Metal catalysed reactions of β,β′-tricarbonyl derivatives with isocyanates

Article abstract of DOI:10.1016/j.tet.2010.07.070

The reactions of β,β′-tricarbonyl derivatives with isocyanates are catalysed by 2 mol % transition metal acetylacetonates (e.g., [Co(acac)₂] and [Zn(acac)₂]) at room temperature. 3-Oxo-1,5-pentanedioic acid dimethylester (1) reacts with RNCO (R=Et, CH ₂CHCH₂, CH₂Ph, Ph, 4-Cl-Ph) to give 1:1 adducts involving the formation of a new C-C bond between the intercarbonylic methylene and the isocyanato group. Under similar conditions 2,4,6-heptanetrione (2) reacts with the same isocyanates to afford pyridinone and pyranone derivatives resulting from the cyclisation of unstable 1:1 and 1:2 adducts.

Full text of DOI:10.1016/j.tet.2010.07.070

Tetrahedron 66 (2010) 8313e8316
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Metal catalysed reactions of b,b
0-tricarbonyl derivatives with isocyanates
,
a
b
c
,
c
Augusto C. Veronese a , Elisa Durini , Valerio Bertolasi , Marino Basato , Cristina Tubaro
*
*
a Dipartimento di Scienze Farmaceutiche, University of Ferrara, via Fossato di Mortara 17, I-44100 Ferrara, Italy
b Dipartimento di Chimica, University of Ferrara, via Luigi Borsari 46, I-44100 Ferrara, Italy
c Dipartimento di Scienze Chimiche, University of Padova, via Marzolo 1, I-35131 Padova, Italy
a r t i c l e i n f o
a b s t r a c t
0-tricarbonyl derivatives with isocyanates are catalysed by 2 mol % transition metal
Article history:
The reactions of
b
,
b
Received 25 January 2010
Received in revised form 5 July 2010
Accepted 26 July 2010
acetylacetonates (e.g., [Co(acac)2] and [Zn(acac)2]) at room temperature. 3-Oxo-1,5-pentanedioic acid
dimethylester (1) reacts with RNCO (R¼Et, CH2CH]CH2, CH2Ph, Ph, 4-ClePh) to give 1:1 adducts in-
volving the formation of a new CeC bond between the intercarbonylic methylene and the isocyanato
group. Under similar conditions 2,4,6-heptanetrione (2) reacts with the same isocyanates to afford
pyridinone and pyranone derivatives resulting from the cyclisation of unstable 1:1 and 1:2 adducts.
Ó 2010 Published by Elsevier Ltd.
Available online 3 August 2010
Keywords:
3-Oxo-1,5-pentanedioic acid dimethylester
2,4,6-Heptanetrione
Metal catalysis
Metal acetylacetonates
CeC bond formation
1. Introduction
b
-dicarbonyls with electrophiles,3e7 and on the alkylation of Cu(II)
and Co(III) metal complexes of diethyl 3-oxopentane-dionate,2 it is
expected that also
0-tricarbonyl derivatives should give similar
Polyketides represent a class of natural products, which cyclise
to a great number of aromatic and heteroaromatic derivatives or are
transformed in fatty acids.1
Tricarbonyl derivatives, such as dialkyl 3-oxopentane-dionates,
have been studied as simple polyketide models. In particular the
regioselective alkylation of Cu(II) and Co(II) complexes of ethyl 3,5-
dioxohexanoate has been reported.2
b,b
interesting CeC bond formations.
In this paper we report the reactions of 3-oxo-1,5-pentanedioic
acid dimethylester (1) and of 2,4,6-heptanetrione (2), chosen as
model compounds, with isocyanates in the presence of catalytic
amounts of metal acetylacetonates.
Itiswellknownthatb-dicarbonylsderivatives react in the presence
2. Results and discussion
of metal catalysts with carbon electrophiles,3 such as isocyanates,4
Michael acceptors5 and nitriles,6 in the presence of metal catalysts to
give adducts derived from the formation of new CeC bonds between
the methylene group of dicarbonyls and the reactive atom of the
electrophile.
The reactions of the two tricarbonyl substrates 1 and 2 with the
various isocyanates were performed in dichloroethane in the
presence of 2 mol % transition metal acetylacetonates, at room
temperature and times changing from 1 day for 1 to 3 days for 2.
Under these conditions 3-oxo-1,5-pentanedioic acid dimethylester
(1) was allowed to react with ethyl isocyanate: high yields of the
1:1 adduct 3a (Scheme 1) were obtained using as catalyst [Co
(acac)2] (yield 98%), [Zn(acac)2] (97%), [Ni(acac)2] (95%), [Cu(acac)2]
In an interesting recent extension new chiral bifunctional ruthe-
nium-based catalysts are very efficiently used in Michael reactions
involving a series of dicarbonyls and activated olefins.7 In all cases
deprotonation of 1,3-dicarbonyl compounds to give coordination to
the metal of C- or O-bonded enolates is the key step of the catalytic
process.
In this context, it is surprising that, to the best of our knowledge,
no catalytic reactions of b,b
0-tricarbonyl derivatives with electro-
philes have been up to now reported. In fact, on the basis of the
previously reported results on the metal catalysed reactions of
* Corresponding authors. Tel.: þ39 049 8275217; fax: þ39 049 825223; e-mail
Scheme 1.
addresses: vra@unife.it (A.C. Veronese), marino.basato@unipd.it (M. Basato).
0040-4020/$ e see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.07.070

8314
A.C. Veronese et al. / Tetrahedron 66 (2010) 8313e8316
(91%) and [Mn(acac)2] (95%). No product was obtained in a test
reaction of 1 with ethyl isocyanate in the absence of catalyst.
The formation of compound 3a clearly indicates that the presence
of a metal catalyst is able to promote CeC bond formation between
one intercarbonylic and one isocyanato carbon atom, thus closely
explains the 1H NMR absorptions of OH and of NH hydrogens at
very high frequency.
By contrast with the reactions of the b,b
0-ketodiester 1, the tri-
ketone 2,4,6-heptanetrione (2) reacts with isocyanates (R¼Et,
CH2]CHeCH2, PhCH2, 4-MeePh) in the presence of [Zn(acac)2]
(2 mol %) to give two types of products, the pyridinones 4 and the
4-pyranones 5 (Scheme 2).
resembling the behaviour observed with
b
-dicarbonyls substrates.
[Co(acac)2] was employed in the reactions of
b,b
0-ketodiester 1
with different R substituted isocyanates. The results were very
similar: higher yields (ca. 90%) were obtained in the reactions with
R¼ethyl, vinyl and benzyl, whereas with aryl isocyanates (R¼Ph,
4-ClePh) (Scheme 1) yields dropped to ca. 65%.
Although compound 3 series could present more than one
species in solution, the 1H NMR spectra in CDCl3 show the presence
of only one tautomer characterised by two resonances at ca. 9.0 and
ca. 18.5 ppm, attributable, respectively, to an NH and an OH in-
volved in hydrogen bonds. Moreover the 13C NMR spectrum shows
an absorption at 186.9 ppm attributable to the enolic carbon atom.
On the basis of these data the more probable species present in
solution is the enolic tautomer depicted in Figure 1.
Scheme 2.
The pyridinone 4 can simply be derived from an 1:1 adduct
analogous to compound 3, which cyclises to give 4 with elimination
of a molecule of water, whereas the formation of the 4-pyranone 5
requires the addition/insertion of two molecules of isocyanate to
triketone 2. One can envisage the formation of an unstable 1:2
adduct followed by its cyclisation involving also in this case elim-
ination of a water molecule. As expected the reactions carried out
with a higher RNCO/(2) molar ratio (Table 1) afford the double
insertion product 5 in higher yields.
Figure 1.
X-ray diffraction analysis of the crystalline compound 3e de-
rived from the reaction of 1 with 4-chlorophenylisocyanate dem-
onstrated that in the solid-state this compound has the structure
depicted in Figure 2. The presence of two strong hydrogen bonds
Table 1
Reaction of 2,4,6-heptanetrione (2) with isocyanates catalysed by [Zn(acac)2] with
varying reagents ratios
R
RNCO/(2) molar ratio
Yield (%)
Et
Et
1.1/1
4/1
1.1/1
4/1
1.1/1
4/1
1.1/1
4/1
35 (4a)
6 (4a)
8 (5a)
41 (5a)
14 (5b)
40 (5b)
15 (5c)
65 (5c)
14 (5d)
42 (5d)
CH2]CHCH2
CH2]CHCH2
PhCH2
PhCH2
4-MeC6H5
4-MeC6H5
45 (4b)
20 (4b)
35 (4c)
10 (4c)
35 (4d)
10 (4d)
The different behaviour exhibited by the two types of tricarbonyls
requires a few comments. The reaction mechanism implies the for-
mation of the real catalyst via ligand exchange of the tricarbonyl
substrate with the acetylacetonato metal complex. This reaction
involves the deprotonation of the intercarbonylic methylene group.
Metal(II) complexes of this type (M¼Mg,8 Ca,8 Mn,9 Co,9 Ni,9 Cu,8,9
Zn8,9) are well known, and this exchange reaction represents
a reported synthetic procedure to give triketonato complexes.10 With
b,b
0-ketodiesters only one of the methylene groups can be deproto-
nated, giving a monoanionic ligand coordinated to only one metal
center (Fig. 3, form A). The situation drastically changes with the
1,3,5-triketones, in fact here deprotonation of one or both methylene
groups can occur, giving rise to coordination of one or two metal
centers for each triketonato ligand (Fig. 3, forms A and B).11e13
Figure 2. An ORTEP view of compound 3e displaying the thermal ellipsoids at 30%
probability.
Figure 3. Possible coordination modes of tricarbonyl compounds.

A.C. Veronese et al. / Tetrahedron 66 (2010) 8313e8316
8315
Electrophilic addition by the isocyanate can occur only to the CH
moiety of the coordinated carbonyl enolato fragment. This in-
terpretation fits well with the observed behaviour of
diester 1, which gives only one type of CeC bond product. This
acetylacetonates: [Zn(acac)2] (97%), [Ni(acac)2] (95%), [Cu(acac)2]
(91%) and [Mn(acac)2] (95%).
b,b
0-keto-
4.2.2. Reaction with allyl isocyanate: 2-allylcarbamoyl-3-oxo-pen-
tanedioic acid dimethylester (3b). Yield 92%, yellow oil. Anal. Calcd
for C11H15NO6 (257.24): C, 51.36; H, 5.88; N, 5.45%. Found: C, 50.78;
H, 6.14; N, 5.17%. IR (oil): 3450 (br),1750 (br),1570 (br) cmꢀ1.1H NMR
catalysis closely resembles that observed with
b-dicarbonyl
compounds.3,5,6
Along these lines the results obtained with 1,3,5-triketone 2 can
be easily interpreted. In fact, one or two methine groups can un-
dergo electrophilic addition, giving rise to the two observed type of
products.
(300.1 MHz, CDCl3):
d 3.69 (s, 3H, OMe), 3.72 (s, 3H, OMe), 3.74 (s,
2H, CH2), 3.96 (m, 2H, CH2N), 5.1e5.3 (m, 2H, CH2]), 5.7e5.9 (m,1H,
CH), 9.2 (br,1H, NH),18.68 (s, 1H, OH). 13C NMR (75.5 MHz, CDCl3)
41.1, 44.8, 50.7, 51.6, 92.7, 115.9, 132.6, 167.5, 168.1, 171.6, 186.3.
d:
3. Conclusion
4.2.3. Reaction with benzyl isocyanate: 2-benzylcarbamoyl-3-oxo-
pentanedioic acid dimethylester (3c). Yield 86%, colourless crystals,
mp 165e167 ꢁC (ethanol). Anal. Calcd for C15H17NO6 (307.30): C,
58.63; H, 5.58; N, 4.56%. Found: C, 59.02; H, 5.70; N, 4.72%. IR (KBr):
The results detailed in this paper demonstrate that metal ace-
tylacetonates are catalysts for the reactions of b,b
0-tricarbonyl de-
3320 (br), 1760, 1690, 1580 cmꢀ1 1H NMR (300.1 MHz, CDCl3):
.
rivatives 1 and 2 with isocyanates. A new CeC bond between the
methylene carbon and the isocyanate carbon atoms is formed at
room temperature and neutral pH giving 1:1 or 1:2 adducts.
Stoichiometric additions or addition/insertions of electrophiles
d
3.71 (s, 3H, OMe), 3.73 (s, 3H, OMe), 3.75 (s, 2H, CH2), 4.53 (d,
J¼5.8 Hz, 2H, CH2), 7.2e7.4 (m, 5H, Ph), 9.60 (br, 1H, NH), 18.73 (s,
1H, OH). 13C NMR (75.5 MHz, CDCl3):
43.6, 45.6, 51.5, 52.5, 95.0,
d
to coordinated b,b
0-ketodiesters were known but, to our knowl-
128.1, 128.3, 129.5, 137.9, 169.2, 169.6, 173.2, 187.9.
edge, these ones are the first examples of a metal-catalysed
process.8
4.2.4. Reaction with phenyl isocyanate: 3-oxo-2-phenylcarbamoyl-
pentanedioic acid dimethylester (3d). Yield 60%, colourless crystals,
mp 58e61 ꢁC. Anal. Calcd for C14H15NO6 (293.27): C, 57.34; H, 5.16;
N, 4.78%. Found: C, 57.10; H, 5.19; N, 4.74%. IR (KBr): 3000 (br), 1740,
The reactivity of the 1,3,5-triketones towards electrophiles ap-
pears rather unexplored and the catalytic formation of compounds
4 and 5 is particularly interesting. In fact, cyclic compounds similar
to 4 are well known and used, for example, in the gene transcrip-
tion therapy.14 The success for this catalytic procedure opens the
way to a variety of CeC bond forming reactions between tricarbonyl
substrates and different electrophiles.
1670, 1600, 1540 cmꢀ1. 1H NMR (300.1 MHz, CDCl3):
d 3.75 (s, 5H,
OMeþCH2), 3.80 (s, 3H, OMe), 7.1e7.6 (m, 5H, Ph),11.30 (br,1H, NH),
18.56 (s,1H, OH). 13C NMR (75.5 MHz, CDCl3)
121.5, 125.2, 129.0, 136.4, 168.4, 170.6, 186.8.
d: 45.5, 51.6, 52.3, 95.3,
4.2.5. Reaction with 4-chlorophenyl isocyanate: 2-(4-chloro-phenyl-
carbamoyl)-3-oxo-pentanedioic acid dimethylester (3e). Yield 65%,
colourless crystals, mp 118e119 ꢁC. Anal. Calcd for C14H14ClNO6
(327.71): C, 51.31; H, 4.31; N, 4.27%. Found: C, 51.40; H, 3.77; N,
4. Experimental
4.1. General remarks
4.91%. IR (KBr): 3100 (br), 1730, 1670, 1540 cmꢀ1
.
1H NMR
3.62 (s, 3H, OMe), 3.71 (s, 5H, OMeþCH2),
7.40e7.60 (m, 4H, Ph), 10.54 (br, 1H, NH), 16.81 (br, 1H, OH). 13C
NMR (75.5 MHz, CDCl3) : 45.3, 51.8, 52.4, 95.6, 121.3, 122.7, 129.1,
The reagents and the solvents were high purity products and
generally used as received. 2,4,6-Heptanetrione (2) was syn-
thesised according to literature procedures.15 The solution 1H- and
13C{1H}-NMR spectra were recorded on a Bruker Avance 300
(300.1 MHz, DMSO-d6):
d
d
(300.1 MHz for 1H and 75.5 MHz for 13C); chemical shifts (
d) are
135.1, 168.3, 168.5, 170.5, 186.7.
reported in units of parts per million relative to the residual solvent
signals, using tetramethylsilane as an internal standard. The FT IR
spectra were recorded on a Bruker Tensor 27 spectrophotometer at
2 cmꢀ1 resolution.
4.3. X-ray crystal structure analysis of 3e
C14H14ClNO6, Mr¼327.71, triclinic, space group P-1 (no. 2) with
a¼5.7960(2), b¼9.0652(4), c¼15.0964(7) Å,
a
¼100.898(2), ¼95.957
b
(3),
g
¼108.220(3) , V¼728.47(5) Å3, Z¼2, Dc¼1.494 g cmꢀ3, 8883
4.2. Reaction of 3-oxo-1,5-pentanedioic acid dimethylester (1)
with isocyanates
reflections measured, 3320 independent, Rint¼0.031, (3<
q
<27.7ꢁ,
T¼295 K, Mo K
a
radiation,
l¼0.71073 Å) on a Nonius Kappa CCD
diffractometer. The structure was solved by direct methods (SIR97)16
and refined on F2 (SHELXL-97)17. Refinement converged at a final
wR2 value of 0.1141 (all reflections), R1¼0.0426 (for 2629 reflections
General procedure: To a solution of 3-oxo-1,5-pentanedioic acid
dimethylester (1) (0.87 g, 5.0 mmol) in anhydrous dichloroethane
(2 mL), isocyanate (6.0 mmol) and [Co(acac)2] (0.1 mmol) were
added. The reaction mixture was stirred at room temperature for
24 h and diluted with diethyl ether. The resulting suspension was
filtered on CeliteÔ and the obtained solution was concentrated
under reduced pressure to give compound 3.
with I>2
s(I)), S¼1.045. All non-H atoms were refined anisotropically
and the hydrogens isotropically. The compound displays two strong
intramolecular hydrogen bonds: N1eH/O3 [N1/O3¼2.636(2) Å,
N1-H/O3¼143(2)ꢁ] and O2eH/O1 [O2/O1¼2.430(2) Å,
O2eH/O1¼157(2)ꢁ]. Complete crystallographic data (excluding
structural factors) have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication number
CCDC 212155. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
þ44(0) 1223 336033 or e-mail: deposit@ccdc.com.ac.uk].
4.2.1. Reaction with ethyl isocyanate: 2-ethylcarbamoyl-3-oxo-pen-
tanedioic acid dimethylester (3a). Yield 98%, colourless crystals, mp
50e52 ꢁC. Anal. Calcd for C10H15NO6 (245.23): C, 48.98; H, 6.17; N,
5.71%. Found: C, 48.74; H, 6.15; N, 5.55%. IR (KBr): 3300 (br), 1740,
1670, 1560 cmꢀ1. 1H NMR (300.1 MHz, CDCl3):
d
1.21 (t, J¼7.3 Hz,
3H, Me), 3.3e3.5 (m, 2H, CH2), 3.72 (s, 5H, OMeþCH2), 3.75 (s, 3H,
4.4. Reaction of 2,4,6-heptanetrione (2) with isocyanates
OMe), 9.20 (br, 1H, NH), 18.80 (s, 1H, OH). 13C NMR (75.5 MHz,
CDCl3)
d
: 14.2, 34.3, 45.5, 51.0, 52.0, 93.6, 168.1, 168.6, 171.9,
General procedure: To a solution of 2,4,6-heptanetrione (2)
186.9. Quite similar yields were obtained with different metal
(0.142 g, 1.0 mmol) in anhydrous dichloroethane (1 mL), isocyanate

8316
A.C. Veronese et al. / Tetrahedron 66 (2010) 8313e8316
(1.1 mmol or 4.0 mmol) and [Zn(acac)2] (5 mg, 0.02 mmol) were
added. The reaction mixture was stirred at room temperature un-
der argon atmosphere for 3 days. The reaction mixture was con-
centrated under reduced pressure and the residue was purified by
column chromatography (SiO2, eluent: ethyl acetate/light petro-
leum 1:1).
CH2N), 7.32-7.36 (m, 10H, 2 Ph), 9.53 (br, 2H, 2 NH). 13C NMR
(75.5 MHz, CDCl3):
172.4, 178.3.
d 21.1, 43.3, 117.9, 127.3, 127.6, 128.7, 138.2, 163.2,
4.4.4. Reaction with p-tolyl isocyanate to give 3-Acetyl-4-hydroxy-6-
methyl-1-p-tolyl-1H-pyridin-2-one (4d) and 2,6-Dimethyl-4-oxo-
4H-pyran-3,5-dicarboxylic acid bis-p-tolylamide (5d). (4d).20 Yellow
crystals, mp 197-200 ꢁC. IR (KBr): 1658, 1622, 1655, 1631 cm-1. 1H
4.4.1. Reaction with ethyl isocyanate to give 3-Acetyl-1-ethyl-4-hy-
droxy-6-methyl-1H-pyridin-2-one (4a) and 2,6-Dimethyl-4-oxo-4H-
pyran-3,5-dicarboxylic acid bis-ethylamide (5a). (4a).18 Yellow
crystals, mp 116-118 ꢁC. IR (KBr): 1654, 1610, 1427, 1361 cm-1. 1H
NMR (300.1 MHz, CDCl3): d 1.90 (s, 3H, Me), 1.97 (s, 3H, Me), 2.79 (s,
3H, COMe), 5.85 (s, 1H, CH), 6.97 (A2B2 system, J¼8.1 Hz, 2H, Ph),
7.24 (A2B2 system, J¼8.1 Hz, 2H, Ph), 15.71 (s, 1H, OH). (5d). Col-
ourless crystals, mp 138-140 ꢁC. Anal. Calcd for C23H22N2O4
(390.43): C, 70.75; H, 5.68; N, 7.17%. Found: C, 70.51; H, 5.69; N,
7.23%. IR (KBr): 3055 (br),1688,1609,1542,1513,1405,1162 cm-1. 1H
NMR (300.1 MHz, CDCl3):
d
1.28 (t, J¼7.1 Hz, 3H, CH2CH3), 2.37 (s,
3H, Me), 2.71 (s, 3H, MeCO), 4.01 (q, J¼7.0 Hz, 2H, CH2CH3), 5.80 (s,
1H, CH), 15.48 (s, 1H, OH). (5a). Yellow crystals, mp 86-88 ꢁC. Anal.
Calcd for C13H18N2O4 (266.29): C, 58.63; H, 6.81; N, 10.52%. Found:
C, 58.51; H, 6.86; N, 10.37%. IR (KBr): 3273 (br), 1676 (br), 1541, 1408
NMR (300.1 MHz, DMSO-d6): d 2.26 (s, 6H, 2 Me), 2.45 (s, 6H, 2 Me),
7.14 (A2B2 system, J¼8.3 Hz, 4H, Ph), 7.54 (A2B2 system, J¼8.3 Hz,
(br), 1261, 1097 (br) cm-1. 1H NMR (300.1 MHz, CDCl3):
d
1.23 (t,
4H, Ph), 10.62 (s, 2H, 2 NH).
J¼7.1 Hz, 6H, 2 CH2CH3), 2.78 (s, 6H, 2Me), 3.43 (q, J¼7.2 Hz, 4H,
2CH2CH3), 9.05 (br, 2H, 2 NH). 13C NMR (75.5 MHz, CDCl3)
20.9, 34.2, 118.0, 163.0, 171.9, 178.4.
d: 14.6,
References and notes
4.4.2. Reaction with allyl isocyanate to give 3-Acetyl-1-allyl-4-hy-
droxy-6-methyl-1H-pyridin-2-one (4b) and 2,6-Dimethyl-4-oxo-4H-
pyran-3,5-dicarboxylic acid bis-allylamide (5b). (4b). Colourless
crystals, mp 78-80 ꢁC. Anal. Calcd for C11H13NO3 (207.23): C, 63.76;
H, 6.32; N, 6.76%. Found: C, 63.52; H, 6.25; N, 6.59%. IR (KBr): 3435
(br), 1653 (br), 1612, 1560, 1361 cm-1. 1H NMR (300.1 MHz, CDCl3):
1. (a) Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach, 3rd ed.; J.
Wiley: Chichester, UK, 2009; (b) Samuelson, G. Drugs of Natural Origin. A
Textbook of Pharmacognosy, 5th ed.; Swedish Pharmacetical: Stockholm, 2004;
(c) Comprehensive Natural Product Chemistry; Barton, D., Nakanishi, K., Meth.
Conn, O., Eds., Polyketides and Other Secondary Methabolites Including Fatty Acids
and Their Derivatives; Pergamon: Oxford, 1999; Vol. 1.
2. (a) Cervelló, J.; Marquet, J.; Moreno-Mañas, M. J. Chem. Soc., Chem. Commun.
1987, 644; (b) Cervelló, J.; Marquet, J.; Moreno-Mañas, M. Tetrahedron 1990, 46,
2035.
3. Marquet, J.; Moreno-Mañas, M.; Vallribera, A. Tetrahedron 1996, 52, 3377.
4. Eckberg, R. P.; Nelson, J. H.; Kenney, J. W.; Howells, P. N.; Henry, R. A. Inorg.
Chem. 1977, 16, 3128.
5. (a) Christoffers, J. Eur. J. Org. Chem. 1998, 7, 1259; (b) Nelson, J. H.; Howells, P. N.;
DeLullo, G. C.; Landen, G. L.; Henry, R. A. J. Org. Chem. 1980, 45, 1246; (c) Corsico
Coda, A.; Desimoni, G.; Righetti, P.-P.; Tacconi, G. Gazz. Chim. Ital. 1984, 114, 417.
6. Corain, B.; Basato, M.; Veronese, A. C. J. Mol. Catal. 1993, 81, 133.
7. Ikariya, T.; Murata, K.; Noyori, R. Org. Biomol. Chem. 2006, 4, 393.
8. (a) Yamato, M.; Kusunoki, Y. Chem. Pharm. Bull. 1981, 29, 1214; (b) Yamato, M.;
Kusunoki, Y. Chem. Pharm. Bull. 1981, 29, 2832.
d
2.35 (s, 3H, Me), 2.71 (s, 3H, COMe), 4.62 (d, J¼4.5 Hz, 2H, CH2),
5.02 (d, J¼16.7 Hz, 1H, ¼CH2), 5.20 (d, J¼11.2 Hz, 1H, ¼CH2), 5.83 (s,
1H, CH), 5.90-5.98 (m, 1H, CH¼), 15.57 (s, 1H, OH). 13C NMR
(75.5 MHz, CDCl3):
d 21.0, 31.5, 45.8, 101.1, 105.6, 116.4, 132.1, 153.8,
162.6, 175.3, 205.9. (5b). Colourless crystals, mp 74-76 ꢁC. Anal.
Calcd for C15H18N2O4 (290.31): C, 62.06; H, 6.25; N, 9.65%. Found: C,
61.80; H, 6.09; N, 9.48%. IR (KBr): 3249 (br), 3086,1682, 1602,
1534 cm-1. 1H NMR (300.1 MHz, CDCl3):
d 2.79 (s, 6H, 2 Me), 4.03
(m, 4H, 2 CH2N), 5.17 (d, J¼10.3 Hz, 2H, CH2¼CH), 5.20 (d, J¼15.5 Hz,
9. Hay, R. W.; Caughley, B. P. Aust. J. Chem. 1967, 20, 1829.
2H, CH2¼CH), 5.85-5.99 (m, 2H, 2 CH2¼CH), 9.25 (br s, 2H, 2 NH).
10. Sagara, F.; Kobayashi, H.; Ueno, K. Bull. Chem. Soc. Jpn. 1973, 46, 484.
11. Aromí, G.; Gamez, P.; Reedijk, J. Coord. Chem. Rev. 2008, 252, 964, and references
cited herein.
13C NMR (75.5 MHz, CDCl3):
172.9, 178.9.
d 21.6, 42.3, 116.7, 118.4, 134.5, 163.6,
12. Siedle, A. R. Diketones and Related Ligands. In Comprehensive Coordination
Chemistry; Wilkinson, G., Ed.; Pergamon: Great Britain, 1987; Vol. 2.
13. Casellato, U.; Vigato, P. A.; Vidali, M. Coord. Chem. Rev. 1977, 23, 31.
14. Shiraki, H.; Higashi, K.; Takahashi, J.; Tomigahara, Y. PCT Int. Appl. WO
2007132948, 2007.
15. Stoddart, M. W.; Brownie, J. H.; Baird, M. C.; Schmider, H. L. J. Organomet. Chem.
2005, 690, 3440.
16. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Gua-
gliardi, A.; Moliterni, A. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 1999, 32,
115.
4.4.3. Reaction with benzyl isocyanate to give 3-Acetyl-1-benzyl-4-
hydroxy-6-methyl-1H-pyridin-2-one (4c) and 2,6-Dimethyl-4-oxo-
4H-pyran-3,5-dicarboxylic acid bis-benzylamide (5c). (4c).18,19
Colourless crystals, mp 119-122 ꢁC. IR (KBr): 3447 (br), 1648, 1615,
1560, 1363 cm-1. 1H NMR (300.1 MHz, CDCl3):
d
2.29 (s, 3H, Me),
2.74 (s, 3H, COMe), 5.27 (s, 2H, CH2), 5.86 (s, 1H, CH), 7.11-7.34 (m,
5H, Ph), 15.63 (s, 1H, OH). 13C NMR (75.5 MHz, CDCl3):
21.5, 31.6,
d
17. Sheldrick, G. M. SHELXL-97. Program for the Refinement for Crystal Structures;
46.8, 101.4, 105.7, 126.1, 127.6, 129.0, 136.2, 154.1, 175.5. (5c). Col-
ourless crystals, mp 98-100 ꢁC. Anal. Calcd for C23H22N2O4 (390.43):
C, 70.75; H, 5.68; N, 7.17%. Found: C, 70.98; H, 5.80; N, 7.29%. IR
(KBr): 3234 (br), 1680, 1654, 1543, 1403, 1165 cm-1. 1H NMR
€
€
University of Gottingen: Gottingen, Germany, 1997.
18. Kato, T.; Kubota, Y. Yakugaku Zasshi 1969, 89, 1477.
19. (a) Rubinov, D. B.; Zheldakova, T. A.; Rubinova, I. L.; Baranovskii, A. V. Russ. J.
Org. Chem. 2008, 44, 432; (b) Katagiri, N.; Sato, M.; Yoneda, N.; Saikawa, S.;
Sakamoto, T.; Muto, M.; Kanedo, C. J. Chem. Soc., Perkin Trans. 1 1986, 1289.
20. Kato, T.; Kubota, Y. Yakugaku Zasshi 1967, 87, 1212.
(300.1 MHz, CDCl3):
d
2.82 (s, 6H, 2 Me), 4.58 (d, J¼5.8 Hz, 4H, 2