Spirocyclization of 2,3-seco-19β,28-epoxy-28-oxo-18α-olean-2,3- dicarboxylic anhydride with benzylamines

Full text of DOI:10.1134/S0012500809110081

ISSN 0012ꢀ5008, Doklady Chemistry, 2009, Vol. 429, Part 1, pp. 286–289. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.V. Shernyukov, I.Ya. Mainagashev, D.V. Korchagina, Yu.V. Gatilov, N.F. Salakhutdinov, G.A. Tolstikov, 2009, published in Doklady Akademii Nauk,
009, Vol. 429, No. 3, pp. 339–342.
2
CHEMISTRY
Spirocyclization of 2,3ꢀSecoꢀ19
β
,28ꢀepoxyꢀ28ꢀoxoꢀ18 ꢀoleanꢀ
α
2,3ꢀdicarboxylic Anhydride with Benzylamines
A. V. Shernyukov, I. Ya. Mainagashev, D. V. Korchagina, Yu. V. Gatilov,
N. F. Salakhutdinov, and Academician G. A. Tolstikov
Received June 8, 2009
DOI: 10.1134/S0012500809110081
The cyclization of secoꢀdicarboxylic acids and cleavage of triterpene and steroid alcohols and ketones
their cyclic anhydrides into norketones upon heating into secoꢀcarboxylic acids and the further reaction of
pyrolysis) in vacuum is widely used in steroid and tritꢀ the latter with acetic anhydride followed by pyrolysis
(
erpene chemistry [1]. For example, the oxidative were used to establish their structure [2].
R
1
0' 9'
8'
11'
29
30
7'
R
12'
6'
20 21
19
1
9
O
1
)
, THF
O
O
1'
12
18
1
8
N
2'
22
5
'
NH2
O
11 13
26
17
28
2
8
4'
O
O
25
H
14 16
15
H
O
3'
O
O
O
2)
1
9
2
3
10
8
Cl
Cl
O
2
O
5
7
27
4
6
24
O
23
IIa: R = H (50%)
IIb: R = OMe (44%)
I
R
O
HN
RNH2
O
R
O
a
HN
HOOC
IV
R
O
N
b
III
O
O
Cl
O
V
Scheme 1.
Vorozhtsov Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, pr. Lavrent’eva 9, Novosibirsk,
30090 Russia
6
286

SPIROCYCLIZATION
287
We have found a new transformation of a similar
type resulting from the reaction of sevenꢀmembered
cyclic anhydride , readily available from correspondꢀ
ing 2,3ꢀsecoꢀdicarboxylic acid [3], with benzylamine
or ꢀmethoxybenzylamine in THF followed by treatꢀ
ment with oxalyl chloride (Scheme 1). The reaction
C(8')
I
C(12')
C(7')
N(1')
O(4)
C(2')
C(6')
O(6)
C(5')
p
leads to spironorketones IIa, IIb containing a pyrroꢀ
lidinetrione fragment.
C(29)
C(19)
O(1)
C(11)
C(4')
O(5)
C(1)
C(20)
The structure of compound IIa determined by
Xꢀray diffraction study is shown in the figure. The sixꢀ
membered rings of oleanic skeleton have a common
chair conformation, while the fiveꢀmembered carbon
ring has an envelope conformation with the C(10)
atom being 0.710(5) Å out of the plane of the other
C(2)
C(13)
O(2)
C(9)
C(17)
C(15)
C(22)
O(3)
C(5)
C(24)
C(26)
atoms. The pyrrolidine ring is flat within
±
0.022 Å. It
C(6)
is worth noting that the Cambridge Structural Dataꢀ
base involves several structures containing the 4ꢀmethꢀ
ylenepyrrolidineꢀ2,3,5ꢀtrione moiety and no data on
the structure of the pyrrolidineꢀ2,3,5ꢀtrione fragment.
However, in both cases, the C(4')–C(5') bond
lengths—1.533(5) Å in IIa and 1.544 and 1.530 Å in
The structure of IIa molecule in crystal (30% ellipsoids are
shown). Selected bond lengths (Å): N(1')–C(2'), 1.399(5);
N(1')–C(5'), 1.373(5); C(1)–C(2'), 1.522(5); C(1)–
C(4'), 1.527(5); C(2')–O(4), 1.205(4); C(4')–O(5),
.197(4); C(4')–C(5'), 1.533(5); C(5')–O(6), 1.201(4);
C(1)–C(2), 1.571(5); C(1)–C(10), 1.596(5); C(8)–
C(14), 1.588(5). Selected torsion angles:
C(5')N(1')C(6')C(7'), 83.7(4) ; N(1')C(6')C(7')C(12'),
7.7(5)
1
[
4, 5]—are close to each other and to the length of
.550 Å in bicyclo[3.2.2]nonaneꢀ6,7,8,9ꢀtetraone [6].
The angle between the planes of spiro connected rings
is 86.8(2) . In the crystal, IIa molecules form chains
along owing to C(10')–H···O(3) interactions
H···O is 2.53 Å, C–H···O angle is 151 ) (the figure).
1
°
6
°.
°
a
+ b
the preparation of spironorketones of oleanic series
comprising 2ꢀazaspiro[4.4]nonaneꢀ1,3,4,6ꢀtetraone
(
°
A new stereogenic center C(1) in IIa and IIb molꢀ fragment.
ecules results from the above reactions; therefore, they
can exist as diastereomer pairs. However, according to
NMR spectra, ketones IIa and IIb are individual comꢀ
pounds. We assign the configuration of the chiral cenꢀ
ter at C(1) in compounds IIa and IIb on the basis of
the Xꢀray diffraction study of compound IIa. It is
interesting to note that we found in the literature no
EXPERIMENTAL
IR spectra were recorded on a VECTOR 22 specꢀ
trophotometer as KBr pellets. Specific rotation was
determined on a PolAAr 3005 spectrometer. Mass
spectra (ionizing energy of 70 eV) were obtained on a
other
compounds
containing
the
2ꢀazaꢀ
Finnigan MAT 8200 instrument. 1
H
and C NMR
13
spiro[4.4]nonaneꢀ1,3,4,6ꢀtetraone fragment.
spectra of CDCl solutions were recorded on a Bruker
3
The formation of spironorketones IIa and IIb can
be explained by the following mechanism (Scheme 1).
It is known that acetamides can form pyrrolidineꢀ
DRX 500 spectrometer operating at 500.13 and
25.76 MHz, respectively. Chloroform solvent signals
were used as the internal reference ( 7.24 ppm,
1
δ
H
2
,3,5ꢀtriones in the reaction with oxalyl chloride [7–
δ
76.90 ppm). Signal assignment in the obtained
C
9
]; therefore, intermediate amido acid III, resulting
1
compounds was made on the basis of analysis of H
from the opening of the anhydride ring with amine,
1
1
NMR spectra with the use of H– H double resonance
can produce compounds IIa and IIb under the action
1
1
spectra and 2D spectra of homonuclear H– H correꢀ
of oxalyl chloride through two routes. Route
a
13
includes the initial assembly of norketone ring IV folꢀ lation and the analysis of C NMR spectra recorded
lowed by acylation of the resulting
ꢀdiketone fragꢀ in the Jꢀmodulation mode (JMOD) with offꢀresoꢀ
ment with oxalyl chloride and final intramolecular nance proton decoupling and 2D spectra of heteronuꢀ
β
13
1
Nꢀacylation. Route
the pyrrolidinetrione ring to form acid chloride
which undergoes intramolecular acylation of the
resultant ꢀdiketone fragment to give compounds IIa
and IIb
b involves the initial assembly of clear C– H correlation on direct and remote spin–
1
V,
spin coupling constants (C–H COSY, JC,H 135 Hz
and COLOC JC,H 10 Hz, respectively). The Xꢀray
diffraction study of compound IIa was accomplished
on a Bruker P4 diffractometer (Mo
2,3
β
.
K radiation,
α
Thus, we have shown the new transformation of graphite monochromator,
,3ꢀsecoꢀdicarboxylic acid anhydride of oleanic series empirical absorption correction was applied. The
λ
0.71073 Å, 2
θ
< 52
°
). An
2
into spiro derivatives of Aꢀnorketones. The disclosed structure was solved by direct methods with SIR2002
transformation is probably to be a general method for software [10]. Structure refinement was made by fullꢀ
DOKLADY CHEMISTRY Vol. 429
Part 1
2009

288
SHERNYUKOV et al.
matrix least squares for all F 2 in the anisotropic 1.36–1.50 (m, 2Hꢀ21, 2Hꢀ7, 2Hꢀ22), 1.51–1.57 (m,
approximation for the nonꢀhydrogen atoms using the 2Hꢀ6), 1.65 (d, Hꢀ18a,
J18a,13a = 11.1), 1.82 (dm,
SHELXLꢀ97 program [11]. The hydrogen atoms were Hꢀh16e, J16e,16a = 13.4), 1.90 (dd, Hꢀ9a, J9a,11a = 13.0,
included in geometrically calculated positions and J9a,11e = 3.0), 2.66 (t, Hꢀ5, J5.6 = 7.6), 3.72 (s, Hꢀ19),
refined using the riding model.
4
.88 (s, 2Hꢀ6'), 7.26–7.33 (m, 2Hꢀ9', Hꢀ10'), 7.39 (br
13
d, 2Hꢀ8', J8',9' = 7.9). C NMR (
Cꢀ2), 189.13 (s, Cꢀ4'), 179.25 (s, Cꢀ28), 170.09 (s, Cꢀ5'),
58.90 (s, Cꢀ2'), 133.83 (s, Cꢀ7'), 129.00 (d, Cꢀ8' and
δ
, ppm): 209.80 (s,
2
,3ꢀSecoꢀ19 ,28ꢀepoxyꢀ28ꢀoxoꢀ18 ꢀoleanꢀ2,3ꢀ
β
α
dicarboxylic anhydride I was obtained by procedure
1
[
3]: decomp. >280
°
C (decomp. 290–292
°
C [3]).
Cꢀ12'), 128.67 (d, Cꢀ9' and Cꢀ11'), 128.28 (d, Cꢀ10'),
85.75 (d, Cꢀ19), 76.60 (s, Cꢀ1), 56.90 (s, Cꢀ10), 53.08
2
D
3.4
18
D
[
α]
+86.7
°
(
c
0.782, pyridine) ([α] +85.7 (c
°
–
1
0
.782, pyridine [3]). IR (
ν
, cm ): 1796 (O=C–O– (d, Cꢀ5), 48.32 (s, Cꢀ4), 46.38 (d, Cꢀ18), 45.82 (s, Cꢀ
C=O), 1765 (COOR). H NMR (
1
1
4
3
7), 43.19 (t, Cꢀ6'), 42.72 (d, Cꢀ9), 41.70 (s, Cꢀ8),
0.59 (s, Cꢀ14), 35.38 (d, Cꢀ13), 33.36 (s, Cꢀ20),
2.30 (t, Cꢀ7), 32.01 (t, Cꢀ21), 31.74 (t, Cꢀ22), 28.65
δ
, ppm,
J, Hz): 0.86
(
s, 3Hꢀ27), 0.91 (s, 3Hꢀ26), 0.92 (s, 3Hꢀ30), 0.99 (s,
Hꢀ29), 1.02 (s, 3Hꢀ25), 1.22 (s, 3Hꢀ24), 1.33 (s, 3Hꢀ
3
2
1
4
(
q, Cꢀ29), 27.76 (t, Cꢀ15), 27.04 (q, Cꢀ23), 25.47 (t,
3), 1.09 (dddd, Hꢀ12a, J12а,12e J12а,11а J12а,13а
2.8, 1 3.8), 1.17 (ddd, Hꢀ15e J15e,15а 13.3, J15e,16а
.0, J15e,16e 2.4), 1.20–1.31 (m, Hꢀ11 and Hꢀ15a), 1.34
J16а,16e J16а,15а 13.8,
J16а,15e 4.0), 1.38–1.61 (m, 10H), 1.69 (dm, Hꢀ12e,
J12e,12а = 12.8, 3 < 4), 1.76 (dd, Hꢀ9a, J9а,11а = 12.3,
J9а,11e 2.2), 1.80 (d, Hꢀ18a, J18а,13а = 11.1), 1.84 (ddd,
Hꢀ16e, J16e,15а = 13.8, J16e,15а = 3.6, J16e,15e = 2.4), 2.21
=
=
=
Cꢀ12), 25.21 (t, Cꢀ16), 24.65 (t, Cꢀ11), 23.81 (q, Cꢀ
J
,
2а,11e
3
1
0), 22.07 (q, Cꢀ24), 17.02 (t, Cꢀ6), 16.70 (q, Cꢀ25),
5.89 (q, Cꢀ26), 13.63 (q, Cꢀ27). MS ( ): calcd. for
m/z
(
m, Hꢀ13a), 1.37 (ddd, Hꢀ16a
,
=
+
C H NO , 627.3554; found, 627.3552 [M] . Crysꢀ
tallographic data for IIa: C H NO , MW 627.79,
colorless prism of 0.8
39
49
6
39
49
6
J
×
0.6
×
0.18 mm, orthorhombic
= 12.070(2) Å,
=
space group
3.462(2) Å,
(Mo
P
c
2 2 21, at 296 K,
= 20.500(3) Å, V = 3330.9(9) Å , Z = 4,
a
b =
1
1
3
1
(
(
1
5
d, Hꢀ1, J1',1 = 13.9), 2.83 (d, Hꢀ1', J1',1 = 13.9), 3.90
–1
–3
μ
K
)
= 0.083 mm , dcalcd = 1.252 g
669 independent reflections, 2445 observed reflecꢀ
tions with Fo > 4 Fo , 415 parameters. Final parameꢀ
ters: = 0.0440 (observed) and wR2 = 0.1231 (for all
reflections), GOOF = 1.008, largest difference peaks
· cm ,
13
α
s, Hꢀ19e). C NMR (
δ
, ppm): 179.45 (s, Cꢀ28),
76.23 (s, Cꢀ3), 165.92 (s, Cꢀ2), 85.62 (d, Cꢀ19),
3.26 (d, Cꢀ5), 46.57 (t, Cꢀ1), 46.56 (s, Cꢀ4), 46.34 (d,
3
σ( )
R
Cꢀ18), 45.88 (s, Cꢀ17), 45.53 (d, Cꢀ9), 41.76 (s, Cꢀ
1
3
0), 41.18 (s, Cꢀ8), 40.26 (s, Cꢀ14), 35.93 (d, Cꢀ13),
3.36 (s, Cꢀ20), 33.11 (t, Cꢀ7), 32.11 (t, Cꢀ21), 31.69
3
0
.18 and –0.14 e/A .
)ꢀ1'ꢀpꢀMethoxybenzylꢀ2,2',4',5',28ꢀpentaoxoꢀ
9b,28ꢀepoxyspiro[3ꢀnorꢀ18aꢀoleanꢀ1,3'ꢀpyrrolidiꢀ
ꢀmethoxybenzylamine (0.172 g,
.23 mmol) in 2 mL of THF was added to a solution of
(
t, Cꢀ22), 30.02 (q, Cꢀ23), 28.54 (q, Cꢀ29), 27.56 (t,
(1S
Cꢀ15), 26.05 (t, Cꢀ12), 25.30 (t, Cꢀ16), 23.71 (q, Cꢀ
1
3
1
0), 21.53 (t, Cꢀ11), 20.50 (q, Cꢀ25), 19.36 (q, Cꢀ24),
8.28 (q, Cꢀ6), 16.02 (q, Cꢀ26), 13.25 (t, Cꢀ27). MS
ne] IIb. A solution of
p
1
(
[
m/z): calcd. for C H O , 484.3183; found, 484.3180
M] .
30 44 5
compound I (0.553 g, 1.14 mmol) in 5 mL of THF.
+
The mixture was kept for 1 day. A solution of oxalyl
chloride (0.30 mL, 3.43 mmol) in THF was added and
the mixture was kept for 2 days. The solvent was
removed. The residue was purified by column chromaꢀ
(
1
S
)ꢀ1'ꢀBenzylꢀ2,2',4',5',28ꢀpentaoxoꢀ19
epoxyspiro[3ꢀnorꢀ18 ꢀoleanꢀ1,3'ꢀpyrrolidine] IIa. A
solution of benzylamine (0.126 g, 1.18 mmol) in 3 mL
of THF was added to a solution of compound
0.554 g, 1.14 mmol) in 8 mL of THF. The mixture was
kept for 1 day. A solution of oxalyl chloride (0.15 mL,
.72 mmol) in 1 mL of THF was added and the mixꢀ
β
,28ꢀ
α
tography on SiO (Merck, 60–200
bent, CH Cl –Et O (40 : 1) as eluent). Recrystallizaꢀ
tion from EtOH afforded 0.333 g (44%) of compound
μm, 10 g of the sorꢀ
2
I
2
2
2
(
–1
IIb, mp 252–255
°
C. IR ( , cm ): 1773 (COOR),
ν
1
1
736 (C=O), 1712 (C=O).
ture was kept for 1 day. Additional portion of oxalyl
chloride (0.15 mL, 1.72 mmol) was added and the
mixture was kept for 4 days. The precipitate was filꢀ
1H NMR (
, ppm, , Hz): 0.10 (dm, Hꢀ11e,
= 13.2), 0.54 (dddd, Hꢀ12a
13.0, J12a,11e = 4.3), 0.76 (s, 3Hꢀ27), 0.84 (s,
, cm ): 1757 (COOR), 3Hꢀ26), 0.89 (s, 3Hꢀ30), 0.99 (s, 3Hꢀ29), 1.02 (dm,
δ
J
J
11e,11
, J = J =
12a,12e 12a,11a
a
tered off to give 0.358 g (50%) of compound IIa
,
J12a,13a =
–
1
decomp. above 290
1
°
C. IR (
ν
1
736 (C=O), 1715 (C=O). H NMR (
.78 (s, 3Hꢀ27), 0.86 (s, 3Hꢀ26), 0.89 (s, 3Hꢀ30), 1.00 Hꢀ11a), 1.09 (s, 3Hꢀ24), 1.14 (s, 3Hꢀ23), 1.21 (s,
J16a,15a = 13.5,
δ
, ppm, J
, Hz): Hꢀ12e, J12e,12a = 13.0), 1.07–1.29 (m, Hꢀ13a, 2Hꢀ15,
0
(
s, 3Hꢀ29), 1.09 (s, 3Hꢀ24), 1.14 (s, 3Hꢀ23), 1.23 (s, 3Hꢀ25), 1.33 (ddd, Hꢀ16a, J16a,16e
=
3Hꢀ25), 0.23 (dddd, Hꢀ11e, J11e,11a = 13.0, J11e,12a
=
J16a,15e = 3.8), 1.36–1.50 (m, 2Hꢀ21, 2Hꢀ7, 2Hꢀ22),
4
.3, J11e,9a = 3.0, J11e,12e = 2.0), 0.63 (dddd, Hꢀ12a
,
1.50–1.56 (m, 2Hꢀ6), 1.63 (d, Hꢀ18, J18a,13a = 11.1),
J12a,12e
=
J12a,11a = J12a,13a = 13.0, J12a,11e = 4.3), 1.03– 1.79–1.85 (m, Hꢀ16e, Hꢀ9a), 2.64 (t, Hꢀ5, J5,6 = 7.7),
1
1
.21 (m, Hꢀ12e, Hꢀ13a, and 2Hꢀ15), 1.26 (dddd, Hꢀ 3.71 (s, Hꢀ19), 3.76 (s, 3Hꢀ13'), 4.79 and 4.85 (d, 2Hꢀ
1a, 1
J
=
J11a,9a
=
J11a,12a = 13.0, J11a,12e = 4.2), 1.34 6',
J16a,15a = 13.4, J16a,15e = 3.8), 7.34 (d, Hꢀ8', Hꢀ12',
J = 13.7, AB system), 6.80 (d, Hꢀ9', Hꢀ11', J = 8.6),
1a,11e
13
(
ddd, Hꢀ16a, J16a,16e
=
J
= 8.6). C NMR (
δ
, ppm):
DOKLADY CHEMISTRY Vol. 429
Part 1
2009

SPIROCYCLIZATION
289
2
1
1
9
09.88 (s, Cꢀ2), 189.36 (s, Cꢀ4'), 179.25 (s, Cꢀ28),
3. Dischendorfer, O. and Polak, O., Monatsh. Chem.
929, vol. 51, pp. 43–58.
4. Kawakami, M., Suzuki, M., Kawai, H., Ogawa, K.,
and Shishido, T., Tetrahedron Lett., 1998, vol. 39,
pp. 1763–1766.
,
1
69.93 (s, Cꢀ5'), 159.60 (s, Cꢀ10'), 158.87 (s, Cꢀ2'),
30.63 (d, Cꢀ8', Cꢀ12'), 126.06 (s, Cꢀ7'), 113.95 (d, Cꢀ
' and Cꢀ11'), 85.71 (d, Cꢀ19), 76.46 (s, Cꢀ1), 57.09 (s,
Cꢀ10), 55.17 (q, Cꢀ13'), 52.93 (d, Cꢀ5), 48.23 (s, Cꢀ
4
), 46.33 (d, Cꢀ18), 45.78 (s, Cꢀ17), 42.77 (d, Cꢀ9),
2.64 (t, Cꢀ6'), 41.69 (s, Cꢀ8), 40.51 (s, Cꢀ14), 35.56
5. Ostrowska, K., CiechanowiczꢀRutkowska, M., Pilaꢀ
ti, T., and Zuchowski, G., Monatsh. Chem., 1999,
vol. 130, pp. 555–562.
6. Gleiter, R., Doerner, T., and Irngartinger, H., Liebigs
Ann., 1996, pp. 381–391.
4
(
d, Cꢀ13), 33.33 (s, Cꢀ20), 32.26 (t, Cꢀ7), 31.99 (t, Cꢀ
1), 31.70 (t, Cꢀ22), 28.57 (q, Cꢀ29), 27.73 (t, Cꢀ15),
6.90 (q, Cꢀ23), 25.41 (t, Cꢀ12), 25.18 (t, Cꢀ16),
4.58 (t, Cꢀ11), 23.76 (q, Cꢀ30), 22.08 (q, Cꢀ24),
7.02 (t, Cꢀ6), 16.73 (q, Cꢀ25), 15.86 (q, Cꢀ26), 13.59
7. Skinner, G.S. and Perkins, J.F., J. Am. Chem. Soc.
950, vol. 72, pp. 5569–5573.
8. Sheehan, J.C. and Corey, E.J., J. Am. Chem. Soc., 1952,
vol. 74, pp. 360–365.
. Skinner, G.S. and Ludwig, R.E., J. Am. Chem. Soc.,
956, vol. 78, pp. 4656–4659.
,
1
m/z): calcd. for C H NO , 657.3660;
40 51 7
+
found, 657.3649 [M] .
9
1
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0. Altomare, A., Cascarano, G., Giacovazzo, C., and Vitꢀ
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. Simonsen, J.L. and Ross, W.C.J., The Terpenes, Camꢀ
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. Fieser, L. and Fieser, M., Steroids, London: Reinholt, 11. Sheldrick, G.M., SHELXꢀ97, Program for Crystal
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Germany, 1997.
DOKLADY CHEMISTRY Vol. 429
Part 1
2009