 4J = 1.2 Hz, 3J = 7.6 Hz, 3J = 7.6 Hz, 1 H,
CH), 7.58 (ddd, 4J = 1.6 Hz, 3J = 7.5 Hz, 3J = 7.6 Hz, 1 H, CH), 8.14
(dd, 4J = 1.4 Hz, 3J = 7.8 Hz, 1 H, CH).
13C NMR (50 MHz, CDCl3): d = 31.8 (CH2), 44.6 (CH), 66.7
(CH2O), 127.9 (CH), 127.9 (C), 130.5 (CH), 132.3 (CH), 133.8
(CH), 139.4 (C), 171.5 (COO), 177.5 (COO).
Anal. Calcd for C15H10Cl2O3: C, 58.28; H, 3.26. Found: C, 58.11; H,
3.28.
MS (DEI): m/z (%) = 206 (3) [M]+, 188 (100) [M – H2O]+, 147 (35)
[M – (CH2-COO) – H]+, 77 (20) [C6H5]+.
2-[2-(4-Bromophenyl)-2-oxoethyl)benzoic Acid (3c)
Anal. Calcd for C11H10O4: C, 64.08; H, 4.89. Found: C, 64.19; H,
4.76.
Mp 163–165 °C (Lit.10 162 °C).
2-[2-(4-Cyanophenyl)-2-oxoethyl]benzoic Acid (3d)
Mp 165–167 °C.
3-Hydroxy-3,4-dimethyl-3,4-dihydroisocoumarin (3h¢)
Mp 121–122 °C (Lit.11 119 °C).
IR (KBr): 3361 (vs, OH), 1708 (vs, C=O), 1691 cm–1 (vs, C=O).
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

2704
J. Langer et al.
PAPER
1H NMR (400 MHz, CDCl3): major pair of diastereomers, hydroxy-
lactone form: d = 1.32 (d, 3J = 7.2 Hz, 3 H, CH3), 1.68 (s, 3 H, CH3),
3.15 (q, 3J = 7.2 Hz, 1 H, CH), 3.97 (br, 1 H, OH), 7.28 (d, 3J = 8.0
Hz, 1 H, CH), 7.37 (ddd, 4J = 0.8 Hz, 3J = 7.6 Hz, 3J = 7.6 Hz, 1 H,
CH), 7.56 (ddd, 4J = 1.6 Hz, 3J = 7.4 Hz, 3J = 7.6 Hz, 1 H, CH), 8.07
(d, 3J = 8.0 Hz, 1 H, CH); minor pair of diastereomers, hydroxylac-
tone form: d = 1.46 (d, 3J = 7.2 Hz, 3 H, CH3), 1.71 (s, 3 H, CH3),
3.25 (q, 3J = 7.2 Hz, 1 H, CH), 3.90 (br, 1 H, OH), 7.34–7.40 (m, 1
1H NMR (400 MHz, THF-d8): d = 5.17 (br, H2O), 7.36 (s, 1 H,
4
3
3
HC=), 7.54 (ddd, J = 1.2 Hz, J = 7.8 Hz, J = 7.8 Hz, 1 H, CH),
7.59 (t, 3J = 8.0 Hz, 1 H, CH), 7.68 (d, 3J = 7.6 Hz, 1 H, CH), 7.77
(ddd, 4J = 1.4 Hz, 3J = 7.8 Hz, 3J = 7.8 Hz, 1 H, CH), 8.06–8.15 (m,
3
4
3 H, CH), 8.25 (d, J = 8.0 Hz, 1 H, CH), 8.28 (dd, J = 1.0 Hz,
3J = 7.6 Hz, 1 H, H8), 9.31 (s, 1 H, CH).
13C NMR (100 MHz, THF-d8): d = 103.7 (-CH=), 121.8 (C), 123.4
(CH), 123.9 (CH), 126.1 (CH), 127.2 (CH), 129.1 (2 × CH), 129.4
(C), 129.9 (CH), 130.0 (CH), 132.1 (C), 133.7 (CH), 135.5 (CH),
135.5 (C), 138.3 (C), 138.4 (C), 154.1 (=C<), 161.7 (COO).
3
4
H, CH), 7.38 (t, J = 7.6 Hz, 1 H, CH), 7.59 (ddd, J = 1.6 Hz,
3J = 7.4 Hz, 3J = 7.6 Hz, 1 H, CH), 8.09 (d, 1 H, CH).
13C NMR (100 MHz, CDCl3): major pair of diastereomers, hy-
droxylactone form: d = 18.7 (CH3), 25.5 (CH3), 41.7 (CH), 104.6
(C-OH), 126.2 (C), 127.4 (CH), 127.5 (CH), 130.0 (CH), 134.3
(CH), 143.8 (C), 165.0 (COO).
MS (DEI): m/z (%) = 352 (68) [M]+, 324 (63) [M – CO]+, 272 (61)
[M – SO3]+, 244 (46) [M – CO – SO3]+, 215 (55).
Anal. Calcd for C19H16O7S: C, 58.76; S, 8.25; H, 4.15. Found: C,
58.51; S, 8.23; H, 4.21.
MS (DEI): m/z (%) = 193 (5) [M + 1]+, 175 (17) [M – OH]+, 132
(100), 104 (51), 77 [C6H5]+ (27), 43 (42).
3-(2,4-Dichlorophenyl)isocoumarin (4b)
Anal. Calcd for C11H12O3: C, 68.73; H, 6.29. Found: C, 68.70; H,
6.36.
Mp 146–148 °C.
IR (KBr): 1740 (s, C=O), 1699 (w, C=O), 1644 (m, C=C), 1051
cm–1 (m, C–Cl).
1H NMR (400 MHz, CDCl3): d = 6.98 (s, 1 H, HC=), 7.34 (dd,
4J = 2.0 Hz, 3J = 8.4 Hz, 1 H, CH), 7.47–7.51 (m, 2 H, CH), 7.54 (t,
3J = 7.6 Hz, 1 H, CH), 7.67 (d, 3J = 8.4 Hz, 1 H, CH¢), 7.74 (t,
3J = 7.6 Hz, 1 H, CH), 8.31 (d, 3J = 8.0 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 107.9 (-HC=), 120.7 (C), 126.3
(CH), 127.4 (CH), 128.9 (CH), 129.6 (CH), 130.1 (C), 130.5 (CH¢),
131.3 (CH), 133.0 (C), 135.0 (CH), 136.0 (C), 136.7 (C), 150.3
(=C<), 162.0 (COO).
MS (DEI): m/z (%) = 294 (10) [M(37Cl,37Cl)]+, 292 (52)
[M(35Cl,37Cl)]+, 290 (100) [M(35Cl,35Cl)]+, 266 (6) [M(37Cl,37Cl) –
CO]+, 264 (41) [M(37Cl,35Cl) – CO]+, 262 (74) [M(35Cl,35Cl) –
CO]+, 229 (18) [M(37Cl) – CO – Cl]+, 227 (51) [M(35Cl) – CO –
Cl]+, 145 (10) [C9H5O2]+, 89 (30) [C6H4-CH]+.
2-(1-Methyl-2-oxo-2-phenylethyl)benzoic Acid (3i)
Mp 106–108 °C.
IR (KBr): 3200–2800 (br, OH), 1705 (s, C=O), 1686 (vs, C=O),
1374 cm–1 (m).
1H NMR (400 MHz, CDCl3): keto acid form: d = 1.53 (d, 3J = 6.8
3
Hz, 3 H, >CHCH3), 5.87 (q, J = 6.8 Hz, 1 H, >CHCH3), 7.26 (d,
3J = 8.0 Hz, 1 H, CH), 7.30 (ddd, 4J = 0.8 Hz, 3J = 7.6 Hz, 3J = 7.9
Hz, 1 H, CH), 7.32–7.38 (m, 2 H, CH Ph), 7.41–7.45 (m, 1 H, CH
4
3
3
Ph), 7.45 (ddd, J = 1.6 Hz, J = 7.4 Hz, J = 7.6 Hz, 1 H, CH),
7.93–7.99 (m, 2 H, CH Ph), 8.10 (dd, 4J = 1.4 Hz, 3J = 7.6 Hz, 1 H,
CH), 11.0 (br, 1 H, COOH).
13C NMR (100 MHz, CDCl3): keto acid form: d = 18.9 (>CHCH3),
43.9 (>CHCH3), 126.8 (CH), 127.0 (C), 128.5 (2 × CH), 128.7 (2 ×
CH), 128.8 (CH), 132.2 (CH), 132.7 (CH), 133.7 (CH), 136.5 (C),
144.0 (C), 172.9 (COO), 201.1 (>C=O).
MS (DEI): m/z (%) = 255 (4) [M + 1]+, 237 (52) [M – OH]+, 208
(11) [M – H2O – CO]+, 132 (100) [C6H5-CO-C(CH3)]+, 105 [C6H5-
CO]+ (100), 77 (100) [C6H5]+.
Anal. Calcd for C15H8Cl2O2: C, 61.88; H, 2.77. Found: C, 61.68; H,
2.66.
3-(4-Bromophenyl)isocoumarin (4c)
Mp 135–138 °C (Lit.10 132 °C).
Anal. Calcd for C16H14O3: C, 75.57; H, 5.55. Found: C, 75.35; H,
5.57.
(1S,4R)-4,11,11-Trimethyl-1,2,3,4-tetrahydro-1,4-methano-6H-
dibenzo[b,d]pyran-6-one (4f)
3-(2-Naphthyl)isocoumarin (4a)
Mp 150 °C (dec.).
Mp 161–163 °C.
IR (KBr): 1724 (vs, C=O), 1693 (m, C=O), 1636 cm–1 (C=C).
IR (KBr): 2962 (s), 2876 (m), 1728 (vs, C=O), 1639 (vs, C=C),
1474 (w), 1375 cm–1 (m).
1H NMR (400 MHz, CDCl3): d = 6.99 (s, 1 H, HC=), 7.42–7.51 (m,
4 H, CH), 7.67 (ddd, 4J = 1.2 Hz, 3J = 7.8 Hz, 3J = 8.4 Hz, 1 H, CH),
7.76–7.90 (m, 4 H, CH), 8.27 (d, 3J = 8.0 Hz, 1 H, CH), 8.38 (s, 1
H, CH).
13C NMR (100 MHz, CDCl3): d = 102.1 (-HC=), 120.5 (C), 121.9
(CH), 125.2 (CH), 126.0 (CH), 126.8 (CH), 127.1 (CH), 127.6
(CH), 128.1 (CH), 128.5 (CH), 128.8 (CH), 128.9 (C), 129.6 (CH),
133.1 (C), 133.8 (C), 134.8 (CH), 137.5 (C), 153.5 (=C<), 162.3
(COO).
1H NMR (400 MHz, CDCl3): d = 0.87 (s, 3 H, CH3), 0.92 (s, 3 H,
CH3), 1.09 (ddd, 3J = 3.6 Hz, 3J = 9.2 Hz, 2J = 11.8 Hz, 1 H, CHH¢),
1.21 (s, 3 H, CH3), 1.32 (ddd, 3J = 3.6 Hz, 3J = 9.2 Hz, 2J = 11.8 Hz,
1 H, CHH¢), 1.81 (ddd, 3J = 3.6 Hz, 3J = 9.2 Hz, 2J = 12.6 Hz, 1 H,
CHH¢), 2.04 (ddt, 3J = 3.6 Hz, 3J = 8.8 Hz, 2J = 12.0 Hz, 1 H,
3
3
CHH¢), 2.98 (d, J = 3.6 Hz, 1 H, CH), 7.32 (d, J = 8.0 Hz, 1 H,
CH), 7.35 (ddd, 4J = 0.8 Hz, 3J = 8.0 Hz, 3J = 8.0 Hz, 1 H, CH), 7.66
4
3
3
(ddd, J = 1.2 Hz, J = 8.0 Hz, J = 8.0 Hz, 1 H, CH), 8.27 (dd,
4J = 0.8 Hz, 3J = 8.0 Hz, 1 H, CH).
13C NMR (50 MHz, CDCl3): d = 9.1 (CH3), 19.3 (CH3), 19.4 (CH3),
26.0 (CH2), 32.8 (CH2), 48.0 (CH), 54.4 (C), 56.5 (C), 116.3 (>C=),
120.1 (C), 121.4 (CH), 126.1 (CH), 130.9 (CH), 134.7 (CH), 135.8
(C), 161.8 (=C<), 163.8 (COO).
MS (DEI): m/z (%) = 272 (100) [M]+, 244 (77) [M – CO]+, 127 (23)
[C10H7]+.
Anal. Calcd for C19H12O2: C, 83.80; H, 4.44. Found: C, 83.59; H,
4.22.
MS (DEI): m/z (%) = 224 (30) [M – 2 × CH3]+, 180 (100) [M – CO2
– 2 × CH3]+, 152 (45), 76 (20).
7-(1-Oxo-1H-2-benzopyran-3-yl)naphthalene-1-sulfonic Acid
Dihydrate [4aa·(H2O)2]
Mp 120 °C (dec.).
Anal. Calcd for C17H18O2: C, 80.29; H, 7.13. Found: C, 80.02; H,
7.14.
IR (KBr): 3424 (vs, OH), 1731 (vs, C=O), 1636 (s, C=C), 1184
cm–1 (vs, SO).
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

PAPER
Nickelacyclic Carboxylates as Reagents
2705
4-Methyl-3-phenylisocoumarin (4i)
Ethyl 2-(1-Hydroxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl)bu-
tanoate (5k¢)
Mp 112–113 °C.
Mp 113–114 °C (Lit.12 109–113 °C).
2-[(2Z)-3-Hydroxy-3-(2-naphthyl)-1-oxoprop-2-enyl]benzoic
Acid (5a)
Mp 169–171 °C.
IR (KBr): 3283 (s, OH), 1742 (vs, C=O), 1733 (vs, C=O), 1466 (m),
1376 cm–1 (s).
1H NMR (400 MHz, CDCl3): major pair of diastereomers: d = 0.92
IR (KBr): 3422 (s, OH), 3200–2800 (br, OH), 1696 (vs, C=O), 1625
cm–1 (s, C=C).
3
3
(t, J = 7.2 Hz, 3 H, CH3), 1.28 (t, J = 7.2 Hz, 3 H, CH3), 1.90
(quint, 3J = 7.6 Hz, 2 H, CH2), 2.73 (dd, 3J = 5.6 Hz, 3J = 9.6 Hz, 1
H, CH), 4.24 (q, 3J = 7.2 Hz, 2 H, CH2O), 6.05 (br, 1 H, OH), 7.54–
7.59 (m, 1 H, CH), 7.63–7.70 (m, 2 H, CH), 7.84 (d, 3J = 7.2 Hz, 1
H, CH); minor pair of diastereomers: d = 0.85 (t, 3J = 7.6 Hz, 3 H,
CH3), 1.27 (t, 3J = 7.2 Hz, 3 H, CH3), 1.71 (quint, 3J = 7.6 Hz, 2 H,
CH2), 2.98 (dd, 3J = 3.2 Hz, 3J = 10.4 Hz, 1 H, CH), 4.24 (q, 3J = 7.2
Hz, 2 H, CH2O), 5.82 (br, 1 H, OH), 7.50 (d, 3J = 7.6 Hz, 1 H, CH),
7.63–7.70 (m, 2 H, CH), 7.81–7.84 (m, 1 H, CH).
1H NMR (400 MHz, THF-d8): d = 6.84 (s, 1 H,=CH-), 7.52–7.62
4
3
(m, 4 H, CH), 7.69 (dd, J = 1.4 Hz, J = 7.4 Hz, 1 H, CH), 7.85–
7.93 (m, 3 H, CH), 8.00 (d, 3J = 7.6 Hz, 1 H, CH), 8.04 (dd, 4J = 1.6
Hz, 3J = 8.8 Hz, 1 H, CH), 8.61 (s, 1 H, CH), 11.54 (br, 1 H, OH),
16.47 (br, 1 H, COOH).
13C NMR (100 MHz, THF-d8): d = 97.7 (=CH-), 123.8 (CH), 127.4
(CH), 128.4 (CH), 128.7 (CH), 128.8 (CH), 128.9 (CH), 129.0
(CH), 130.0 (CH), 130.4 (CH), 130.9 (CH), 131.6 (CH), 132.7 (C),
132.9 (C), 133.8 (C), 136.3 (C), 139.8 (C), 168.5 (COO), 182.4
(=C-OH), 192.7 (>C=O).
13C NMR (100 MHz, CDCl3): major pair of diastereomers: d = 11.8
(CH3), 14.1 (CH3), 21.4 (CH2), 54.2 (CH), 61.7 (CH2O), 106.7 (C-
OH), 124.0 (CH), 125.6 (CH), 127.5 (C), 130.9 (CH), 134.1 (CH),
146.5 (C), 167.6 (COO), 174.2 (COO); minor pair of diastereomers:
d = 12.4 (CH3), 14.1 (CH3), 20.2 (CH2), 54.3 (CH), 61.8 (CH2O),
106.2 (C-OH), 122.4 (CH), 125.5 (CH), 127.1 (C), 130.8 (CH),
134.6 (CH), 147.5 (C), 167.9 (COO), 172.4 (COO).
MS (DEI): m/z (%) = 318 (48) [M]+, 273 (56) [M – CO2 – H]+, 155
(100) [C10H7-CO]+, 127 (72) [C10H7]+.
Anal. Calcd for C20H14O4: C, 75.46; H, 4.43. Found: C, 75.20; H,
4.61.
MS (DEI): m/z (%) = 265 (100) [M + 1]+, 247 (98) [M – OH]+, 149
(98) [HOOC-C6H4-CO]+, 116 (81) [Et-O-C(OH)-CH(Et)]+.
2-[(2Z)-3-(4-Bromophenyl)-3-hydroxy-1-oxoprop-2-enyl]ben-
zoic Acid (5c)
Mp 141–143 °C.
Anal. Calcd for C14H16O5: C, 63.63; H, 6.10. Found: C, 63.69; H,
6.08.
IR (KBr): 3422 (s, OH), 3200–2800 (br, OH), 1697 (vs, C=O), 1654
(m, C=C), 1072 cm–1 (m, C–Br).
Mono(2-methyl-1-phenylprop-1-enyl) Phthalate (6)
Mp 148–150 °C.
1H NMR (400 MHz, CDCl3): d = 6.45 (s, 1 H,=CH-), 7.51–7.62 (m,
2 H, CH), 7.58 (AA¢BB¢, 2 H, CH), 7.68–7,.75 (m, 1 H, CH), 7.74
IR (KBr): 3200–2800 (br, OH), 1740 (vs, C=O), 1694 (vs, C=O),
1383 cm–1 (m).
1H NMR (200 MHz, THF-d8): d = 1.83 (s, 3 H, CH3), 1.86 (s, 3 H,
CH3), 7.19–7.37 (m, 3 H, CH), 7.41–7.49 (m, 2 H, CH), 7.51–7.58
(m, 2 H, CH), 7.67–7.78 (m, 2 H, CH), 11.50 (br, 1 H, COO).
13C NMR (50 MHz, THF-d8): d = 18.5 (CH3), 20.0 (CH3), 122.7
(>C=), 128.3 (CH), 128.4 (2 × CH), 129.5 (CH), 129.7 (CH), 129.9
(2 × CH), 131.3 (CH), 131.5 (CH), 133.1 (C), 133.9 (C), 136.7 (C),
142.4 (=C-O), 165.5 (COO), 168.4 (COO).
MS (DEI): m/z (%) = 297 (6) [M + 1]+, 148 (100) [C6H5-
C(OH)=C(CH3)2]+, 133 (100) [C6H5-C(OH)=C(CH3)]+, 105 (70)
[C6H5-CO]+.
3
(AA¢BB¢, 2 H, CH), 7.91 (d, J = 7.6 Hz, 1 H, CH), 9.48 (br, 1 H,
OH), 15.95 (br, 1 H, COOH).
13C NMR (100 MHz, CDCl3): d = 96.6 (=CH-), 127.3 (C), 128.1
(CH), 128.6 (2 × CH), 129.8 (CH), 130.6 (CH), 130.9 (C), 131.9 (2
× CH), 132.2 (CH), 133.2 (C), 139.0 (C), 171.7 (COO), 181.0 (=C-
OH), 197.9 (>C=O).
MS (DEI): m/z (%) = 348 (9) [M(81Br)]+, 346 (9) [M(79Br)]+, 331
(3) [M(81Br) – OH]+, 329 (4) [M(79Br) – OH]+, 303 (56) [M(81Br) –
COOH]+, 301 (68) [M(79Br) – COOH]+, 185 (98) [OC-C6H4-81Br]+,
183 (100) [OC-C6H4-79Br]+, 149 (89) [HOOC-C6H4-CO]+.
Anal. Calcd for C16H11BrO4: C, 55.36; H, 3.19. Found: C, 55.55; H,
3.10.
Anal. Calcd for C18H16O4: C, 72.96; H, 5.44. Found: C, 72.86, H,
5.46.
3-Hydroxy-3-(2-oxotetrahydrofuran-3-yl)-2-benzofuran-
1(3H)-one (5g¢)
Mp 136–138 °C.
Crystal Structure Determination
The intensity data for the compounds were collected on a Nonius
KappaCCD diffractometer, using graphite-monochromated Mo-Ka
radiation. Data were corrected for Lorentz and polarization effects,
but not for absorption effects.13,14 The structures were solved by di-
rect methods (SHELXS15) and refined by full-matrix least squares
techniques against Fo2 (SHELXL-9716). All hydrogen atoms of
compounds 2a and of the hydroxy groups of 2f¢ were located by dif-
ference Fourier synthesis and refined isotropically. All other hydro-
gen atoms were included at calculated positions with fixed thermal
parameters. All nonhydrogen atoms were refined anisotropically.16
XP (Siemens Analytical X-ray Instruments, Inc.) was used for
structure representations.
Crystal data for 2a:17 C19H20O3, Mr = 296.35 g·mol–1, colorless
prism, size 0.10 × 0.09 × 0.09 mm3, monoclinic, space group P21/n,
a = 4.9198(2), b = 12.1826(4), c = 25.889(1) Å, b = 92.496(2)°,
V = 1550.2(1) Å3, T = –90 °C, Z = 4, rcalcd. = 1.270 g·cm–3, m(Mo-
Ka) = 0.85 cm–1, F(000) = 632, 8952 reflections in h(–6/4), k(–15/
15), l(–33/31), measured in the range 2.30 £ q £ 27.51°, complete-
IR (KBr): 3351 (s, OH), 1766 (vs, C=O), 1750 (vs, C=O), 1467
cm–1 (m).
1H NMR (400 MHz, THF-d8): two pairs of diastereomers (1:1 mix-
3
ture): d = 2.34–2.61 (m, 4 H, 2 × CH2), 3.22 (t, J = 8.8 Hz, 1 H,
CH), 3.52 (t, 3J = 8.6 Hz, 1 H, CH), 4.11–4.40 (m, 4 H, 2 × CH2O),
7.09 (br, 1 H, OH), 7.20 (br, 1 H, OH), 7.56–8.08 (m, 8 H, CH).
13C NMR (100 MHz, THF-d8): d = 25.5 (CH2), 25.8 (CH2), 47.8
(CH), 48.0 (CH), 66.7(CH2-O), 67.4 (CH2-O), 105.7 (C-OH), 106.1
(C-OH), 123.5 (CH), 125.2 (CH), 125.3 (CH), 125.6 (CH), 128.3
(C), 128.7 (C), 131.0 (CH), 131.3 (CH), 134.8 (2 × CH), 149.0 (C),
149.4 (C), 167.4 (COO), 167.6 (COO), 173.5 (COO), 175.0 (COO).
MS (DEI): m/z (%) = 235 (25) [M + 1]+, 217 (44) [M – OH]+, 149
(100) [HOOC-C6H4-CO]+, 105 (100) [C6H5-CO]+, 86 (100)
[C4H6O2]+.
Anal. Calcd for C12H10O5: C, 61.54; H, 4.30. Found: C, 61.77; H,
4.18.
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York

2706
J. Langer et al.
PAPER
Z. Chem. 1989, 29, 417. (e) Hoberg, H.; Ballesteros, A.;
Sigan, A.; Jégat, C.; Milchereit, A. Synthesis 1991, 395.
(3) (a) Schönecker, B.; Walther, D.; Fischer, R.; Nestler, B.;
Bräunlich, G.; Eibisch, H.; Droeschler, P. Tetrahedron Lett.
1990, 31, 1257. (b) Bräunlich, G.; Walther, D.; Eibisch, H.;
Schönecker, B. J. Organomet. Chem. 1993, 453, 295.
(c) Fischer, R.; Schönecker, B.; Walther, D. Synthesis 1993,
1267.
(4) (a) Hoberg, H.; Schaefer, D.; Burkhart, G.; Krüger, C.;
Romão, M. S. J. Organomet. Chem. 1984, 266, 203.
(b) Yamamoto, T.; Igarashi, K.; Komiya, S.; Yamamoto, A.
J. Am. Chem. Soc. 1980, 102, 7448. (c) Hoberg, H.;
Ballesteros, A.; Sigan, A.; Jégat, C.; Bärhausen, D.;
Milchereit, A. J. Organomet. Chem. 1991, 407, C23.
(5) (a) Hoberg, H.; Apotecher, B. J. Organomet. Chem. 1984,
270, C15. (b) Behr, A.; Kanne, U. J. Organomet. Chem.
1986, 317, C41.
ness qmax = 99.1%, 3540 independent reflections, Rint = 0.048, 2284
reflections with Fo > 4s(Fo), 279 parameters, 0 restraints,
R1obs = 0.046, wR2obs = 0.106, R1all = 0.086, wR2all = 0.125,
GOOF = 1.025, largest difference peak and hole: 0.152/–0.187
e·Å–3.
Crystal data for 2f¢:17 C17H26O3, Mr = 278.38 g·mol–1, colorless
prism, size 0.32 × 0.32 × 0.22 mm3, orthorhombic, space group
P212121, a = 13.1784(4), b = 14.4968(4), c = 16.7858(4) Å,
V = 3206.8(1) Å3, T = –90 °C, Z = 8, rcalcd. = 1.153 g·cm–3, m(Mo-
Ka) = 0.77 cm–1, F(000) = 1216, 21743 reflections in h(–16/17),
k(–18/18), l(–21/21), measured in the range 2.09° £ q £ 27.48°,
completeness
qmax = 99.6%, 7334 independent reflections,
Rint = 0.039, 5391 reflections with Fo > 4s(Fo), 369 parameters, 0
restraints,
R1obs = 0.047,
wR2obs = 0.109,
R1all = 0.075,
wR2all = 0.124, GOOF = 1.008, Flack parameter 0.4(9), largest dif-
ference peak and hole: 0.432/–0.174 e·Å–3.
Crystal data for B:17 C17H12N2NiO2, Mr = 335.00 g·mol–1, green or
orange prism, size 0.03 × 0.03 × 0.02 mm3, triclinic, space group P-
1, a = 12.9307(6), b = 12.9653(5), c = 16.2353(4) Å, a = 85.546(2),
b = 86.152(2), g = 88.252(2)°, V = 2706.6(2) Å3, T = –90 °C, Z = 8,
(6) (a) Castaño, A. M.; Echavarren, A. M. Tetrahedron Lett.
1993, 34, 4361. (b) Echavarren, A. M.; Castaño, A. M.
Tetrahedron 1995, 51, 2369.
(7) (a) Hoberg, H.; Peres, Y.; Krüger, C.; Tsay, Y. T. Angew.
Chem. 1987, 99, 799. (b) Hoberg, H.; Schaefer, D. J.
Organomet. Chem. 1982, 238, 383. (c) Walther, D.;
Schönberg, H.; Dinjus, E.; Sieler, J. J. Organomet. Chem.
1987, 334, 377. (d) Tsuda, T.; Morikawa, S.; Sumiya, R.;
Saegusa, T. J. Org. Chem. 1988, 53, 3140. (e) Tsuda, T.;
Morikawa, S.; Hasegawa, N.; Saegusa, T. J. Org. Chem.
1990, 55, 2978. (f) Walther, D.; Bräunlich, G.; Kempe, R.;
Sieler, J. J. Organomet. Chem. 1992, 436, 109.
(8) (a) Takimoto, M.; Mori, M. J. Am. Chem. Soc. 2001, 123,
2895. (b) Takimoto, M.; Mori, M. J. Am. Chem. Soc. 2002,
124, 10008. (c) O’Brien, E. M.; Bercot, E. A.; Rovis, T. J.
Am. Chem. Soc. 2003, 125, 10498.
(9) (a) For a review, see: Napolitano, E. Org. Prep. Proced. Int.
1997, 29, 631. (b) Tirodkar, R. B.; Usgaonkar, R. N. Indian
J. Chem. 1970, 8, 123. (c) Hussain, A.; Nasim, H.;
Muhammad, T.; Malik, A. Indian J. Heterocycl. Chem.
1999, 8, 189.
(10) Hussain, M. T.; Rama, N. H.; Malik, A. Indian J. Chem.,
Sect. B 2001, 40, 372.
r
calcd. = 1.644 g·cm–3, m(Mo-Ka) = 14.42 cm–1, F(000) = 1376,
19330 reflections in h(–13/16), k(–16/16), l(–20/21), measured in
the range 1.58° £ q £ 27.46°, completeness qmax = 99.2%, 12278 in-
dependent reflections, Rint = 0.038, 8362 reflections with Fo
>
4s(Fo), 793 parameters, 0 restraints, R1obs = 0.049, wR2obs = 0.110,
R1all = 0.087, wR2all = 0.129, GOOF = 1.019, largest difference
peak and hole: 1.405/–0.733 e·Å–3.
Crystal data for D:17 C29H26Br2N2NiO4, Mr = 685.05 g·mol–1, green
prism, size 0.04 × 0.04 × 0.03 mm3, triclinic, space group P-1,
a = 10.2075(5), b = 12.0923(6), c = 14.1353(5) Å, a = 76.553(3),
b = 70.056(3), g = 79.315(3)°, V = 1584.3(1) Å3, T = –90 °C, Z = 2,
r
calcd. = 1.436 g·cm–3, m(Mo-Ka) = 31.67 cm–1, F(000) = 688,
11146 reflections in h(–13/11), k(–15/14), l(–15/18), measured in
the range 3.12° £ q £ 27.44°, completeness qmax = 98.4%, 7127 in-
dependent reflections, Rint = 0.031, 5517 reflections with Fo
>
4s(Fo), 323 parameters, 0 restraints, R1obs = 0.067, wR2obs = 0.198,
R1all = 0.087, wR2all = 0.218, GOOF = 1.052, largest difference
peak and hole: 1.651/–0.967 e·Å–3.
Additionally, crystallographic data for compounds A, 2b¢, 2c¢, 2g,
2h¢, 3a, 3b, 3d, 3f, 3g, 3h¢, 4f, 4i, 5a, 5c, 5g¢, 6 (crystal structures
not shown) are also available17 and have been deposited with the
Cambridge Crystallographic Data Centre, CCDC.
(11) Heller, G. Chem. Ber. 1935, 68, 1085.
(12) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L.
Tetrahedron 2003, 59, 2067.
(13) COLLECT, Data Collection Software, Nonius B.V.,
Netherlands, 1998.
(14) Otwinowski, Z.; Minor, W. Processing of X-Ray Diffraction
Data Collected in Oscillation Mode, In Methods in
Enzymology, Vol. 276; Carter, C. W.; Sweet, R. M., Eds.;
Academic Press: San Diego, 1997, 307–326.
(15) Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467.
(16) Sheldrick, G. M. SHELXL-97 (Release 97-2), University of
Göttingen, Germany, 1997.
(17) CCDC-602921 (A), CCDC-602922 (B), CCDC-602923 (D),
CCDC-602924 (2a), CCDC-602925 (2b¢), CCDC-602926
(2c¢), CCDC-602927 (2f¢), CCDC-602928 (2g), CCDC-
602929 (2h¢), CCDC-602930 (3a), CCDC-602931 (3b),
CCDC-602932 (3d), CCDC-602933 (3f), CCDC-602934
(3g), CCDC-602935 (3h¢), CCDC-602936 (4f), CCDC-
602937 (4i), CCDC-602938 (5a), CCDC-602939 (5c),
CCDC-602940 (5g¢) and CCDC-602941 (6) contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via
Acknowledgment
This research was supported by a grant from the Deutsche Bundes-
stiftung Umwelt and by the Deutsche Forschungsgemeinschaft
(SFB 436).
References
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www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK, fax: +44(1223)336033; or
deposit@ccdc.cam.ac.uk].
Synthesis 2006, No. 16, 2697–2706 © Thieme Stuttgart · New York