Synthesis, structure, and keto-enol tautomerism of 3-R1-5,5- R2,R2-6-R3-2,3,5,6-tetrahydropyran-2,4-diones

Article abstract of DOI:10.1007/s11176-005-0477-6

Ethyl esters of 2,4-dibromo-2-R¹-4-R²-3-oxopentanoic and -hexanoic acids react with zinc and aliphatic or aromatic aldehydes under the conditions of the Reformatskii reaction to give 3-R¹-5,5-R ², R²-

Full text of DOI:10.1007/s11176-005-0477-6

Russian Journal of General Chemistry, Vol. 75, No. 10, 2005, pp. 1622 1627. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 10, 2005,
pp. 1699 1704.
Original Russian Text Copyright
2005 by Shchepin, Kodess, Sazhneva, Russkikh.
Synthesis, Structure, and Keto Enol Tautomerism
of 3-R1-5,5-R2,R2-6-R3-2,3,5,6-Tetrahydropyran-2,4-diones
V. V. Shchepin*, M. I. Kodess**, Yu. Kh. Sazhneva*, and N. Yu. Russkikh*
* Perm State University, Perm, Russia
** Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, Yekaterinburg, Russia
Received July 22, 2004
Abstract Ethyl esters of 2,4-dibromo-2-R1-4-R2-3-oxopentanoic and -hexanoic acids react with zinc and
aliphatic or aromatic aldehydes under the conditions of the Reformatskii reaction to give 3-R1-5,5-R2,R2-6-
R3-2,3,5,6-tetrahydropyran-2,4-diones, which are obtained in three forms: keto, enol with enolization of the
keto group, and enol with enolization of the ester group. The keto form is isolated by crystallization from a
mixture of CCl4 and petroleum ether; the first enol form, from MeOH, EtOH, and polar aprotic solvents; and
the second enol form, from CHCl3. The second enol form is oxidized in DMSO to form a keto compound
containing a hydroxy group at the 3-position of the heteroring.
2,3,5,6-Tetrahydropyran-2,4-diones and their ana-
logs as a class of organic compounds are of interest
from the synthetic viewpoint and in the connection
with their biological activity [1 3]. Particular interest
in 3-R1-5,5-R2,R2-6-R3-2,3,5,6-tetrahydropyran-2,4-
diones containing one hydrogen atom in position 3 of
the heteroring is also associated with the keto enol
tautomerism of these compounds, allowing their con-
version into various C and O derivatives [4 12]. We
found previously that the reaction of ethyl 2,4-dibro-
mo-2,4-dimethyl-3-oxopentanoate with zinc and alde-
hydes yielded 3,5,5-trimethyl-6-R-2,3,5,6-tetrahydro-
pyran-2,4-diones in the form of a single geometric
isomer transforming into the enol form in polar solv-
ents [13].
tetrahydropyran-2,4-diones VIa VIn upon hydrolysis
(Table 1).
In our previous study [13] we found that 3-R1-5,5-
R2,R2-6-R3-2,3,5,6-tetrahydropyran-2,4-diones, which
are analogs of -dicarbonyl compounds, can exist in
the form of keto (A) and enol (B) tautomers; the enol
tautomer is formed by enolization of the keto group.
1
Thorough examination of the H and 13C NMR spec-
tra of VIa VIn in various solvents revealed the exis-
tence of one more tautomer, along with A and B,
tentatively identified as enol tautomer C formed by
enolization of the ester carbonyl. Such a enol was
mentioned in the literature [6, 14] as a precursor of
certain pyrandione derivatives. In this study, all the
three tautomers were isolated pure.
In this study we examined in detail the keto enol
equilibrium and the composition and structure of tau-
tomers of 2,3,5,6-tetrahydropyran-2,4-diones.
1
All the three forms were identified by H and 13C
1
NMR spectroscopy. A typical H NMR spectrum of
form A of VIc in CDCl3 contains the following char-
acteristic signals ( , ppm, CDCl3, 400 MHz): 0.98 s,
1.14 s (6H, CMe2), 1.45 d (3H, CHMe), 3.78 q (1H,
CHMe), 5.57 s (1H, CH), 7.35 7.48 m (5H, Ph). The
chemical shifts of form A of the same compound VIc
in DMSO-d6 are somewhat different ( , ppm, DMSO-
d6, 500 MHz): 0.81 s (6H, CMe2), 1.22 d (3H,
CHMe), 4.51 q (1H, CHMe), 5.97 s (1H, CH), 7.38 s
(5H, Ph). The 13C NMR spectrum is also consistent
To prepare new 3-R1-5,5-R2,R2-6-R3-2,3,5,6-tetra-
hydropyran-2,4-diones, we performed the reactions of
ethyl esters of 2,4-dibromo-2-R1-4-R2-3-oxopentanoic
and -hexanoic acids Ia Ic with zinc and aliphatic and
aromatic aldehydes in diethyl ether ethyl acetate
under the conditions of the Reformatskii reaction. The
process follows the scheme given below, which sum-
marizes the results of the present and previous [13]
studies. Intermediates IIa IIc formed in the first step
are polydent agents and react with aldehydes IIIa IIIj
at the -C atoms to form zinc bromide alcoholates
IVa IVn. These compounds spontaneously cyclize
under the reaction conditions to form compounds Va
Vn transforming into 3-R1-5,5-R2,R2-6-R3-2,3,5,6-
with the suggested structure A ( , ppm, CDCl3,
C
100 MHz): 207.01 (C4), 169.54 (C2), 133.35 (Ci),
128.82 (Cp), 128.08 (Co), 127.70 (Cm), 83.26 (C6),
49.13 (C3), 47.72 (C5), 21.35 (C5 ), 18.10 (C5 ), 8.26
(C3 ).
1070-3632/05/7510-1622 2005 Pleiades Publishing, Inc.

SYNTHESIS, STRUCTURE, AND KETO ENOL TAUTOMERISM
Br
1623
OZnBr
R2
R2
O
O
R1
R2
R3CH=O
IIIa IIIj
Zn
O
O
R2
Zn
R2
R2
BrZn
OEt
R3
BrZn
R1
OO
Et
IVa IVn
O
Br
Br
OEt
R1
Ia Ic
OZnBr
IIa IIc
R2
OH
O
R2
O
R2
R2
R2
.
.
<>H
R1
O
.
R1
OH
>
R1
<
R2
R3
.
R2
R3
<
R2
>
<
H2O
1
>
<
R
.
R2
.
|
.
H
EtOZnBr
Zn(OH)Br
R3
Va Vn
O
O
O
O
O
O
C
A
B
VIa VIn
I, II, R1 = R2 = Me (a), R1 = Me, R2 = Et (b), R1 = Et, R2 = Me (c). III, R3 = Et (a), Pr (b), Ph (c), 4-FC6H4 (d),
4-ClC6H4 (e), 4-BrC6H4 (f), 2,4-Cl2C6H3 (g), 2-FC6H4 (h), 4-MeOC6H4 (i), 3,4-(MeO)2C6H3 (j). IV VI, R1 = R2 = Me;
R3 = Et (a), Pr (b), Ph (c), 4-FC6H4 (d), 4-ClC6H4 (e), 4-BrC6H4 (f), 2,4-Cl2C6H3 (g), 2-FC6H4 (h), 4-MeOC6H4 (i),
3,4-(MeO)2C6H3 (j); R1 = Me, R2 = Et, R3 = 4-BrC6H4 (k); R1 = Et, R2 = Me, R3 = Ph (l), 4-ClC6H4 (m), 4-BrC6H4 (n).
1
Typical H NMR spectra of enol forms B and C in
DMSO-d6 (with VIc as example) are similar and dif-
fer only in the chemical shifts of the related protons:
form B ( , ppm, DMSO-d6, 400 MHz), 0.90 s, 1.00 s
(6H, CMe2), 1.74 s (3H, Me), 5.20 s (1H, CH), 7.38
m (5H, Ph), 10.30 br.s (1H, OH); form C ( , ppm,
DMSO-d6, 60 MHz), 0.93 s (6H, CMe2), 1.52 s (3H,
Me), 5.60 s (1H, CH), 7.33 s (5H, Ph), 12.43 s (1H,
OH). Based on the characteristic chemical shifts of the
protons of the CH3 group at the double bond and of
carbonyl carbon atom, C4, is in the range 200
205 ppm. Enolization of the keto group decreases the
chemical shift of the C4 atom to 172 173 ppm, and
enolization of the lactone carbonyl exerts virtually no
effect on the chemical shift of the C4 atom [4, 6, 14
16]. Thus, the compound whose 13C NMR spectrum
contains two signals with chemical shifts of 167.48
and 172.07 ppm, corresponding to the C2 and C4
atoms, should be identified as enol B. The following
signals are observed in the 13C NMR spectrum of this
1
the enol proton in the H NMR spectra in DMSO-d6,
we identified compounds VIa VIn as enols B and C.
The H NMR data alone do not allow these enol
forms to be distinguished unambiguously; therefore,
we also recorded the 13C NMR spectra. According to
published data, the chemical shift of the lactone car-
bonyl carbon atom, C2, in 2,3,5,6-tetrahydropyran-
2,4-diones is 165 170 ppm, and that of the ketone
tautomer ( , ppm, DMSO-d6, 100 MHz): 172.07
C
(C4), 167.48 (C2), 135.57 (Ci), 128.22 (Cp), 127.88,
127.69 (Co, Cm), 96.08 (C3), 83.33 (C6), 38.96 (C5),
20.43 (C5 ), 18.99 (C5 ), 9.50 (C3 ). The 13C NMR
1
spectrum of the other tautomer is as follows ( , ppm,
C
DMSO-d6, 100 MHz): 206.42 (C4), 169.13 (C2),
133.98 (Ci), 128.67 (Cp), 127.91 (Cm), 127.86 (Co),
Table 1. Yields, melting points, and elemental analyses of VIh VIn
Found, %
Calculated, %
Comp. no. Yield, % mp, C (solvent for crystallization)
Formula
C
H
C
H
VIh
VIi
VIj
VIk
VIl
VIm
VIn
55
30
43
69
63
72
69
165 166 (hexane CHCl3)
160 161 (EtOH)
67.04
68.85
65.83
56.65
73.00
63.98
55.25
5.95
6.93
6.94
5.65
7.28
5.97
5.17
C14H15FO3
C15H18O4
C16H20O5
C16H19BrO3
C15H18O3
C15H17ClO3
C15H17BrO3
67.20
68.70
65.75
59.79
73.17
64.17
55.38
6.00
6.87
6.85
5.74
7.32
6.06
5.23
132 133 (petroleum ether CCl4)
148 151 (petroleum ether CCl4)
153 154 (hexane CHCl3)
166 167 (petroleum ether CCl4)
154 155 (petroleum ether CCl4)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 10 2005

1624
SHCHEPIN et al.
84.38 (C3), 79.81 (C6), 46.51 (C5), 19.84 (C3 ), 19.77
(C5 ), 16.84 (C5 ), which, on the whole, is consistent
with structure C, although the C4 chemical shift is
somewhat larger than the expected [6, 14] value of
190 200 ppm.
into enol form C. Further studies of the behavior of
these tautomers showed that in CHCl3 keto form A
gradually transformed into enol form C. In particular,
on keeping VIc in CHCl3 for 25 days, the relative
content of enol form C increased from 15 to 50%.
Refluxing of diketone A in chloroform for 5 h virtu-
ally completely shifted the equilibrium toward enol
form C (Table 2).
The two-dimensional correlation experiments
1
HSQC (based on direct coupling constants JCH) and
2 3
HMBC (based on remote coupling constants
J )
O
CH
R2
R1
OH
with tautomers B and C allowed accurate assignment
of the 13C signals. However, these experiments still
did not allow unambiguous determination of the posi-
tion of the hydroxy group. In particular, in the HMBC
spectra we observed all the expected cross peaks of
the carbon atoms with CH protons, except the cross
peaks of the OH protons with any carbon atoms. This
fact is apparently due to participation of this proton
in fast exchange (most probably intermolecular). The
two-dimensional NOESY spectrum also contained no
cross peaks of the OH proton with any protons. How-
ever, the OH proton gives a relatively strong positive
cross peak with the proton signal of water in the solv-
ent, confirming that these protons are involved in fast
exchange.
R2
B
DMSO,
R3
EtOH
MeOH
O
E
O
A
O
R2
R2
R1
[O]
C
DMSO
CH3Cl
R3
OOH
O
D
In the course of studying the keto enol tautomer-
ism, we detected gradual oxidation of enol form C in
DMSO, which in many cases behaves as oxidant [17].
In particular, the mass spectra of some compounds
show the presence of an impurity ( 5 10 wt %) with
the molecular ion differing from that of the major
compound by 16 amu, which corresponds to an oxy-
Thus, all the NMR data obtained are mutually con-
sistent and support the suggested structure C. Its mass
spectrum contains a strong peak of the molecular ion.
The spectra obtained are inconsistent with the struc-
tures of the possible alternative products; therefore,
we believe structure C to be the most probable.
1
gen atom. On the other hand, the H NMR spectra of
the compounds containing enol form C, recorded in
DMSO-d6, almost always exhibit signals of one more
compound, tentatively termed oxidized form. Pre-
sumably, oxidation of enol form C yields 2-hydroper-
oxy-3-R1-5,5-dimethyl-6-R3-5,6-dihydropyran-4-one
D. On the other hand, 3-hydroxy-3-R1-5,5-dimethyl-
6-R3-2,3,5,6-tetrahydropyran-2,4-diones E may also
In the course of the further study, we found that all
the three tautomers can be formed in the reaction; the
major tautomer is A, and enol C is formed in consid-
erably smaller amounts. After recrystallization of the
products from a mixture of CCl4 and petroleum ether,
be formed. The rearrangement D
E in DMSO also
1
mainly form A is detected in the H and 13C NMR
1
seems possible. The H NMR spectrum of oxidized
form D or E is qualitatively similar to that of enol
form C, with insignificant changes in the chemical
shifts of all the protons, except the OH (or OOH) pro-
ton signal which is shifted upfield [ , ppm, DMSO-d6,
400 MHz): 0.85 s, 0.97 s (6H, CMe2), 1.59 s (3H,
Me), 5.90 s (1H, CH), 6.39 s (1H, OH), 7.42 m (5H,
Ph). However, this fact does not allow unambiguous
choice of particular structure. The 13C NMR spectrum
spectra (CDCl3, Table 2). When studying the keto
enol equilibrium, we found that both polar protic and
bipolar aprotic solvents stabilize enol form B.
When the compounds whose major tautomer was A
1
were dissolved in DMSO-d6 to record the H NMR
spectra, the tautomeric equilibrium shifted virtually
completely toward fomr B. Recrystallization from
methanol and ethanol favors partial or complete trans-
formation of keto form A into enol form B (Table 2).
On the other hand, keto form A or enol form B did
not transform into enol form C on keeping compounds
VIc and VIf in DMSO-d6 for 12 h (Table 2). Repeated
recrystallizations from alcohols (EtOH, MeOH) of
compounds VIc and VIf consisting exclusively from
enol form B (Table 2) did not result in appearance of
even traces of form C either. Thus, it can be con-
cluded that polar aprotic and protic solvents do not
favor the transition of keto form A and enol form B
( , ppm, DMSO-d6, 100 MHz): 209.12 (C4), 172.24
C
(C2), 134.42 (Ci), 128.71 (Cp), 127.99 (Cm), 127.97
(Co), 80.42 (C6), 75.44 (C3), 46.22 (C5), 24.05 (C3 ),
20.27 (C5 ), 17.99 (C5 ), though being fully consistent
with the structure of 3-hydroxy-3-R1-5,5-dimethyl-6-
R3-2,3,5,6-tetrahydropyran-2,4-dione E, does not
prove it unambiguously. To prove this structure more
unambiguously, we performed two-dimensional corre-
lation experiments HSQC and HMBC.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 10 2005

SYNTHESIS, STRUCTURE, AND KETO ENOL TAUTOMERISM
1625
1
Table 2. Content of tautomers A C and oxidized form E of VIa VIn, according to the H NMR spectra in various
solvents
Comp.
no.
Solvent
(working frequency)
mp, C (solvent for crystallization)
Content, wt % (form)
100 (B)
100 (A)
35 (C), 65 (E)
100 (A)
35 (A), 45 (B), 20 (C)
85 (A), 15 (C)
50 (A), 50 (C)
100 (C)
VIa
VIb
65 67 (petroleum ether CCl4)
89 90 (petroleum ether CCl4)
95 97 (C6H14 CHCl3)
CDCl3, DMSO-d6 (60 MHz)
CCl4 (60 MHz)
DMSO-d6 (500 MHz)
CDCl3 (400 MHz)
CDCl3, DMSO-d6 (60 MHz)
CDCl3 (400 MHz)b
CDCl3 (400 MHz)
VIc 145 147 (petroleum ether CCl4)
133 137a
149 151 (petroleum ether CCl4)
172 174 (CHCl3)
145 147 (petroleum ether CCl4)
141 142 (MeOH)
DMSO-d6, CDCl3 (80 MHz)c
DMSO-d6 (500 MHz)
DMSO-d6 (400 MHz)
CDCl3, DMSO-d6 (60 MHz)
DMSO-d6 (400 MHz)e
DMSO-d6 (400 MHz)e
CDCl3 (60 MHz)
CDCl3 (60 MHz)
CDCl3 (60 MHz)
DMSO-d6 (60 MHz)
DMSO-d6 (400 MHz)
DMSO-d6 (400 MHz)
CDCl3 (400 MHz)
10 (A), 90 (B)
100d (B)
170 171 (C6H14 CHCl3)
100 (C)
85 (C), 15 (E)
100 (E)
VId 132 134 (petroleum ether CCl4)
VIe 129 131 (MeOH)
100 (A)
60 (A), 40 (B)
95 (A), 5 (B)
100 (B)
133 135 (petroleum ether CCl4)
180 (C6H14 CHCl3)
168 170 (EtOH)
100d (B)
VIf
5 (B), 25 (C), 70 (E)
100 (A)
80 (A), 20 (C)
15 (C), 85 (E)
20 (A), 80 (B)
100 (A)
VIg 138 140 (petroleum ether CCl4)
VIh 165 167 (C6H14 CHCl3)
150 151 (C6H14 CHCl3)
VIi
VIj
CDCl3 (400 MHz)
DMSO-d6 (300 MHz)
CDCl3, DMSO-d6 (60 MHz)
CDCl3 (60 MHz)
160 161 (EtOH)
132 133 (petroleum ether CCl4)
DMSO-d6 (300 MHz)
CDCl3 (60 MHz)
10 (A), 90 (B)
100 (A)
VIk 148 151 (petroleum ether CCl4)
DMSO-d6 (500 MHz)
CDCl3 (60 MHz)
DMSO-d6 (300 MHz)
DMSO-d6 (500 MHz)
CDCl3 (60 MHz)
100 (B)
100 (C)
VIl
153 154 (C6H14 CHCl3)
163 164 (C6H14 CHCl3)
5 (B), 45 (C), 50 (E)
<5 (B), <5 (C), 95 (E)
70 (A), 30 (B)
40 (B), 25 (C), 35 (E)
100 (C)
VIm 147 148 (petroleum ether CCl4)
166 167 (petroleum ether CHCl3)
VIn 154 155 (petroleum ether CHCl3)
DMSO-d6 (300 MHz)
CDCl3 (60 MHz)
a
b
c
Immediately after isolation (without purification). Recorded immediately after dissolution in CDCl and 25 days later. Re-
3
d
e
corded after refluxing the diketone in chloroform. No changes after keeping the solution for 12 h. Recorded immediately after
dissolution in DMSO-d and 2 days later.
6
The 2D HSQC spectrum revealed correlations
coupling constants of carbon atoms with the OH pro-
ton, nJCH, are not always observed in the unidimension-
al 13C spectra and in 2D HMBS spectra; they are only
observed when the OH protons give a narrow signal
and are not involved in intermolecular or intramolecu-
lar exchange, which is characteristic of the OH group
at the saturated carbon atom. Similarly, the C3Me
protons give cross peaks with C2 and C4 carbonyl
atoms. At the same time, the H6 proton and protons of
two Me groups at C5 give cross peaks only with the
C4 carbonyl atom. The suggested structure is also
between signals of certain H and C atoms. In particu-
lar, the spectrum allowed us to reliably distinguish the
C6 (cross peak with H6) and C3 (no cross peak with
proton) atoms and to assign the signal at 6.39 ppm to
OH and that at 5.91 ppm to CH6, and not vice versa.
In the 2D HMBC spectra, we found features that con-
vincingly proved structure E. In particular, we ob-
served cross peaks between the OH proton and the C2,
C3, C4, and C3 Me carbon atoms, which is possible
only in structure E. It should be noted that the remote
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 10 2005

1626
SHCHEPIN et al.
confirmed by other cross peaks (e.g., between H6 and
ipso- or ortho-C atoms of the aromatic ring, etc.).
2CH2Me), 4.13 q (2H, OCH2Me). Ic: yield 70%,
bp 132 138 C (2 3 mm Hg), n2D01 1.4962. IR spec-
1
trum, , cm : 1720, 1770 (C=O). H NMR spectrum
Thus, the whole set of the spectral data allows
a conclusion that the oxidation product has, indeed,
(CCl4), , ppm: 0.93 t (3H, CH2Me), 1.27 t (3H,
OCH2Me), 1.83 s (3H, Me), 1.90 s (3H, Me), 2.20 q
(2H, CH2Me), 4.18 q (2H, OCH2Me).
the structure of 3-hydroxy-3-R1-5,5-dimethyl-6-R3-
2,3,5,6-tetrahydropyran-2,4-dione E. Furthermore, it
should be noted that this compound is formed as a
single diastereomer, i.e., the oxidation mechanism is
stereospecific, although it is not yet fully understood.
3-R1-5,5-R2,R2-6-R3-2,3,5,6-Tetrahydropyran-
2,4-diones VIa VIn). A mixture of 0.05 mol of ethyl
2,4-dibromo-2,4-dimethyl-3-oxopentanoate and
0.05 mol of appropriate aldehyde in 10 ml of diethyl
ether ethyl acetate was added dropwise with stirring
to 10 g of fine zinc turnings and catalytic amount of
HgCl2 in 10 ml of diethyl ether + 30 ml of ethyl
acetate. The mixture was heated to reflux to initiate
the reaction, after which the reaction occurred sponta-
neously with refluxing of the solvents. After adding
the reactants, the mixture was refluxed for 15 min,
cooled, hydrolyzed with 10% HCl, and treated with
diethyl ether; the organic phase was dried over sodium
sulfate, and the solvents were removed. The final re-
action products were recrystallized.
The fact that in the mass spectra the impurity of the
oxidized form is detected only in three of six cases
and in minor amounts, whereas in the NMR spectra
the relative content of the oxidized form exceeds 50%
in most cases, stimulated us to monitor in time the
transformation C
E in DMSO, with 3,5,5-trimeth-
yl-6-phenyl-2,3,5,6-tetrahydropyran-2,4-dione VIc as
example. We found that the relative content of the
oxidized form in DMSO very rapidly increases with
time, starting from 15% (this amount is detected im-
mediately after dissolution) and reaching 100% in
2 days. Thus, enol form C is relatively readily oxi-
dized in DMSO. The oxidized form is fairly stable
and undergoes no changes in DMSO during a period
of 2.5 months, despite the fact that the solvent takes
up much moisture in this time. For comparison, we
ACKNOWLEDGMENTS
The study was financially supported by the Russian
Foundation for Basic Research (project nos. 04-03-
96036, 04-03-97505).
1
performed a similar study with enol C. The H NMR
spectra of VIc and VIf (enol form B), recorded 12 h
after the dissolution, indicate that enol B is more
stable and is not oxidized in DMSO, at least under
the examined conditions.
REFERENCES
1. Hagiwara, H. and Uda, H., J. Chem. Soc., Perkin
Trans. 1, 1985, no. 6, p. 1157.
EXPERIMENTAL
2. Kashihara, H., Shinoki, H., Suemune, H., and Sa-
kai, K., Chem. Pharm. Bull., 1986, vol. 34, no. 11,
p. 4527.
The IR spectra were recorded on a UR-20 spec-
1
trometer (thin films). The H NMR spectra were taken
3. Ayer, W.A., Villar, J.D.F., and Migaj, B.S., Can. J.
Chem., 1988, vol. 66, no. 3, p. 506.
in CCl4, CDCl3, and DMSO-d6 on an RYa-2310
spectrometer (60 MHz) for Ia Ic and VI and on Bru-
ker DRX-500, Bruker DRX-400, Bruker AM-300, and
Tesla BS-567A (100 MHz) spectrometers for VI. The
13C NMR spectra of compounds VI were recorded in
CDCl3 and DMSO-d6 on a Bruker DRX-400 spec-
trometer (100 MHz), internal reference TMS.
4. Tanabe, Y., Miyakado, M., Ohno, N., and Yoshio-
ka, H., Chem. Lett., 1982, no. 10, p. 1543.
5. Bacardit, R. and Moreno-Manas, M., Tetrahedron Lett.,
1980, vol. 21, no. 6, p. 551.
6. Angelo, J. and Gomez-Pardo, D., Tetrahedron Lett.,
1991, vol. 32, no. 26, p. 3063.
Ethyl esters of 2,4-dibromo-2-R1-4-R2-3-oxopen-
tanoic and -hexanoic acids Ia Ic were prepared as de-
scribed in [13]. Ia: yield 67%, bp 124 125 C (10 mm
7. Sugita, Y., Sakaki, J., Sato, M., and Kaneko, C.,
J. Chem. Soc., Perkin Trans. 1, 1992, no. 21, p. 2855.
8. Tait, B.D., Hagen, S., Domagala, J., Ellsworth, E.L.,
Gajda, C., Hamilton, H., Vara, P.J.V.N., Ferguson, D.,
Graham, N., Hupe, D., Nouhan, C., Tummino, P.J.,
Humblet, C., Lunney, E.A., Pavlovsky, A., Rubin, J.,
Grachek, S.J., Baldwin, E.T., Bhat, T.N., Erick-
son, J.W., Gulnik, S.V., and Liu, B., J. Med. Chem.,
1997, vol. 40, no. 23, p. 3781.
1
Hg), d240 1.5645, n2D01 1.4959. IR spectrum, , cm :
1735, 1765 (C=O). H NMR spectrum (CDCl3),
,
ppm: 1.26 t (3H, OCH2Me), 1.86 s (3H, Me), 1.93 s
(6H, CMe2), 4.16 q (2H, OCH2Me). Ib: yield 65%,
bp 120 130 C (2 3 mm Hg), n2D0 1.4954. IR spec-
1
1
trum, , cm : 1730, 1770 (C=O). H NMR spec-
trum (CCl4), , ppm: 0.87 t (6H, 2CH2Me), 1.25 t
(3H, OCH2Me), 1.93 s (3H, Me), 2.00 q (4H,
9. Shchepin, V.V., Sazhneva, Yu.Kh., Russkikh, N.Yu.,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 10 2005

SYNTHESIS, STRUCTURE, AND KETO ENOL TAUTOMERISM
1627
and Vakhrin, M.I., Zh. Org. Khim., 2001, vol. 37,
no. 10, p. 1580.
and Litvinov, D.N., Zh. Org. Khim., 2000, vol. 36,
no. 6, p. 808.
14. Castellino, S. and Sims, J.J., Tetrahedron Lett., 1984,
vol. 25, no. 22, p. 2307.
10. Shchepin, V.V., Russkikh, N.Yu., and Sazhne-
va, Yu.Kh., Khim. Geterotsikl. Soedin., 2003, no. 2,
p. 300.
15. Willson, T.M., Kocienski, P., Jarowicki, K., Isaac, K.,
Hitchock, P.M., Faller, A., and Campbell, S.F.,
Tetrahedron, 1990, vol. 46, no. 5, p. 1767.
16. Wulferding, A., Jankowski, J.H., and Hoffman, M.R.,
Chem. Ber., 1994, vol. 127, no. 7, p. 1275.
17. Fieser, L.F. and Fieser, M., Reagents for Organic
Synthesis, New York: Wiley, 1967. Translated under
the title Reagenty dlya organicheskogo sinteza,
Moscow: Mir, 1970, vol. 1, p. 327.
11. Shchepin, V.V., Sazhneva, Yu.Kh., Russkikh, N.Yu.,
and Vakhrin, M.I., Zh. Obshch. Khim., 2003, vol. 73,
no. 5, p. 804.
12. Shchepin, V.V., Sazhneva, Yu.Kh., Bagara, M.V., and
Russkikh, N.Yu., Zh. Obshch. Khim., 2003, vol. 73,
no. 8, p. 1336.
13. Shchepin, V.V., Sazhneva, Yu.Kh., Russkikh, N.Yu.,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 10 2005