Diastereoselective synthesis of spiro derivatives of 3-substituted 2,3,4,4a,5,6-hexahydro-1H-benzo[c]quinolizines

Article abstract of DOI:10.1134/S1070428009050170

The cyclization via the mechanism of "tert-amino effect" of 2-(4-R-piperidino)benzaldehydes with cyclic active methylene components (Meldrum's acid, 1,3-cyclohexanedione, and N,N-disubstituted barbituric acids) proceeded stereoselectively giving spiro-joi

Full text of DOI:10.1134/S1070428009050170

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 743−754. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © T.V. Glukhareva, E.V. Deeva, A.Yu. Platonova, I.V. Geide, M.I. Kodess, Yu.Yu. Morzherin, 2009, published in Zhurnal
Organicheskoi Khimii, 2009, Vol. 45, No. 5, pp. 757−767.
Diastereoselective Synthesis of Spiro Derivatives
of 3-Substituted 2,3,4,4a,5,6-Hexahydro-1H-benzo[c]quinolizines
T. V. Glukharevaa, E. V. Deevaa, A. Yu. Platonovaa, I. V. Geidea,
M. I. Kodessb, andYu. Yu. Morzherina
aUral State Technical University, Yekaterinburg, 620002 Russia
e-mail: morzherin@mail.ustu.ru
bPostovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences
Received March 27, 2008
Abstract—The cyclization via the mechanism of “tert-amino effect” of 2-(4-R-piperidino)benzaldehydes with
cyclic active methylene components (Meldrum’s acid, 1,3-cyclohexanedione, and N,N-disubstituted barbituric
acids) proceeded stereoselectively giving spiro-joined 2,3,4,4a,5,6-hexahydro-1H-benzo[c]quinolizines with axially
oriented hydrogen atoms in the positions 3 and 4a of the benzo[c]quinolizine ring.
DOI: 10.1134/S1070428009050170
The cyclization reactions of o-vinyldialkylanilines I to
form partially hydrogenized fused pyridines II are
described in the literature like occurring via the mecha-
nism of “tert-amino effect” [1–3]. The designation “tert-
amino effect” was introduced in [4], and this approach
was further developed for the creation of a C–C bond
[5]. It was shown formerly that the cyclization of o-vinyl-
dialkylanilines III containing a substituent at the α-carbon
of the dialkylamino group proceeded with a high regio-
and stereoselectivity [6, 7]. We described in a short
communication [8] that at the introduction of substituents
into the β-position with respect to the nitrogen of the cyclic
amino group the selective cyclization of compound III
was also possible.
2-(4-R-piperidino)benzaldehydes IVa–IVj. Prior to our
preliminary communication [9] no published data existed
on a stereoselective cyclization by the mechanism of
“tert-amino effect” at the use of 4-substituted piperidines
[10–13].
The reactions of 2-(4-R-piperidino)benzaldehydes IVa–
IVj with cyclic CH-active compounds Va–Ve at boiling
in toluene led to the formation of products of a tandem
process of the Knoevenagel reaction and cyclization via
‘tert-amino effect”. The reactions proceeded stereo-
selectively affording exclusively isomers VI–X in 65–
91% yields (Scheme 1).
In the 1H NMR spectra of compounds VI–X in some
cases was found the presence of the second isomer in
an amount less than 2–3%, and we failed to separate it
in a pure form. The structure and relative configuration
of the asymmetric carbon atoms on the positions 4a and
3 of spiro compounds VI–X were established by means
A
A
A
A
A
A
Y
X
R
R
α
β
N
α
1
of 2D correlation H and 13C NMR spectroscopy, and
β
γ
N
N
Y
also by XRD analysis.
R
X
Y
In the 1H NMR spectra of spiro compounds VI–X the
proton H4a of the benzoquinolizine ring gave rise to a doublet
of doublets in the region 3.4–4.1 ppm (J4a,4a 10–15,
J4a,4e 1–4 Hz) revealing its axial position. The axial orienta-
tion of the proton H3 of the ring is shown by the multiplicity
of the signal of H4a proton whose resonance appeared
as a doublet of doublets (J4a,4a 10–15, J4e,4a 10–15, J3,4a
Y
R
III
I
II
In this report we treat the case when the substituent
is located in the γ-position with respect to the nitrogen of
the dialkylamino group and descried the stereoselective
synthesis of spiro-joined fused quinolines starting from
743

GLUKHAREVA et al.
744
Scheme 1.
Y
O
X
H
O
X
X
X
H
R2
R3
CHO
N
O
O
O
Y
R2
R3
R2
X
X
toluene
6
+
Y
4a
O
4
R3
N
N
R1
R1
1
2
R1
3
IVà_IVj
Và_Ve
H
VIà_VIe, VIg, VIi, VIIà_VIIe, VIIi,
VIIj, VIIIà_VIIIi, IXa, IXd, IXg,
IXh, Xà, Xb, Xd, Xf_Xi
IV, VI–X, R1 = Me, R2 = H, R3 = H (a), Cl (b); R1 = Ph: R2 = H, R3 = H (c), Cl (d), Br (e), F (f); R2 = CF3, R3 = H (g); R1 = CH2 Ph,
R2 = H, R3 = H (h), Cl (i), Br (j); X = Y= CH2 (Va, VI); X = CH2, Y = CMe2 (Vb, VII); X = O, Y= CMe2 (Vc, VIII); X = NPh,
Y= CO (Vd, IX), X = NMe, Y= CO (Ve, X).
is located in the equatorial position due to the effect of
the sterical hindrances caused by the presence of a bulky
cyclic substituent at the double bond.
10–15 Hz) in the region 0.8–1.1 ppm. The multiplet of
proton H3 was observed in the region 1.68–1.89 ppm. In
the two-dimensional. 1H–1H NMR correlation spectrum
the interactions were observed between the atoms H4a,
H3, and H6 confirming their axial orientation (Fig. 1). Thus
three axial protons H4a, H3, and H6 are located in the
reciprocal cis-position on the same side of the molecule.
This effect is lacking in the reaction with the malono-
dinitrile [8]; presumably, in this case the cyclization occurs
with a high energy barrier and therefore it is accompanied
by the isomerization of the intermediate resulting in the
formation of two isomers .
The carbon atoms in the spiro ring are nonequivalent
and have different chemical shifts in the 13C NMR
spectrum.
In reaction of piperidinobenzaldehydes IVa, IVg, and
IVh with the malonodinitrile in boiling toluene formed
benzylidenemalonodinitriles XIa–XIc (Scheme 2). Their
cyclization along the mechanism of “tert-amino effect”
occurred at boiling in butanol and resulted in the formation
of isomers mixture of benzo[c]quinolizines XII and XIII,
1:1.
In the 1H NMR spectra of compounds obtained a double
set of signals was observed demonstrating the formation
of diastereomers. Isomers XII and XIII are distinguished
by the axial and equatorial position of the H3 atom.
The final proof of the structure of compound Xf was
obtained by XRD analysis (Fig. 2).
The diastereoselective reaction course may occur by
spatial reasons. Evidently at the formation of the benzylid-
ene the double bond is so turned that the equatorial proton
at the α-carbon is approached to the double bond, and
the substituent in the β-position of the piperidine fragment
O
H3C
N
6'
Isomer XIIIb with the axial proton at the nodal atom
C4a and with the equatorial proton at C3 is less soluble in
ethanol, and we succeeded in its isolation by fractional
crystallization in 25% yield.
N
O
2'
CH3
H
O
H
2
He
H
N C
C
1
6
4a
Ha
H
4
Thus at the presence of a substituent in the γ-position
with respect to the nitrogen atom of the cyclic amine the
cyclization by the mechanism of “tert-amino effect”
proceeded diastereoselectively in the case of ortho-vinyl-
anilines obtained by the condensation of benzaldehydes
with cyclic CH-active compounds.
H
Ha
3
H
Ha
Fig. 1. Relative configuration of spiro compound Xh.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

DIASTEREOSELECTIVE SYNTHESIS OF SPIRO DERVATIVES
745
Fig. 2. Structure of compound Xf according to XRD data.
TMS. Mass spectra were measured on mass spectrom-
eters Varian MAT 311A and Finnigan MAT 8200 at the
ionizing electrons energy 70 eV at the direct admission
of the sample into the ion source. The solvents were
purified and dried by standard procedures. Compound
IVc was described in [8].
EXPERIMENTAL
The reaction progress was monitored and the
homogeneity of compounds obtained was checked by
TLC on Silufol UV-254 plates, eluents chloroform,
chloroform–ethanol, 9:1, 15:1, 20:1, ethyl acetate–hexane,
1.5:2, 1:2. IR spectra were recorded on a spectrophotom-
eter UR-20 from KBr pellets. NMR spectra were
registered from solutions in DMSO-d6 on spectrometers
Aldehydes IV. To a solution of 10 mmol of 2-fluoro-
benzaldehyde in 8.0 ml of DMF was added 11 mmol of
dialkylamine and 1.52 g (11 mmol) of K2CO3. The mixture
was boiled on a glycerol bath at 150°C for 20 h. On
1
Βruker WM-250 (250 MHz for H) and Βruker DRX-
400 (400 for 1H and 100 MHz for 13C), internal reference
Scheme 2.
N
N
H
R2
R3
toluene
+
NCCH2CN
IVà, IVg, IVh
N
R1
NC
XIà_XIc
NC
6
R2
R3
6
R2
CN
CN
H
H
4
butanol
4a
4a
4
+
R3
N
N
H
H
H
H
2
2
R1
H
1
1
3
3
R1
H
XIIà_XIIc
XIIIà_XIIIc
XI–XIII, R1 = CH3, R2 = R3 = H (a); R1 = CH2Ph, R2 = R3 = H (b); R1 = Ph, R2 = CF3, R3 = H (c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

GLUKHAREVA et al.
746
completion of the reaction (TLC monitoring) the reaction
mixture was cooled to room temperature, diluted with 75
ml of water, the reaction product was extracted with ethyl
acetate (3×60 ml). The combined extracts were washed
with an ammonium chloride solution, dried with Na2SO4,
and evaporated in a vacuum.
2NCH2), 7.11–7.55 m (8HAr), 10.43 s (1H, CHO). Mass
spectrum, m/z (Irel, %): 283 (100) [M]+. Found, %:
C 76.36; H 6.44; N 5.04. C18H18FNO. Calculated, %:
C 76.30; H 6.40; N 4.94.
2-(4-Phenylpiperidin-1-yl)-5-trifluoromethyl-
benzaldehyde (IVg). Yield 89%, mp 122°C. Mass spec-
trum, m/z (Irel, %): 347 (100) [M]+. Found, %: C 69.36;
H 5.90; N 4.14. C20H20F3NO. Calculated, %: C 69.15;
H 5.80; N 4.03.
2-(4-Methylpiperidin-1-yl)benzaldehyde (IVa).
Yield 1.62 g (80%), oily compound. 1H NMR spectrum,
δ, ppm: 1.01 d (3H, CH3, J 5.8 Hz), 1.44 d.d.q.d (1H,
CH, J 11.9, 10.2, 5.8, 3.3 Hz), 1.48–1.58 m (2H, 2CH),
1.76 br.d (2H, 2CH, J 11.9 Hz), 2.86 d.d (2H, 2NCH,
J 11.6, 12.2 Hz), 3.21 br.d (2H, 2NCH, J 12.2 Hz),
7.05 d.d.d (1HAr, J 8.3, 7.3, 0.8 Hz), 7.12 d.d (1HAr, J 8.3,
0.8 Hz), 7.50 d.d.d (1HAr, J 7.3, 7.8, 1.5 Hz), 7.65 d.d
(1HAr, J 7.8, 1.5 Hz) 10.18 s (1H, CHO). Mass spectrum,
m/z (Irel, %): 203 (98) [M]+. Found, %: C 76.87; H 8.50;
N 6.95. C13H17NO. Calculated, %: C 76.81; H 8.43;
N 6.89.
2-(4-Benzylpiperidin-1-yl)benzaldehyde (IVh).
Yield 2.29 g (82%), mp 70–72°C. 1H NMR spectrum, δ,
ppm: 1.42–1.49 m (2H, 2CH), 1.62–1.69 m (3H, 3CH),
2.59 d (2H, CH2, J 6.6 Hz), 2.80 d.d (2H, 2NCH, J 11.6,
12.2 Hz), 3.21 br.d (2H, 2NCH, J 12.2 Hz), 7.09 t (1H,
Ph, J 7.0 Hz), 7.16–7.22 m (4H, Ph+ArH), 7.28 d.d (2H,
Ph, J 7.0, 7.0 Hz), 7.48 d.d.d (1HAr, J 6.0, 7.0, 1.7 Hz),
7.67 d.d (1HAr, J 6.0, 1.7 Hz), 10.16 s (1H, CHO). Mass
spectrum, m/z (Irel, %): 279 (100) [M]+. Found, %: C 81.67;
H 7.59; N 5.04. C19H21NO. Calculated, %: C 81.68;
H 7.58; N 5.01.
2-(4-Methylpiperidin-1-yl)-4-chlorobenz-
aldehyde (IVb). Yield 2.04 g (86%), mp 110–112°C. 1H
NMR spectrum, δ, ppm: 1.01 d (3H, CH3, J 6.1 Hz),
2.77–2.93 m (2H, NCH), 3.21–3.27 m (2H, NCH), 3.21–
3.27 m (5H, CH, 2CH2), 7.04 d (1HAr, J 8.2 Hz), 7.10 s
(1HAr), 7.65 d (1HAr, J 8.2 Hz), 10.07 s (1H, CHO). Mass
spectrum, m/z (Irel, %): 239 (30) [M + 2]+, 237 (78) [M]+.
Found, %: C 65.78; H 7.00; N 6.01. C13H16ClNO.
Calculated, %: C 65.68; H 6.78; N 5.89.
2-(4-Benzylpiperidin-1-yl)-4-chlorobenzaldehyde
1
(IVi). Yield 90%, mp 65–67°C. H NMR spectrum, δ,
ppm: 1.38–1.49 m (2H, 2CH), 1.62–1.70 m (3H, 3CH),
2.57 d (2H, CH2, J 6.4 Hz), 2.81 d.d (2H, 2NCH,
J 11.6, 12.0 Hz), 3.23 br.d (2H, 2NCH, J 12.0 Hz), 7.06–
7.42 m (7H, Ph + ArH), 7.66 d (1HAr, J 8.3 Hz), 10.06 s
(1H, CHO). Mass spectrum, m/z (Irel, %): 315 (38) [M +
2]+, 313 (100) [M]+. Found, %: C 72.77; H 5.50; Cl 11.54;
N 4.54. C19H20ClNO. Calculated, %: C 72.72; H 6.42;
Cl 11.30; N 4.46.
2-(4-Phenylpiperidin-1-yl)-4-chlorobenzaldehyde
1
(IVd). Yield 2.27 g (76%), mp 124–126°C. H NMR
spectrum, δ, ppm: 1.89–1.99 m (4H, 2CH2), 2.68 quintet
(1H, CHPh, J 8.2 Hz), 2.97–3.09 m (2H, NCH2), 3.34–
3.41 m (2H, NCH2), 7.07 d.d (1HAr, J 8.2, 1.1 Hz), 7.13–
7.33 m (6HAr), 7.68 d (1HAr, J 8.3 Hz), 10.16 s (1H,
CHO). Mass spectrum, m/z (Irel, %): 301 (30) [M + 2]+,
299 (78) [M]+. Found, %: C 72.11; H 6.00; N 4.69.
C18H18ClNO. Calculated, %: C 72.11; H 6.05; N 4.67.
2-(4-Benzylpiperidin-1-yl)-4-bromobenzaldehyde
(IVj). Yield 82%, mp 76°C. 1H NMR spectrum, δ, ppm:
1.37–1.47 m (2H, 2CH), 1.62–1.70 m (3H, 3CH), 2.57 d
(2H, CH2, J 6.4 Hz), 2.81 d.d (2H, 2NCH, J 11.9,
12.0 Hz), 3.23 br.d (2H, 2NCH, J 12.0 Hz), 7.12–7.35 m
(7H, Ph + ArH), 7.57 d (1HAr, J 8.3 Hz), 10.06 s (1H,
CHO). Mass spectrum, m/z (Irel, %): 359 (100) [M + 2]+,
357 (97) [M]+. Found, %: C 63.76; H 5.65; N 4.04.
C19H20BrNO. Calculated, %: C 63.70; H 5.63; N 3.91.
4-Bromo-2-(4-phenylpiperidin-1-yl)benz-
aldehyde (IVe). Yield 3.03 g (88%), mp 105–108°C. 1H
NMR spectrum δ, ppm: 1.85–2.02 m (4H, 2CH2), 2.60–
2.69 m (1H, CHPh), 2.99–3.11 m (2H, NCH2), 3.39 d
(2H, NCH2, J 11.9 Hz), 7.15–7.33 m (7HAr), 7.60 d
(1HAr, J 8.2 Hz), 10.17 s (1H, CHO). Mass spectrum,
m/z (Irel, %): 346 (80) [M + 2]+, 344 (79) [M]+. Found,
%: C 62.99; H 5.35; N 4.09. C18H18BrNO. Calculated,
%: C 62.80; H 5.27; N 4.07.
Spiro compounds VI–X. To a solution of 1 mmol of
benzaldehyde IV in 10 ml of toluene was added 1 mmol
of compound Va–Ve. The reaction mixture was boiled
for 3–6 h (TLC monitoring). The reaction mixture was
cooled to room temperature, the solvent was evaporated
in a vacuum, the residue was ground with ethanol.
2-(4-Phenylpiperidin-1-yl)-4-fluorobenzaldehyde
1
(IVf). Yield 2.69 g (95%), mp 76–78°C. H NMR
3-Methyl-2,3,4,4a,5,6-hexahydro-1H-spiro-
[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-dione
spectrum, δ, ppm: 1.62–1.69 m (3H, 3CH), 1.82–1.95 m
(4H, 2CH2), 2.59–2.73 m (1H, CH), 3.21–3.45 m (4H,
1
(VIa). Yield 0.19 g (65%), mp 217–220°C. H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

DIASTEREOSELECTIVE SYNTHESIS OF SPIRO DERVATIVES
747
dione (VId). Yield 0.34 g (86%), mp 182–185°C. 1H NMR
spectrum, δ, ppm: 1.23 d.d.d (1H, H4, J 12.0, 12.4,
11.9 Hz), 1.25–1.29 m (1H, CH), 1.45–1.64 m (3H, 3CH),
2.11–2.19 m (1H, CH), 2.35 br.d (1H, CH, J 13.6 Hz),
2.42 br.d (1H, CH, J 14.2 Hz), 2.69 br.d (1H, CH,
J 13.6 Hz), 3.02–3.40 m (7H, 7CH), 4.08 br.d (1H, H4a,
J 14.4 Hz), 4.50 br.d (1H, H1, J 10.1 Hz), 6.63 d.d (1HAr,
J 8.0, 1.6 Hz), 6.78 d (1HAr, J 1.6 Hz), 6.97–7.21 m (6H,
Ph, ArH). Mass spectrum, m/z (Irel, %): 395 [M + 2]+
(36), 393 [M]+ (100). Found, %: C 73.21; H 6.07; N 3.66.
C24H24ClNO2. Calculated, %: C 73.18; H 6.14; N 3.56.
spectrum, δ, ppm: 0.81 d (3H, CH3, J 6.5 Hz), 0.82 d.d.d
(1H, H4, J 13.3, 11.3, 12.5 Hz), 1.08 br.d (1H, H2,
J 13.3 Hz), 1.10 br.d (1H, H4, J 13.3 Hz), 1.38 br.d (1H,
H2, J 12.5 Hz), 1.50–1.55 m (1H, H5'), 1.80–1.85 m (1H,
H5'), 2.09–2.20 m (1H, H3), 2.32 br.d (1H, H6',
J 17.0 Hz), 2.44 br.d (1H, H4', J 14.0 Hz), 2.67 br.d (1H,
H6', J 17.0 Hz), 2.97 d.d.d (1H, H1, J 15.0, 13.3, 2.8 Hz),
3.06 and 3.09 AB (2H, ArCH2, J 17.4 Hz), 3.31 d.d.d
(1H, H4', J 14.0, 14.4, 7.0 Hz), 3.98 br.d (1H, H1,
J 15.0 Hz), 4.27 br.d (1H, H4a, J 11.3 Hz), 6.61 d.d (1HAr,
J 7.9, 8.0 Hz), 6.70 d (1HAr, J 7.9 Hz), 6.94 d.d (1HAr,
J 8.0, 7.0 Hz), 7.00 d (1HAr, J 7.0 Hz). Mass spectrum,
m/z (Irel, %): 297 (100) [M]+. Found, %: C 76.87; H 7.99;
N 4.84. C19H23NO2. Calculated, %: C 76.74; H 7.80;
N 4.71.
9-Bromo-3-phenyl-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-
dione (VIe). Yield 0.38 g (86%), mp 191–193°C.
1H NMR spectrum, δ, ppm: 1.22–1.29 m (2H, 2CH),
1.45–1.64 m (3H, 3CH), 2.11–2.19 m (1H, CH), 2.35 br.d
(1H, CH, J 13.7 Hz), 2.44 br.d (1H, CH, J 14.2 Hz),
2.66 d (1H, CH, J 17.4 Hz), 3.00–3.40 m (5H, 5CH),
4.08 br.d (1H, H4a, J 14.4 Hz), 4.50 br.d (1H, H1,
J 9.4 Hz), 6.77 d.d (1HAr, J 8.0, 1.5 Hz), 6.91 d (1HAr,
J 1.5 Hz), 6.98 d (1HAr, J 8.0 Hz), 7.02–7.23 m (5HPh).
Mass spectrum, m/z (Irel, %): 440 (99) [M + 2]+, 438 (100)
[M]+. Found, %: C 65.87; H 5.57; N 3.25. C24H24BrNO2.
Calculated, %: C 65.76; H 5.52; N 3.20.
3-Methyl-9-chloro-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-
dione (VIb). Yield 0.26 g (78%), mp 121–123°C.
1H NMR spectrum, δ, ppm: 0.89 d.d.d (1H, H4, J 11.2,
12.9, 11.6 Hz), 0.95 d (3H, CH3, J 6.1 Hz), 1.16 d.d.d.d.d
(1H, H2, J 10.3, 12.8, 11.9, 3.5, 1.8 Hz), 1.45–1.85 m
(9H, 9CH), 2.84 d.d.d (1H, H1, J 10.3, 12.8, 2.3 Hz),
3.26 and 3.27 AB (2H, ArCH2, J 14.2 Hz), 3.44 d.d (1H,
H4a, J 12.9, 2.4 Hz), 4.01 br.d (1H, H1, J 12.8 Hz),
6.62 d.d (1HAr, J 2.7, 8.2 Hz), 6.85 d (1HAr, J 2.7 Hz),
6.93 d (1HAr, J 8.2 Hz). Mass spectrum, m/z (Irel, %): 333
(25) [M + 2]+, 331 (68) [M]+. Found, %: C 68.67; H 6.65;
N 4.29. C19H22ClNO2. Calculated, %: C 68.77; H 6.68;
N 4.22.
8-Trifluoromethyl-3-phenyl-2,3,4,4a,5,6-hexa-
hydro-1H-spiro[benzo[c]quinolizine-5,2'-cyclo-
hexane]-1',3'-dione (VIg). Yield 0.24 g (67%), mp
1
214°C. H NMR spectrum, δ, ppm: 1.19–1.69 m (6H,
3-Phenyl-2,3,4,4a,5,6-hexahydro-1H-spiro-
[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-dione
(VIc). Yield 0.24 g (68%), mp 228–230°C. 1H NMR
spectrum, δ, ppm: 0.89 d.d.d (1H, H4, J 12.2, 14.4,
12.9 Hz), 1.26 d.d.d.d (1H, H2, J 10.3, 11.7, 11.2, 1.8 Hz),
1.44–1.60 m (3H, H2, H4, H5'), 2.08–2.18 m (1H, H5'),
2.33 br.d (1H, H6', J 14.2 Hz), 2.46 br.d (1H, H4',
J 16.8 Hz), 2.69 br.d (1H, H6', J 14.2 Hz), 3.08 d (1H, H6,
J 14.6 Hz), 3.14 d.d.d (1H, H1, J 14.4, 11.2, 5.0 Hz),
3.14 d (1H, H6, J 14.6 Hz), 3.24 d.d.d.d (1H, H3, J 11.7,
14.1, 2.9, 3.8 Hz), 3.38 d.d.d (1H, H4', J 12.2, 16.8,
4.8 Hz), 4.15 br.d (1H, H1, J 14.4 Hz), 4.55 br.d (1H, H4a,
J 12.2 Hz), 6.56 d.d (1HAr, J 7.4, 7.4 Hz), 6.87 d (1HAr,
J 8.2 Hz), 7.00 d (1HAr, J 7.4 Hz), 7.05 d (2HPh,
J 7.2 Hz), 7.08 d.d (1HAr, J 7.4, 8.2 Hz), 7.14 d.d (1HPh,
J 7.6, 7.2 Hz), 7.23 d.d (2HPh, J 7.2, 7.6 Hz). Mass
spectrum, m/z (Irel, %): 359 (100) [M]+. Found, %: C 80.14;
H 7.15; N 3.79. C24H25NO2. Calculated, %: C 80.19;
H 7.01; N 3.90.
CH), 2.13–2.21 m (1H, CH), 2.42 br.d (1H, CH,
J 14.0 Hz), 2.75 d (1H, CH, J 17.1 Hz), 3.00–3.20 m
(3H, 3CH), 3.26–3.40 m (2H, 2CH), 4.20 br.d (1H, H4a,
J 14.0 Hz), 4.57 br.d (1H, H1, J 10.3 Hz), 6.93 d (1HAr,
J 8.6 Hz), 7.00–7.33 m (7H, Ph, ArH). Mass spectrum,
m/z (Irel, %): 427 (100) [M]+. Found, %: C 70.29; H 6.00;
N 3.26. C25H24F3NO2. Calculated, %: C 70.25; H 5.66;
N 3.28.
3-Benzyl-9-chloro-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-
1
dione (VIi). Yield 0.36 g (89%), mp 176°C. H NMR
spectrum, δ, ppm: 0.90 d.d.d (1H, H4, J 11.9, 12.5,
11.3 Hz), 1.01–1.18 m (1H, H5’), 1.23 br.d (1H, H2,
J 12.8), 1.35 br.d (1H, H4, J 11.9 Hz), 1.52 br.d (1H, H2,
J 12.8 Hz), 2.00–2.20 m (2H, H3, H5'), 2.26 d.d.d, (1H,
CH2, J 8.9, 10.1, 13.3 Hz), 2.31 d.d.d (1H, CH2, J 14.0,
14.1, 7.0 Hz), 2.38 br.d (1H, H4', J 14.1 Hz), 2.44–2.56 m
(2H, H1, H6'), 2.67 d (1H, H6', J 13.1 Hz), 2.98 and 3.02
AB (2H, ArCH2, J 14.7 Hz), 3.26 br.d (1H, H4',
J 14.1 Hz), 3.63 br.d (1H, H4a, J 14.3 Hz), 4.29 br.d (1H,
3-Phenyl-9-chloro-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-
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GLUKHAREVA et al.
748
H1, J 11.3 Hz), 6.62 d.d (1HAr, J 1.9, 7.9 Hz), 6.69 d
(1HAr, J 1.9 Hz), 7.01 d (1HAr, J 7.9 Hz), 7.02–7.25 m
(5HPh). Mass spectrum, m/z (Irel, %): 409 (40) [M + 2]+,
407 (100) [M]+. Found, %: C 73.63; H 6.49; N 3.53.
C25H26ClNO2. Calculated, %: C 73.61; H 6.42; N 3.43.
Hz), 7.05–7.10 m (2HAr), 7.07 d (1HAr, J 7.6 Hz), 7.16 t.t
(1HPh, J 7.6, 1.3 Hz), 7.23 d.d (2HPh, J 7.6, 7.6 Hz).
13C NMR spectrum, δ, ppm: 23.56 (Me), 26.18 (Me),
27.91 (C5), 29.46 (C4), 30.69 (C6), 31.14 (C3), 42.11 (C5'),
48.09 (C6'), 49.09 (C4'), 50.83 (C5), 60.09 (C1), 67.32 (C4a),
113.22 (Ar), 117.66 (Ar), 122.32 (Ar), 125.37 (Ar), 126.15
(Ar), 126.45 (Ar), 128.37 (Ar), 129.32 (Ar), 141.67 (Ar),
145.22 (Ar), 205.01 (CO), 205.99 (CO). Mass spectrum,
m/z (Irel, %): 387 (100) [M]+. Found, %: N 3.47.
C26H29NO2. Calculated, %: N 3.61.
3,5',5'-Trimethyl-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,2'-cyclohexane]-1',3'-
dione (VIIa). Yield 0.23 g (71%), mp 147–150°C.
1H NMR spectrum, δ, ppm: 0.71 c (3H, CH3), 0.80 d
(3H, CH3, J 6.4 Hz), 0.82 d.d.d (1H, H4, J 12.3, 11.0,
11.9 Hz), 1.00–1.20 m (2H, H2, H4), 1.23 s (3H, CH3),
1.38 br.d (1H, H2, J 15.3 Hz), 1.83–1.93 m (1H, H3),
2.09 d.d (1H, H6', J 17.0, 2.3 Hz), 2.23 d.d (1H, H4',
J 13.4, 2.3 Hz), 2.59 d (1H, H6', J 17.0 Hz), 3.12 d.d.d
(1H, H1, J 11.2, 12.3, 3.5 Hz), 3.08 and 3.12 AB (2H,
ArCH2, J 16.4 Hz), 3.40 d (1H, H4', J 13.4 Hz), 3.97 br.d
(1H, H1, J 13.3 Hz), 4.29 d (1H, H4a, J 11.0 Hz), 6.61 d.d
(1HAr, J 7.9, 8.2 Hz), 6.70 d (1HAr, J 7.9 Hz), 6.94 d.d
(1HAr, J 8.2, 7.0 Hz), 7.00 d (1HAr, J 7.0 Hz). Mass
spectrum, m/z (Irel, %): 325 (100) [M]+. Found, %: C 77.57;
H 8.39; N 4.55. C21H27NO2. Calculated, %: C 77.50;
H 8.36; N 4.30.
5',5'-Dimethyl-3-phenyl-9-chloro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,2'-
cyclohexane]-1',3'-dione (VIId). Yield 0.3 g (71%),
mp 256–259°C. 1H NMR spectrum, δ, ppm: 0.72 s (3H,
CH3), 1.15–1.25 m (2H, H2, H4), 1.24 c (3H, CH3), 1.50–
1.70 m (2H, H2, H4), 2.15 d (1H, H6', J 17.1 Hz), 2.25 d
(1H, H3', J 13.6 Hz), 2.61 d (1H, H6', J 17.1 Hz), 3.02–
3.25 m (4H, 4CH), 3.28 d (1H, H3', J 13.6 Hz), 4.05 d
(1H, H4a, J 14.0 Hz), 4.52 br.d (1H, H1, J 9.1 Hz), 6.63 d
(1HAr, J 8.0 Hz), 6.78 s (1HAr), 6.91–7.28 m (6H, Ph,
ArH). Mass spectrum, m/z (Irel, %): 423 (36) [M + 2]+,
421 (100) [M]+. Found, %: C 74.11; H 6.88; N 3.33.
C26H28ClNO2. Calculated, %: C 74.01; H 6.69; N 3.32.
3,5',5'-Trimethyl-9-chloro-2,3,4,4a,5,6-hexa-
hydro-1H-spiro[benzo[c]quinolizine-5,2'-cyclo-
hexane]-1',3'-dione (VIIb). Yield 0.29 g (82%), mp
190–192°C. 1H NMR spectrum, δ, ppm: 0.77 s (3H, CH3),
0.82 d (3H, CH3, J 6.4 Hz), 0.79–0.82 m (1H, H2), 1.00–
1.20 m (2H, H2, H4), 1.23 s (3H, CH3), 1.43 br.d (1H,
H4, J 13.1 Hz), 1.80–1.99 m (1H, H3), 2.10 d.d (1H, H6',
J 14.1, 2.5 Hz), 2.25 d.d (1H, H4', J 15.4, 2.5 Hz), 2.58 d
(1H, H6', J 14.1 Hz), 3.12 d.d (1H, H4, J 11.2, 12.9,
2.3 Hz), 3.04 and 3.11 AB (2H, ArCH2, J 17.4 Hz),
3.39 d (1H, H4', J 15.4 Hz), 3.93 br.d (1H, H4a, J 14.3 Hz),
4.28 br.d (1H, H1, J 11.2 Hz), 6.59 d.d (1HAr, J 1.5,
8.0 Hz), 6.68 d (1HAr, J 1.5 Hz) 6.99 d (1HAr, J 8.0 Hz).
Mass spectrum, m/z (Irel, %): 361 (35) [M + 2]+, 359
(100) [M]+. Found, %: C 70.07; H 7.32; N 3.99.
C21H26ClNO2. Calculated, %: C 70.08; H 7.28; N 3.89.
9-Bromo-5',5'-dimethyl-3-phenyl-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,2'-
cyclohexane]-1',3'-dione (VIIe). Yield 0.32 g (69%),
mp 252–254°C. 1H NMR spectrum, δ, ppm: 0.71 s (3H,
CH3), 1.15–1.25 m (2H, 2CH), 1.24 s (3H, CH3), 1.50–
1.65 m (2H, 2CH), 2.13 d (1H, H6', J 13.8 Hz), 2.23 d
(1H, H3', J 13.1 Hz), 2.58 and 3.12 AB (2H, ArCH2,
J 17.7 Hz), 3.12 d.d.d (1H, H1, J 12.1, 9.3, 1.9 Hz), 3.25 d
(1H, H6', J 13.8 Hz), 3.29 d.d.d.d (1H, H3, J 12.2, 12.0,
3.0, 4.9 Hz), 3.45 d (1H, H3', J 13.1 Hz), 4.08 d (1H, H4a,
J 14.3 Hz), 4.53 d (1H, H1, J 9.3 Hz), 6.77 d (1HAr,
J 7.9 Hz), 6.90 c (1HAr), 6.98 d (1HAr, J 7.9 Hz), 7.00–
7.22 m (5HPh). Mass spectrum, m/z (Irel, %): 468 (89)
[M + 2]+, 466 (88) [M]+. Found, %: C 67.05; H 6.08;
N 3.22. C26H28BrNO2. Calculated, %: C 66.95; H 6.05;
N 3.00.
5',5'-Dimethyl-3-phenyl-2,3,4,4a,5,6-hexahydro-
1H-spiro[benzo[c]quinolizine-5,2'-cyclohexane]-
1',3'-dione (VIIc). Yield 0.26 g (68%), mp 228–230°C.
1H NMR spectrum, δ, ppm: 0.68 s (3H, CH3), 1.23 s
(3H, Me), 1.18–12.3 m (2H, 2CH), 1.47–1.59 m (2H,
2CH), 2.14 d.d (1H, CH, J 13.8, 2.1 Hz), 2.27 d.d (1H,
CH, J 13.8, 2.1 Hz), 2.64 d (1H, H4', J 16.9 Hz), 3.11 d
(1H, H6, J 13.3 Hz), 3.11–3.32 m (3H, 3CH), 3.48 d (1H,
H6, J 13.3 Hz), 4.13 d (1H, H4a, J 14.5 Hz), 4.59 d.d (1H,
H1, J 12.2, 3.1 Hz), 6.66 d.d.d (1HAr, J 7.3, 7.4, 1.0 Hz),
6.86 d (1HAr, J 7.9 Hz), 7.00 d.d.d (1HAr, J 7.9, 7.2, 1.3
9-Benzyl-5',5'-dimethyl-2,3,4,4a,5,6-hexahydro-
1H-spiro[benzo[c]quinolizine-5,2'-cyclohexane]-
1',3'-dione (VIIh). Yield 0.36 g (89%), mp 154–156°C.
1H NMR spectrum, δ, ppm: 0.65 C (3H, CH3), 0.82 d.d.d
(1H, H4, J 11.8, 14.2, 12.3 Hz), 1.03 d.d.d.d (1H, H2,
J 14.2, 13.4, 10.1, 2.3 Hz), 1.11 br.d (1H, H2, J 13.4 Hz),
1.19 s (3H, CH3), 1.23 br.d (1H, H4, J 14.2 Hz), 2.06–
2.14 m (1H, H3), 2.08 d (1H, H3', J 17.3 Hz), 2.23 d.d
(1H, CH2Ph, J 13.1, 8.1 Hz), 2.28 d (1H, H6', J 16.9 Hz),
2.42 d.d (1H, CH2Ph, J 13.1, 6.3 Hz), 2.60 d (1H, H6',
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DIASTEREOSELECTIVE SYNTHESIS OF SPIRO DERVATIVES
749
J 16.9 Hz), 3.02 d.d.d (1H, H1, J 11.3, 10.9, 1.8 Hz),
3.05 d (1H, H3', J 17.3 Hz), 3.16 and 3.41 AB (2H,ArCH2,
J 13.4 Hz), 3.98 br.d (1H, H4a, J 14.1 Hz), 4.40 br.d (1H,
H1, J 11.3 Hz), 6.65 d.d.d (1HAr, J 7.4, 8.0, 1.1 Hz),
6.77 d (1HAr, J 8.0 Hz), 6.97 d.d.d (1HAr, J 7.4, 8.0, 1.1
Hz), 7.06 br.d (1HAr, J 7.4 Hz), 7.10 d (2HPh, J 7.1 Hz),
7.16 t (1HPh, J 7.5 Hz), 7.25 d.d (2HPh, J 7.1, 7.5 Hz).
Mass spectrum, m/z (Irel, %): 401 (100) [M]+. Found, %:
C 80.77; H 7.81; N 3.52. C27H31NO2. Calculated, %:
C 80.76; H 7.78; N 3.49.
3,2',2'-Trimethyl-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,5'-dioxane]-4',6'-dione
(VIIIa). Yield 0.17 γ (72%), mp 108–110°C. 1H NMR
spectrum, δ, ppm: 0.93 d.d.d (1H, H4, J 11.9, 11.6,
12.0 Hz), 0.95 d (3H, CH3, J 6.1 Hz), 1.18 d.d.d.d (1H,
H2, J 13.4, 12.6, 13.0, 3.8 Hz), 1.56 br.d (1H, H4,
J 11.6 Hz), 1.70 br.d (1H, H2, J 13.4 Hz), 1.70–1.80 m
(1H, H3), 1.77 s (6H, 2CH3), 2.78 d.d.d (1H, H1, J 12.6,
13.2, 2.8 Hz), 3.22 and 3.27 AB (2H, ArCH2, J 17.1 Hz),
3.39 d.d (1H, H4a, J 11.9, 2.4 Hz), 4.05 br.d (1H, H1,
J 13.2 Hz), 6.63 d.d (1HAr, J 6.3, 8.4 Hz), 6.85 d (1HAr,
J 8.4 Hz), 6.94 d (1HAr, J 7.3 Hz) 7.03 d.d (1HAr, J 6.3,
7.3 Hz). Mass spectrum, m/z (Irel, %): 329 (70) [M]+.
Found, %: C 69.22; H 7.15; N 4.32. C19H23NO4.
Calculated, %: C 69.28; H 7.04; N 4.25.
9-Benzyl-5',5'-dimethyl-9-chloro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,2'-
cyclohexane]-1',3'-dione (VIIi). Yield 0.34 g (78%),
mp 221–233°C. 1H NMR spectrum, δ, ppm: 0.88 d.d.d
(1H, H4, J 11.6, 12.2, 11.6 Hz), 0.71 s (3H, CH3), 1.22 s
(3H, CH3), 1.11 d.d.d.d (1H, H2, J 11.0, 13.4, 10.9,
1.8 Hz), 1.15 br.d (1H, H2, J 13.4 Hz), 1.35 br.d (1H, H4,
J 12.8 Hz), 2.10 d (1H, H3', J 11.7 Hz), 2.08–2.14 m (1H,
H3), 2.24 d (1H, H6', J 17.1 Hz), 2.28 d.d (1H, CH2Ph,
J 15.9, 7.4 Hz), 2.47 d.d (1H, CH2Ph, J 6.0, 15.9 Hz),
2.60 d (1H, H6', J 17.1 Hz), 3.03 d.d.d (1H, H1, J 11.0,
10.9, 1.8 Hz), 3.05 d (H, H6, J 13.7 Hz), 3.11 d (H, H3',
J 11.7 Hz), 3.35 d (H, H6, J 13.7 Hz), 3.63 br.d (1H, H4a,
J 14.0 Hz), 4.15 br.d (1H, H1, J 11.0 Hz), 6.61 d.d (1HAr,
J 1.5, 8.0 Hz), 6.68 d (1HAr, J 1.5 Hz), 7.01 d (1HAr,
J 8.0 Hz), 7.03–7.26 m (5HPh). Mass spectrum, m/z (Irel,
%): 437 (36) [M + 2]+, 435 (100) [M]+. Found, %:
C 74.44; H 6.99; N 3.30. C27H30ClNO2. Calculated, %:
C 74.38; H 6.94; N 3.21.
3,2',2'-Trimethyl-9-chloro-2,3,4,4a,5,6-hexa-
hydro-1H-spiro[benzo[c]quinolizine-5,5'-dioxane]-
4',6'-dione (VIIIb). Yield 0.30 g (83%), mp 208–210°C.
1H NMR spectrum, δ, ppm: 0.94 d.d.d.d (1H, H4, J 12.8,
12.6, 11.6 Hz), 0.95 d (3H, CH3, J 6.1 Hz), 1.16 d.d.d
(1H, H2, J 12.6, 10.1, 3.4 Hz), 1.50–1.80 m (3H, H2, H3,
H4), 1.77 s (6H, 2CH3), 2.83 d.d.d (1H, H1, J 11.0, 10.1,
2.7 Hz), 3.25 and 3.22 AB (2H, ArCH2, J 17.3 Hz),
3.43 d.d (1H, H4a, J 11.6, 2.2 Hz), 4.00 br.d (1H, H1,
J 11.0 Hz), 6.61 d.d (1HAr, J 1.6, J 7.9 Hz), 6.85 d (1HAr,
J 1.6 Hz), 6.94 d (1HAr, J 7.9 Hz). Mass spectrum, m/z
(Irel, %): 365 (30) [M + 2]+, 363 (98) [M]+. Found, %:
C 62.78; H 6.22; N 3.89. C19H22ClNO4. Calculated, %:
C 62.72; H 6.09; N 3.85.
2',2'-Dimethyl-3-phenyl-2,3,4,4a,5,6-hexahydro-
1H-spiro[benzo[c]quinolizine-5,5'-dioxane]-4',6'-
dione (VIIIc). Yield 0.31 g (80%), mp 237–240°C.
1H NMR spectrum (CDCl3), δ, ppm: 1.15 d.d.d (1H, H2,
J 12.8, 12.8, 12.8 Hz), 1.36 d.d.d (1H, H2, J 12.8, 12.8,
4.6 Hz), 1.75 s (3H, CH3), 1.76 s (3H, CH3), 1.72–
1.78 m (1H, H4), 2.50 d.d (1H, H3, J 13.7, 7.8 Hz),
2.60 d.d (1H, H4, J 13.7, 6.0 Hz), 2.72 d.d.d (1H, H1,
J 12.8, 12.8, 2.6 Hz), 3.11 d (1H, H6, J 16.4 Hz), 3.43 d.d
(1H, H4a, J 11.8, 2.4 Hz), 3.52 d (1H, H6, J 16.4 Hz),
4.10 d.d.d (1H, H1, J 12.8, 4.6, 2.6 Hz), 6.74 d.d.d (1HAr,
J 7.4, 7.4, 1.0 Hz), 6.93 d (1HAr, J 8.3 Hz), 6.97 d (1HAr,
J 7.3 Hz), 7.09–7.12 m (2HAr), 7.15 d.d.d (1HAr,
J 8.2, 6.9, 1.3 Hz), 7.19 t.t (1HPh, J 7.4, 1.9 Hz), 7.27 d.d
(2HPh, J 7.4, 7.4 Hz). 13C NMR spectrum (CDCl3), δ,
ppm: 28.20 (Me), 30.28 (Me), 30.62 (C2), 34.56 (C4),
34.72 (C6), 37.63 (C3), 43.00 (C5), 48.27 (C1), 52.21
(OCO), 61.24 (C4a), 113.52 (Ar), 118.49 (Ar), 119.50
(Ar), 126.23 (Ar), 127.67 (Ar), 128.37 (Ar), 128.71 (Ar),
129.06 (Ar), 139.46 (Ar), 144.60 (Ar), 164.78 (CO),
3-Benzyl-9-bromo-5',5'-dimethyl-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,2'-
cyclohexane]-1',3'-dione (VIIj). Yield 0.35 g (72%),
mp 161–164°C. 1H NMR spectrum, δ, ppm: 0.71 s (3H,
CH3), 0.90 d.d (1H, H4, J 12.1, 10.2 Hz), 1.21 s (3H,
CH3), 1.09 d.d.d.d (1H, H2, J 12.9, 11.2, 13.4, 2.4 Hz),
1.20 br.d (1H, H2, J 13.4 Hz), 1.34 br.d (1H, H4, J 12.9
Hz), 2.00–2.12 m (1H, H3), 2.10 d (1H, H3', J 13.4 Hz),
2.23 d (1H, H6', J 12.8 Hz), 2.26 d.d (1H, CH2Ph, J 14.1,
6.8 Hz), 2.49 d.d (1H, CH2Ph, J 14.1, 5.4 Hz), 2.55 d
(1H, H6', J 12.8 Hz), 3.02 d.d.d (1H, H1, J 11.5, 10.9,
1.9 Hz), 3.04 d (1H, H6, J 17.7 Hz), 3.08 d (1H, H6,
J 17.7 Hz), 3.34 d (1H, H3', J 13.4 Hz), 3.90 d.d (1H, H4a,
J 14.8, 2.8 Hz), 4.28 d (1H, H1, J 11.5 Hz), 6.75 d (1HAr,
J 8.0 Hz), 6.82 s (1HAr), 6.96 d (1HAr, J 8.0 Hz), 7.00–
7.29 m (5HPh). Mass spectrum, m/z (Irel, %): 482 (99)
[M + 2]+, 480 (100) [M]+. Found, %: C 67.57; H 6.28;
N 2.21. C27H30BrNO2. Calculated, %: C 67.50; H 6.29;
N 2.92.
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GLUKHAREVA et al.
750
169.28 (CO). Mass spectrum, m/z (Irel, %): 391 (78) [M]+.
Found, %: N 3.55. C24H25NO4. Calculated, %: N 3.58.
quinolizine-5,5'-dioxane]-4',6'-dione (VIIIg). Yield
0.25 g (85%), mp 218–220°C. H NMR spectrum, δ,
1
ppm: 1.42 d.d.d (1H, H4, J 12.2, 13.1, 11.5 Hz), 1.60–
1.80 m (2H, H2, H4), 1.75 s (3H, CH3), 1.79 s (3H, CH3),
1.90 br.d (1H, H2, J 11.9 Hz), 2.89 d.d.d.d (1H, H3,
J 11.9, 12.2, 2.8, 3.1 Hz), 3.08 d.d.d (1H, H1, J 13.1, 10.4,
2.4 Hz), 3.32 and 3.42 AB (2H, ArCH2, J 16.8 Hz),
3.73 d.d (1H, H4a, J 11.5, 2.2 Hz), 4.28 br.d (1H, H1,
J 13.1 Hz), 7.04 d (1HAr, J 8.5 Hz), 7.12–7.35 m (7H, Ph,
ArH). Mass spectrum, m/z (Irel, %): 459 (100) [M]+.
Found, %: C 65.48; H 5.25; N 3.03. C25H24F3NO4.
Calculated, %: C 65.35; H 5.27; N 3.05.
2',2'-Dimethyl-3-phenyl-9-chloro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
dioxane]-4',6'-dione (VIIId). Yield 0.30 g (71%), mp
189–191°C. 1H NMR spectrum, δ, ppm: 1.44 d.d.d (1H,
H4, J 11.8, 13.2, 12.2 Hz), 1.60–1.80 m (2H, H2, H4),
1.73 s (3H, CH3), 1.76 s (3H, CH3), 1.90 br.d (1H, H2,
J 12.2 Hz), 2.82 d.d.d.d (1H, H3, J 12.2, 11.8, 2.8, 3.0 Hz),
3.02 d.d.d (1H, H1, J 12.2, 11.3, 3.0 Hz), 3.27 and 3.28
AB (2H, ArCH2, J 17.0 Hz), 3.63 d.d (1H, H4a, J 11.3,
2.5 Hz), 4.15 br.d (1H, H1, J 13.2 Hz), 6.65 d.d (1HAr,
J 1.8, 8.0 Hz), 6.91 d (1HAr, J 1.8 Hz), 6.96 d (1HAr,
J 8.0 Hz), 7.12–7.29 m (5HPh). Mass spectrum, m/z (Irel,
%): 427 (38) [M + 2]+, 425 (100) [M]+. Found, %: C 67.85;
H 5.44; N 3.33. C24H24ClNO4. Calculated, %: C 67.68;
H 5.68; N 3.29.
9-Benzyl-2',2'-dimethyl-2,3,4,4a,5,6-hexahydro-
1H-spiro[benzo[c]quinolizine-5,5'-dioxane]-4',6'-
dione (VIIIh). Yield 0.36 g (88%), mp 155–157°C.
1H NMR spectrum, δ, ppm: 0.95 d.d.d (1H, H4, J 11.5,
14.9, 12.1 Hz), 1.17 d.d.d.d (1H, H2, J 15.2, 14.9, 9.9,
1.9 Hz), 1.52 br.d (1H, H2, J 15.2 Hz), 1.56 br.d (1H, H4,
J 14.9 Hz), 1.74 s (6H, 2CH3), 1.69–1.84 m (1H, H3),
2.42–2.50 m (2H, CH2Ph), 2.71 d.d.d (1H, H1, J 13.0,
14.9, 2.1 Hz), 3.24 and 3.28 AB (2H, ArCH2, J 17.1 Hz),
3.37 d.d (1H, H4a, J 11.5, 2.3 Hz), 4.05 br.d (1H, H1,
J 14.9 Hz), 6.65 d.d.d (1HAr, J 8.5, 7.9, 1.7 Hz), 6.91 d.d
(1HAr, J 6.9, 1.4 Hz), 6.98 d.d (1HAr, J 7.9, 1.4 Hz),
7.04 d.d.d (1HAr, J 6.9, 8.5, 1.7 Hz), 7.16 d (2HPh,
J 7.0 Hz), 7.18 t (1HPh, J 7.4 Hz), 7.27 d.d (2HPh, J 7.0,
7.4 Hz). Mass spectrum, m/z (Irel, %): 405 (100) [M]+.
Found, %: C 74.08; H 6.92; N 3.49. C25H27NO4.
Calculated, %: C 74.05; H 6.71; N 3.45.
9-Bromo-2',2'-dimethyl-3-phenyl-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
dioxane]-4',6'-dione (VIIIe). Yield 0.30 g (84%), mp
183–186°C. 1H NMR spectrum, δ, ppm: 1.41 d.d.d (1H,
H4, J 13.2, 11.9, 12.2 Hz), 1.60–1.71 m (2H, H2, H4),
1.88 br.d (1H, H2, J 12.5 Hz), 1.74 s (3H, CH3), 1.77 s
(3H, CH3), 2.85 d.d.d.d (1H, H3, J 12.2, 11.6, 3.3, 3.0 Hz),
2.99 d.d.d (1H, H1, J 12.8, 11.3, 3.0 Hz), 3.28 and 3.25
AB (2H, ArCH2, J 17.2 Hz), 3.63 d.d (1H, H1, J 11.2,
2.1 Hz), 4.15 br.d (1H, H1, J 12.8 Hz), 6.78 d.d (1HAr,
J 7.9, 1.2 Hz), 6.92 d (1HAr, J 7.9 Hz), 7.00 d (1HAr,
J 1.2 Hz), 7.12–7.30 m (5HPh). Mass spectrum, m/z (Irel,
%): 472 (98) [M + 2]+, 470 (100) [M]+. Found, %: C 61.51;
H 5.41; N 3.11. C24H24BrNO4. Calculated, %: C 61.29;
H 5.14; N 2.98.
9-Benzyl-2',2'-dimethyl-9-chloro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
dioxane]-4',6'-dione (VIIIi). Yield 77%, mp 175–
177°C. 1H NMR spectrum, δ, ppm: 0.97 d.d.d (1H, H4,
J 11.6, 14.8, 11.9 Hz), 1.23 d.d.d.d (1H, H2, J 11.9, 13.4,
15.2, 7.2 Hz), 1.58 br.d (1H, H2, J 15.2 Hz), 1.70 br.d
(1H, H4, J 14.8 Hz), 1.74–1.86 m (1H, H3), 1.74 s (6H,
2CH3), 2.52 d.d (2H, CH2Ph, J 13.1, 6.6 Hz), 2.56 d.d
(1H, CH2Ph, J 13.1, 7.2 Hz), 2.76 d.d.d (1H, H1, J 13.4,
12.9, 2.3 Hz), 3.20 and 3.22 AB (2H, ArCH2, J 17.2 Hz),
3.39 d.d (1H, H4a, J 11.6, 2.4 Hz), 3.98 br.d (1H, H1,
J 13.4 Hz), 6.61 d.d (1HAr, J 8.2, 1.8 Hz), 6.93 d (1HAr,
J 8.2 Hz), 6.82 d (1HAr, J 1.8 Hz), 7.11 d (2HPh, J 7.3 Hz),
7.15 t (1HPh, J 6.7 Hz), 7.24 d.d (2HPh, J 6.7, 7.3 Hz).
Mass spectrum, m/z (Irel, %): 441 (39) [M + 2]+, 439
(100) [M]+. Found, %: C 68.29; H 5.99; N 3.30.
C25H26ClNO4. Calculated, %: C 68.25; H 5.96; N 3.18.
2',2'-Dimethyl-3-phenyl-9-fluoro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
dioxane]-4',6'-dione (VIIIf). Yield 0.36 g (88%), mp
142–145°C. 1H NMR spectrum, δ, ppm: 1.54 d.d.d (1H,
H4, J 11.0, 12.8, 11.6 Hz), 1.60–1.80 m (2H, H2, H4),
1.69 s (3H, CH3), 1.78 s (3H, CH3), 1.88 d.d.d.d (1H,
H2, J 11.6, 4.0, 3.4, 4.0 Hz), 2.84 d.d.d.d (1H, H3, J 11.6,
11.0, 4.0, 5.8 Hz), 3.00 d.d.d (1H, H1, J 13.6, 12.8, 6.3
Hz), 3.27 and 3.42 AB (2H, ArCH2, J 15.8 Hz), 3.69 d.d
(1H, H4a, J 11.0, 1.9 Hz), 4.36 d.d.d (1H, H1, J 12.8, 3.4,
3.8 Hz), 6.66 d.d.d (1HAr, J 4.8, 7.3, 7.0 Hz), 6.91 d (1HAr,
J 7.3 Hz), 6.86 d.d.d (1HAr, J 7.0, 14.3, 1.2 Hz), 7.12–
7.30 m (5HPh). Mass spectrum, m/z (Irel, %): 409 (100)
[M]+. Found, %: C 70.44; H 5.98; N 3.33. C24H24FNO4.
Calculated, %: C 70.40; H 5.91; N 3.42.
2',2'-Dimethyl-8-trifluoromethyl-3-phenyl-
3-Methyl-1',3'’-diphenyl-2,3,4,4a,5,6-hexahydro-
2,3,4,4a,5,6-hexahydro-1H-spiro[benzo[c]-
1H-spiro[benzo[c]quinolizine-5,5'-pyrimidine]-4',6'-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

DIASTEREOSELECTIVE SYNTHESIS OF SPIRO DERVATIVES
751
spectrum, m/z (Irel, %): 541 (87) [M]+. Found, %: C 77.68;
H 5.79; N 7.88. C35H31N3O3. Calculated, %: C 77.61;
H 5.77; N 7.76.
dione (IXa). Yield 0.35 g (76%), mp 238–240°C. 1H NMR
spectrum, δ, ppm: 0.86 d (3H, CH3, J 6.8 Hz), 1.04 d.d.d
(1H, H4, J 12.8, 1.3, 12.9 Hz), 1.26 br.d (1H, H2,
J 12.8 Hz), 1.45–1.53 m (2H, H2, H4), 1.92–2.01 m (1H,
H3), 3.13 d.d.d (1H, H1, J 11.3, 12.5, 2.3 Hz), 3.05 and
3.45 AB (2H, ArCH2, J 17.1 Hz), 4.11 br.d (1H, H4a,
J 10.8 Hz), 4.15 br.d (1H, H1, J 11.3 Hz), 6.62 d.d (1HAr,
J 7.4, 8.3 Hz), 6.79 d (1HAr, J 8.3 Hz), 6.98 d.d (1HAr,
J 7.3, 7.4 Hz), 7.03 d (1HAr, J 7.3 Hz), 7.23–7.51 m (10H,
2 Ph). Mass spectrum, m/z (Irel, %): 465 (100) [M]+.
Found, %: C 74.95; H 5.87; N 9.18. C29H27N3O3.
Calculated, %: C 74.82; H 5.85; N 9.03.
1',3,3'-Trimethyl-2,3,4,4a,5,6-hexahydro-1H-
spiro[benzo[c]quinolizine-5,5'-pyrimidine]-4',6'-
dione (Xa). Yield 0.25 g (74%), mp 178–180°C. 1H NMR
spectrum, δ, ppm: 0.84 d (3H, CH3, J 6.4 Hz), 1.08 d.d.d
(1H, H4, J 13.1, 11.3, 12.6 Hz), 1.11 d.d.d.d (1H, H2,
J 11.5, 12.8, 10.8, 3.2, 1.8 Hz), 1.32 br.d (1H, H4,
J 12.6 Hz), 1.52 br.d (1H, H2, J 12.8 Hz), 1.59–1.68 m
(1H, H3), 2.88 d.d.d (1H, H1, J 11.3, 13.1, 1.8 Hz), 3.16 s
(3H, CH3), 3.17 s (3H, CH3), 3.01 and 3.28 AB (2H,
ArCH2, J 1.1 Hz), 3.44 d.d (1H, H4a, J 11.3, 1.1),
4.01 d.d.d (1H, H1, J 13.1, 3.2, 1.8 Hz), 6.60 d.d (1HAr,
J 6.8, 8.0 Hz), 6.77 d (1HAr, J 8.0 Hz), 6.95 d (1HAr,
J 6.1 Hz), 6.98 d.d (1HAr, J 6.4, 6.1 Hz). Mass spectrum,
m/z (Irel, %): 341 (100) [M]+. Found, %: C 66.84; H 6.72;
N 12.33. C19H23N3O3. Calculated, %: C 66.84; H 6.79;
N 12.31.
1',3,3'’-Triphenyl-9-chloro-2,3,4,4a,5,6-hexa-
hydro-1H-spiro[benzo[c]quinolizine-5,5'-pyrimi-
dine]-4',6'-dione (IXd). Yield 0.5 g (91%), mp 172–
174°C. 1H NMR spectrum, δ, ppm: 1.47 d.d.d (1H, H2,
J 12.5, 9.8, 12.8 Hz), 1.62–1.75 m (3H, 3CH), 3.00 and
3.02 AB (2H,ArCH2, J 18.9 Hz), 3.20–3.30 m (2H, 2CH),
4.20 br.d (1H, H4a, J 14.0 Hz), 4.48 br.d (1H, H1,
J 10.1 Hz), 6.64 d.d (1HAr, J 8.2, 1.8 Hz), 6.86 d (1HAr,
J 1.8 Hz), 7.04 d (1HAr, J 8.2 Hz), 7.00–7.50 m (15H,
3Ph). Mass spectrum, m/z (Irel, %): 563 (20) [M + 2]+,
561 (65) [M]+. Found, %: C 72.58; H 6.48; N 7.48.
C34H28ClN3O3. Calculated, %: C 72.66; H 5.02; N 7.48.
1',3,3''-Trimethyl-9-chloro-2,3,4,4a,5,6-hexa-
hydro-1H-spiro[benzo[c]quinolizine-5,5'-
pyrimidine]-4',6'-dione (Xa). Yield 0.27 g (72%), mp
188–190°C. 1H NMR spectrum, δ, ppm: 0.82 d.d.d (1H,
H4, J 12.8, 12.8, 12.9 Hz), 0.87 d (3H, CH3, J 6.4 Hz),
1.14 d.d.d (1H, H2, J 12.8, 12.8, 3.0 Hz), 1.35 br.d (1H,
H4, J 12.8 Hz), 1.56 br.d (1H, H2, J 13.4 Hz), 1.63–
1.69 m (1H, H3), 2.87 d.d.d (1H, H1, J 12.8, 13.4,
1.8 Hz), 3.17 c (6H, 2CH3), 3.25 and 2.98 AB (2H,ArCH2,
J 16.7 Hz), 3.47 d.d (1H, H4a, J 11.6, 1.5 Hz), 3.98 br.d
(1H, H1, J 12.8 Hz), 6.60 d.d (1HAr, J 1.8, 8.2 Hz), 6.76 d
(1HAr, J 1.8 Hz), 6.92 d (1HAr, J 8.2 Hz). Mass spectrum,
m/z (Irel, %): 377 (38) [M + 2]+, 375 (100) [M]+. Found,
%: C 60.84; H 6.02; N 11.09. C19H22ClN3O3. Calculated,
%: C 60.72; H 5.90; N 11.18.
1',3,3'’-Triphenyl-8-trifluoromethyl-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
pyrimidine]-4',6'-dione (IXg). Yield 0.49 g (82%), mp
262°C. 1H NMR spectrum, δ, ppm: 1.48 d.d.d (1H, H4,
J 12.5, 11.6, 13.7 Hz), 1.62–1.75 m (3H, 3CH), 3.31 d.d.d.d
(1H, H3, J 12.5, 11.6, 4.5, 2.9 Hz), 3.44 d.d.d (1H, H1,
J 10.7, 11.6, 4.8 Hz), 3.58 and 3.12 AB (2H, ArCH2,
J 17.4 Hz), 4.31 br.d (1H, H4a, J 13.7 Hz), 4.57 br.d (1H,
H1, J 10.7 Hz), 7.00 d (1HAr, J 8.8 Hz), 7.08–7.50 m
(17H, 3Ph, ArH). Mass spectrum, m/z (Irel, %): 595 (100)
[M]+. Found, %: C 70.58; H 4.77; N 7.04. C35H28F3N3O3.
Calculated, %: C 70.58; H 4.74; N 7.05.
1',3''-Dimethyl-3-phenyl-9-chloro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
pyrimidine]-4',6'-dione (Xd). Yield 0.34 g (77%), mp
204–206°C. 1H NMR spectrum, δ, ppm: 1.28 d.d.d (1H,
H2, J 12.8, 12.0, 11.8 Hz), 1.52 br.d (1H, H2, J 12.5 Hz),
1.58–1.79 m (2H, 2CH), 2.80–3.00 m (1H, CH), 3.16 s
(6H, 2CH3), 3.10–3.20 m (1H, CH), 2.98 and 3.31 AB
(2H, ArCH2, J 17.0 Hz), 3.72 br.d (1H, H4a, J 9.8 Hz),
4.12 br.d (1H, H1, J 13.7 Hz), 6.62 d.d (1HAr, J 6.7,
1.6 Hz), 6.84 d (1HAr, J 1.6 Hz), 6.97 d (1HAr, J 6.7 Hz),
7.06–7.25 m (5HPh). Mass spectrum, m/z (Irel, %): 439
(30) [M + 2]+, 437 (87) [M]+. Found, %: C 65.55; H 5.80;
N 9.69. C24H24ClN3O3. Calculated, %: C 65.83; H 5.52;
N 9.60.
3-Benzyl-1',3'’-diphenyl-2,3,4,4a,5,6-hexahydro-
61-spiro[benzo[c]quinolizine-5,5'-pyrimidine]-4',6'-
dione (IXh). Yield 0.47 g (86%), mp 232–234°C.
1H NMR spectrum, δ, ppm: 0.97 d.d.d (1H, H4, J 11.7,
12.4, 10.9 Hz), 1.24 d.d.d.d (1H, H2, J 11.4, 13.5, 10.1,
2.8 Hz), 1.45 br.d (1H, H2, J 13.2 Hz), 1.53 br.d (1H, H4,
J 12.5 Hz), 2.20–2.30 m (1H, H3), 2.33 d.d (1H, CH2Ph,
J 9.2, 12.9 Hz), 2.62 d.d (1H, CH2Ph, J 5.1, 12.9 Hz),
3.16 d.d.d (1H, H1, J 14.8, 12.8, 2.8 Hz), 3.02 and 3.40
AB (2H, ArCH2, J 17.3 Hz), 4.10 br.d (1H, H4a,
J 10.9 Hz), 4.12 br.d (1H, H1, J 14.8 Hz), 6.64 d.d.d
(1HAr, J 6.7, 7.8, 0.7 Hz), 6.87 br.d (1HAr, J 8.1 Hz),
6.98–7.08 m (4HPh), 7.12–7.47 m (13H, Ph, ArH). Mass
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

GLUKHAREVA et al.
752
3-Benzyl-1',3'’-dimethyl-9-chloro-2,3,4,4a,5,6-
1',3''-Dimethyl-3-phenyl-9-fluoro-2,3,4,4a,5,6-
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
pyrimidine]-4',6'-dione (Xi). Yield 0.35 g (78%), mp
151–154°C. H NMR spectrum, δ, ppm: 0.89 d.d (1H,
hexahydro-1H-spiro[benzo[c]quinolizine-5,5'-
pyrimidine]-4',6'-dione (Xf). Yield 0.39 g (89%), mp
187–189°C. 1H NMR spectrum, δ, ppm: 1.47 d.d.d (1H,
H2, J 11.6, 12.5, 11.8 Hz), 1.62 br.d (1H, H2, J 14.0 Hz),
1.70–1.82 m (2H, H2, H4), 2.80–3.00 m (1H, H1), 3.12 s
(3H, CH3), 3.21 s (3H, CH3), 3.10–3.20 m (1H, H3), 3.23
and 3.08 AB (2H, ArCH2, J 16.9 Hz), 3.69 d.d (1H, H4a,
J 11.0, 1.9 Hz), 4.36 d.d.d (1H, H1, J 12.8, 3.4, 3.8 Hz),
6.61 d.d (1HAr, J 4.8, 7.2 Hz), 6.82 d.d (1HAr, J 7.2,
1.8 Hz), 6.87 d.d.d (1HAr, J 7.2, 14.3, 1.8 Hz), 7.09–
7.32 m (5HPh). Mass spectrum, m/z (Irel, %): 439 (30)
[M + 2]+, 437 (87) [M]+. Found, %: C 65.55; H 5.80;
N 9.69. C24H24ClN3O3. Calculated, %: C 65.83; H 5.52;
N 9.60.
1
H4, J 11.5, 12.9 Hz), 1.15 d.d.d.d (1H, H2, J 12.6, 12.5,
9.9, 1.8 Hz), 1.45 br.d (1H, H4, J 12.9 Hz), 1.50 br.d (1H,
H2, J 12.6 Hz), 1.68–1.89 m (1H, H3), 2.33 d.d (1H,
CH2Ph, J 13.4, 7.9 Hz), 2.52 d.d (1H, CH2Ph, J 13.4,
7.9 Hz), 2.77 d.d.d (1H, H1, J 12.9, 12.7, 1.8 Hz), 3.13 s
(3H, CH3), 3.13 s (3H, CH3), 3.08 and 3.21 AB (2H,
ArCH2, J 17.0 Hz), 3.41 d.d (1H, H4a, J 11.5, 1.8 Hz),
3.95 br.d (1H, H1, J 12.5 Hz), 6.60 d.d (1HAr, J 7.9,
1.6 Hz), 6.75 d (1HAr, J 1.6 Hz), 6.93 d (1HAr, J 7.9 Hz)
7.03–7.26 m (5HPh). Mass spectrum, m/z (Irel, %): 453
(41) [M + 2]+, 451 (97) [M]+. Found, %: C 66.52; H 5.80;
N 9.45. C25H26ClN3O3. Calculated, %: C 66.44; H 5.80;
N 9.30.
1',3'’-Dimethyl-8-trifluoromethyl-3-phenyl-
2,3,4,4a,5,6-hexahydro-1H-spiro[benzo[c]quino-
lizine-5,5'-pyrimidine]-4',6'-dione (Xg). Yield 0.38 g
2-[2-(4-R-Piperidino)benzylidene]malononitriles
XIa–XIc. To a solution of 1 mmol of benzaldehyde IVa,
IVg, and IVh in 10 ml of toluene was added 1 mmol of
malononitrile, and the mixture was boiled for 3–6 h (TLC
monitoring). The reaction mixture was cooled to room
temperature, the solvent was evaporated in a vacuum,
the residue was ground with ethanol.
1
(80%), mp 224–226°C. H NMR spectrum, δ, ppm:
1.28 d.d.d (1H, H4, J 12.5, 10.7, 11.8 Hz), 1.52 br.d (1H,
H2, J 12.5 Hz), 1.64 br.d (H, H4, J 13.7 Hz), 1.65 br.d (H,
H2, J 11.6 Hz), 2.92 d.d.d.d (1H, H3, J 11.6, 10.7, 4.2,
3.2 Hz), 3.16 s (3H, CH3), 3.17 s (3H, CH3), 3.10–
3.20 m (1H, H1), 3.05 and 3.32 AB (2H, ArCH2,
J 17.1 Hz), 3.82 br.d (1H, H4a, J 10.0 Hz), 4.25 br.d (1H,
H1, J 13.7 Hz), 6.98 d (1HAr, J 8.5 Hz), 7.06–7.32 m (7H,
Ph, ArH). Mass spectrum, m/z (Irel, %): 471 (100) [M]+.
Found, %: C 63.77; H 5.18; N 9.09. C25H24F3N3O3.
Calculated, %: C 63.69; H 5.13; N 8.91.
2-[2-(4-Methylpiperidino)benzylidene]-
malononitrile (XIa). Yield 0.22 g (88%), mp 105–108°C.
1H NMR spectrum, δ, ppm: 1.90–2.09 m (4H, 2CH2),
2.60–2.70 m (1H, CH), 2.94–3.05 m (2H, 2NCH), 3.20–
3.25 m (2H, 2NCH), 7.03 d.d (1HAr, J 7.9, 1.4 Hz),
7.14 d (1HAr, J 8.4 Hz), 7.58 d.d.d (1HAr, J 8.4, 8.1,
1.4 Hz), 7.94 d.d (1HAr, J 8.1, 7.9), 8.12 s (1H, CH=).
Mass spectrum, m/z (Irel, %): 251 (100) [M]+. Found, %:
C 76.47; H 6.85; N 16.40. C16H17N3. Calculated, %:
C 76.46; H 6.82; N 16.72.
3-Benzyl-1',3'’-dimethyl-2,3,4,4a,5,6-hexahydro-
1H-spiro[benzo[c]quinolizine-5,5'-pyrimidine]-
4',6'-dione (Xh). Yield 0.38 g (91%), mp 220–222°C.
1H NMR spectrum, δ, ppm: 0.95 d.d.d (1H, H4, J 11.7,
14.4, 11.4 Hz), 1.09 d.d.d.d (1H, H2, J 11.4, 13.2, 13.6,
4.1 Hz), 1.35 br.d (1H, H2, J 13.0 Hz), 1.39 br.d (1H, H4,
J 14.4 Hz), 1.75–1.88 m (1H, H3), 2.36 d.d (1H, CH2Ph,
J 7.9, 13.4 Hz), 2.46 d.d (1H, CH2Ph, J 7.6, 13.4 Hz),
2.72 d.d.d (1H, H1, J 13.1, 13.6, 2.8 Hz), 3.08 s (3H,
CH3), 3.10 s (3H, CH3), 3.05 and 3.26 AB (2H, ArCH2,
J 17.2 Hz), 3.42 d.d (1H, H4a, J 11.7, 1.6 Hz), 4.00 d.d.d
(1H, H1, J 13.1, 4.1, 2.8 Hz), 6.65 d.d.d (1HAr, J 6.5, 7.4,
1.7 Hz), 6.84 d.d (1HAr, J 8.1, 1.4 Hz), 7.00 d.d (1HAr,
J 7.4, 1.4 Hz), 7.01 d.d.d (1HAr, J 6.5, 8.1, 1.7 Hz),
7.10 d.d (2HPh, J 7.0, 8.2 Hz), 7.17 t (1HPh, J 7.6 Hz),
7.26 d.d.d (2HPh, J 7.0, 8.2, 7.6 Hz). Mass spectrum, m/z
(Irel, %): 417 (100) [M]+. Found, %: C 71.97; H 6.52;
N 10.04. C25H27N3O3. Calculated, %: C 71.92; H 6.52;
N 10.06.
2-[2-(4-Benzylpiperidino)benzylidene]-
malononitrile (XIb). Yield 0.12 g (90%), mp 105–107°C.
1H NMR spectrum, δ, ppm: 1.48–1.78 m (2H, 2CH),
1.82–2.94 m (3H, 3CH), 2.61 d (2H, CH2Ph, J 6.4 Hz),
2.79 d.d (2H, 2NCH, J 11.3, 11.9 Hz), 3.09 br.d (2H,
2NCH, J 11.9 Hz), 7.10–7.18 m (7H, Ph, ArH), 7.54 d.d
(1HAr, J 7.9, 7.6 Hz), 7.94 d (1HAr, J 7.3 Hz), 8.14 s (1H,
CH=). Mass spectrum, m/z (Irel, %): 327 (100) [M]+.
Found, %: C 80.75; H 6.47; N 12.88. C22H21N3.
Calculated, %: C 80.70; H 6.46; N 12.83.
2-[2-(4-Phenylpiperidino)-5-trifluoromethyl-
benzylidene]malononitrile (XIc). Yield 0.34 g (89%),
1
mp 111–112°C. H NMR spectrum, δ, ppm: 1.90–
2.08 m (4H, 2CH2), 2.69–2.75 m (1H, CH), 2.97–3.16 m
(2H, 2NCH), 3.33–3.42 m (2H, 2NCH), 7.10–7.30 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

DIASTEREOSELECTIVE SYNTHESIS OF SPIRO DERVATIVES
753
(5HAr), 7.35 d (1HAr, J 8.8 Hz), 7.79 d.d (1HAr, J 8.8,
2.2 Hz), 8.16 br.s (1HAr), 8.25 s (1H, CH=). Mass
spectrum, m/z (Irel, %): 381 (100) [M]+. Found, %:
C 69.25; H 4.75; N 11.32. C22H18F3N3. Calculated, %:
C 69.28; H 4.76; N 11.02.
2.7 Hz), 6.73 d.d (1HAr, J 7.5, 7.5 Hz), 6.75 d.d (1HAr,
J 6.9, 7.5 Hz), 6.98 d (1HAr, J 7.5 Hz), 7.09 d (1HAr,
J 6.9 Hz), 7.19 d (2HPh, J 7.1 Hz), 7.22 t (1HPh,
J 7.3 Hz), 7.30 d.d (2HPh, J 7.1, 7.3 Hz). Mass spectrum,
m/z (Irel, %): 327 (100) [M]+. Found, %: C 80.88; H 6.49;
N 12.93. C22H21N3. Calculated, %: C 80.70; H 6.46;
N 12.83.
Quinolizinedicarbonitriles XIIa–XIIc, XIIIa–
XIIIc. Asolution of 2 mmol of compound XI in 20 ml of
butanol was boiled for 2–10 h (TLC monitoring). The
reaction mixture was cooled to room temperature, the
solvent was evaporated in a vacuum, the residue was
ground with ethanol.
(3R*,4aR*)-3-Benzyl-2,3,4,4a,5,6-hexahydro-
1H-benzo[c]quinolizine-5,5-dicarbonitrile (XIIIb).
Yield 0.21 g (38%), mp 107–109°C. 1H NMR spectrum,
δ, ppm: 1.20–1.30 m (2H, H2, H4), 1.88 br.d (1H, H4,
J 13.5 Hz), 1.80–1.90 m (1H, H3), 2.17 d.d (1H, H2,
J 12.1, 1.6 Hz), 2.55 d.d (1H, CH2Ph, J 7.5, 13.3 Hz),
2.69 d.d (1H, CH2Ph, J 6.5, 13.3 Hz), 2.73 d.d.d (1H, C1,
J 11.3, 10.1, 2.5 Hz), 3.53 d.d (1H, H4a, J 12.7, 2.5 Hz),
3.47 and 3.58 AB (2H, ArCH2, J 16.1 Hz), 4.02 d.d.d
(1H, H1, J 11.3, 2.3, 2.8 Hz), 6.73 d.d (1HAr, J 7.0,
7.1 Hz), 6.92 d (1HAr, J 7.1 Hz), 7.00 d (1HAr, J 7.6 Hz),
7.13 d.d (1HAr, J 7.6, 7.0 Hz), 7.19 d (2HPh, J 8.2 Hz),
7.23 t (1HPh, J 7.2 Hz), 7.28 d.d (2HPh, J 8.2, 7.2 Hz).
Mass spectrum, m/z (Irel, %): 327 (100) [M]+. Found, %:
C 80.88; H 6.49; N 12.93. C22H21N3. Calculated, %:
C 80.98; H 6.49; N 13.08.
(3S*,4aR*)-3-Methyl-2,3,4,4a,5,6-hexahydro-
1H-benzo[c]quinolizine-5,5-dicarbonitrile (XIIa).
Yield 0.12 g (44%), mp 106–108°C. 1H NMR spectrum,
δ, ppm: 1.05 d (3H, CH3, J 6.3 Hz), 1.27 d.d.d (1H, H4,
J 11.3, 12.1, 12.5 Hz), 1.74–2.00 m (2H, H4, H2),
2.12 br.d (1H, H2, J 12.2 Hz), 2.22–2.29 m (1H, H3),
2.77 d.d.d (1H, H1, J 13.1, 12.5, 2.5 Hz), 3.47 and 3.61
AB (2H, ArCH2, J 15.5 Hz), 3.78 d.d (1H, H4a, J 11.3,
4.0 Hz), 4.03 d.d.d (1H, H1, J 13.1, 5.1, 2.6 Hz), 6.74 d.d
(1HAr, J 8.6, 9.2 Hz), 6.95 d (1HAr, J 8.2 Hz), 7.07 d
(1HAr, J 9.2 Hz), 7.14 d.d (1HAr, J 8.2, 8.6 Hz). Mass
spectrum, m/z (Irel, %): 251 (100) [M]+. Found, %:
C 76.54; H 6.85; N 16.78. C16H17N3. Calculated, %:
C 76.46; H 6.82; N 16.72.
(3S*,4aR*)-8-Trifluoromethyl-3-phenyl-
2,3,4,4a,5,6-hexahydro-1H-benzo[c]quinolizine-5,5-
dicarbonitrile (XIIc). Yield 0.30 g (39%), mp 109°C.
1H NMR spectrum, δ, ppm: 2.21–2.35 m (2H, 2CH),
2.52–2.62 m (2H, 2CH), 3.19 d.d.d.d (H, CHPh,
J 5.8, 4.5, 2.5, 1.2 Hz), 3.37 d.d.d (1H, H1, J 6.3, 12.5,
10.5 Hz), 3.63 and 3.73 AB (2H, ArCH2, J 16.5 Hz),
3.84 d.d (1H, H1, J 12.3, 2.0 Hz), 4.08 d.d (1H, H4a,
J 11.3, 3.6 Hz) 7.10–7.42 m (7HAr), 7.03 d (1HAr,
J 8.8 Hz). Mass spectrum, m/z (Irel, %): 381 (100) [M]+.
Found, %: C 69.33; H 4.65; N 11.11. C22H18F3N3.
Calculated, %: C 69.28; H 4.76; N 11.02.
(3R*,4aR*)-3-Methyl-2,3,4,4a,5,6-hexahydro-
1H-benzo[c]quinolizine-5,5-dicarbonitrile (XIIIa).
Yield 0.20 g (40%), mp 107–109°C. 1H NMR spectrum,
δ, ppm: 1.13 d (3H, CH3, J 7.0 Hz), 1.62 br.d (1H, H2,
J 14.2 Hz), 1.89 d.d.d (1H, H4, J 14.2, 12.5, 3.0 Hz),
1.94–2.05 m (2H, H4, H2), 2.22–2.29 m (1H, H3),
3.02 d.d.d (1H, H1, J 13.6, 12.5, 3.1 Hz), 3.70 and 3.52
AB (2H, ArCH2, J 15.8 Hz), 3.77 d.d.d (1H, H1, J 11.6,
5.5, 4.2 Hz), 3.80 d.d (1H, H4a, J 10.5, 2.8 Hz), 6.74 d.d
(1HAr, J 8.6, 9.2 Hz), 6.95 d (1HAr, J 8.2 Hz), 7.07 d
(1HAr, J 9.2 Hz), 7.14 d.d (1HAr, J 8.2, 8.6 Hz). Mass
spectrum, m/z (Irel, %): 251 (100) [M]+. Found, %:
C 76.49; H 6.95; N 16.89. C16H17N3. Calculated, %:
C 76.46; H 6.82; N 16.72.
(3R*,4aR*)-8-Trifluoromethyl-3-phenyl-
2,3,4,4a,5,6-hexahydro-1H-benzo[c]quinolizine-5,5-
dicarbonitrile (XIIIc). Yield 0.30 g (39%), mp 105–
(3S*,4aR*)-3-Benzyl-2,3,4,4a,5,6-hexahydro-
1H-benzo[c]quinolizine-5,5-dicarbonitrile (XIIb).
Yield 0.21 g (32%), mp 112–113°C. 1H, δ, ppm: 1.66 br.d
(1H, H4, J 13.1 Hz), 1.78 d.d.d (1H, H4, J 14.9, 2.7,
2.1 Hz), 1.88 d.d.d.d (1H, H2, J 14.9, 15.0, 10.0, 4.3 Hz),
2.03 br.d (1H, H2, J 13.7 Hz), 2.20–2.40 m (1H, H3),
2.69 d.d (1H, CH2Ph, J 7.2, 11.1 Hz), 2.81 d.d (1H, CH2Ph,
J 6.1, 11.1 Hz), 3.12 d.d.d (1H, H1, J 11.6, 12.2, 2.7 Hz),
3.68 and 3.49 AB (2H, ArCH2, J 16.2 Hz), 3.80 d.d.d
(1H, H1, J 12.2, 3.0, 4.3 Hz), 3.97 d.d (1H, H4a, J 13.9,
1
106°C. H NMR spectrum, δ, ppm: 2.21–2.35 m (2H,
2CH), 2.52–2.62 m (2H, 2CH), 3.00 d (1H, CHPh,
J 10.8, 14.3 Hz), 3.38 d.d.d.d (1H, H1, J 10.8, 12.2, 3.2,
1.8 Hz), 3.68 and 3.84 AB (2H, ArCH2, J 12.3 Hz),
3.95 d.d (1H, H4a, J 10.8, 2.0 Hz), 4.28 br.d (1H, H1,
J 12.8 Hz), 7.03 d (1HAr, J 8.8 Hz), 7.10–7.42 m (7HAr).
Mass spectrum, m/z (Irel, %): 381 (100) [M]+. Found, %:
C 69.25; H 4.75; N 11.32. C22H18F3N3. Calculated, %:
C 69.28; H 4.76; N 11.02.
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GLUKHAREVA et al.
ma, S., Heesink, G.J.T., Lehmusvaara, E., van Hulst, N.F.,
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