Synthesis of dispiro hetero analogs of pyrrolizidine alkaloids

Full text of DOI:10.1134/S1070428012090205

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 9, pp. 1257–1258. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.V. Konovalova, Yu.V. Shklyaev, A.N. Maslivets, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 9,
pp. 1257–1258.
SHORT
COMMUNICATIONS
Synthesis of Dispiro Hetero Analogs of Pyrrolizidine Alkaloids
V. V. Konovalovaa, Yu. V. Shklyaeva, and A. N. Maslivetsb
a Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences, Perm, Russia
b Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
Received September 27, 2011
DOI: 10.1134/S1070428012090205
Reactions of spiro heterocyclic enamines with
1H-pyrrole-2,3-diones, including those fused at the
N1–C5 bond to nitrogen-containing heterocycles, were
not studied. We have found that 3-aroyl-1H-pyrrolo-
[2,1-c][1,4]benzoxazine-1,2,4-triones Ia and Ib react
with an equimolar amount of 2′,5′,5′-trimethyl-4′,5′-di-
hydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-one (II)
(which may be regarded as potential 1,3-C,N-binu-
cleophile) in boiling anhydrous benzene (reaction time
2–5 min, until bright violet color typical of the initial
pyrrolobenzoxazinetriones disappeared) to give
3″-aroyl-4″-hydroxy-1″-(2-hydroxyphenyl)-3′,3′-di-
methyl-2′,3′-dihydrodispiro[naphthalene-1,1′-pyrroli-
zine-6′,2″-pyrrole]-4,5′,5″(1″H)-triones IIIa and IIIb
in almost quantitative yield. The spectral parameters of
compounds IIIa and IIIb are very similar to those
found for model ethyl 4-benzoyl-3-hydroxy-1-(2-hy-
droxyphenyl)-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]-
nona-3,8-diene-9-carboxylate whose structure was
proved by X-ray analysis [1].
Presumably, the first step is addition of the activat-
ed β-CH group in the enamino tautomer of II at the C3a
atom in Ia or Ib, followed by closure of pyrrole ring
via intramolecular attack by the amino group of the
enamine fragment on the lactone carbonyl carbon atom
in the oxazine ring and opening of the latter at the
C4–O5 bond, as was reported by us previously for the
reaction of pyrrolobenzoxazinetriones with 1-methyl-
3,4-dihydroisoquinolines [2]. The described reaction is
an example of regioselective synthesis of previously
inaccessible dispiro heterocyclic system with various
substituents in several positions of both heterocyclic
fragments. The products may be regarded as dispiro
heterocyclic analogs of pyrrolizidine alkaloids [3].
4″-Hydroxy-1″-(2-hydroxyphenyl)-3′,3′-dimeth-
yl-3″-(4-methylbenzoyl)-2′,3′-dihydrodispiro[naph-
O
O
O
N
O
+
COAr
Me
CH2
O
N
NH
O
Me
Me
Me
Me
O
Ia, Ib
II
Me
Me
Me
H
N
Me
H
O
N
O
N
C
HO
N
COAr
O
COAr
O
O
HO
O
OH
IIIa, IIIb
Ar = 4-MeC6H4 (a), 4-ClC6H4 (b).
1257

KONOVALOVA et al.
1258
The IR spectra were recorded on a Bruker IFS 66
spectrometer with Fourier transform from samples
dispersed in mineral oil. The 1H NMR spectra were run
on a Varian Mercury-300 spectrometer at 300 MHz
using DMSO-d6 as solvent and tetramethylsilane as
internal reference. The purity of the products was
checked by thin-layer chromatography on Sorbfil
plates using ethyl acetate as eluent; spots were devel-
oped by treatment with a 0.5% solution of chloranil in
toluene.
thalene-1,1′-pyrrolizine-6′,2″-pyrrole]-4,5′,5″(1″H)-
trione (IIIa). A solution of equimolar amounts
(1.0 mmol) of compounds Ia and II in 20 ml of anhy-
drous benzene was heated for 5 min under reflux (until
it lost its color). The mixture was cooled, and the
precipitate was filtered off. Yield 97%, mp 213–215°C
(from ethyl acetate). IR spectrum, ν, cm–1: 3225 br
(OH), 1714 (C5″=O, C5′=O), 1664 (C4=O), 1625
1
(3″-C=O). H NMR spectrum, δ, ppm: 1.60 s and
1.70 s (3H each, Me), 2.03 s (3H, MeC6H4), 2.54 (2H,
2′-H, AB), 4.54 s (1H, 7′-H), 6.14 d (1H, 3-H), 6.38 d
(1H, 2-H), 6.98–7.94 m (12H, Harom), 9.56 s (1H,
C6H4OH), 12.31 br.s (1H, 4″-OH). Found, %: C 73.26;
H 5.05; N 4.70. C35H28N2O6. Calculated, %: C 73.41;
H 4.93; N 4.89.
This study was performed under financial support
by the Presidium of the Russian Academy of Sciences
(program nos. 18, 21), by the Russian Foundation for
Basic Research (project nos. 12-03-00146, 12-03-
00696), and by the Council for Grants at the President
of the Russian Federation (project no. MK-
2998.2011.3).
3″-(4-Chlorobenzoyl)-4″-hydroxy-1″-(2-hy-
droxyphenyl)-3′,3′-dimethyl-2′,3′-dihydrodispiro-
[naphthalene-1,1′-pyrrolizine-6′,2″-pyrrole]-
4,5′,5″(1″H)-trione (IIIb) was synthesized in a simi-
lar way. Yield 96%, mp 204–205°C (from ethyl
acetate). IR spectrum, ν, cm–1: 3219 br (OH), 1708
(C5″=O, C5′=O), 1663 (C4=O), 1620 (3″-C=O). 1H NMR
spectrum, δ, ppm: 1.60 s and 1.70 s (3H each, Me),
2.62 (2H, 2′-H, AB), 4.55 s (1H, 7′-H), 6.13 d (1H,
3-H), 6.39 d (1H, 2-H), 6.89–7.94 m (12H, Harom),
9.57 s (1H, C6H4OH), 11.93 br.s (1H, 4″-OH). Found,
%: C 68.80; H 4.25; N 4.55. C34H25ClN2O6. Calculat-
ed, %: C 68.86; H 4.25; N 4.72.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012