Synthesis of 1-substituted 2-azaspiro[4.5]deca-6,9-diene-8-ones and 2-azaspiro[4.5]deca-1,6,9-triene-8-ones by a three-component condensation of 1,2,3-, 1,2,4- or 1,3,5-trimethoxybenzene with isobutyric aldehyde and nitriles

Article abstract of DOI:10.1016/j.tet.2009.11.055

A three-component condensation of 1,2,3- or 1,2,4-trimethoxybenzene with isobutyric aldehyde and alkyl cyanoacetates in the presence of sulfuric acid resulted in the formation of substituted 2-azaspiro[4.5]deca-6,9-diene-8-ones. The same reaction of aromatic nitriles yielded 2-azaspiro[4.5]deca-1,6,9-triene-8-ones; in the case of 1,2,3-trimethoxybenzene corresponding Ritter amides were also observed. The condensation of 1,3,5-trimethoxybenzene with isobutyric aldehyde and alkyl cyanoacetates provided the compounds of the formal Kn?evenagel condensation.

Full text of DOI:10.1016/j.tet.2009.11.055

Tetrahedron 66 (2010) 721–729
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 1-substituted 2-azaspiro[4.5]deca-6,9-diene-8-ones and
2-azaspiro[4.5]deca-1,6,9-triene-8-ones by a three-component condensation of
1,2,3-, 1,2,4- or 1,3,5-trimethoxybenzene with isobutyric aldehyde and nitriles
,
a
a
a
Vladimir A. Glushkova , Olga G. Stryapunina , Alexey A. Gorbunov , Olga A. Maiorova ,
Pavel A. Slepukhin b, Sandra Ya. Ryabukhina c, Elena V. Khorosheva c, Valentina I. Sokol a,
Yurii V. Shklyaeva
*
a Institute of Technical Chemistry, Urals Branch of the Russian Academy of Sciences, Academician Korolev Street 3, Perm 614013, Russia
b I. Ya. Postovsky Institute of Organic Synthesis, Urals Branch of the Russian Academy of Sciences, S. Kovalevskoy Street 22, Ekaterinburg 620041, Russia
c Perm State University, Bukireva Street 15, Perm 614990, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A three-component condensation of 1,2,3- or 1,2,4-trimethoxybenzene with isobutyric aldehyde and
alkyl cyanoacetates in the presence of sulfuric acid resulted in the formation of substituted
2-azaspiro[4.5]deca-6,9-diene-8-ones. The same reaction of aromatic nitriles yielded 2-azaspiro[4.5]deca-
1,6,9-triene-8-ones; in the case of 1,2,3-trimethoxybenzene corresponding Ritter amides were also
observed. The condensation of 1,3,5-trimethoxybenzene with isobutyric aldehyde and alkyl cyanoacetates
provided the compounds of the formal Kno¨evenagel condensation.
Received 28 May 2009
Received in revised form
24 October 2009
Accepted 12 November 2009
Available online 15 November 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
1,3,5-Trimethoxybenzene
Nitriles
2-Azaspiro[4.5]deca-6,9-diene-8-ones
Three-component condensation
1. Introduction
2. Results and discussion
The 2-azaspiro[4.5]decane skeleton is found in natural products
(alkaloids spirostaphylotrichin A1 and annosqualine2); some azas-
pirocyclic derivatives are immunomodulators3 or HIV-1 protease
inhibitors.4 Current synthetic methods leading to 2-azaspiro
[4.5]decanes and 2-azaspiro[5.5]undecanes include radical
cyclizations of chloroacetamides,5 N-allylamides6 or para-
methoxybenzylamides,7 acid-catalyzed cyclizations of aromatic
diazoacetamides,8 intramolecular Heck reaction.9 Last years some
new synthetic approaches to azaspirocyclization were introduced:
one-pot Lewis acid or site-isolated base–acid-catalyzed cycliza-
tions,10 the Pummerer reaction,11 olefin metathesis,12 ipso-iodo-
cyclization,13 multicomponent reactions,14 cyclization of Fe–diene
complexes,15 dearomatization of Ru complexes.16 Sometimes
2-azaspiro[4.5]decanes appeared as the intermediates in the
synthesis of isoquinolines.17
Most of the above-mentioned methods are based on the
dearomatization of suitable aromatic substrates. Recently we have
introduced
a new protocol for the construction of 2-aza-
spiro[4.5]deca-6,9-diene-8-one framework by a three-component
[C2þC2þCN] domino condensation of anisole with dicarbon
synthon (isobutyric aldehyde or isobutylene oxide) and nitriles in
the presence of concentrated sulfuric acid.18 This original one-pot
approach resulted in the formation of the substituted 2-aza-
spiro[4.5]deca-6,9-diene-8-ones in good yields from the simple
starting aromatic compounds. 2-Methylanisole19 or 1-methoxy,
and 2-methoxynaphthalenes20 were also successfully involved in
this transformation. In a similar manner 2-azaspiro[5.5]undecanes
can be synthesized.21 It was found that the result of the three-
component condensation depended on the character of the
aromatic compound: in the case of veratrole or 1,4-dimethoxy-
benzene the reaction gave rise to substituted 3,4-dihy-
droisoquinolines.22 Here we report the extension of this
methodology to 1,2,3-, 1,2,4- and 1,3,5-trimethoxybenzene. The
aim of present work was to evaluate the influence of the
* Corresponding author. Tel.: þ7 342 2378266; fax: þ7 342 2378272.
E-mail address: glusha55@gmail.com (V.A. Glushkov).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.055

722
V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
substitution pattern of the aromatic moiety in this three-compo-
nent condensation. The same reaction of anisole is also discussed.
In all these cases nucleophilic attack of water on the transient
intermediate B is responsible for spirane formation.26
Part of this work has been the subject of
a
preliminary
Compounds 1a,b and 2a,b exist in an enamine form, which was
communication.23
confirmed by 1H NMR spectrum analysis. Enamines 1a,b and 2a,b
We have tested methylcyanoacetate, ethyl cyanoacetate, meth-
ylthiocyanate, and aromatic nitriles. In some cases (compounds
13a–c) better results were obtained when we used 2,2-dimethyl-
oxirane (isobutylene oxide) as a dicarbon synthon. 2,2-Dimethyl-
oxirane is known to convert into isobutyric aldehyde (undergo the
Meinwald rearrangement) under the reaction conditions.18a,24,25
The proposed mechanism of the reaction was discussed
previously.18 Anisole, isobutyric aldehyde, and alkyl cyanoacetates
afforded 2-azaspiro[4.5]decanes 1a,b (Scheme 1). The structure of
compound 1b was unambiguously confirmed by the single-crystal
X-ray diffraction analysis (Fig. 1).
showed the singlet of an unsaturated proton ]CH
and broadened singlet at 7.91–7.99 ppm (NH). Protons C(9)H,
C(10)Hof thecyclohexadienoneringresonate at 6.03 and6.45 ppm,
respectively (J¼9.6 Hz). Compounds 2a,b are formed as a mixture
(1:1) of enantiomers relative to the spiro-C(5) atom; as a conse-
quence diastereotopic protons H2C(4) resonate as two discrete
d 4.18–4.23 ppm
d
d
doublets at
d 1,95 and 2.35 ppm (J 14 Hz). The (Z)-configuration of
compounds 2a,b is due to an intramolecular hydrogen bond (IHB).
Indeed, the absorption band of the ester group in the IR spectra of
2a,b is shifted to the low-frequency region (1640–1656 cmꢀ1), which
indicates the existence of IHB between the carbonyl and NH group.
OMe
Me
Me
Me
Me
Me
Me
Me Me
MeO
H2O
MeO
RO2CCH2C
O
H2SO4
N
N
-MeOH
-H
H
N
+
CHO
C
CH2CO2R
H
H
O
H
O
N
O
O
R
R
1a
R = Me, 53%
1b R = Et, 30%
Scheme 1.
The two-component condensation of alkyl cyanoacetates with
alcohol C afforded spiranes 2a,b, while the same reaction of alcohol
D27 gave isoquinolines 3a,b exclusively (Scheme 3).
OMe OH
MeO
O
OMe
Me
Me
NCCH2CO2R
H2SO4
MeO
MeO
Me
NH
Me
H
CO2R
C
2a R = Me, 48%
2b R = Et, 55%
OH
MeO
Me
NCCH2CO2R
H2SO4
MeO
MeO
Me
Me
NH
Me
MeO
OMe
OMe
CO2R
D
3a R = Me, 42%
3b R = Et, 46%
Scheme 3.
Isoquinolines 3a,b were not formed in the three-component
condensation (Scheme 2), but 3a,b were the main products of the
two-component reaction of alcohol D (Scheme 3). After the corre-
lation of these results we reached the conclusion that the pro-
tonated isobutyric aldehyde attacks 1,2,3-trimethoxybenzene
exclusively at C(4) position of the aromatic ring.
Figure 1. Structure of compound 1b.
The three-componentcondensation of 1,2,3-trimethoxybenzene,
isobutyric aldehyde, and alkyl cyanoacetates in the presence of
concentrated sulfuric acid afforded 2-azaspiro[4.5]deca-6,9-diene-
8-ones (2a,b) (Scheme 2).
OMe
MeO
MeO
H2O
OMe
MeO
MeO
OMe
MeO
O
OMe
Me
Me
MeO
MeO
Me
Me
Me Me
CHO
Me
Me
H2SO4
N
- MeOH
- H
N
H
N
+
H
RO2CCH2C
H
O
H
O
N
C
CH2CO2R
B
A
O
O
R
R
2a
R = Me, 37%
2b R = Et, 52%
Scheme 2.

V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
723
Methylthiocyanate reacts in much the same way (Scheme 4), but
some quantity of a corresponding isoquinoline 5 was still obtained,
along with a condensation product 6.
and methyl (benzyl) thiocyanates afforded unequivocally spiranes
9a,b, formed as a mixture of enantiomers (1:1) at the spiro-C(5)
atom (Scheme 7).
OMe
OMe
MeO
O
OMe
MeO
OMe
OMe
Me
Me
MeO
MeO
Me
Me
MeO
MeO
Me
+
Me
+
+
H2SO4
N
N
CHO
MeO
OMe
Me
MeS
OMe
Me
SMe
N
C
SMe
4
73%)
6
5
(20%)
(3%)
Scheme 4.
In a similar manner, alcohols C,D react with methylthiocyanate
(Scheme 5). Alcohol C afforded spirane 5; isoquinoline 6 was
a minor product (4% yield); the mixture was separated by column
chromatography. Alcohol D gave isoquinoline 7 exclusively, due to
the interplay of the two methoxy groups.
OMe
Me
Me
MeO
MeO
OMe
+
Me Me
CHO
O
N
H2SO4
MeO
S
N C SR
R
9a R = Me, 55%
9b R = Bn, 15%
OMe
MeO
O
OMe
MeO
MeO
Me
Me
Me
Me
N C SMe
H2SO4
+
Scheme 7.
C
N
N
MeS
SMe
1,3,5-Trimethoxybenzene was found to react with alkyl cya-
noacetates in an unusual way: besides the spiranes 10a,b (yields
26–36%), the products of a four-component condensation 11a,b
(18–25%) were isolated, which can be regarded as a result of formal
Kno¨evenagel condensation (Scheme 8). Compounds 11a,b have
been characterized by 1H NMR spectra and by single-crystal X-ray
crystallography (for 11b, Fig. 2).
5
(4%)
4
(73%)
MeO
MeO
Me
Me
N C SMe
H2SO4
D
N
OMe SMe
7 (53%)
Scheme 5.
H2O
a
MeO
OMe
Me
OMe
Me
Me
Me
CHO
Next, the reactions of 1,2,4-trimethoxybenzene were studied.
Spiranes 8a,b were found to be the single products of the three-
component condensation with isobutyric aldehyde and alkyl cya-
noacetates (Scheme 6).
MeO
H2SO4
NH
+
OMe
NC
b
O
O
O
Me
O
N C CH2COOR
E
O
R
R
OMe
Me
a
MeO
MeO
OMe
+
Me Me
CHO
b
O
Me
H
N
H2SO4
Me
Me
MeO
N C CH2CO2R
H
O
Me
O
O
Me
N
Me
NH
Me
NH
O
O
R
O
8a
8b
R = Me, 50%
R = E , 39%
O
R
O
O
O
O
Me
Me
O
O
Scheme 6.
R
R
11a
10a
R = Me (18%)
R = Et (25%)
R = Me (36%)
11b
10b
R = Et (26%)
As for spiranes 1 and 2, compounds 8a,b exist in an enamine
Scheme 8.
form (1H NMR spectra showed one singlet of unsaturated proton
]CH
d 5.46–5.55 ppm and a broad singlet at d 8.00–8.27 ppm
(NH)). Compounds 8a,b form a mixture (1:1) of enantiomers rela-
tive to the spiro-C(5) atom, as it was previously found for spiranes
2a,b, and the diastereotopic protons H2C(4) gave two discrete
doublets at
spiranes 8a,b.
It is evident that the initially formed spiro-intermediate E is
attacked by the alkyl cyanoacetate as a nucleophile (Scheme 8).
Such an uncommon behavior can be explained by the two com-
petitive reaction pathways a and b (Scheme 8) and the high sta-
bility (along with relatively strong electrophilicity) of the
intermediate E (carbocations on the base of 1,3,5-trimethoxy-
benzene usually can be regarded as the species of high stability28).
It should be mentioned that in the case of 1,2,3-trimethoxy-
benzene, the corresponding Kno¨evenagel products were barely
observed. According to our results, 1,2,4-trimethoxybenzene was
not inclined to react by route b. This fact can be explained by
electron-donating properties of the ortho-methoxy group; the
steric bulk of this substituent must also be taken into account.
d
1,95 and 2.35 ppm (J 14 Hz) in the 1H NMR spectra of
As for enamines 2a,b, the (Z)-configuration of compounds 8a,b
is due to intramolecular hydrogen bond, so the absorption band of
the ester group in the IR spectra of 8a,b is shifted to the low-fre-
quency region (1645–1650 cmꢀ1). The IR spectra of 8a,b also
display absorption bands at 3325–3340 (NH), 1630 (C]O) and
1590–1625 (C]C) cmꢀ1
.
Unlike for 1,2,3-trimethoxybenzene, a three-component con-
densation of 1,2,4-trimethoxybenzene with isobutyric aldehyde

724
V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
(9:1, v/v); compound spots were visualized by UV light (254 nm)
and/or by staining with a solution of chloranil in toluene. Flash
chromatography was performed on silica gel 60 (220–440 mesh, Alfa
Aesar). IR spectra were recorded on Specord M-80 spectrometer in
Nujol. 1H and 13C NMR spectra were obtained on a Varian Mercu-
ryþ300 instrument at 300 and 75 MHz, respectively, in CDCl3 or
DMSO-d6 and were referenced to HMDS (1H NMR
d
¼0.055 ppm),
residual CHCl3
(
13C NMR
d
¼77.0 ppm) or residual DMSO (13C NMR
d
¼39,6 ppm). Mass-spectra were recorded on GC–MS system Agilent
6890N series with mass-selective detector MSD 5975B (EI, 70 eV).
Elemental analyses (C, H, N) were obtained using Leco CHNS 9321P
elemental analyzer at the Institute of Technical Chemistry, Perm.
4.2. General procedures for the three-component
condensation
Figure 2. Structure of compound 11b in thermal ellipsoid of 50% probability.
Procedure A. A mixture of anisole (1.09 mL, 1.08 g, 10 mmol) or
trimethoxybenzene (1.68 g, 10 mmol), isobutyric aldehyde (0.79 g,
1.00 mL, 11 mmol), nitrile (10 mmol), and dichloromethane (3 mL)
was added to concentrated H2SO4 (6 mL) and stirred for 5 min in
a cold water bath followed by 40 min at room temperature. The
reaction mixture was poured into a mixture of 100 g crushed ice,
25% NH4OH (30 mL), concentrated aqueous NH4Cl (30 mL), and
CH2Cl2 (50 mL) (pH of water phase w8). The organic phase was
separated, the water phase was extracted with CH2Cl2 (20 mL), the
combined organic phase was washed with 50 mL of brine, dried
over MgSO4, and filtered. The residue after evaporation of organic
solvent was crystallized (compounds 1a, 2a,b, 8a,b, 9a,b, 12a) or
purified by flash chromatography on silica gel (compounds 4, 5, 6,
10a,b, 11a,b, 12b,c, 13a–d, 13aa, 13bb, 13dd, 14a–d, 14bb).
Finally, we studied the three-component condensation of
aromatic nitriles with isobutyric aldehyde and anisole, 1,2,3-tri-
methoxybenzene, 1,2,4-trimethoxybenzene or 1,3,5-trimethoxy-
benzene. Spiranes 12–15 were obtained as expected (Scheme 9).
In the case of 1,2,3- and 1,2,4-trimethoxybenzene, along with
spiranes 13a–d and 14a–d, Ritter amides (13aa, 13bb, 13dd, 14bb)
were isolated as byproducts (yields 9–47%, Scheme 9). Anisole
gives a poor yield of spiranes 12a–c (22–48%). The reaction of
anisole with isobutyric aldehyde and 4-bromobenzonitrile was
sluggish, and we failed to obtain 1-(4-bromophenyl)-3,3-di-
methyl-2-azaspiro[4.5]deca-1,6,9-triene-8-one (compound 12d)
by this method.
R5
R2
R3
R6
R2
R3
Me
Me
R2
R3
Me Me
CHO
R1
+ NC
R5
R6
+
R1
Me
+
O
N
H2SO4
R4
Me
N
H
R4
O
R6
R = OMe, R = R = R4 =H
1
2
3
12
13
R = R2 = R3 = OMe, R4 = H
1
R5
14 R1 = R2 = R4 = OMe, R3 = H
12a-c
(10-48%)
(27-74%)
(41-77%)
13aa (47%), 13bb (33%),
13dd 14bb
15 R1 = R3 = R4 = OMe, R2 = H
13a-d
14a-d
(41%),
(13%)
5
6
5
6
a,aa
b,bb
R = R = H,
R = OMe, R = H
R = R = OMe,
R = Br, R6 = H
5
6
5
c
d,dd
15a-d (46-86%)
Scheme 9.
3. Conclusion
Procedure B. A mixture of carbinols C or D (2.40 g, 10 mmol)
and 10 mmol of nitrile and dichloromethane (3 mL) was
added to concentrated H2SO4 (6 mL) and stirred for 5 min in
a cold water bath followed by 40 min at room temperature. The
subsequent workup was performed according to procedure
A. The residue after evaporation of organic solvent was
crystallized (compounds 2a,b, 3b, 7) or purified by flash chro-
matography on silica gel (compound 3a, 4, 5; eluent hexanes/
ethylacetate, 5/1).
In summary, we have described the three-component con-
densation of 1,2,3-, 1,2,4- and 1,3,5-trimethoxybenzene with
isobutyric aldehyde and a variety of nitriles in the presence of
concentrated sulfuric acid. This method offers an elegant
approach to the 1-substituted 2-azaspiro[4.5]deca-6,9-diene-8-
ones and 2-azaspiro[4.5]deca-1,6,9-triene-8-ones. The sub-
stitution pattern in arene changes the conversion and the
reactivity profile: anisole gives poor yields of spiro-compounds;
1,2,3-trimethoxybenzene is prone to Ritter amides formation,
and 1,3,5-trimethoxybenzene provides the compounds of the
formal Kno¨evenagel condensation.
Procedure
C (for compounds 15a–d). Synthesis was per-
formed according to procedure A; the reaction mixture was
poured into cold water, treated by solid NaHCO3 (pH w7),
extracted with CH2Cl2 (20 mL), the combined organic phase
was washed with 50 mL of brine, dried over MgSO4, and fil-
tered. The residue after evaporation of organic solvent was
crystallized.
Products of alkyl cyanoacetate condensation (1a, 2a,b, 3a,b,
8a,b, 10a,b, 11a,b) are not stable under conditions of mass-spec-
trometric experiments; compounds 13,14 decompose mainly
through loss of aromatic nitriles and the methyl groups.
For compound 1b see Ref. 18b.
4. Experimental
4.1. General
All the chemicals used were reagent grade as supplied from Alfa
Aesar (Lancaster). Analytical thin-layer chromatography was per-
formed using silica gel plates Sorbfil in chloroform/acetone mixture

V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
725
4.2.1. Methyl [(2Z)-(3,3-dimethyl-8-oxo-2-azaspiro[4,5]deca-6,9-dien-
1-ylidene)] acetate (1a). Procedure A. Yield 1.31 g (53%), colorless
plates, mp 157–159 ꢁC (from ethanol), Rf 0.60; nmax (Nujol) 3320
ethylacetate, 5/1) compounds 5 (yield 4%, Rf 0.73), 6 (yield 20%,
Rf 0.67), and 4 (yield 73%, Rf 0.57).
(NH), 1630 (C]O), 1575, 1250, 1200, 1140, 1045 cmꢀ1
;
1H NMR
4.2.6. 6,7-Dimethoxy-3,3-dimethyl-1-methylsulfanyl-2-azaspiro[4.5]-
(300 MHz, CDCl3)
d
7.91 (1H, br s, NH), 6.77 (2H, d, 3J¼10.2 Hz,
deca-1,6,9-triene-8-one (4). Colorless prisms, mp 70–71 ꢁC (from
C(6)H and C(10)H), 6.18 (2H, d, 3J¼10.2 Hz, C(7)H and C(9)H), 4.23
hexanes), nmax (Nujol) 1645 (C]O), 1625 (C]C), 1590 (C]N) cmꢀ1
;
(1H, s, CH]), 3.56 (3H, s, OMe), 2.41 (2H, s, CH2), 1.41 (6H, s, 2Me);
1H NMR (300 MHz, DMSO-d6)
d
6.65 (1H, d,3J¼10 Hz, C(10)H), 6.10
13C NMR (75 MHz, CDCl3)
d
184.9, 170.8, 161.5, 149.8, 127.9, 77.9,
(1H, d, 3J¼10 Hz, C(9)H), 4.00 (3H, s, OMe), 3.65 (3H, s, OMe), 2.32
(3H, s, SMe), 2.23 (1H, d, 2J¼14 Hz, C(4)H), 2.08 (1H, d, 2J¼14 Hz,
C(4)H), 1.35 (3H, s, Me), 1.32 (3H, s, Me); 13C NMR (75 MHz, CDCl3)
61.3, 52.9, 50.3, 46.6, 31.1. Anal. Calcd for C14H17NO3: C, 68.00; H,
6.93; N, 5.66. Found: C, 68.14; H, 6.81; N, 5.66.
d
184.1, 165.7, 159.6, 144.5, 138.4, 127.0, 74.5, 66.2, 60.9, 60.3, 47.5,
4.2.2. Methyl-(2Z)-[5-(R,S)-(6,7-dimethoxy-3,3-dimethyl-8-oxo-2-
azaspiro[4,5]deca-6,9-dien-1-ylidene)] acetate (2a). Procedure A.
Yield 1.14 g (37%), colorless plates, mp 139–140 ꢁC (from ethanol), Rf
0.50; nmax (Nujol) 3320 (NH), 1640 (C]O), 1610, 1585, 1315, 1265,
31.2, 30.1, 13.7; m/z (I,%): 208 (100) (Mþ$ꢀCH3SCN). Anal. Calcd for
C14H19NO3S: C, 59.76; H, 6.81; N, 4.98; S, 11.39. Found: C, 59.85; H,
6.83; N, 4.89; S, 12.46. Procedure B from alcohol C gives rise to
compounds 4 (yield 73%) and 5 (yield 4%).
1215, 1140, 1060, 850, 810 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 7.94
(1H, br s, NH), 6.46 (1H, d, 3J¼9.6 Hz, C(10)H), 6.03 (1H, d, 3J¼9.6 Hz,
C(9)H), 4.18 (1H, s, CH]), 4.01 (3H, s, OMe), 3.69 (3H, s, OMe), 3.56
(3H, s, OMe), 2.35 (1H, d, 2J¼13.8 Hz, C(4)H), 1.95 (1H, d, 2J¼13.8 Hz,
C(4)H), 1.38 (3H, s, Me), 1.37 (3H, s, Me); 13C NMR (75 MHz, CDCl3)
4.2.7. 3,3-Dimethyl-1-methylsulfanyl-5,6,7-trimethoxy-3,4-dihydro-
isoquinoline (5). Colorless oil, 1H NMR (300 MHz, CDCl3)
d 7.01 (1H,
s, C(8)H), 3.90 (3H, s, OMe), 3.87 (3H, s, OMe), 3.81 (3H, s, OMe),
2.62 (2H, s, CH2), 2.41 (3H, s, SMe), 1.19 (6H, s, 2Me); m/z 295 (Mþ).
Anal. Calcd for C15H21NO3S: C, 60.99; H, 7.17; N, 4.72; S, 10.85.
Found: C, 60.77; H, 7.32; N, 4.53; S, 11.12.
d
184.2, 184.1, 170.9, 162.1, 160.7, 145.3, 138.1, 125.6, 75.7, 61.7, 61.2,
60.6, 57.5, 50.1, 45.1, 31.8, 30.3. Anal. Calcd for C16H21NO5: C, 62.53;
H, 6.89; N, 4.56. Found: C, 62.59; H, 6.74; N, 4.57. Procedure B
afforded 48% yield of 2a from alcohol C.
4.2.8. 1,1-Bis-(2,3,4-trimethoxyphenyl)-2-methylpropane
(6). Colorless oil, nmax (slim film) 2959, 2938, 2872, 2836, 1598,
1493, 1464, 1435 (w), 1413, 1384 (w), 1281, 1256, 1227 (w), 1199,
4.2.3. Ethyl (2Z)-[5-(R,S)-(6,7-dimethoxy-3,3-dimethyl-8-oxo-2-aza-
spiro[4,5]deca-6,9-dien-1-ylidene)] acetate (2b). Procedure A. Yield
1.67 g (52%), transparent prisms, mp 140–143 ꢁC (from ethanol), Rf
0.66; nmax (Nujol) 3396 (NH), 1656 (C]O), 1604, 1324, 1260, 1212,
1170 (w), 1120, 1094, 1040, 1017, 964, 906, 797, 757, 688 cmꢀ1 1H
;
NMR (CDCl3, 300 MHz)
d
6.97 (2H, d, 3J¼9 Hz, C(60)H), 6.59 (2H, d,
3J¼9 Hz, C(50)H), 4.25 (1H, d, 3J¼10.4 Hz, CH), 3.81 (6H, s, OMe),
3.80 (6H, s, OMe), 3.77 (6H, s, OMe), 2.27 (1H, m, CH), 0.86 (6H, d,
3J¼6.3 Hz, 2Me); m/z 390 (Mþ).
1144, 1056, 856, 840 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 7.99 (br s,
1H, NH), 6.51 (1H, d, 3J¼9.9 Hz, C(10)H), 6.08 (1H, d, 3J¼9.9 Hz,
C(9)H), 4.23 (1H, s, CH]), 4.07 (5H, m, OMeþOCH2CH3), 3.74 (3H, s,
OMe), 2.40 (1H, d, 2J¼13.5 Hz, C(4)H), 1.99 (1H, d, 2J¼13.5 Hz,
C(4)H), 1.43 (3H, s, Me), 1.42 (3H, s, Me), 1.23 (3H, t, J¼7.5 Hz,
4.2.9. 3,3-Dimethyl-1-methylsulfanyl-6,7,8-trimethoxy-3,4-dihydro-
isoquinoline (7). Procedure B. Yield 1.56 g (53%) from alcohol D,
transparent prisms, mp 84–85 ꢁC (hexanes), Rf 0.62; nmax (Nujol)
1584, 1556, 1340, 1316, 1252, 1196, 1132, 1088, 1040 cmꢀ1; 1H NMR
OCH2CH3); 13C NMR (75 MHz, CDCl3)
d 183.6, 169.0, 161.4, 160.9,
146.6, 137.5, 124.8, 74.4, 62.1, 61.1, 60.2, 57.9, 57.4, 44.5, 30.9, 29.8,
14.6. Anal. Calcd for C17H23NO5: C, 63.54; H, 7.21; N, 4.36. Found: C,
63.89; H, 7.01; N, 4.39. Procedure B afforded 55% yield of 2b from
alcohol C.
(300 MHz, CDCl3)
d 6.40 (1H, s, 5-H), 3.89 (3H, s, OMe), 3.82 (3H, s,
OMe), 3.78 (3H, s, OMe), 2.48 (2H, s, CH2), 2.28 (3H, s, SMe),1.11 (6H,
s, 2Me); 13C NMR (75 MHz, CDCl3)
d 154.8, 151.5, 140.7, 133.3, 115.3,
107.0, 61.2, 60.7, 55.8, 55.0, 40.0, 27.9, 13.3; m/z 295 (Mþ). Anal.
Calcd for C15H21NO3S: C, 60.99; H, 7.17; N, 4.72; S, 10.85. Found: C,
60.80; H, 7.27; N, 4.72; S, 11.42.
4.2.4. Methyl (2Z)-(3,3-dimethyl-6,7,8-trimethoxy-1,2,3,4-tetrahydro-
isoquinoline-1-ylidene) acetate (3a). Procedure B. Yield 1.35 g (42%)
from alcohol D, colorless prisms,107–109 ꢁC (hexanes), Rf 0.80; nmax
(Nujol) 3267 (NH), 1641 (C]O), 1595 (C]C), 1561 (C]C) cmꢀ1; 1H
4.2.10. Methyl (2Z)-[5-(R,S)-(6,9-dimethoxy-3,3-dimethyl-8-oxo-2-
azaspiro[4,5]deca-6,9-dien-1-ylidene)]acetate (8a). Procedure A.
Yield 1.54 g (50%), colorless prisms, mp 190–192 ꢁC (from ethanol),
Rf 0.59; nmax (Nujol) 3340 (NH), 1650 (O–C]O), 1615 (C]C), 1595
NMR (300 MHz, CDCl3)
d 9.12 (1H, s, NH), 6.38 (1H, s, C(5)H), 5.66
(1H, s, CH]), 3.80 (3H, s, OMe), 3.77 (3H, s, OMe), 3.76 (3H, s, OMe),
3.58 (3H, s, OMe), 2.63 (2H, s, CH2), 1.16 (6H, s, 2Me); 13C NMR
(75 MHz, DMSO-d6)
d
172.2, 154.6, 153.6, 153.2, 141.6, 132.9, 115.3,
(C]C) cmꢀ1 1H NMR (300 MHz, DMSO-d6)
; d 8.00 (1H, br s, NH),
107.6, 80.2, 60.9, 60.8, 55.8, 50.0, 48.7, 43.5, 28.2. Anal. Calcd for
C17H23NO5: C, 63.54; H, 7.21; N, 4.36. Found: C, 63.64; H, 7.07; N,
4.38.
5.63 (1H, s, C(10)H), 5.46 (1H, s, C(7)H), 4.20 (1H, s, CH]), 3.73 (3H,
s, OMe), 3.65 (3H, s, OMe), 3.61 (3H, s, OMe), 2.44 (1H, d, C(4)H,
2J¼13.5 Hz), 2.04 (1H, d, C(4)H, 2J¼13.5 Hz), 1.46 (3H, s, Me), 1.44
(3H, s, Me); 13C NMR (75 MHz, DMSO-d6)
d 180.9, 174.5,169.6, 163.5,
4.2.5. Ethyl (2Z)-(3,3-dimethyl-6,7,8-trimethoxy-1,2,3,4-tetrahydro-
isoquinoline-1-ylidene) acetate (3b). Procedure B. Yield 1.54 g (46%)
from alcohol D, colorless prisms, mp 174–175 ꢁC (aq MeOH), Rf 0.74;
nmax (Nujol) 3260 (NH), 1640 (C]O), 1596, 1332, 1280, 1256, 1232,
148.5, 115.6, 102.0, 74.2, 62.0, 56.7, 55.4, 54.9, 49.6, 46.7, 31.2, 29.8.
Anal. Calcd for C16H21NO5: C, 62.53; H, 6.89; N, 4.56. Found: C,
62.70; H, 6.69; N, 4.57.
1192, 1176, 1156, 1140, 1112, 1032, 896, 868 cmꢀ1
;
1H NMR
4.2.11. Ethyl
(2Z)-[5-(R,S)-(6,9-dimethoxy-3,3-dimethyl-8-oxo-2-
(300 MHz, CDCl3)
d
9.13 (1H, s, NH), 6.39 (1H, s, C(5)H), 5.66 (1H, s,
azaspiro[4,5]deca-6,9-dien-1-ylidene)]acetate (8b). Procedure A.
Yield 1.25 g (39%), bright yellow plates, mp 179–180 ꢁC (from eth-
anol), Rf 0.44; nmax (Nujol) 3325 (NH); 1645 (O–C]O); 1630 (C]O);
CH]), 4.08 (2H, q, 3J¼7.6 Hz, OCH2), 3.82 (3H, s, OMe), 3.79 (6H, s,
2OMe), 2.65 (2H, s, CH2), 1.22 (3H, t, 3J¼7.6 Hz, Me), 1.18 (6H, s,
2Me). Anal. Calcd for C18H25NO5: C, 64.46; H, 7.51; N, 4.18. Found: C,
63.79; H, 7.59; N, 4.05.
1640, 1625, 1590 (C]C) cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 8.27
(1H, s, NH), 5.56 (1H, s, CH]), 5.55 (1H, s, CH]), 3.88 (2H, q,
3J¼7.2 Hz, OCH2), 3.82 (1H, s, CH]), 3.67 (3H, s, OMe), 3.50 (3H, s,
OMe), 2.24 (1H, d, 2J¼13.8 Hz, C(4)H), 2.02 (1H, d, 2J¼13.8 Hz,
C(4)H), 1.38 (3H, s, Me), 1.33 (3H, s, Me), 1.06 (3H, t, 3J¼7.2 Hz,
The reaction of 1,2,3-trimethoxybenzene (1.68 g, 10 mmol),
isobutyric aldehyde (0.79 g, 1.00 mL, 11 mmol), and methyl-
thiocyanate (0.73 g, 0.68 mL, 10 mmol) according to procedure A
afforded after flash chromatography on silica gel (hexanes/
OCH2CH3); 13C NMR (75 MHz, DMSO-d6)
d 181.5, 175.0, 170.0, 164.1,

726
V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
149.2, 116.3, 102.6, 75.1, 62.5, 58.4, 57.3, 56.0, 55.6, 47.4, 31.9, 30.5,
15.2; m/z 321 (Mþ). Anal. Calcd for C17H23NO5: C, 63.54; H, 7.21; N,
4.36. Found: C, 63.28; H, 6.87; N, 4.24.
195 ꢁC (from ethanol); nmax (Nujol) 3320 (NH), 1640 (C]O), 1610,
1585 (C]C) cmꢀ1; 1H NMR (CDCl3, 300 MHz)
d 7.96 (1H, s, NH), 5.41
(2H, s, C(7)H, C(9)H), 4.11 (1H, s, CH]), 4.00 (2H, q, 2J¼7.5 Hz,
OCH2), 3.64 (6H, s, 2OMe), 2.23 (1H, d, 2J¼13.5 Hz, C(4)H), 2.19 (1H,
d, 2J¼13.5 Hz, C(4)H), 1.37 (6H, s, 2Me), 1.16 (3H, t, 3J¼7.5 Hz, Me);
4.2.12. 5-(R,S)-6,9-Dimethoxy-3,3-dimethyl-1-methylsulfanyl-2-
azaspiro[4.5]deca-1,6,9-triene-8-one (9a). Procedure A. Yield 1.54 g
(55%), white solid, mp 190–191 ꢁC (EtOAc/hexanes), Rf 0.43; nmax
13C NMR (75 MHz, CDCl3)
d 187.4, 171.6, 170.9, 162.6, 100.5, 74.6,
62.1, 58.5, 58.2, 56.1, 45.1, 30.4, 14.4. Anal. Calcd for C17H23NO5: C,
63.54; H, 7.21; N, 4.36. Found: C, 63.66; H, 7.53; N, 4.32.
(Nujol) 1640 (C]O), 1615 (C]C), 1590 (C]N) cmꢀ1 1H NMR
;
(300 MHz, CDCl3)
d 5.66 (1H, s, C(10)H), 5.34 (1H, s, C(7)H), 3.74
(3H, s, OMe), 3.68 (3H, s, OMe), 2.44 (1H, d, 2J¼14.5 Hz, C(4)H), 2.37
4.2.17. Ethyl {(1Z)-6,10-dimethoxy-3,3-dimethyl-1-(2-methoxy-2-oxo-
ethylidene)-2-azaspiro[4,5]-deca-6,9-diene-8-ilidene}-cyanoacetate
(11b). Bright yellow plates, mp 167–169 ꢁC (from ethanol), nmax
(Nujol) 3310 (NH), 2175 (C^N), 1700 (shoulder, O–C]O), 1670
(3H, s, SMe), 2.07 (1H, d, 2J¼14.5 Hz, C(4)H), 1.42 (3H, s, Me), 1.41
(3H, s, Me); 13C NMR (75 MHz, DMSO-d6):
d 180.8, 172.8, 166.3,
149.4, 114.1, 102.8, 74.2, 63.7, 56.7, 55.0, 49.3, 31.4, 30.2, 13.5; m/z
281 (Mþ). Anal. Calcd for C14H19NO3S: C, 59.76; H, 6.81; N, 4.98; S,
11.39. Found: C, 59.53; H, 6.88; N, 4.94; S, 12.30.
(O–C]O), 1600 (C]C), 1265, 1170, 1075, 860 cmꢀ1
;
1H NMR
(300 MHz, CDCl3)
d 8.30 (1H, s, NH), 7.33 (1H, s, CH], C(9)H or
C(7)H), 5.95 (1H, s, CH], C(7)H or C(9)H), 4.21 (2H, q, 3J¼7.8 Hz,
OCH2), 3.93 (2H, q, 3J¼7.8 Hz, OCH2), 3.82 (3H, s, OMe), 3.79 (4H, m,
OMeþCH]), 2.18 (2H, s, CH2), 1.38 (6H, s, 2Me), 1.27 (3H, t,
3J¼7.8 Hz, Me), 1.12 (3H, t, 3J¼7.8 Hz, Me); 13C NMR (75 MHz, CDCl3)
4.2.13. 5-(R,S)-1-Benzylsulfanyl-6,9-dimethoxy-3,3-dimethyl-2-
azaspiro[4.5]deca-1,6,9-triene-8-one (9b). Procedure A. Yield 0.54 g
(15%), colorless solid, mp 124–125 ꢁC (EtOAc/hexanes), Rf 0.55; nmax
(Nujol) 1645 (C]O), 1625 (C]C), 1590 (C]N) cmꢀ1
;
1H NMR
d 169.9, 169.9, 168.9, 163.4, 161.77, 158.0, 117.6, 95.1, 93.4, 88.9, 73.0,
(300 MHz, DMSO-d6)
d
7.21 (5H, m, Ph), 5.56 (1H, s, C(10)H), 5.49
62.7, 60.7, 58.4, 57.8, 56.7, 45.1, 29.8, 14.5, 14.1; m/z 416 (Mþ). Anal.
Calcd for C22H28N2O6: C, 63.45; H, 6.78; N, 6.73. Found: C, 63.22; H,
6.64; N, 6.75.
(1H, s, C(7)H), 4.16 (1H, d, J¼13.2 Hz, SCH), 4.05 (1H, d, J¼13.2 Hz,
SCH), 3.59 (3H, s, OMe), 3.47 (3H, s, OMe), 2.28 (1H, d, J¼13.2 Hz,
C(4)H), 2.07 (1H, d, J¼13.2 Hz, C(4)H), 1.34 (3H, s, Me), 1.29 (3H, s,
Me), 13C NMR (75 MHz, CDCl3)
d
181.8, 173.1, 166.0, 150.2, 137.7,
4.2.18. 3,3-Dimethyl-1-phenyl-2-azaspiro[4.5]deca-1,6,9-triene-8-
one (12a). Procedure A. The residue after evaporation of organic
solvent crystallized on standing. It was filtered and crystallized
from hexanes. Yield 0.25 g (10%), colorless needles, mp 132–134 ꢁC,
Rf 0.53; nmax (Nujol) 1660 (C]O), 1625 (C]N), 1605 (C]C),
129.0, 128.2, 127.1, 113.2, 103.2, 74.6, 56.2, 55.2, 49.7, 35.6, 31.6, 30.1;
Anal. Calcd for C20H23NO3S: C, 67.20; H, 6.49; N, 3.92; S, 8.97.
Found: C, 67.14; H, 6.58; N, 3.87; S, 9.18.
The reaction of 1,3,5-trimethoxybenzene (1.68 g, 10 mmol),
isobutyric aldehyde (0.79 g, 1.00 mL, 11 mmol), and methyl-
cyanoacetate (0.99 g, 0.88 mL, 10 mmol) according to procedure A
afforded after flash chromatography on silica gel (hexanes/ethyl-
acetate, 5/1) compounds 10a (yield 36%, Rf 0.48) and 11a (yield 18%,
Rf 0.73).
1575 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 7.64 (2H, m, Ph), 7.40 (1H,
m, Ph), 7.32 (2H, m, Ph), 7.15 (2H, d, 3J¼10.2 Hz, C(6)H, C(10)H), 6.28
(2H, d, 3J¼10.2 Hz, C(7)H, C(9)H), 2.23 (2H, s, CH2),1.45 (6H, s, 2Me);
13C NMR (75 MHz, DMSO-d6)
d 183.8, 164.0, 152.0, 133.5, 130.3,
128.0, 127.9, 127.3, 72.4, 60.7, 49.0, 30.2; m/z 148 (MþꢀPhCN). Anal.
Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 81.35; H,
6.90; N, 5.42.
4.2.14. Methyl
(2Z)-(3,3-dimethyl-6,10-dimethoxy-8-oxo-2-aza-
spiro[4,5]deca-6,9-diene-1-ylidene) acetate (10a). Colorless plates,
mp 188–190 ꢁC (from ethanol); nmax (Nujol) 3340 (NH), 1630
4.2.19. 3,3-Dimethyl-1-(4-methoxyphenyl)-2-azaspiro[4.5]deca-
1,6,9-triene-8-one (12b). Procedure A. The residue after evaporation
of organic solvent was purified by flash chromatography on silica
gel (hexanes/ethylacetate/Et3N, 80/20/1, Rf 0.58). Yield 22%, color-
less powder, mp 142–143 ꢁC (hexanes–CH2Cl2); nmax (Nujol) 1670
(C]O), 1565 (C]C) cmꢀ1; 1H NMR (300 MHz, CDCl3)
d
7.96 (1H, br
s, NH), 5.41 (2H, s, C(7)H, C(9)H), 4.12 (1H, s, HC]), 3.65 (6H, s,
2OMe), 3.55 (3H, s, OMe), 2.20 (2H, s, C(4)H2), 1.38 (6H, s, 2Me); 13
NMR (75 MHz, CDCl3) 187.6, 171.5, 171.1, 162.6, 100.3, 73.8, 62.2,
C
d
57.9, 56.1, 50.0, 44.8, 30.3; Anal. Calcd for C16H21NO5: C, 62.53; H,
6.89; N, 4.56. Found: C, 62.16; H, 6.95; N, 4.47.
(C]O), 1630 (C]N), 1600 (C]C), 1260, 1175, 1030, 860 cmꢀ1 1H
;
NMR (300 MHz, CDCl3)
d
7.59 (2H, d, 3J¼9 Hz, C(20)H, C(60)H), 6.95
3
(2H, d, 3J¼9.6 Hz, C(6)H, C(10)H), 6.72 (2H, d, J¼9 Hz, C(30)H,
4.2.15. Methyl {(1Z)-6,10-dimethoxy-3,3-dimethyl-1-(2-methoxy-2-oxo-
ethylidene)-2-azaspiro[4,5]-deca-6,9-diene-8-ilidene}-cyanoacetate
(11a). Bright yellow plates, mp 185.5–187 ꢁC (from ethanol), nmax
(Nujol) 3320 (NH), 2180 (C^N), 1690 (O–C]O), 1660 (O–C]O);
C(50)H), 6.33 (2H, d, 3J¼9.6 Hz, C(7)H, C(9)H), 3.73 (3H, s, OMe), 2.17
(2H, s, CH2), 1.43 (6H, s, 2Me); 13C NMR (75 MHz, CDCl3)
d 184.9,
164.4, 161.5, 152.0, 129.3, 128.3, 126.1, 113.5, 72.3, 61.0, 55.1, 49.9,
30.6; Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C,
76.77; H, 6.62; N, 5.02. If we used 2,2-dimethyloxirane as C2-syn-
thon, the yield of compound 12b was 32%.
1630 (C]C); 1580 (C]C) cmꢀ1 1H NMR (300 MHz, DMSO-d6)
;
d
8.36 (1H, s, NH), 7.35 (1H, s, CH], C(9)H or C(7)H), 5.94 (1H, s,
CH], C(7)H or C(9)H), 3.81 (4H, m, OMe and CH]), 3.78 (3H, s,
OMe), 3.74 (3H, s, OMe), 3.45 (3H, s, OMe), 2.17 (2H, s, CH2), 1.38
4.2.20. 1-(3,4-Dimethoxyphenyl)-3,3-dimethyl-2-azaspiro[4.5]deca-
1,6,9-triene-8-one (12c). Procedure A. The residue after evaporation
of organic solvent was purified by flash chromatography on silica
gel (hexanes/ethylacetate/Et3N, 80/20/1, Rf 0.53). Yield 48%, color-
less plates, mp 190–192 ꢁC (hexanes); nmax (Nujol) 1650 (C]O),
(6H, s, 2Me); 13C NMR (75 MHz, DMSO-d6)
d 170.1, 170.0, 169.5,
164.0, 162.0, 158.3, 117.5, 95.4, 93.7, 89.0, 73.3, 62.7, 58.6, 56.79,
56.75, 51.9, 49.6, 45.5, 30.0; m/z 289 (MþꢀNCCH2CO2Me). Anal.
Calcd for C20H24N2O6: C, 61.85; H, 6.23; N, 7.21. Found: C, 61.20; H,
6.10; N, 7.21.
1620, 1600, 1570, 1510 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 7.33 (1H,
The reaction of 1,3,5-trimethoxybenzene (1.68 g, 10 mmol),
isobutyric aldehyde (0.79 g, 1.00 mL, 11 mmol), and ethyl cyano-
acetate (1.13 g, 1.06 mL, 10 mmol) according to procedure A affor-
ded after flash chromatography on silica gel (hexanes/ethylacetate,
5/1) compounds 10b (yield 26%, Rf 0.41) and 11b (yield 24%, Rf 0.69).
d, 4J¼2 Hz, C(20)H), 7.14 (1H, dd, 3J¼9 Hz, 4J¼2 Hz, C(60)H), 6.97 (2H,
d, 3J¼10 Hz, C(6)H, C(10)H), 6.67 (1H, d, 3J¼9 Hz, C(50)H), 6.34 (2H,
d, 3J¼10 Hz, C(7)H, C(9)H), 3.80 (3H, s, OMe), 3.78 (3H, s, OMe), 2.17
(2H, s, CH2), 1.44 (6H, s, 2Me). Anal. Calcd for C19H21NO3: C, 73.29;
H, 6.80; N, 4.50. Found: C, 73.40; H, 6.55; N, 4.45.
The reaction of 1,2,3-trimethoxybenzene (1.68 g, 10 mmol),
isobutyric aldehyde (0.79 g, 1.00 mL, 11 mmol), and benzonitrile
(1.03 g, 1.02 mL, 10 mmol) according to procedure A afforded after
4.2.16. Ethyl (2Z)-(3,3-dimethyl-6,10-dimethoxy-8-oxo-2-azaspiro[4,5]-
deca-6,9-diene-1-ylidene) acetate (10b). Colorless plates, mp 192–

V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
727
flash chromatography on silica gel (hexanes/ethylacetate, gradient
elution from 100/0 to 50/50, v/v) compounds 13aa (yield 47%, Rf
0.65) and 13a (yield 27%, Rf 0.56). The same method was used for
the synthesis and purification of compounds 13b–d, 13bb, 13dd,
14a–d, 14bb.
J¼13.2 Hz, C(4)H), 1.42 (3H, s, CH3), 1.40 (3H, s, CH3); 13C NMR
(75 MHz, CDCl3) d 184.2, 162.9, 151.1, 148.7, 146.9, 138.0, 126.6, 126.3,
120.4,110.3,110.2, 72.5, 65.3, 61.0, 60.5, 55.8, 55.7, 49.9, 30.9, 30.4; m/
z 371 (Mþ). Anal. Calcd for C21H25NO5: C, 67.91; H, 6.78; N, 3.77.
Found: C, 68.20; H, 6.52; N, 3.66.
4.2.21. 5-(R,S)-6,7-Dimethoxy-3,3-dimethyl-1-phenyl-2-azaspiro[4.5]-
deca-1,6,9-triene-8-one (13a). Colorless prisms, mp 100–102 ꢁC
(hexanes); nmax (Nujol) 1664 (C]O), 1636 (C]C), 1620 (C]N),
1600, 1576, 1496, 1324, 1280, 1218, 1212, 1204, 1176, 1156, 1136,
4.2.26. 5-(R,S)-1-(4-Bromophenyl)-6,7-dimethoxy-3,3-dimethyl-2-
azaspiro[4.5]deca-1,6,9-triene-8-one (13d). Yield 41%, colorless
prisms, mp 143–144 ꢁC (hexanes), Rf 0.58; nmax (Nujol) 1653 (C]O),
1639, 1618, 1596 (C]C), 1565, 1324, 1312, 1285, 1217, 1178, 1139,
1052, 1016, 940, 900, 836 cmꢀ1
;
1H NMR (300 MHz, DMSO-d6)
1069, 1052, 1009, 838 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 7.55 (2H,
d
7.67 (2H, m, C(20), C(60)H), 7.36 (1H, m, C(40)H), 7.27 (2H, m, C(30)H,
d, 3J¼8.4 Hz, C(20)H, C(60)H), 7.41 (2H, d, 3J¼8.4 Hz, C(30)H, C(50)H),
6.68 (1H, d, 3J¼9.6 Hz, C(10)H), 6.26 (1H, d, 3J¼9.6 Hz, C(9)H), 3.94
(3H, s, OCH3), 3.71 (3H, s, OCH3), 2.41 (1H, d, J¼13.5 Hz, C(4)H), 2.14
(1H, d, J¼13.5 Hz, C(4)H), 1.47 (3H, s, CH3), 1.45 (3H, s, CH3); 13C
C(50)H), 6.71 (1H, d, C(10)H, 3J¼10 Hz), 6.26 (1H, d, C(9)H,
3J¼10 Hz), 3.91 (3H, s, OMe), 3.70 (3H, s, OMe), 2.32 (1H, d,
2J¼13.2 Hz, C(4)H), 2.14 (1H, d, 2J¼13.2 Hz, C(4)H), 1.49 (3H, s, Me);
13C NMR (75 MHz, CDCl3)
d
184.2, 164.2, 162.3, 146.2, 138.1, 133.5,
NMR (75 MHz, CDCl3) d 184.0, 163.6, 161.9, 145.8, 138.0, 132.3, 131.5,
130.5, 128.3, 127.2, 126.9, 72.8, 66.4, 60.9, 60.5, 49.6, 30.8, 30.3; m/z
208 (MþꢀC6H5CN). Anal. Calcd for C19H21NO3: C, 73.29; H, 6.80; N,
4.50. Found: C, 73.35; H, 6.74; N, 4.60.
128.8, 127.1, 125.1, 72.9, 65.2, 61.0, 60.5, 49.7, 30.7, 30.2; m/z 389
(Mþ). Anal. Calcd for C19H20BrNO3: C, 58.47; H, 5.17; N, 3.59. Found:
C, 58.23; H, 4.86; N, 3.77.
4.2.22. N-[2-Methyl-1-(2,3,4-trimethoxyphenyl)-propan-2-yl]benz-
amide (13aa). Colorless oil; nmax (Nujol) 3380 (NH), 1664 (C]O),
1604, 1580, 1536, 1496, 1284, 1256, 1232, 1200, 1128, 1092, 1048,
4.2.27. 4-Bromo-N-[2-methyl-1-(2,3,4-trimethoxyphenyl)-propan-2-
yl]benzamide (13dd). Yield 41%, colorless powder, mp 77–78 ꢁC
(hexanes), Rf 0.67; nmax (Nujol) 3350 (NH), 1664 (C]O), 1592,
1012 cmꢀ1
;
1H NMR (300 MHz, DMSO-d6)
d
7.79 (2H, m, Ph), 7.48
1536 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d
7.65 (2H, d, J¼8.4 Hz, 20,60-
(1H, br s, NH), 7.32–7.42 (3H, m, Ph), 6.85 (1H, d, 3J¼8.7 Hz, C(60)H),
6.64 (1H, d, 3J¼8.7 Hz, C(50)H), 3.96 (3H, s, OMe), 3.86 (3H, s, OMe),
3.83 (3H, s, OMe), 2.82 (2H, s, CH2), 1.52 (6H, s, 2Me); 13C NMR
H), 7.56 (1H, br s, NH), 7.50 (2H, d, J¼8.4 Hz, 30,50-H), 6.84 (1H, d,
J¼8.4 Hz, C(6)H), 6.65 (1H, d, J¼8.4 Hz, C(5)H), 3.97 (3H, s, OMe),
3.87 (3H, s, OMe), 3.85 (3H, s, OMe), 2.79 (2H, s, CH2), 1.51 (6H, s,
(75 MHz, CDCl3)
d
126.6, 152.5, 151.1, 141.9, 135.7, 130.6, 128.0, 126.8,
2Me); 13C NMR (75 MHz, CDCl3)
d 165.6, 152.7, 151.0, 142.0, 134.7,
126.6, 122.7, 107.4, 60.8, 60.6, 55.8, 54.9, 42.5, 25.8; m/z 343 (Mþ).
Anal. Calcd for. C20H25NO4$1/2H2O: C, 68.20; H, 7.44; N, 3.97.
Found: C, 68.72; H, 7.87; N, 3.96.
131.2, 128.4, 126.9, 125.3, 122.7, 107.8, 61.0, 60.7, 55.9, 55.1, 42.9,
25.7; m/z 421 (Mþ). Anal. Calcd for C20H24BrNO4: C, 56.88; H, 5.73;
N, 3.32. Found: C, 57.24; H, 5.61; N, 3.26.
4.2.23. 5-(R,S)-6,7-Dimethoxy-3,3-dimethyl-1-(4-methoxyphenyl)-
2-azaspiro[4.5]deca-1,6,9-triene-8-one (13b). Yield 37%, colorless
plates, mp 130–131 ꢁC (hexanes–AcOEt), Rf 0.50; nmax (Nujol) 1640
4.2.28. 5-(R,S)-6,9-Dimethoxy-3,3-dimethyl-1-phenyl-2-azaspiro[4.5]-
deca-1,6,9-triene-8-one (14a). Yield 41%, colorless plates, mp 182–
183 ꢁC (hexanes/chloroform), Rf 0.42; nmax (Nujol) 1640 (C]O),
(C]O), 1590, 1500, 1310, 1260, 1205, 1170, 1055 cmꢀ1
;
1H NMR
1620 (C]C), 1585 (C]N) cmꢀ1 1H NMR (300 MHz, DMSO-d6)
;
4
(300 MHz, CDCl3)
d
7.58 (2H, dd, 3J¼9.0 Hz, J¼1.8 Hz, C(20,60)H),
d
7.59 (2H, d, 3J¼8.4 Hz, Ph) 7.36 (3H, m, Ph), 5.83 (1H, s, C(10)H),
6.71 (2H, dd, 3J¼9.0 Hz, 4J¼1.8 Hz, C(30,50)H), 6.65 (1H, d, 3J¼9.6 Hz,
C(10)H), 6.20 (1H, d, 3J¼9.6 Hz, C(9)H), 3.87 (3H, s, OMe), 3.72 (3H,
s, OMe), 3.66 (3H, s, OMe), 2.34 (1H, d, 2J¼13.8 Hz, C(4)H), 2.06 (1H,
d, 2J¼13.8 Hz, C(4)H), 1.41 (3H, s, Me), 1.37 (3H, s, Me); 13C NMR
5.72 (1H, s, C(7)H), 3.56 (3H, s, OMe), 3.53 (3H, s, OMe), 2.34 (1H, d,
2J¼13.5 Hz, C(4)H), 2.17 (1H, d, 2J¼13.5 Hz, C(4)H), 1.44 (3H, s, Me),
1.38 (3H, s, Me); 13C NMR (75 MHz, DMSO-d6)
d 180.6, 175.3, 164.0,
149.2, 133.3, 130.3, 128.3, 127.1, 115.1, 102.3, 72.2, 61.3, 56.7, 55.0,
51.2, 30.7, 30.2; m/z 208 (MþꢀC6H5CN). Anal. Calcd for C19H21NO3:
C, 73.29; H, 6.80; N, 4.50. Found: C, 73.03; H, 6.59; N, 4.48.
(75 MHz, CDCl3) d 184.3,163.6,162.7,161.4, 146.6, 138.1,128.9, 126.2,
113.6, 72.5, 65.3, 61.0, 60.5, 55.2, 49.8, 30.9, 30.4; m/z 341 (Mþ).
Anal. Calcd for C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C,
70.12; H, 6.89; N, 3.98.
4.2.29. 5-(R,S)-6,9-Dimethoxy-3,3-dimethyl-1-(4-methoxyphenyl)-
2-azaspiro[4.5]deca-1,6,9-triene-8-one (14b). Yield 71%, colorless
prisms, mp 144–145 ꢁC (hexanes–AcOEt), Rf 0.52; nmax (Nujol) 1653
(C]O), 1618, 1598 (C]C), 1514, 1298, 1259, 1247, 1193, 1170, 1136,
1113, 1046, 1010, 934, 873, 810, 784, 742 cmꢀ1; 1H NMR (300 MHz,
4.2.24. 4-Methoxy-N-[2-methyl-1-(2,3,4-trimethoxyphenyl)-propan-
2-yl]benzamide (13bb). Yield 33%, colorless oil, Rf 0.64; nmax (Nujol)
3350 (NH), 1660 (C]O), 1602, 1496 cmꢀ1 1H NMR (300 MHz,
;
CDCl3)
d
7.75 (2H, d, 3J¼8.4 Hz, C(20,60)H), 6.83–6.88 (3H, m, C(6)Hþ
CDCl3)
d
7.63 (2H, dd, 3J¼9.0 Hz, 4J¼2.1 Hz, C(20,60)H), 6.76 (2H, dd,
C(30,50)H), 6.63 (1H, d, 3J¼8.4 Hz, C(5)H), 3.97 (3H, s, OMe), 3.87
3J¼9.0 Hz, J¼2.1 Hz, C(30,50)H), 5.74 (1H, s, C(10)H), 5.61 (1H, s,
C(7)H), 3.78 (3H, s, OMe), 3.66 (3H, s, OMe), 3.65 (3H, s, OMe), 2.44
(1H, d, 2J¼13.5 Hz, C(4)H), 2.15 (1H, d, 2J¼13.5 Hz, C(4)H), 1.47 (6H,
4
(3H, s, OMe), 3.84 (3H, s, OMe), 3.82 (3H, s, OMe), 2.80 (2H, s,
C(4)H2), 1.51 (6H, s, 2Me); 13C NMR (75 MHz, CDCl3)
d 166.2, 161.5,
152.6, 151.2, 142.0, 128.4, 128.1, 126.82, 122.9, 113.2, 107.4, 60.9, 60.7,
55.8, 55.1, 54.8, 42.6; m/z 373 (Mþ). Anal. Calcd for C21H27NO5: C,
67.54; H, 7.29; N, 3.75. Found: C, 67.45; H, 7.33; N, 3.54.
s, 2Me); 13C NMR (75 MHz, CDCl3)
d 181.8, 176.1, 164.0, 161.1, 149.3,
128.8, 125.6, 114.8, 113.4, 102.1, 71.9, 62.4, 56.2, 55.0, 54.9, 51.7, 30.9,
30.2; m/z 341 (Mþ). Anal. Calcd for C20H23NO4: C, 70.36; H, 6.79; N,
4.10. Found: C, 70.33; H, 6.65; N, 4.20.
4.2.25. 5-R,S-6,7-Dimethoxy-1-(3,4-dimethoxyphenyl)-3,3-dimethyl-
2-azaspiro[4.5]deca-1,6,9-triene-8-one (13c). Yield 74%, transparent
plates, mp 139–140 ꢁC (hexanes–AcOEt), Rf 0.51; nmax (Nujol) 1652
(C]O), 1592, 1520, 1320, 1276, 1256, 1224, 1176, 1128, 1052, 1024,
4.2.30. 4-Methoxy-N-[2-methyl-1-(2,4,5-trimethoxyphenyl)-propan-
2-yl]benzamide (14bb). Yield 13%, colorless plates, mp 111–112 ꢁC
(hexanes), Rf 0.68; nmax (Nujol) 3340 (NH), 1665 (C]O), 1598,
836 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d
7.33 (1H, d, 3J¼8.4 Hz,
1498 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d
7.63 (2H, dd, 3J¼9.0 Hz,
4
3
C(20)H), 7.14 (1H, dd, 3J¼8.4 Hz, J¼1.2 Hz, C(60)H), 6.67 (1H, d,
20,60-H), 6.87 (2H, dd, J¼9.0 Hz, 30,50-H), 6.66 (1H, s, Harom.), 6.56
3J¼9.6 Hz, C(10)H), 6.66 (1H, d, J¼8.4 Hz, C(50)H), 6.20 (1H, d,
(1H, s, Harom.), 3.88 (3H, s, OMe), 3.85 (3H, s, OMe), 3.83 (3H, s,
3
3J¼9.6 Hz, C(9)H), 3.90 (3H, s, OCH3), 3.79 (3H, s, OCH3), 3.78 (3H, s,
OCH3), 3.67 (3H, s, OCH3), 2.35 (1H, d, J¼13.2 Hz, C(4)H), 2.07 (1H, d,
OMe), 3.72 (3H, s, OMe), 2.89 (2H, s, C(4)H2), 1.51 (6H, s, 2Me); 13
C
NMR (75 MHz, CDCl3) d 161.9, 160.2, 129.7, 129.6, 128.7, 121.5, 116.0,

728
V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
115.8, 113.8, 113.5, 94.7, 70.0, 56.7, 55.3, 55.2, 48.7, 39.9, 30.0, 27.4;
m/z 373 (Mþ). Anal. Calcd for C21H27NO5: C, 67.54; H, 7.29; N, 3.75.
Found: C, 67.88; H, 7.15; N, 3.85.
55.8, 51.1, 30.1; m/z 371 (Mþ). Anal. Calcd for C21H25NO5: C, 67.91; H,
6.78; N, 3.77. Found: C, 67.59; H, 6.61; N, 3.67.
4.2.36. 1-(4-Bromophenyl)-6,10-dimethoxy-3,3-dimethyl-2-aza-
spiro[5.4]deca-1,6,9-triene-8-one (15d). Procedure C. Yield 46%,
colorless powder, mp 162–163 ꢁC (hexanes–CH2Cl2); Rf 0.50; nmax
4.2.31. 5-(R,S)-6,9-Dimethoxy-1-(3,4-dimethoxyphenyl)-3,3-di-
methyl-2-azaspiro[4.5]deca-1,6,9-triene-8-one (14c). Yield 77%,
transparent prisms, mp 169–171 ꢁC (hexanes–CHCl3), Rf 0.36; nmax
(Nujol) 1590 (C]N), 1620 (C]C), 1635 (C]O) cmꢀ1 1H NMR
;
(Nujol) 1635 (C]O), 1605 (C]C), 1580 (C]N) cmꢀ1
;
1H NMR
(300 MHz, CDCl3)
d
7.55 (2H, d, 3J¼8.4 Hz, C(20)H, C(60)H), 7.39 (2H,
4
(300 MHz, CDCl3)
d
7.41 (1H, d, J¼1.8 Hz, C(20)H), 7.13 (1H, dd,
d, 3J¼8.4 Hz, C(30)H, C(50)H), 5.55 (2H, s, C(7)H, C(9)H), 3.65 (6H, s,
3J¼8.4 Hz, J¼1.8 Hz, C(60)H), 6.68 (1H, d, J¼8,4 Hz, C(50)H), 5.75
(1H, s, C(10)H), 5.63 (1H, s, C(7)H), 3.85 (3H, s, OMe), 3.84 (3H, s,
OMe), 3.67 (3H, s, OMe), 3.66 (3H, s, OMe), 2.45 (1H, d, 2J¼13,2 Hz,
C(4)H), 2.15 (1H, d, 2J¼13,2 Hz, C(4)H), 1.48 (6H, s, 2Me); 13C NMR
2OMe), 2.28 (2H, s, CH2), 1.45 (6H, s, 2Me); 13C NMR (75 MHz,
4
3
CDCl3)
d 187.3, 172.2, 161.5, 132.3, 131.5, 128.7, 124.8, 100.7, 73.3,
65.3, 56.1, 51.0, 29.9; m/z 390 (Mþ). Anal. Calcd for C19H20BrNO3: C,
58.47; H, 5.17; N, 3.59. Found: C, 58.78; H, 4.94; N, 3.75.
(75 MHz, DMSO-d6)
d 181.8, 176.4, 164.0, 150.9, 149.4, 148.5, 126.0,
120.3, 115.7, 110.3, 110.2, 102.1, 72.1, 62.5, 56.3, 55.8, 55.7, 55.1, 52.0,
31.0, 30.3; m/z 371 (Mþ). Anal. Calcd for C21H25NO5: C, 67.91; H,
6.78; N, 3.77. Found: C, 67.88; H, 6.55; N, 3.65.
4.3. X-ray crystallography
Intensity data for compound 1b (Fig. 1) were collected on an
Enraf-Nonius CAD-4 diffractometer using the
u scan method
(2qmax¼59.9ꢁ). Structure solution and structure refinement were
performed bythe directmethod using SHELX-97 program package.29
Nonhydrogen atoms were refined by full-matrix least-squares pro-
cedures (with F2) in an anisotropic approximation (SHELXL-97).30
The position of hydrogen NH atom was found by a difference Fourier
synthesis and refined in an isotropic approximation. Co-ordinates
and thermal parameters of the hydrogen atoms were fixed (UH
0.08 Å, C–H 0.96 Å). Molecular packing of the compound 1b is
formed by the intermolecular hydrogen bond (3.107 Å) between NH
group of pyrrolidine and C]O group of cyclohexadienone. Intra-
molecular H–bond NH/O]C(OEt) (2.207 Å) was also found. Crys-
tallographic data for compound 1b are given in Table 1. The
parameters for hydrogen bonds are given in Table 2.
4.2.32. 5-(R,S)-1-(4-Bromophenyl)-6,9-dimethoxy-3,3-dimethyl-2-
azaspiro[4.5]deca-1,6,9-triene-8-one (14d). Yield 50%, colorless
plates, mp 186–188 ꢁC (hexanes–CH2Cl2), Rf 0.60; nmax (Nujol) 1635
(C]O), 1620 (C]N), 1590 (C]C) cmꢀ1; 1H NMR (300 MHz, DMSO-
3
d6)
d
7.53 (2H, d, J¼8.4 Hz, C(20)H, C(60)H), 7.38 (2H, d, 3J¼8.4 Hz,
C(30)H, C(50)H), 5.73 (1H, s, C(6)H), 5.57 (1H, s, C(9)H), 3.65 (6H, s,
2OMe), 2.46 (1H, d, 2J¼13.5 Hz, C(4)H), 2.17 (1H, d, 2J¼13.5 Hz,
C(4)H), 1.48 (6H, s, 2Me); 13C NMR (75 MHz, DMSO-d6)
d 180.5,
174.9, 163.4, 149.4, 132.5, 131.4, 129.1, 124.0, 114.8, 102.1, 72.4, 62.3,
56.7, 55.1, 51.3, 30.7, 30.1; m/z 390 (Mþ). Anal. Calcd for
C19H20BrNO3: C, 58.47; H, 5.17; N, 3.59. Found: C, 58.67; H, 5.00; N,
3.65.
4.2.33. 6,10-Dimethoxy-3,3-dimethyl-1-phenyl-2-azaspiro[5.4]deca-
1,6,9-triene-8-one (15a). Procedure C. Yield 86%, colorless prisms,
mp 176–178 ꢁC (hexanes–CH2Cl2), Rf 0.47; nmax (Nujol) 1648 (C]O),
1620 (C]N), 1588 (C]C), 1284, 1232, 1212, 1188, 1160, 1064, 1000,
The molecular structure of compound 11b determined by crys-
tallography is shown in Figure 2. Main sp3-atom C(7) is tetrahedral
with lengths of C–C bonds 1.50–1.55 Å. Cyclohexadienyl and cya-
noacetic fragments form general planar system of
bonds. Bond lengths and angles of cyclohexadienyl moiety are
typical for system of -conjugated C–C bond.
p-conjugated
936, 852 cmꢀ1 1H NMR (300 MHz, CDCl3) 7.66 (2H, m, C(20)H,
; d
C(60)H), 7.33 (1H, m, C(40)H), 7.26 (2H, m, C(30)H, C(50)-H), 5.55 (2H,
s, C(7)H, C(9)H), 3.64 (6H, s, 2OMe), 2.29 (2H, s, C(4)H2), 1.47 (6H, s,
p
Molecular packing of the compound 11b is formed by polymeric
chain through hydrogen bond association of CN groups and NH
groups of pyrrolidine moiety (Fig. 3). Also NH group forms intra-
molecular H bond with O(3) of COOEt group to fix cis-conformation
2Me); 13C NMR (75 MHz, CDCl3)
d 187.9, 172.6, 133.1, 130.8, 130.2,
128.3, 127.1, 100.4, 73.2, 65.3, 56.2, 50.8, 30.0; m/z 311 (Mþ). Anal.
Calcd for C19H21NO3: C, 73.20; H, 6.80; N, 4.50. Found: C, 73.05; H,
6.56; N, 4.42.
Table 1
Crystal data and structure refinement for compounds 1b and 11b
4.2.34. 6,10-Dimethoxy-3,3-dimethyl-1-(4-methoxyphenyl)-2-aza-
spiro[5.4]deca-1,6,9-triene-8-one (15b). Procedure C. Yield 77%,
colorless plates, mp 169–171 ꢁC (hexanes–EtOAc), Rf 0.43; nmax
(Nujol) 1648 (C]O), 1624 (C]N), 1592, 1516 (C]C), 1312, 1292,
1b
11b
Empirical formula
Formula weight
C15H18NO3
261.31
C22H28N2O6
416.46
Temperature, K
293
120(2)
1260, 1232, 1208, 1180, 1160, 1068, 1024, 940, 860 cmꢀ1
;
1H NMR
Crystal system
Space group
a, Å
b, Å
Rhombic
P212121
9.199 (1)
9.469 (2)
16.801 (3)
1463.6 (5)
4
1.186
0.082
2–29ꢁ
Monoclinic
P2(1)/c
3
(300 MHz, CDCl3)
d
7.65 (2H, dd, J¼8.7 Hz, 20,60-H), 6.77 (2H, dd,
3J¼8.7 Hz, 30,50-H), 5.55 (2H, s, C(7)H, C(9)H), 3.78 (3H, s, OMe),
10.0832 (14)
12.6658 (11)
17.622 (3)
2225.9 (5)
4
3.64 (6H, s, 2OMe), 2.27 (2H, s, C(4)H2), 1.45 (6H, s, 2Me); 13C NMR
c, Å
(75 MHz, CDCl3)
d 188.0, 173.0, 161.6, 161.1, 128.7, 125.7, 113.6,
Volume Å3
100.3, 72.9, 65.2, 56.2, 55.1, 50.9, 30.0; m/z 341 (Mþ). Anal. Calcd
for C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C, 70.27; H, 6.59;
N, 4.02.
Z
Density (calculated) g/cm3
1.243
0.091
Absorption coefficient, mmꢀ1
q
Range for data collection
2.72–26.37ꢁ
ꢀ12<h<12, ꢀ15<k<15,
ꢀ22<l<21
15,807
Limiting indices
0ꢂhꢂ12, 0ꢂkꢂ13,
0ꢂlꢂ23
2405
4.2.35. 6,10-Dimethoxy-1-(3,4-dimethoxyphenyl)-3,3-dimethyl-2-
azaspiro[5.4]deca-1,6,9-triene-8-one (15c). Procedure C. Yield 63%,
colorless prisms, mp 155–156 ꢁC (hexanes–CH2Cl2), Rf 0.44; nmax
(Nujol) 1652 (C]O), 1624 (C]N), 1588, 1524 (C]C), 1340, 1280,
1240, 1212, 1156, 1068, 1028, 848 cmꢀ1; 1H NMR (300 MHz, CDCl3)
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
659 (Rint¼0.069)
659/0/177
0.948
4491 (Rint¼0.0551)
4491/0/283
1.006
R1 [I>2
wR2 [I>2
1 (all data)
s
(I)]
0.048
0.127
0.237
0.0513
0.1097
0.1207
d
7.42 (1H, d, 4J¼2.1 Hz, 20-H), 7.18 (1H, dd, 3J¼8.4 Hz, 4J¼2.1 Hz, 60-
s(I)]
H), 6.69 (1H, d, 3J¼8.4 Hz, 50-H), 5.56 (2H, s, C(7)H, C(9)H), 3.85 (3H,
R
wR2 (all data)
0.204
0.1209
s, OMe), 3.84 (3H, s, OMe), 3.66 (6H, s, 2OMe), 2.28 (2H, s, C(4)H2),
1.46 (6H, s, 2Me); 13C NMR (75 MHz, CDCl3)
d
181.6, 173.0, 162.5,
Largest diff. peak and hole,
eÅꢀ3
0.178 and ꢀ0.171
0.505 and ꢀ0.287
133.4, 130.1, 128.3, 127.2, 120.3, 110.8, 100.6, 73.2, 65.6, 56.1, 55.9,

V.A. Glushkov et al. / Tetrahedron 66 (2010) 721–729
729
Table 2
Crystallographic Data Centre as supplementary publication nos.
733250 (1b) and 726668 (11b). Copies of the data can be obtained,
free of charge, on application to CCDC,12 Union Road, Cambridge CB2
1EZ, UK (fax:þ44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
Hydrogen bonds with H/A<r(A)þ2.000 Å and<DHA> 110 deg for compounds 1b
and 11b
ꢁ
D–H
d (D–H), Å d (H/A), Å <DHA,
d(D/A), Å
A
1b
N1–H1 0.905
N1–H1 0.905
2.211
2.399
123.03
147.53
2.809
3.200
O3
Acknowledgements
N2 [ꢀxþ1, yþ1/2,
ꢀzþ3/2]
The authors are very much obliged to Elena Baigacheva for el-
emental analysis and Valery Karmanov for recording IR spectra.
This work was supported by the Presidium of Russian Academy
of Sciences (the program ‘Development of methods for synthesis of
chemical substances and creation of new materials’, coordinator:
academician V.A. Tartakovsky).
11b
123
131
N1–H1 0.89 (4)
N1–H1 0.89 (4)
2.22 (4)
2.44 (4)
2.806 (3)
3.108 (3)
O2
O1 [x, yþ1, z]
of C]C–C]O fragment. The parameters for these hydrogen bonds
are given in Table 2. The -system of substituted vinyl moiety of
compound 11b formed
p
p
–
p
stacking interactions with (1ꢀx, 2ꢀy,
Supplementary data
1ꢀz) symmetry equivalents with 3.383 Å between planes (Fig. 4).
X-ray structure of compound 11b was determined using the
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2009.11.055.
Oxford Diffraction Xcalibur S system (Mo K
a
radiation,
l¼0.71093
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Figure 4.
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A, graphite monochromator,
u/2q scan). Structure solution and
structure refinement were performed using SHELX-97 program
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crystallographic data for compound 11b are given in Table 1.
Crystallographic data (excluding structure factors) for structures
1b and 11b in this paper have been deposited with the Cambridge