Synthesis of indole-containing analogs of (1R)-cis-chrysanthemic acid and N-substituted (1R)-cis-chrysanthemylamines

Article abstract of DOI:10.1023/A:1020969017314

The indolic analogs of (1R)-cis-chrysanthemic acid and N-substituted (1R)-cis-chrysanthemylamines were obtained by Fischer indole synthesis using the acetonylcyclopropanes derived from (+)-car-3-ene. The cyano- and N-cyanamido groups in the starting carbo

Full text of DOI:10.1023/A:1020969017314

1308
Russian Chemical Bulletin, International Edition, Vol. 51, No. 7, pp. 1308—1318, July, 2002
Synthesis of indoleꢀcontaining analogs of (1R)ꢀcisꢀchrysanthemic
acid and Nꢀsubstituted (1R)ꢀcisꢀchrysanthemylamines
b
O. N. Burchak,a A. M. Chibiryaev,b and А. V. Tkachev
ꢀ
аN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752.
bDepartment of Natural Sciences, Novosibirsk State University,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752. Eꢀmail: chibirv@nioch.nsc.ru
The indolic analogs of (1R)ꢀcisꢀchrysanthemic acid and Nꢀsubstituted (1R)ꢀcisꢀchrysanꢀ
themylamines were obtained by Fischer indole synthesis using the acetonylcyclopropanes
derived from (+)ꢀcarꢀ3ꢀene. The cyanoꢀ and Nꢀcyanamido groups in the starting carbonyl
compounds did not hinder indolization. The reduction of the nitrile group bound to the
asymmetrical atom of the cyclopropane ring by LiAlH4 in ether can be accompanied by
epimerization or racemization.
Key words: (+)ꢀcarꢀ3ꢀene, cyclopropane methyl ketones, Fischer indole synthesis,
Nꢀcyanamides, decyanation, nitriles, hydrolysis, reduction, amides, indolic analogs of
chrysanthemylamine, epimerization, racemization.
Pyrethroid insecticides represent presently the most
(1, X = Y = Me; R = H) and its halogenꢀcontaining
analogs (1, X,Y = Me, Cl, Br; R = H), as well as
Nꢀsubstituted (1R)ꢀchrysanthemylamines 2.14,15 The
purpose of this work is to synthesize indolic anaꢀ
logs of (1R)ꢀcisꢀchrysanthemic acid and Nꢀsubstituted
(1R)ꢀcisꢀchrysanthemylamines (compounds of type 3)
in the enantiomerically pure form.
efficient chemical facility for combating harmful insects.
The modern tendencies in synthesis of new pyrethroids
are primarily related to design of acid components, which
appears, in particular, as the development of pyrethroid
molecules, whose acid components contain heterocyclic
fragments. It follows from the review of licensed literaꢀ
ture1 that a set of the known synthetic pyrethroids, whose
acid component includes the Nꢀheterocyclic fragment,
is very scarce2—12 and mainly presented by compounds
of the indole or isoindole series.3—5,12 However, even
this group contains a few substances related to the
most efficient pyrethroid insecticides, such as chrysanꢀ
themates,8—13 viz., derivatives of (1R)ꢀchrysanthemic acid
Results and Discussion
Ketone 4 16 was used as the key initial compound in
synthesis of the indicated indolic analogs (Scheme 1).
Scheme 1
Reagents, conditions, and yields, see Refs.: 16 (a), 17 (b), 18 (c).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1209—1218, July, 2002.
1066ꢀ5285/02/5107ꢀ1308 $27.00 © 2002 Plenum Publishing Corporation

Indolic analogs of (1R)ꢀcisꢀchrysanthemates
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1309
Scheme 2
Reagents, conditions, and yields: i. 1) PhNHNH2/MeOH, ∼20 °C, 2 h; 2) PPE/CH2Cl2, ∼20 °C, 20 h; 75% yield.
ii. 1) PhNHNH2/EtOH, ∼20 °C, 2—4 h; 2) PPA, ∼50 °C, 8 h; 37% yield, ratio 7 : 8 ≈ 2 : 1. iii. H2O2/NaOH/MeOH/H2O, ∼20 °C,
2 days; 45% yield. iv. KOH/ButOH, ∆, 1 h; 83% yield. v. EtOH/H2O/H2SO4, ∆, 2 h, 30% yield.
This compound can readily be prepared in high yield
from enantiomerically pure natural (+)ꢀcarꢀ3ꢀene, whose
molecule already has the main structural unit of chrysanꢀ
themates, viz., 2,2ꢀdimethylcyclopropane fragment. The
chemical properties of the CH2CN group and the absoꢀ
lute configuration of molecule 4 make it possible to synꢀ
thesize enantiomerically pure ketones 5 17 and 6 18 using
the minimum number of steps.
Compounds 5 and 6 are the closest precursors of
target products 3 because have the (R)ꢀconfiguration of
the С(1) atom and the 2ꢀoxopropyl group in position
С(3). The latter can be used for the formation of the
indole cycle using Fischer method, as shown19 for keꢀ
tone 4. Thus, the problem was a search for conditions
under which ketones 5 and 6 would undergo Fischer
indole synthesis and other structural fragments of the
initial molecules would remain unchanged.
Ketone 5 reacted rapidly with phenylhydrazine in an
ethanolic solution without heating to yield the correꢀ
sponding hydrazone, which underwent Fischer indole
synthesis in the presence of polyphosphoric acid (PPA)
or its ethyl ester to form indole 7. However, in the presꢀ
ence of PPA, the yield of indole was only 37% (twofold
lower than that in the case of PPE) and the target prodꢀ
uct was a mixture of cisꢀ and transꢀisomers 7 and 8 in a
transformation of nitrile 7 into the corresponding acid
failed. It turned out that the appearance of the 3ꢀindolyl
substituent at the С(3) atom of cyclopropane had a subꢀ
stantial effect on hydrolysis of the cyano group. It is
known that optically active 2,2ꢀdimethylcyclopropaneꢀ
carbonitriles close in structure to compound 7, being
heated in an aqueous ethanolic solution20,21 or in a soluꢀ
tion of ethylene glycol22 and treated with KOH, are easꢀ
ily hydrolyzed to form the corresponding acids, although
the inversion of the C(1) atom configuration (epimerꢀ
ization) occurs simultaneously with hydrolysis when ethꢀ
ylene glycol is used. However, hydrolysis of nitrile 7
under these conditions affords lactam 10 due to cycloꢀ
propane ring opening. Amide 9 prepared by hydrolysis of
compound 7 using the Radziszewski method is more
easily transformed into lactam 10. As shown by 1H NMR
spectroscopy, this process also occurs during prolonged
storage without a solvent or when amide 9 is kept in
CHCl3 for several days at ∼20 °С. Attempts to perform
alcoholysis of the amide group in compound 7 to the ester
group in an aqueousꢀethanolic medium in the presence
of H2SO4 were also unsuccessful (cf. Ref. 21), and lactam
10 was the main product (30% yield) among numerous
reaction products. Thus, nitrile 7 and amide 9, viz., indolic
analogs of the corresponding (1R)ꢀcisꢀchrysanthemic acid
derivatives, are more labile than their nonheterocyclic
prototypes, which is also demonstrated in the reduction
of the nitrile group by LiAlH4 (Scheme 3).
ratio of 2 : 1 (Scheme 2).* Isomerization 7
8 should
be considered as epimerization at one of two asymmetric
С(1) or С(3) atoms of the cyclopropane ring. However,
it remains yet unclear at which of the atoms it occurs.
Compound 7 is an indolic analog of nitrile of
(1R)ꢀcisꢀchrysanthemic acid, however, attempts of the
The cyano group in compound 7 is easily reduced to
the aminomethyl group by LiAlH4 in Et2O (5 h at 20 °С,
∼97% yield of amine). However, according to the data of
the 1Н NMR spectrum, the product obtained was a mixꢀ
ture of cisꢀ and transꢀisomers in a ratio of 1 : 2 (correꢀ
spondingly, 11 and 13). The replacement of diethyl ether
by tertꢀbutyl methyl ether increased the reaction duraꢀ
* Numeration of atoms in schemes does not correspond to the
IUPAC nomenclature and serves only for interpretation of NMR
spectra.

1310
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Burchak et al.
Scheme 3
Reagents, conditions, and yields: i. LiAlH4/ether, ∼20 °C, 5 h, 97% yield, ratio 11 : 13 ∼1 : 2; ii. LiAlH4/ButOMe, ∼20 °C, 2 days,
63% yield; iii. AcCl/NEt3/CH2Cl2, ∼20 °C, 15 min, 45% yield; iv. 1) ArCHO/C6H6, ∆, 2 h; 2) NaBH4/MeOH, ∆, 0.5 h, 73% yield
(15ꢀ( )), 64% yield (16ꢀ( )).
tion, decreased the yield of amine, and increased the
relative content of transꢀisomer 13 among the reduction
products: the maximum yield of the latter was 63% along
with the absence of noticeable amounts of cisꢀamine 11.
As follows from the results of a series of experiments in
tertꢀbutyl methyl ether, the reduction of nitrile 7 is very
sensitive to hydrogenation conditions and quality of the
initial reactants, and the yields of amine 13 range within
40—63% (cf. Ref. 23). cis/transꢀIsomerization and the
complete racemization of the reduction product 13 are
observed even at 20 °С. The predominant formation of
transꢀamine 13 in both diethyl and tertꢀbutyl methyl ethers
is explained by a higher thermodynamic stability of the
transꢀisomer. According to calculations by the molecuꢀ
lar mechanics MM2 and quantumꢀchemical PM3 methꢀ
ods, the heat of formation of transꢀamine 13 is lower
of reduction of nitrile 7 with LiAlH4 in tertꢀbutyl methyl
ether. The racemization of optically active cyclopropane
compounds by LiAlH4 is a known process,23 which ocꢀ
curs, however, only when the reaction center is directly
bound to one of the atoms of the cyclopropane ring as,
for example, in the initial nitrile 7. To verify this asꢀ
sumption, we reduced compound 17,19 which is a
homolog of compound 7, under similar conditions
(Scheme 4).
Scheme 4
than that of its cisꢀisomer 11 by ∼3 kcal mol–1
.
The acetylation of amine 13 with acetyl chloride afꢀ
forded the corresponding acetamide 14, whose signals in
1
the Н and 13С NMR spectra were completely assigned.
Taking into account these spectral data, we assigned the
signals for cisꢀacetamide 12, which was obtained only in
a mixture with transꢀacetamide 14 by the acetylation of
the product of reduction of nitrile 7 with LiAlH4 in
diethyl ether. The condensation of transꢀamine 13 with
metaꢀphenoxybenzaldehyde or benzaldehyde followed by
the reduction of Schiff´s bases with NaBH4 easily affords
the corresponding arylmethylamines 15 and 16 in high
yields.
Reagents, conditions, and yields: i. LiAlH4/ether, ∼20 °C, 2 days,
70% yield (18). ii. AcCl/NEt3/CH2Cl2, ∼20 °C, 15 min,
86% yield (19).
The absence of optical activity for both acetamide 14
and amines 15 and 16 indicates racemization at the stage
Nitrile 17 is reduced in diethyl ether without epiꢀ
merization much more slowly and in a lower yield (70%)

Indolic analogs of (1R)ꢀcisꢀchrysanthemates
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1311
than nitrile 7. This is indicated by the vicinal spinꢀspin
coupling constant JH(4),H(6) = 9.0 Hz, which is characꢀ
teristic of cisꢀ1,2ꢀdisubstituted cyclopropanes. In addiꢀ
tion, the product of reduction of 17 is not noticeably
racemized during the reaction.
chrysanthemylamines 20 and 21 possessed a considerꢀ
able optical activity and has the cisꢀarrangement of subꢀ
stituents in the cyclopropane ring, i.e., represented
(1R)ꢀcisꢀchrysanthemylamine derivatives. Moreover,
compounds 20d and 21d are heterocyclic aza anaꢀ
logs of the known pyrethroid insecticide cyphenothrin
(cf. Ref. 18). It is important that the Nꢀcyanamide group
is retained in the final products because, in particular,
Nꢀcyanamides exhibit different biological activities.25—28
In addition, many possibilities of the chemical transforꢀ
mation of the —N(CN)R group are known,29—33 includꢀ
ing those into other pharmacophoric groups.34—38 It also
seems significant that cyanamides can be involved
in heterocyclization to form oxazoles,39 oxazines,40
oxazolines,41,42 thiazoles,43 pyrrolidines,44 triazines,45 and
pyrimidines.46 Thus, Nꢀcyanamides 20—21 can serve as
intermediates in synthesis of other, practically signifiꢀ
cant compounds.
3
Since either a mixture of cisꢀ (11) and transꢀisomers
(13), or racemic transꢀamine 13 was obtained in the
synthesis of the indolic analog of chrysanthemylamine,
we applied another sequence of transformations to synꢀ
thesize analogs of Nꢀsubstituted (1R)ꢀcisꢀchrysanthemylꢀ
amines in the enantiomerically pure form. ωꢀKetonitrile
4 has recently been shown24 to be easily transformed
into various Nꢀsubstituted Nꢀcyanamides 6a—d containꢀ
ing the metaꢀphenoxybenzyl and polyfluorobenzyl subꢀ
stituents, which are the most promising from the viewꢀ
point of the insecticidal activity of pyrethroids. Based on
ωꢀketoꢀNꢀcyanamides 6a—d, we synthesized a series of
heterocyclic compounds 20a—d and 21a—d containing
the indole fragment (Scheme 5).
Fischer indole synthesis as a method for heterocycle
formation turned out to be appropriate for ketocyanꢀ
amides and allowed the preparation of indole derivaꢀ
tives 20a—d in high yields (51—95%). In the case of
1ꢀnaphthylhydrazine and 8ꢀquinolylhydrazine, the tarꢀ
get products were obtained in moderate yields (except
for 21a (69%)). All synthesized indolic analogs of
The Nꢀcyano group, which is used as protective for
amines, can easily be removed under the action of reꢀ
ducing agents or by hydrolysis.47—52 In fact, the reducꢀ
tion of Nꢀcyanamide 20а with LiAlH4 in ButOMe afꢀ
fords benzylamine 22, viz., cisꢀisomer of compound 16
(Scheme 5). A comparison of the chemical shifts of sigꢀ
1
nals and the spinꢀspin coupling character in the Н and
13С NMR spectra of compounds 16 and 22 shows that
Scheme 5
X = N (21a,b,d), CH (21c)
Reagents, conditions, and yields: i. 1) ArNHNH2/MeOH, ∼20 °C, 2 h; 2) PPE/CH2Cl2, ∼20 °C, 20 h; 95% (20a), 79% (20b),
51% (20c), 74% (20d); 69% (21a), 33% (21b), 30% (21c), 41% (21d) yields. ii. LiAlH4/ButOMe, ∼20 °C, 2 h, 53% yield (22).

1312
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Burchak et al.
(100), 193 (11), 184 (18), 182 (20), 181 (12), 168 (13), 167
(11), 144 (28), 143 (30), 131 (11). Found: m/z 224.1315 [М]+.
С15H16N2. Calculated: М = 224.1313.
the NMR spectra of samples 16 and 22 differ signifiꢀ
cantly despite the structural similarity of these amines.
Thus, the NMR spectra allow these compounds and their
closest analogs and derivatives to be unambiguously disꢀ
tinguished.
Synthesis of indolonitriles 7 and 8 in РРА. Phenylhydrazine
(0.48 g, 4.4 mmol) was added to a solution of ketone 5 (0.60 g,
4.0 mmol) in MeOH (10 mL). The mixture was stored for 2 h
at ∼20 °C, the solvent was removed in vacuo, and PPA54 (10.0 g)
was added to the residue (light yellow oil). The mixture was
stirred to complete dissolution of the hydrazone, and the reꢀ
sulting solution was stored for 8 h at 50 °C. The mixture was
diluted with water (30 mL), neutralized by a 25% aqueous
solution of NH3 to рН ∼9, and extracted with ButOMe
(3×10 mL). The ether extract was dried with anhydrous Na2SO4,
and the solvent was removed in vacuo. The residue (0.85 g) was
chromatographed on a column packed with SiO2 (eluent
AcOEt—petroleum ether, 1 : 4), and a mixture (0.040 g) of cisꢀ
and transꢀcyclopropanecarbonitriles 7 and 8 was obtained in a
Experimental
Thin layer chromatography was carried out on Silufol plates.
To develop spots, plates were sprayed with ethanolic solutions
of vanillin (1 g of vanillin + 10 mL of concentrated H2SO4 in
100 mL in 95% EtOH) or ninhydrin (0.25 g of ninhydrin and
25 mL of АсОН in 100 mL of 95% EtOH) and heated. Silica
gel (KSK trade mark) with a pore size of 0.140—0.315 mm
activated at 140 °C for 6—7 h was used for preparative column
chromatography.
1
UV spectra were obtained on a Specord Mꢀ40 spectrophoꢀ
tometer in 95% EtOH (c 1•10–4 mol L–1). IR spectra were
recorded on a Bruker Vectorꢀ22 instrument. Mass spectra were
obtained on a Finnigan MAT 8200 spectrometer (50—100 °C,
ratio of 2 : 1 according to the Н NMR spectral data (overall
yield 44%).
transꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)cycloꢀ
1
propanecarbonitrile (8). H NMR ((СD3)2СO), δ: 0.98 (s, 3 H,
1
EI, 70 eV). H and 13C NMR spectra were recorded on Bruker
H3С(8)); 1.54 (s, 3 H, H3С(9)); 1.78 (d, 1 H, H(6), J = 5.8 Hz);
2.30 (dq, 1 H, H(4), J1 = 5.8 Hz, J2 = 1.2 Hz); 2.43 (d,
3 H, H3С(1), J = 1.2 Hz); 6.99 (m, 2 H, H(3a), H(4a));
7.26 (m, 1 H, H(2a)); 7.46 (m, 1 H, H(5a)); 10.00 (br.s,
1 H, NHindole).
ACꢀ200 (1H, 200.13 MHz; 13C, 50.32 MHz), Bruker AMꢀ400
(1H, 400.13 MHz; 13C, 100.61 MHz), and Bruker DRXꢀ500
(1H, 500.13 MHz; 13С, 125.77 MHz) spectrometers for soluꢀ
tions with a concentration of 70—100 mg mL–1 at 25—27 °C.
The signal from the solvent was used as internal standard:
chloroformꢀd (δ 76.90 ppm, δ 7.24), dimethylsulfoxideꢀd6
Amide of (+)ꢀ(1R,3S)ꢀ2,2ꢀdimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ
3ꢀyl)cyclopropanecarboxylic acid (9). NaOH (0.40 g, 10 mmol)
was added to a solution of nitrile 7 (0.45 g, 2.0 mmol) in 15 mL
of MeOH, and 15 mL of a 33% aqueous solution of H2O2 was
added dropwise with stirring. The reaction mixture was stored
for 2 days at ∼20 °C, diluted with water (50 mL), saturated with
solid NaCl, and extracted with ButOMe (3×10 mL). The ether
extract was dried with anhydrous Na2SO4, and the solvent was
removed in vacuo. The yellow oil that obtained (0.42 g) was
chromatographed on a column packed with SiO2 (eluent
AcOEt—petroleum ether, 1 : 1). Glassy amide 9 was obtained
С
Н
(δ 39.50, δ 2.50), acetoneꢀd6 (δ 29.80, δ 2.04), and С6F6
С
Н
С
Н
(δ 162.90). Angles of optical rotation were measured on a
F
Polamat A polarimeter for solutions in CHCl3. Melting points
were determined on a Kofler stage.
(+)ꢀ(1R,3S)ꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)cycloꢀ
propanecarbonitrile (7). Phenylhydrazine (0.36 g, 3.3 mmol)
was added to a solution of ketone 5 17 (0.45 g, 3.0 mmol) in
MeOH (10 mL), the mixture was stored for 2 h at ∼20 °C, and
the solvent was removed in vacuo. The residue (light yellow oil)
was dissolved in 10 mL of anhydrous CH2Cl2, PPE (2.0 g) was
added,53 and the mixture was left for 12 h at ∼20 °C. The
solvent was removed in vacuo, and the dark brown oil that
formed was mixed with 15 mL of an aqueous solution of Na2CO3
(0.5 mol L–1) and extracted with ButOMe (3×10 mL). The
ether extract was dried with anhydrous Na2SO4, and the solꢀ
vent was removed in vacuo. The residue (0.80 g) was chromatoꢀ
graphed on a column packed with SiO2 (eluent AcOEt—petroꢀ
leum ether, 1 : 4), and crystalline indole 7 was obtained
(0.5 g, 75%) with m.p. 154—157 °С (from EtOAc—hexane).
28
in 45% yield (0.22 g), [α]578 +95 (с 1.98). UV (EtOH),
λ
max/nm (ε): 226 (33900), 283 (6500), 291 (6000). IR (in
CHCl3), ν/cm–1: 3500 (NHamide), 3475 (NHindole), 1670
(C=Oamide), 1650 (NHamide), 1455 (C=Carom). 1H NMR
(СDCl3), δ: 1.24 (s, 3 H, H3С(8)); 1.40 (s, 3 H, H3С(9)); 1.74
(d, 1 H, H(6), J = 8.5 Hz); 2.13 (d, 1 H, H(4), J = 8.3 Hz);
2.24 (s, 3 H, H3С(1)); 5.43, 5.63 (both br.s, 1 H + 1 H, NH2);
6.99—7.05 (m, 2 H, H(3a), H(4a)); 7.15 (m, 1 H, H(2a)); 7.44
(m, 1 H, H(5a)); 8.52 (br.s, 1 H, NHindole). 13C NMR (СDCl3),
δ: 12.61 (q, C(1)); 17.39 (q, C(8)); 24.26 (s, C(5)); 28.09 and
31.97 (both d, С(4), C(6)); 29.41 (q, C(9)); 31.97 (d, C(4));
104.93 (s, C(3)); 110.32 (d, C(5a)); 118.92, 118.97 and
120.80 (all d, C(2a), C(3a), C(4a)); 128.88 (s, C(1a)); 134.96
and 135.37 (both s, C(2), C(6a)); 174.34 (s, С(7)). MS,
m/z (Irel (%)): 242 [М]+ (22), 199 (15), 198 (100), 183 (16),
182 (14), 168 (15), 43 (15). Found: m/z 242.1415 [М]+.
С15H18N2O. Calculated: М = 242.1419.
30
[α]578 +106 (c 2.44). UV (EtOH), λmax/nm (ε): 224 (30500),
282 (6700), 290 (5600). IR (film), ν/cm–1: 3375 (NHindole),
2240 (C=N), 1455 (C=Carom), 1235, 735 (C—Harom). 1H NMR
((СD3)2СO: 1.22 (s, 3 H, H3С(8)); 1.45 (s, 3 H, H3С(9)); 1.97
(d, 1 H, H(6), J = 8.3 Hz); 2.28 (dq, 1 H, H(4), J1 = 8.3 Hz,
J2 = 1.2 Hz); 2.50 (d, 3 H, Н3С(1), J = 1.2 Hz); 6.99 and 7.03
(both ddd, 1 H, H(3a), H(4a), J1 = J2 = 7.1 Hz, J3 = 1.3 Hz);
7.28 (m, 1 H, H(2a)); 7.49 (m, 1 H, H(5a)); 9.98 (br.s, 1 H,
NHindole). 13C NMR ((СD3)2СO), δ: 13.11 (q, C(1)); 16.21
(d, C(6)); 19.27 (q, C(8)); 24.02 (s, C(5)); 26.38 (q, C(9));
27.87 (d, C(4)); 105.62 (s, C(3)); 111.20 (d, C(5a)); 119.43,
119.66 and 121.36 (all d, C(2a), C(3a), C(4a)); 120.26 (s, С(7));
129.83 (s, C(1a)); 135.92 and 136.60 (both s, C(2), C(6a)).
MS, m/z (Irel (%)): 225 (13), 224 [М]+ (76), 210 (16), 209
( )ꢀ4,4ꢀDimethylꢀ5ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)pyrrolidinꢀ
2ꢀone (10). Powdered KOH (0.56 g, 10.0 mmol) was added to a
solution of nitrile 7 (0.45 g, 2.0 mmol) in 10 mL of ButOH, and
the mixture was boiled with stirring at 1 h. The reaction mixꢀ
ture was cooled, diluted with water (50 mL), and extracted
with ButOMe (3×10 mL). The ether extract was dried with
anhydrous Na2SO4, the solvent was removed in vacuo, and

Indolic analogs of (1R)ꢀcisꢀchrysanthemates
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1313
crystalline product 10 was obtained in 83% yield (0.40 g)
with m.p. 265—267 °С (from MeOH), [α]578 0.0 (с 2.14).
Cꢀ[cisꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)cycloꢀ
propyl]methylamine (11). H NMR (СDCl3—СCl4), δ: 1.04 (s,
30
1
UV (EtOH), λmax/nm (ε): 224 (36600), 282 (7000), 290 (6100).
IR (in KBr), ν/cm–1: 3250, 3225 (NHindole and NHlactam);
1670 (C=Olactam); 1455 (C=Carom); 755 and 740 (C—Harom).
1H NMR ((СD3)2SO), δ: 0.72 (s, 3 H, H3С(8)); 1.20 (s, 3 H,
H3С(9)); 2.16 (m, 2 H, Н2С(6)); 2.37 (s, 3 H, H3С(1)); 4.64
(s, 1 H, H(4)); 6.92 and 6.99 (both m, 1 H, H(3a), H(4a));
7.26 (m, 1 H, H(2a)); 7.43 (m, 1 H, H(5a)); 7.83 (br.s, 1 H,
NHindole); 10.85 (br.s, 1 H, NHamide). 13C NMR ((СD3)2SO),
δ: 11.95 (q, C(1)); 24.21 (q, C(8)); 28.12 (q, C(9)); 40.52 (s,
C(5)); 46.08 (t, C(6)); 61.12 (d, C(4)); 107.48 (s, C(3)); 110.41
(d, C(5a)); 118.30, 118.74 and 119.84 (all d, C(2a), C(3a),
C(4a)); 127.47 (s, C(1a)); 132.81 and 135.17 (both s, C(2),
C(6a)); 175.60 (s, С(7)). MS, m/z (Irel (%)): 243 (16), 242 [М]+
(53), 185 (11), 159 (36), 158 (100), 157 (27), 143 (17), 130
(16). Found: m/z 242.1418 [М]+. С15H18N2O. Calculated:
М = 242.1419.
3 H, H3С(8)); 1.34 (m, 1 Н, H(6)); 1.35 (s, 3 H, H3С(9)); 1.52
(br.s, 2 H, NH2); 1.76 (dq, 1 H, H(4); J1 = 9.0 Hz, J2 = 1.0 Hz);
2.33 (d, 3 H, H3С(1), J = 1.0 Hz),); 2.85 (m, 2 H, H2С(7));
6.96 (m, 2 H, H(3a), H(4a)); 7.10 (m, 1 H, H(2a)); 7.42 (m,
1 H, H(5a)); 7.86 (br.s, 1 H, NHindole).
( )ꢀNꢀ[transꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropylmethyl]acetamide (14). Et3N (0.08 g, 0.75 mmol)
was added to a solution of amine 13 (0.11 g, 0.50 mmol) in
anhydrous CH2Cl2, and AcCl (0.06 g, 0.75 mmol) was added
dropwise with stirring. After 15 min the solvent was removed in
vacuo, the residue was stirred with H2O (10 mL) and ButOMe
(10 mL), and the organic layer was extracted with ButOMe
(3×5 mL). The combined organic extracts were washed with a
1 М aqueous solution of HCl and a 0.5 М solution of Na2СO3,
and the solvent was removed in vacuo. The brown oil that
formed (0.12 g) was chromatographed on a column packed
with SiO2 (eluent AcOEt—petroleum ether, 1 : 1, AcOEt,
5% MeOH in AcOEt). Amide 14 was obtained in 45% yield
Reaction of amide 9 with EtOH in the presence of H2SO4.
Water (1.9 mL) and concentrated H2SO4 (3.6 mL) were added
to a solution of amide 9 (0.48 g, 2.0 mmol) in 16.3 mL of
EtOH. The mixture was boiled with a reflux condenser for
10 h. After cooling Н2О (50 mL) was added, and the mixture
was extracted with ButOMe (3×10 mL). The ether extract was
15
(0.11 g), [α]578 0.0 (с 1.27). UV (EtOH), λmax/nm (ε): 227
(21900), 284 (6000), 292 (5500). IR (in CHCl3), ν/cm–1: 3470
(NHindole), 3315 (NHamide), 1665 (C=Oamide), 1515 (NHamide),
1460 (C=Carom). 1H NMR ((СD3)2СO), δ: 0.81 (s, 3 H,
Н3С(8)); 1.26 (m, 1 H, H(6)); 1.35 (s, 3 H, Н3С(9)); 1.48 (dq,
1 H, H(4), J1 = 6.0 Hz, J2 = 1.0 Hz); 1.94 (s, 3 H, Н3С(2b));
2.37 (d, 3 H, Н3С(1), J = 1.0 Hz); 3.37 (ddd, 1 H, Н(7α),
J1 = 14.0 Hz, J2 = 8.0 Hz, J3 = 6.5 Hz); 3.59 (ddd, 1 H, Н(7β),
J1 = 14.0 Hz, J2 = 7.0 Hz, J3 = 6.0 Hz); 6.94 (m, 2 H, H(3a),
H(4a)); 7.22 (m, 1 H, H(2a)); 7.41 (m, 1 H, NHamide); 7.46
(m, 1 H, H(5а)); 9.87 (br.s, 1 H, NHindole). 13C NMR
((СD3)2СO), δ: 12.29 (q, C(1)); 21.45 (q, C(8)); 21.58 (s,
C(5)); 22.97 (q, C(9)); 23.17 (d, C(4)); 26.03 (d, C(6)); 30.56
(q, С(2b)); 40.69 (t, C(7)); 109.66 (s, C(3)); 111.05 (d, C(5a));
119.17, 119.17 and 120.82 (all d, C(2a), C(3a), C(4a)); 130.86
(s, C(1b)); 134.29 and 136.50 (both s, C(2), C(6a)); 170.10
(s, (1b)). MS, m/z (Irel (%)): 270 [М]+ (7), 199 (16), 198 (100),
183 (18), 182 (12), 168 (16), 167 (7), 144 (11), 28 (7). Found:
m/z 270.1729 [М]+. С17H22N2O. Calculated: М = 270.1732.
Acetylation of a mixture of amines 11 and 13. A mixture of
acetamides 12 and 14 (0.15 g, 56%) was obtained similarly to
the previous procedure from a mixture of amines 11 and 13
(0.23 g, 1.0 mmol), Et3N (0.15 g, 1.5 mmol), and AcCl (0.12 g,
1.5 mmol).
washed with an aqueous solution of Na2СO3 (0.5 mol L–1
,
15 mL) and a saturated solution of NaCl (15 mL) and dried
with anhydrous Na2SO4. The solvent was removed in vacuo,
and a glassy brown mixture (0.34 g) was obtained and chromaꢀ
tographed (SiO2, eluent AcOEt). Crystalline lactam 10 was
obtained in 30% yield (0.15 g).
Reduction of nitriles to amines (general procedure А).
A solution of nitrile in the corresponding ether (20 mL) was
added dropwise to a suspension of LiAlH4 in Et2O or ButOMe.
The mixture was stirred at ∼20 °C for several hours until the
reaction completed (TLC monitoring). Then ether (20 mL)
was added, and the reaction mixture was poured into water
(50 mL). The organic layer was separated, and the aqueous
phase was extracted with ether (3×15 mL). The combined orꢀ
ganic phase was treated with a 1 N solution of HCl (3×10 mL).
The aqueous phase was neutralized with a 25% aqueous soluꢀ
tion of NH3 to pH ∼9 and extracted with ether (3×10 mL). The
extract was dried with anhydrous Na2SO4, the solvent was reꢀ
moved in vacuo, and the corresponding amine was obtained.
( )ꢀCꢀ[transꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropyl]methylamine (13) was prepared by procedure А
from a suspension of LiAlH4 (0.51 g, 13.5 mmol) in freshly
distilled ButOMe (10 mL) and a solution of nitrile 7 (1.01 g,
4.5 mmol) in ButOMe (20 mL). The reaction was carried out
for 2 days at ∼20 °C. After standard treatment amine 13 was
Nꢀ[cisꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)cycloꢀ
propylmethyl]acetamide (12). 1H NMR (СDCl3), δ: 1.02 (s,
3 H, Н3С(8)); 1.19 (m, 1 H, H(6)); 1.32 (s, 3 H, Н3С(9)); 1.72
(dq, 1 H, H(4), J1 = 9.0 Hz, J2 = 1.2 Hz); 1.93 (s, 3 H,
СН3CO); 2.26 (d, 3 H, Н3С(1), J = 1.2 Hz); 2.77 (ddd, 1 H,
Н(7α), J1 = 14.0 Hz, J2 = 9.5 Hz, J3 = 5.0 Hz); 3.70 (ddd, 1 H,
Н(7β), J1 = 14.0 Hz, J2 = J3 = 6.0 Hz); 5.76 (br.t, 1 H,
NHamide, J1 = 6.0 Hz, J2 = 5.0 Hz); 7.03 (m, 2 H, H(3a),
H(4a)); 7.18 (m, 1 H, H(2a)); 7.46 (m, 1 H, H(5а)); 8.30 (br.s,
1 H, NHindole). 13C NMR (СDCl3), δ: 12.76 (q, C(1)); 16.92
(q, C(8)); 18.22 (s, C(5)); 22.92 (d, C(4)); 23.11 (q, C(2b));
26.16 (d, C(6)); 28.88 (q, C(9)); 38.28 (t, C(7)); 107.46 (s,
C(3)); 110.05 (d, C(5a)); 118.54, 118.84 and 120.55 (all d,
C(2a), C(3a), C(4a)); 129.60 (s, C(1a)); 133.86 and 135.38
(both s, C(2), C(6a)); 169.94 (s, C(1b)).
1
obtained in 63% yield (0.65 g). H NMR (СDCl3—СCl4), δ:
0.83 (s, 3 H, H3С(8)); 1.32 (m, 1 Н, H(6)); 1.34 (s, 3 H,
H3С(9)); 1.60 (br.s, 2 H, NH2); 1.66 (dq, 1 H, H(4), J1
=
9.0 Hz, J2 = 1.0 Hz); 2.35 (d, 3 H, H3С(1), J = 1.0 Hz); 3.05
(m, 2 H, H2С(7)); 6.96 (m, 2 H, H(3a), H(4a)); 7.10 (m, 1 H,
H(2a)); 7.42 (m, 1 H, H(5a)); 7.81 (br.s, 1 H, NHindole).
A mixture (0.33 g, 97%) of cisꢀ and transꢀamines 11 and 13
1
(according to the data of the Н NMR spectrum, 1 : 2 ratio,
respectively) was obtained after standard treatment using proꢀ
cedure А from a suspension of LiAlH4 (0.15 g, 4.5 mmol) in
anhydrous Et2O (10 mL) and a solution of nitrile 7 (0.34 g,
1.5 mmol) in Et2O (20 mL).
Synthesis of disubstituted amines (general procedure B). Aroꢀ
matic aldehyde (1.1 mmol) was added to a solution of amine 13

1314
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Burchak et al.
(0.23 g, 1 mmol) in C6H6 (15 mL). The mixture was boiled
with a DeanꢀStark trap for 2 h until the initial amide disapꢀ
peared (TLC monitoring), after which the solvent was removed
in vacuo. The resulting imine obtained as a yellowish oil was
dissolved in MeOH (10 mL), and NaBH4 (0.19 g, 5 mmol) was
added by portions for 10—15 min. The reaction mixture was
boiled for 0.5 h, and the solvent was removed in vacuo. The
residue was mixed with ButOMe (10 mL), and 20 mL of water
were added. The organic layer was separated, and the aqueous
phase was extracted with ButOMe (3×10 mL). The combined
organic extracts were dried with anhydrous Na2SO4, and the
solvent was removed in vacuo. The residue was chromatographed
on a column packed with SiO2 (eluent ethyl acetate—hexane,
2 : 3) to isolate the corresponding amine.
109.89 (d, C(5a)); 118.81, 119.00 and 120.65 (all d, C(2a),
C(3a), C(4a)); 126.81 (d, С(5b)); 128.00 and 128.30 (both d,
2 С, C(3b), С(4b)); 129.98 (s, C(1a)); 132.66 and 135.02
(both s, C(2), C(6a)); 140.41 (s, C(2b)). MS, m/z (Irel (%)):
318 [М]+ (3), 254 (13), 199 (33), 198 (100), 183 (10), 168 (11),
120 (45), 91 (72). Found: m/z 318.2098 [М]+. С22H26N2. Calꢀ
culated: М = 318.2096.
(+)ꢀ(1R,3S)ꢀ2ꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropyl]ethylamine (18) was synthesized according to proꢀ
cedure A from a suspension of LiAlH4 (0.19 g, 5.0 mmol) in
anhydrous Et2O (10 mL) and a solution of nitrile 17 (0.48 g,
2.0 mmol) in 20 mL of Et2O. The reaction was carried out for
2 days at ∼20 °C. Amine 18 was obtained in 70% yield (0.34 g)
after standard treatment. 1H NMR (СDCl3—СCl4), δ: 0.84
(m, 1 H, Н(6)); 0.95 (s, 3 H, Н3С(8)); 1.28 (s, 3 H, Н3С(9));
1.38 (br.s, 2 H, NH2); 1.59 (dq, 1 H, H(4), J1 = 8.6 Hz,
J2 = 1.0 Hz); 1.80 (m, 2 H, Н2С(7)); 2.25 (d, 3 H, Н3С(9);
J1 = 1.0 Hz); 2.70 (m, 2 H, H2С(8)); 6.94 (m, 2 Н, H(3a),
H(4a)); 7.03 (m, 1 H, Н(2а)); 7.41 (m, 1 H, H(5a)); 8.12 (br.s,
1 H, NHindole).
( )ꢀNꢀ[transꢀ2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropylmethyl]ꢀNꢀ(3ꢀphenoxybenzyl)amine (15) was
prepared using procedure B from amine 13 (0.23 g) and
mꢀC6H5ОC6H4CHO (0.22 g). Chromatography gave amine 15
15
(0.30 g, 73%), [α]578 0.0 (с 1.62). UV (EtOH), λmax/nm (ε):
228 (23700), 280 (5800), 293 (5600). IR (film), ν/cm–1: 3405
(NHindole), 3290 (NHamine), 1585, 1490, 1460 (C=Carom), 1250,
1210, 740 and 695 (C—Harom). H NMR (CDCl3—ССl4), δ:
(+)ꢀ(1R,3S)ꢀNꢀ{2ꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropyl]ethyl}acetamide (19) was synthesized according
to the procedure used for preparation of acetamide 14. Acetaꢀ
mide 19 was obtained in 86% yield (0.12 g) from amine 18
(0.12 g, 0.5 mmol), Et3N (0.07 g, 0.7 mmol), and AcCl
1
0.86 (s, 3 H, Н3С(8)); 1.30—1.46 (m, 2 H, H(4), H(6)); 1.32
(s, 3 H, Н3С(9)); 1.60 (br.s, 1 H, NHamine); 2.36 (s, 3 H,
Н3С(1)); 2.80 (dd, 1 H, Н(7α), J1 = 12.5 Hz, J2 = 8.0 Hz);
3.02 (dd, 1 H, Н(7β), J1 = 14.0 Hz, J2 = 6.5 Hz); 3.89 (m, 2 H,
H(1b)); 6.88—7.19 and 7.26—7.33 (both m, 9 H and 3 H,
respectively, H(2a), H(3a), H(4a), H(3b), H(5b), H(6b), H(7b)
H(9b), H(10b), H(11b)); 7.55 (m, 1 H, H(5a)); 7.73 (br.s, 1 H,
NHindole). 13C NMR (CDCl3—CCl4), δ: 12.33 (q, C(1)); 20.72
(s, C(5)); 21.23 (q, C(8)); 22.97 (q, C(9)); 25.13 (d, C(4));
30.12 (d, C(6)); 50.25 (t, C(7)); 53.73 (t, C(1b)); 109.90 (d,
C(5a)); 109.99 (s, C(3)); 117.33* (d, C(5b)); 118.41, 119.06,
120.70 (all d, C(2a), C(3a), C(4a)); 118.82* (d, 3 C, С(3b),
С(9b)); 122.80 and 123.04 (both d, С(7b), С(11b)); 129.56 (d,
2 С, C(10b); 129.61 (d, С(6b)); 129.96 (s, C(1a)); 132.59 and
135.02 (both s, C(2), C(6a)); 142.65 (s, C(2b)); 157.28 and
157.39 (both s, С(6b), С(8b)). MS, m/z (Irel (%)): 410 [М]+ (3),
212 (29), 199 (45), 198 (100), 184 (13), 183 (69), 182 (11), 168
(14), 167 (11), 149 (13), 28 (12). Found: m/z 410.2359 [М]+.
С28H30N2O. Calculated: М = 410.2358.
24
(0.06 g, 0.7 mmol). [α]578 +84 (с 2.35). UV (EtOH),
λ
max/nm (ε): 227 (23000), 284 (6200), 291 (5700). IR (KBr),
ν/cm–1: 3400 (NHindole), 3285 (NHamide), 1655 (C=Oamide),
1555 (NHamide), 1460 (C=Carom), 740 (С—Нarom). H NMR
1
((СD3)2СO—СDCl3—СCl4), δ: 0.91 (ddd, 1 H, H(6),
J1 = 13.0 Hz, J2 = 9.0 Hz, J3 = 4.5 Hz); 1.05 (m, 1 Н, Н(7α));
1.10 (s, 3 H, Н3С(9)); 1.28 (s, 3 H, Н3С(10)); 1.59 (dq, 1 H,
H(4), J1 = 9.0 Hz, J2 = 1.0 Hz); 1.81 (s, 3 H, СН3СО); 1.89
(m, 1 Н, Н(7β)); 2.33 (d, 3 H, С(1)Me, J = 1.0 Hz); 3.16 (m,
2 H, H2С(8)); 6.86 (m, 2 H, H(3a), H(4a)); 7.05 (br.s, 1 H,
NHamide); 7.14 (m, 1 H, H(2a)); 7.38 (m, 1 H, H(5a)); 9.72
(br.s, 1 H, NHindole). 13C NMR ((СD3)2СO—СDCl3—СCl4),
δ: 13.31 (q, C(1)); 17.45 (q, C(9)); 18.54 (s, C(5)); 22.83
(q, СН3СО); 23.55 (t, C(7)); 23.66 (d, C(4)); 27.74 (d, C(6));
29.70 (q, C(10)); 40.19 (t, C(8)); 108.51 (s, C(3)); 110.62
(d, C(5a)); 118.58, 119.80 and 120.54 (all d, C(2a), C(3a),
C(4a)); 130.53 (s, C(1a)); 134.57 and 136.52 (both s, C(2),
C(6a)); 169.90 (s, C=О). MS, m/z (Irel (%)): 285 [М++1] (10),
284 [М]+ (50), 225 (19), 224 (12), 212 (34), 210 (37), 199 (17),
198 (100), 183 (20), 182 (32), 170 (19), 169 (15), 168 (36), 167
(13), 154 (11), 144 (41), 131 (63). Found: m/z 284.1888 [М]+.
С18H24N2O. Calculated: М = 284.1889.
Synthesis of indoles 20a—d and 21a—d (general procedure C).
Arylhydrazine (or its hydrochloride) (0.55 mmol) and powꢀ
dered Na2CO3 (0.03 g) (only in the case of using arylhydrazine
salt) were added to a solution of ketone 6 (0.50 mmol) in
10 mL of MeOH. The mixture was stored for 2 h at ∼20 °C, and
after filtration the solvent was removed in vacuo. The residue
(hydrazone in the form of a light yellow oil) was dissolved in
10 mL of anhydrous CH2Cl2, and PPE (1.0 g) was added. After
stirring the reaction mixture was left for 12 h at ∼20 °C, and the
solvent was removed in vacuo. A 0.5 М aqueous solution of
Na2CO3 (15 mL) was poured to the obtained dark brown oil, and
the resulting solution was extracted with ButOMe (3×10 mL).
The ether extract was dried with anhydrous Na2SO4, and the
solvent was removed in vacuo. The corresponding indoles were
( )ꢀNꢀBenzylꢀNꢀ[transꢀ2,2ꢀdimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ
3ꢀyl)cyclopropylmethyl]amine (16) was prepared according to
procedure B from amine 13 (0.23 g) and C6H5CHO (0.12 g).
Amine 16 (0.20 g, 64%) was isolated after chromatography,
15
[α]578 0.0 (с 1.62). UV (EtOH), λmax/nm (ε): 227 (22100),
284 (5700), 294 (5400). IR (film), ν/cm–1: 3405 (NHindole),
3285 (NHamine), 1460 (C=Carom), 740 and 700 (C—Harom).
1H NMR (CDCl3—ССl4), δ: 0.87 (s, 3 H, Н3С(8)); 1.29—1.44
(m, 2 H, H(4), H(6)); 1.33 (s, 3 H, Н3С(9)); 1.70 (br.s, 1 H,
NHamine); 2.38 (s, 3 H, Н3С(1)); 2.80 (dd, 1 H, Н(7α),
J1 = 12.0 Hz, J2 = 8.0 Hz); 3.06 (dd, 1 H, Н(7β), J1 = 12.0 Hz,
J2 = 6.2 Hz); 3.92 (m, 2 H, Н2С(1b)); 7.04—7.09 (m, 2 H,
H(3a), H(4a)); 7.15—7.38 (m, 6 H, H(2a), H(3b), H(4b),
H(5b)); 7.55 (m, 1 H, H(5a)); 7.75 (br.s, 1 H, NHindole).
13C NMR (CDCl3—CCl4), δ: 12.31 (q, C(1)); 20.72 (s, C(5));
21.16 (q, C(8)); 22.94 (q, C(9)); 25.13 (d, C(4)); 30.12 (d,
C(6)); 50.31 (t, C(7)); 54.06 (t, C(1b)); 109.89 (s, C(3));
* Alternative assignment of signals is possible.

Indolic analogs of (1R)ꢀcisꢀchrysanthemates
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1315
obtained after chromatography on a column packed with SiO2
(eluent AcOEt—petroleum ether, 1 : 4).
m.p. 160—162 °С (from EtOAc—hexane mixture), [α]57820 +102
(с 0.92). UV (EtOH), λmax/nm (ε): 226 (49000), 283 (10100),
291 (9100). IR (KBr), ν/cm–1: 3375 (NHindole), 2205 (C≡N),
1510 (C=Carom), 745 (C—Harom). 1H NMR ((CD3)2СO), δ:
1.10 (s, 3 H, Н3С(8)); 1.36 (ddd, 1 H, H(6), J1 = 11.0 Hz, J2 =
9.0 Hz, J3 = 5.0 Hz); 1.38 (s, 3 H, Н3С(9)); 1.88 (d, 1 H, H(4),
J = 9.0 Hz); 2.39 (s, 3 H, Н3С(1)); 2.69 (dd, 1 H, H(7α), J1 =
12.0 Hz, J2 = 11.0 Hz); 3.75 (dd, 1 H, H(7β), J1 = 12.0 Hz,
J2 = 5.0 Hz); 4.40 (s, 2 H, Н2С(1b)); 6.94 and 7.00 (both dd,
1 H, H(3a), H(4a), J1 = J2 = 8.0 Hz); 7.24 (d, 1 H, H(2a), J =
8.0 Hz); 7.42 (d, 1 H, H(5a), J = 8.0 Hz); 9.87 (br.s, 1 H,
NHindole). 13C NMR ((CD3)2CO), δ*: 13.11 (q, C(1)); 17.24
(q, C(8)); 20.39 (s, C(5)); 24.75 (d, C(4)); 25.39 (d, C(6));
28.93 (q, C(9)); 43.46 (t, C(7)); 51.04 (t, C(1b)); 107.62 (s,
C(3)); 111.13 (d, C(5a)); 116.73 (s, C(10)); 119.29, 119.61 and
121.29 (all d, C(2a), C(3a), C(4a)); 130.52 (s, С(1a)); 135.23
and 136.90 (both s, C(2), C(6a)). 19F NMR (CDCl3—ССl4),
δ: 0.70 (m, F(4b)); 9.04 (m, F(5b)); 21.29 (m, F(3b)).
MS, m/z (Irel (%)): 433 [М]+ (10), 199 (16), 198 (100),
183 (8), 182 (9), 181 (9), 170 (13), 168 (9), 167 (5). Found:
m/z 433.1579 [М]+. C23H20N3F5. Calculated: М = 433.1577.
(+)ꢀ(1R,3S)ꢀNꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropylmethyl]ꢀNꢀ(3ꢀphenoxybenzyl)cyanamide (20d) was
prepared according to procedure C from ketone 6d (0.18 g) and
phenylhydrazine (0.06 g). After chromatography compound 20d
was obtained in 74% yield (0.16 g) as colorless crystals
(+)ꢀ(1R,3S)ꢀNꢀBenzylꢀNꢀ[2,2ꢀdimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀ
indolꢀ3ꢀyl)cyclopropylmethyl]cyanamide (20а) was obtained acꢀ
cording to procedure C from ketone 6a (0.14 g) and phenylꢀ
hydrazine (0.06 g). After chromatography cyanamide 20a was
isolated as a light yellow oil (0.16 g, 95%), [α]57820 +110 (с 3.68).
UV (EtOH), λmax/nm (ε): 226 (32700), 283 (7300), 291
(6500). IR (CCl4), ν/cm–1: 3480 (NHindole), 2210 (C≡N),
1460 (C=Carom), 800, 740 and 700 (C—Harom). 1H NMR
(CDCl3—ССl4), δ: 1.07 (s, 3 H, Н3С(8)); 1.32 (ddd, 1 H,
H(6), J1 = 11.0 Hz, J2 = 9.0 Hz, J3 = 6.0 Hz); 1.36 (s, 3 H,
Н3С(9)); 1.81 (dq, 1 H, H(4), J1 = 9.0 Hz, J2 = 0.8 Hz); 2.28
(d, 3 H, Н3С(1), J = 0.8 Hz); 2.48 (dd, 1 H, H(7α), J1 = 12.5,
J2 = 11.0 Hz); 3.42 (dd, 1 H, H(7β), J1 = 12.5 Hz, J2
=
6.0 Hz); 4.04 (m, 2 H, Н2С(1b)); 6.92—7.00 (m, 2 H, H(3a),
H(4a)); 7.10—7.14 (m, 1 H, H(2a); 7.14—7.21 (m, 4 H, H(5a),
H(3b), H(4b), H(5b)); 7.81 (br.s, 1 H, NHindole). 13C NMR
(CDCl3—CCl4), δ: 12.95 (q, C(1)); 17.01 (q, C(8)); 19.71 (s,
C(5)); 23.67 (d, C(4)); 24.44 (d, C(6)); 28.68 (q, C(9)); 49.47
(t, C(7)); 55.87 (t, C(1b)); 107.37 (s, C(3)); 110.16 (d, C(5a));
117.54 (s, C(10)); 118.79, 118.92 and 120.87 (all d, C(2a),
C(3a), C(4a)); 128.25 (d, C(5b)); 128.25 and 128.66 (both d,
2 C each, C(3b), С(4b)); 129.42 (s, C(1a)); 133.55 (s, C(2b));
134.80 and 135.49 (both s, C(2), C(6a)). MS, m/z (Irel (%)):
344 (2), 343 [М]+ (7), 199 (16), 198 (100), 183 (6), 182 (7),
168 (7), 167 (4), 91 (11). Found: m/z 343.2049 [М]+. С23H25N3.
Calculated: М = 343.2048.
20
with m.p. 160—163 °С (from MeCN), [α]578 +89 (с 1.65).
UV (EtOH), λmax/nm (ε): 226 (44500), 280 (8800), 291 (7100).
IR (KBr), ν/cm–1: 3290 (NHindole), 2215 (C≡N), 1585, 1490,
1460 (C=Carom), 780, 735 and 690 (C—Harom). 1H NMR
((CD3)2СO), δ: 1.07 (s, 3 H, Н3С(8)); 1.34 (ddd, 1 H, H(6),
J1 = 11.0 Hz, J2 = 9.1 Hz, J3 = 4.7 Hz); 1.36 (s, 3 H, Н3С(9));
1.83 (dq, 1 H, H(4), J1 = 9.1 Hz, J2 = 0.9 Hz); 2.34 (d, 3 H,
Н3С(1), J = 0.9 Hz); 2.59 (dd, 1 H, H(7α), J1 = 12.5 Hz, J2 =
11.0 Hz),); 3.72 (dd, 1 H, H(7β), J1 = 12.5 Hz, J2 = 4.7 Hz);
4.19 (s, 2 H, H2C(1b)); 6.90—7.00, 7.09—7.13 and 7.31—7.37
(all m, 6 Н, 2 Н and 3 H, H(3a), H(4a), H(3b), H(5b), H(6b),
H(7b), H(9b), H(10b), H(11b)); 7.22 (d, 1 H, H(2a), J =
8.0 Hz); 7.39 (d, 1 H, H(5a), J = 8.0 Hz); 9.78 (br.s, 1 H,
NHindole). 13C NMR ((CD3)2CO), δ: 13.15 (q, C(1)); 17.50
(q, C(8)); 20.23 (s, C(5)); 24.54 (d, C(4)); 25.60 (d, C(6));
29.00 (q, C(9)); 50.64 (t, C(7)); 55.99 (t, C(1b)); 107.63
(s, C(3)); 111.12 (d, C(5a)); 118.08 (s, C(10)); 119.18, 119.28,
119.39, 119.64 and 121.23 (all d, C(2a), C(3a), C(4a), C(3b),
C(5b)); 119.68 (d, 2 C, C(9b)); 124.18 and 124.33 (both d,
C(7b), C(11b)); 130.75 (d, 2 С, С(10b)); 131.01 (d, C(6b));
130.57 (s, C(1a)); 135.13 and 136.87 (both s, C(2), C(6a));
138.96 (s, C(2b)); 157.88 and 158.47 (both s, C(4b), C(8b)).
MS, m/z (Irel (%)): 435 [М]+ (3), 199 (15), 198 (100), 196 (9),
183 (19), 182 (10), 181 (9), 168 (16), 45 (13), 31 (25), 28
(13). Found: m/z 435.2309 [M]+. C29H29N3O. Calculated:
М = 435.2311.
(+)ꢀ(1R,3S)ꢀNꢀ(2,6ꢀDifluorophenylmethyl)ꢀNꢀ[2,2ꢀdimꢀ
ethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)cyclopropylmethyl]cyanamide
(20b) was prepared according to procedure C from ketone 6b
(0.15 g) and phenylhydrazine (0.06 g). After chromatography
cyanamide 20b was obtained in 79% yield (0.15 g) as a
20
light yellow viscous oil, [α]578 +107 (с 1.18). UV (EtOH),
λ
max/nm (ε): 226 (30400), 283 (6200), 291 (5600). IR (CCl4),
ν/см–1: 3480 (NHindole), 2215 (C≡N), 1475, 1460 (C=Carom),
1235, 1030, 810 (C—Harom). H NMR ((CD3)2СO), δ: 1.07 (s,
1
3 H, Н3С(8)); 1.38 (ddd, 1 H, H(6), J1 = 11.0 Hz, J2 = 9.0 Hz,
J3 = 5.0 Hz); 1.40 (s, 3 H, Н3С(9)); 1.83 (dq, 1 H, H(4), J1 =
9.0 Hz, J2 = 1.0 Hz); 2.36 (d, 3 H, Н3С(1), J = 1.0 Hz); 2.63
(dd, 1 H, H(7α), J1 = 12.5 Hz, J2 = 11.0 Hz); 3.72 (dd, 1 H,
H(7β), J1 = 12.5 Hz, J2 = 5.0 Hz); 4.27 (m, 2 H, Н2С(1b));
6.91—7.06, 7.21—7.26 and 7.33—7.50 (all m, 4 Н, 1 Н and
2 H, H(2a), H(3a), H(4a), H(5a), H(4b), H(5b)); 9.92 (br.s,
1 H, NHindole). 13C NMR ((CD3)2CO), δ: 13.14 (q, C(1));
17.30 (q, C(8)); 20.37 (s, C(5)); 24.91 (d, C(4)); 25.72 (d, C(6));
28.64 (q, C(9)); 43.61 (t, C(7)); 51.07 (t, С(1b)); 107.84
2
(s, C(3)); 111.19 (d, C(5a)); 112.35 (dd, JC,F = 25.4 Hz,
2
C(4b)); 112.41 (t, JC,F = 6.8 Hz, C(2b)); 117.18 (s, C(10));
119.38, 119.71, 121.33 (all d, C(2a), C(3a), C(4a)); 130.71 (s,
3
С(1a)); 132.30 (dt, JC,F = 10.6 Hz, C(5b)); 135.21 and 137.06
1
3
(both s, C(2), C(6a)); 162.45 (dd, JC,F = 250.4 Hz, JC,F
=
8.1 Hz, C(3b)). 19F NMR (CDCl3—ССl4), δ: 48.04 (t, F(3b),
J = 7.0 Hz). MS, m/z (Irel (%)): 379 [М]+ (6), 199 (16), 198
(100), 183 (7), 182 (10), 170 (5), 168 (10), 127 (17). Found:
m/z 379.1867 [М]+. С23H23N3F2. Calculated: М = 379.1860.
(+)ꢀ(1R,3S)ꢀNꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀ
yl)cyclopropylmethyl]ꢀNꢀ(pentafluorophenylmethyl)cyanamide
(20c) was prepared using procedure C from ketone 6c (0.18 g)
and phenylhydrazine (0.06 g). After chromatography compound
20c was isolated in 51% yield (0.11 g) as colorless crystals with
(+)ꢀ(1R,3S)ꢀNꢀBenzylꢀNꢀ[2,2ꢀdimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀ
pyrrolo[3,2ꢀh]quinolinꢀ3ꢀyl)cyclopropylmethyl]cyanamide (21а)
was prepared according to procedure C from ketone 6a (0.14 g)
and 8ꢀquinolylhydrazine (0.11 g). After chromatography comꢀ
* In the 13C NMR spectra of compounds 20c and 21c chemical
shifts of carbon atoms of the pentafluorobenzyl ring were not
determined because of their low intensity due to multiple SSC
constants JC,F
.

1316
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Burchak et al.
pound 21a was isolated (0.14 g, 69%) as a light yellow oil,
[α]578 +96 (с 1.85). UV (EtOH), λmax/nm (ε): 277 (33100),
334 (1600). IR (KBr), ν/cm–1: 3310 (NHindole), 2210 (C≡N),
1525, 1510 (C=Carom), 1140, 810 and 760 (C—Harom). 1H NMR
((CD3)2СO), δ: 1.13 (s, 3 H, Н3С(8)); 1.39 (ddd, 1 H, H(6),
J1 = 11.0 Hz, J2 = 9.0 Hz, J3 = 4.8 Hz); 1.41 (s, 3 H, Н3С(9));
1.95 (d, 1 H, H(4), J = 9.0 Hz); 2.47 (s, 3 H, Н3С(1)); 2.71
(dd, 1 H, H(7α), J1 = 12.3 Hz, J2 = 11.0 Hz); 3.77 (dd, 1 H,
H(7β), J1 = 12.3 Hz, J2 = 4.8 Hz); 4.35 (s, 2 H, Н2С(1b)); 7.34
and 7.45 (both dd, 1 H, H(8a), H(9a), J1 = J2 = 7.4 Hz); 7.42
and 7.58 (both d, 1 H, H(2a), H(3a), J = 8.7 Hz); 7.87 (d, 1 H,
H(7a), J = 7.4 Hz); 8.21 (d, 1 H, H(10a), J = 7.4 Hz); 10.82
(br.s, 1 H, NHindole). 13C NMR ((CD3)2СO), δ*: 13.11
(q, C(1)); 17.20 (q, C(8)); 20.41 (s, C(5)); 24.70 (d, C(4));
25.38 (d, C(6)); 28.92 (q, C(9)); 43.41 (t, C(7)); 50.97 (t, C(1b));
109.52 (s, C(3)); 116.74 (s, C(10)); 119.92, 120.52, 120.73,
123.85, 125.85 and 129.20 (all d, С(2a), C(3a), C(7a), C(8a),
C(9a), C(10a)); 122.70 and 126.08 (both s, C(4a), C(5a));
130.82 and 133.42 (both s, 2 С and 1 С, respectively, C(2),
C(1a), C(6a)). 19F NMR ((CD3)2CO), δ: 0.65 (m, F(4b)); 8.97
(m, F(5b)); 21.44 (m, F(3b)). MS, m/z (Irel (%)): 483 [М]+
(12), 249 (20), 248 (100), 233 (21), 232 (10), 220 (12), 218
(11), 41 (19). Found: m/z 483.1730 [М]+. C27H22N3F5. Calcuꢀ
lated: М = 483.1734.
20
354 (3200). IR (CCl4), ν/cm–1: 3470 (NHindole), 2205 (C≡N),
1375 (C=Carom), 1030, 825 (C—Harom). 1H NMR ((CD3)2СO),
δ: 1.14 (s, 3 H, Н3С(8)); 1.42 (ddd, 1 H, H(6), J1 = 10.8 Hz,
J2 = 9.2 Hz, J3 = 4.9 Hz); 1.42 (s, 3 H, Н3С(9)); 1.95 (d, 1 H,
H(4), J = 9.2 Hz); 2.50 (s, 3 H, Н3С(1)); 2.65 (dd, 1 H, H(7α),
J1 = 12.6 Hz, J2 = 10.8 Hz); 3.66 (dd, 1 H, H(7β), J1
=
12.6 Hz, J2 = 4.9 Hz); 4.21 (s, 2 H, Н2С(1b)); 7.28—7.36 (m,
6 H, H(9a), H(3b), H(4b), H(5b)); 7.40 and 7.65 (both d, 1 H,
H(2a), H(3a), J = 8.6 Hz); 8.26 (d, 1 H, H(10a), J = 8.1 Hz);
8.74 (d, 1 H, H(8a), J = 4.1 Hz); 11.01 (br.s, 1 H, NHindole).
13C NMR ((CD3)2СO), δ: 13.17 (q, C(1)); 17.45 (q, C(8));
20.33 (s, C(5)); 24.43 (d, C(4)); 25.67 (d, C(6)); 28.98 (q, C(9));
50.45 (t, C(7)); 56.40 (t, C(1b)); 110.08 (s, C(3)); 118.16
(s, C(10)); 118.94, 119.49 and 121.49 (all d, C(2a), C(3a),
C(9a)); 125.05, 129.06, 129.17 and 130.81 (four s, C(1a), C(4a),
C(5a), C(6a)); 128.92 (d, C(5b)); 129.37 (d, C(3b)); 129.42
(d, C(4b)); 135.30 (s, C(2)); 136.84 (d, C(10a)); 138.46
(s, C(2b)); 148.61 (d, C(8a)). MS, m/z (Irel (%)): 394 [М]+ (7),
250 (19), 249 (100), 234 (8), 233 (8), 219 (7), 218 (4), 195 (3),
91 (7). Found: m/z 394.2163 [М]+. C26H26N4. Calculated:
М = 394.2157.
(+)ꢀ(1R,3S)ꢀNꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀpyrroꢀ
lo[3,2ꢀh]quinolinꢀ3ꢀyl)cyclopropylmethyl]ꢀNꢀ(3ꢀphenoxyꢀ
benzyl)cyanamide (21d) was prepared according to procedure C
from ketone 6d (0.18 g) and 8ꢀquinolylhydrazine (0.11 g). Afꢀ
ter chromatography product 21d was isolated in 41% yield
(0.10 g) as a light yellow oil, [α]57820 +81 (с 3.05). UV (EtOH),
(+)ꢀ(1R,3S)ꢀNꢀ(2,6ꢀDifluorophenylmethyl)ꢀNꢀ[2,2ꢀdiꢀ
methylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀpyrrolo[3,2ꢀh]quinolinꢀ3ꢀyl)cycloꢀ
propylmethyl]cyanamide (21b) was prepared according to proꢀ
cedure C from ketone 6b (0.15 g) and 8ꢀquinolylhydrazine
(0.11 g). After chromatography compound 21b was isolated
(0.07 g, 33%) as a light yellow oil, [α]578 +91 (с 1.85).
λ
max/nm (ε): 277 (39000), 354 (3800). IR (CCl4), ν/cm–1: 3460
20
UV (EtOH), λmax/nm (ε): 276 (35500), 353 (3600). IR (CHCl3),
ν/cm–1: 3460 (NHindole), 2210 (C≡N), 1465, 1375 (C=Carom),
1030, 825 (C—Harom). H NMR ((CD3)2СO), δ: 1.10 (s, 3 H,
(NHindole), 2210 (C≡N), 1490, 1375 (C=Carom), 1255, 830, 685
(C—Harom). H NMR ((CD3)2СO), δ: 1.10 (s, 3 H, Н3С(8));
1
1
1.34 (ddd, 1 H, H(6), J1 = 11.0 Hz, J2 = 9.0 Hz, J3 = 4.8 Hz);
1.40 (s, 3 H, Н3С(9)); 1.91 (dq, 1 H, H(4), J1 = 9.0 Hz, J2 =
0.8 Hz); 2.48 (d, 3 H, Н3С(1), J = 0.8 Hz); 2.62 (dd, 1 H,
H(7α), J1 = 12.5 Hz, J2 = 11.0 Hz); 3.68 (dd, 1 H, H(7β), J1 =
12.5 Hz, J2 = 4.8 Hz); 4.19 (s, 2 H, H2С(1b)); 6.91—6.97,
7.02—7.15, 7.26—7.39, 7.61—7.65, 8.21—8.26 and 8.72—8.75
(all m, 4 Н, 2 Н, 5 Н, 1 Н, 1 H, 1 Н, respectively, H(2a),
H(3a), H(8a), H(9a), H(10a), H(3b), H(5b), H(6b), H(7b),
Н3С(8)); 1.36 (ddd, 1 H, H(6), J1 = 11.0 Hz, J2 = 9.0 Hz, J3 =
4.8 Hz); 1.40 (s, 3 H, Н3С(9)); 1.96 (dq, 1 H, H(4), J1
=
9.0 Hz, J2 = 0.8 Hz); 2.53 (d, 3 H, Н3С(1), J = 0.8 Hz); 2.68
(dd, 1 H, H(7α), J1 = 12.3 Hz, J2 = 11.0 Hz); 3.77 (dd, 1 H,
H(7β), J1 = 12.3 Hz, J2 = 4.8 Hz); 4.29 (m, 2 H, Н2С(1b));
6.98—7.06 (m, 2 H, H(4b)); 7.34 (dd, 1 H, H(9a), J1 = 8.0 Hz,
J2 = 4.3 Hz); 7.40 (m, 1 H, H(5b)); 7.41 and 7.67 (both d, 1 H,
H(2a), H(3a), J = 8.5 Hz); 8.26 (dd, 1 H, H(10a), J1 = 8.0 Hz,
J2 = 2.0 Hz); 8.73 (dd, 1 H, H(8a), J1 = 4.3 Hz, J2 = 2.0 Hz);
11.05 (br.s, 1 H, NHindole). 13C NMR ((CD3)2СO), δ: 13.13
(q, C(1)); 17.17 (q, C(8)); 20.39 (s, C(5)); 24.60 (d, C(4));
25.53 (d, C(6)); 28.93 (q, C(9)); 50.78 (t, C(7)); 43.50 (t, C(1a));
H(9b), H(10b), H(11b)); 11.11 (br.s, 1 H, NHindole)
13С NMR
((CD3)2СO), δ: 13.20 (q, C(1)); 17.48 (q, C(8)); 20.35 (s, C(5));
24.47 (d, C(4)); 25.66 (d, C(6)); 29.04 (q, C(9)); 50.50 (t, C(7));
56.07 (t, C(1b)); 110.05 (s, C(3)); 117.09 (s, C(10)); 118.96,
119.20, 119.42, 119.52, 121.43, 124.21, 124.29 and 131.01 (all d,
С(2a), С(3a), С(9a), С(3b), С(5b), C(6b), С(7b), С(11b));
119.65 (d, 2 C, C(9b)); 130.72 (d, 2 C, C(10b)); 136.68
(d, C(10a)); 148.77 (d, C(8a)); 119.52 and 124.87 (both s,
C(4a), C(5a)); 128.88, 131.01 and 135.18 (all s, C(2), C(1a),
C(6a)); 138.91 (s, C(2b)); 157.83 and 158.46 (both s, C(4b),
C(8b)). MS, m/z (Irel (%)): 486 [М]+ (2), 289 (13), 250 (19),
249 (100), 234 (17), 233 (13), 219 (13), 218 (8), 43 (7). Found:
m/z 486.2408 [М]+. C32H30N4O. Calculated: М = 486.2419.
(+)ꢀ(1R,3S)ꢀNꢀBenzylꢀNꢀ[2,2ꢀdimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀ
indolꢀ3ꢀyl)cyclopropylmethyl]amine (22). A solution of indole
20a (0.34 g, 1 mmol) in 15 mL of ButOMe was added dropwise
to a suspension of LiAlH4 (0.19 g, 5 mmol) in 5 mL of anꢀ
2
110.00 (s, C(3)); 112.24 (t, C(2b), JC,F = 6.8 Hz); 112.30 (dd,
2
C(4b), JC,F = 25.1 Hz); 117.11 (s, C(10)); 118.98, 119.52 and
121.42 (all d, C(2a), C(3a), C(9a)); 125.07, 129.01, 130.96 and
130.81 (all s, C(1a), C(4a), C(5a), C(6a)); 132.09 (dt, C(5b),
3JC,F = 10.5 Hz); 135.20 (s, C(2)); 136.73 (d, C(10a)); 148.74
(d, C(8a)); 162.57 (dd, C(3b), 1JC,F = 248.1 Hz, 3JC,F = 8.4 Hz).
19F NMR (CDCl3—ССl4), δ: 48.56 (t, F(3b), J = 7.0 Hz). MS,
m/z (Irel (%)): 430 [М]+ (2), 289 (9), 250 (20), 249 (100), 234
(15), 233 (12), 219 (12), 218 (7), 127 (9), 99 (8). Found:
m/z 430.1973 [М]+. C26H24N4F2. Calculated: М = 430.1969.
(+)ꢀ(1R,3S)ꢀNꢀ[2,2ꢀDimethylꢀ3ꢀ(2ꢀmethylꢀ1Hꢀbenzo[g]inꢀ
dolꢀ3ꢀyl)cyclopropylmethyl]ꢀNꢀ(pentafluorophenylmethyl)cyanꢀ
amide (21c) was obtained according to procedure C from keꢀ
tone 6c (0.18 g) and 1ꢀnaphthylhydrazine (0.11 g). After chroꢀ
matography compound 21c was isolated in 30% yield (0.07 g)
as colorless crystals with m.p. 210—212 °С (from MeCN),
* In the 13C NMR spectrum of compound 21c chemical shifts
of carbon atoms of the pentafluorobenzyl ring were not deterꢀ
mined because of their low intensity due to multiple SSC conꢀ
20
[α]578 +99 (с 1.84). UV (EtOH), λmax/nm (ε): 269 (53900),
stants JC,F.

Indolic analogs of (1R)ꢀcisꢀchrysanthemates
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1317
hydrous ButOMe. The mixture was stirred at ∼20 °C for 2 h
until initial compound 20a disappeared (TLC monitoring). The
reaction mixture was diluted with 20 mL of ButOMe and poured
into water (30 mL). The organic layer was separated, and the
aqueous phase was extracted with ButOMe (3×10 mL). The
combined organic extracts were dried with anhydrous Na2SO4,
and the solvent was removed in vacuo. The residue (0.31 g) was
chromatographed on a column packed with SiO2 (eluent
EtOAc—hexane, 1 : 1), and amine 22 was obtained (0.17 g,
9. E. McDonald and R. Salmon, Brit. UK Pat. Appl.
GB 2,157,288; Chem. Abstrs., 1986, 105, 148216.
10. G. A. Tolstikov, F. Z. Galin, F. Z. Makaev, and V. K.
Ignatyuk, Zh. Org. Khim., 1989, 25, 1337 [J. Org. Chem.
USSR, 1989, 25 (Engl. Transl.)].
11. G. A. Tolstikov, F. Z. Galin, F. Z. Makaev, V. K. Ignatyuk,
V. S. Sultamova, and R. G. Davletov, Zh. Org. Khim.,
1990, 26, 1671 [J. Org. Chem. USSR, 1990, 26 (Engl.
Transl.)].
12. G. Falsone, F. Cateni, A. ElꢀAlali, A. Papaioannou,
L. Ravalico, and A. Furlani, Pharm. Pharmacol. Lett.,
1992, 2, 104.
13. J. Tessier, J. Demassey, and J. P. Demoute, Eur. Pat. Appl.
EP 261,035; Chem. Abstrs., 1988, 109, 110252.
14. K. Kyoguku and S. Murayama, Jpn Pat. 73 06,528; Chem.
Abstrs., 1974, 81, 59353.
15
53%), [α]578 +30 (с 1.62). UV (EtOH), λmax/nm (ε): 227
(31000), 284 (7000), 292 (6400). IR (CCl4), ν/cm–1: 3480
(NHindole), 1460 (C=Carom), 1235, 735 and 700 (C—Harom).
1H NMR (CDCl3—ССl4), δ: 0.98 (s, 3 H, Н3С(8)); 1.10 (ddd,
1 H, H(6), J1 = J2 = 9.0 Hz, J3 = 5.5 Hz); 1.31 (s, 3 H,
Н3С(9)); 1.62 (d, 1 H, H(4), J = 9.0 Hz); 2.07 (br.s, 1 H,
NHamine); 2.26 (s, 3 H, Н3С(1)); 2.29 (dd, 1 H, H(7α), J1 =
12.5 Hz, J2 = 9.0); 2.89 (dd, 1 H, H(7β), J1 = 12.5 Hz, J2 =
5.5 Hz); 3.62 (m, 2 H, Н2С(1b)); 6.81—7.02 (m, 2 H, H(3a),
H(4a)); 7.08—7.14 (m, 1 H, H(2a)); 7.14—7.21 (m, 5 H, H(3b),
H(4b), H(5b)); 7.34—7.40 (m, 1 H, H(5a)); 7.83 (br.s, 1 H,
NHindole). 13C NMR (CDCl3—CCl4), δ: 13.00 (q, C(1)); 17.06
(q, C(8)); 18.32 (s, C(5)); 23.12 (d, C(4)); 27.39 (d, C(6));
29.29 (q, C(9)); 47.58 (t, C(7)); 54.15 (t, C(1b)); 108.68
(s, C(3)); 109.86 (d, C(5a)); 118.90, 119.42 and 120.82 (all d,
C(2a), C(3a), C(4a)); 128.18 and 128.24 (both d, 2 С, C(3b),
С(4b)); 126.68 (d, С(5b)); 129.98 (s, C(1a)); 133.20 и 135.50
(both s, C(2), C(6a)); 139.91 (s, C(2b)). MS, m/z (Irel (%)):
318 [М]+ (2), 249 (10), 199 (30), 198 (100), 183 (9), 182 (13),
168 (15), 144 (8), 120 (46), 91 (81). Found: m/z 318.2095 [М]+.
С22H26N2. Calculated: М = 318.2096.
15. K. Kyoguku and S. Murayama, Jpn Pat. 76 33,107; Chem.
Abstrs., 1977, 86, 90089.
16. A. V. Tkachev, A. V. Rukavishnikov, A. M. Chibirjaev, and
L. B. Volodarsky, Synth. Commun., 1990, 20, 2123.
17. A. V. Rukavishnikov and A. V. Tkachev, Pat. RF
No. 1679761 (priority of 25. 12. 92) (in Russian).
18. S. A. Bakunov, A. V. Rukavishnikov, and A. V. Tkachev,
Synthesis, 1994, 935.
19. O. N. Burchak, A. M. Chibiryaev, and A. V. Tkachev,
Heterocycl. Commun., 2000, 6, 73.
20. Z. Muljiani, A. R. A. S. Deshmukh, S. R. Gadre, and V. S.
Joshi, Synth. Commun., 1987, 17, 25.
21. A. V. Rukavishnikov, Ph. D. (Chem.) Thesis, Novosibirsk
Institute of Organic Chemistry, Novosibirsk, 1993, 222 pp.
(in Russian).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 98ꢀ03ꢀ32910)
and the Presidium of the Siberian Branch of the Russian
Academy of Sciences (Grant 2000 for young scientists).
A. M. Chibiryaev thanks the Science Support Foundaꢀ
tion (grant for talented young researchers) for personal
support.
22. S. Julia, M. Julia, and J. Linstrumelle, Bull. Soc. Chim.
France, 1964, 10, 2693.
23. E. Peralez, J.ꢀC. Negrel, and M. Chanon, Tetrahedron Lett.,
1995, 36, 6457.
24. S. A. Bakunov, A. V. Rukavishnikov, and A. V. Tkachev,
Synthesis, 2000, 1148.
25. D. E. Portlock, W. C. Schwarzel, A. C. Ghosh, H. C.
Dalzell, and R. K. Razdan, J. Med. Chem., 1975, 18, 764.
26. W.ꢀH. Chiu, T. H. Klein, and M. E. Wolff, J. Med. Chem.,
1979, 22, 119.
References
27. H. Tecle, L. Robichaud, and C. F. Schwender, J. Med.
Chem., 1981, 24, 1095.
28. C.ꢀH. Kwon, H. T. Nagasawa, E. G. DeMaster, and F. N.
Shirota, J. Med. Chem., 1986, 29, 1922.
29. V. A. Dorokhov, M. F. Gordeev, Z. K. Dem´yanets, and
V. S. Bogdanov, Izv. Akad. Nauk SSSR, Ser. Khim., 1987,
1683 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1987, 36,
1563 (Engl. Transl.)].
30. K. Iio and E. Ichikawa, Bull. Chem. Soc. Japan, 1984,
57, 2009.
1. K. Naumann, Synthetic Pyrethroid Insecticides: Chemistry and
Patents in Chemistry of Plant Protection, v. 5, Ed. R. Wegler,
SpringerꢀVerlag, Berlin—Heidelberg, 1990, 390 pp.
2. S. Farooq, J. Drabek, L. Gsell, W. Meyer, and F. Karrer,
Ger. Offen. 2,647,368; Chem. Abstrs., 1977, 87, 84808.
3. C. A. Henrick, D. A. Garcia, G. D. Staal, D. C. Gerf, R. J.
Anderson, K. Gill, H. R. Chinn, J. N. Labowitz, M. M.
Leippe, S. L. Woo, R. L. Carney, D. C. Gordon, and G. K.
Krohn, Pestic. Sci., 1980, 224.
4. C. A. Henrick, R. L. Carney, and J. N. Labovitz,
US 4,178,293; Chem. Abstrs., 1980, 92, 128723.
5. C. A. Henrick, in Recent Advances in the Chemistry of Insect
Controll, 133 Proc. Symposium Cambridge, Ed. N. F. Janes,
Royal Chem. Soc., London, 1984.
6. T. N. Wheeler, J. Agric. Food Chem., 1984, 1125.
7. J. Whittle, R. Salmon, and E. McDonald, Eur. Pat. Appl.
EP 227,415; Chem. Abstrs., 1987, 107, 236728.
31. V. A. Dorokhov, M. F. Gordeev, Z. K. Dem´yanets, M. N.
Bochkareva, and V. S. Bogdanov, Izv. Akad. Nauk SSSR,
Ser. Khim., 1989, 1806 [Bull. Acad. Sci. USSR, Div. Chem.
Sci., 1989, 38, 1654 (Engl. Transl.)].
32. Yu. N. Polivin, R. A. Karakhanov, V. I. Kelarev, T. S.
Sheveleva, and B. I. Ugrak, Izv. Akad. Nauk, Ser. Khim.,
1993, 2078 [Russ. Chem. Bull., 1993, 42, 1991 (Engl.
Transl.)].
8. ICI, Jpn. Kokai Tokkyo Koho JP 60,222,444; Chem. Abstrs.,
1986, 105, 24469.
33. R. P. Subrayan and P. G. Rasmussen, Tetrahedron, 1999,
55, 353.

1318
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Burchak et al.
34. H. Lettre, P. Yungmann, and J. Solfeld, Chem. Ber., 1952,
85, 397.
45. G. Seitz and R. John, Arch. Pharm. (Weinheim, Ger.), 1991,
323, 65.
35. S.ꢀH. Jung and H. Kohn, J. Am. Chem. Soc., 1985, 107, 2931.
36. C. G. Francisco, R. Hernandez, E. I. Leon, J. A. Salazar,
and E. Suarez, J. Chem. Soc., Perkin Trans. 1, 1990, 2417.
37. K. W. Morin, R. Kumar, E. E. Knaus, and L. I. Wiebe,
J. Heterocycl. Chem., 1991, 28, 807.
46. W. Zielinski and M. Mazik, Heterocycles, 1994, 38, 375.
47. R. S. Elderfield and H. A. Hageman, J. Org. Chem.,
1949, 14, 605.
48. V. Prelog, B. C. McKusick, J. R. Merchant, S. Julia, and
M. Wilhelm, Helv. Chim. Acta, 1956, 39, 498.
49. A. C. Currie, G. T. Newbold, and F. S. Spring, J. Chem.
Soc., 1961, 4693.
38. F. L. Wagenaar and J. F. Kerwin, Jr., J. Org. Chem., 1993,
58, 4331.
39. Yu. A. Sharanin, Zh. Org. Khim., 1980, 16, 2185 [J. Org.
Chem. USSR, 1980, 16 (Engl. Transl.)].
50. A. Donetti, A. OmodeiꢀSale, and A. Mantegani, Tetraꢀ
hedron Lett., 1969, 39, 3327.
40. T. Kato, T. Chiba, T. Shimizu, and H. Takahashi, Chem.
Pharm. Bull., 1981, 29, 862.
51. G. Pala, A. Mantegani, and E. Zugna, Tetrahedron, 1970,
26, 1275.
41. Yu. S. Andreichikov and D. D. Nekrasov, Zh. Org. Khim.,
1984, 20, 1755 [J. Org. Chem. USSR, 1984, 20 (Engl.
Transl.)].
42. Yu. S. Andreichikov and D. D. Nekrasov, Khim. Geterotsikl.
Soedin., 1985, 166 [Chem. Heterocycl. Compd., 1985 (Engl.
Transl.)].
52. S. A. Bakunov, A. V. Rukavishnikov, and A. V. Tkachev,
Synthesis, 2000, 1148.
53. W. Pollmann and G. Schramm, Biochem. Biophis. Acta,
1964, 1.
54. A. J. Birch, R. Jaeger, and R. Robinson, J. Chem. Soc.,
1945, 582.
43. M. D. Brown, D. W. Gillon, G. D. Meakins, and G. H.
Whitham, J. Chem. Soc., Perkin Trans. 1, 1985, 1623.
44. R. Carrau, R. Hernandez, E. Suarez, and C. Betancor,
J. Chem. Soc., Perkin Trans. 1, 1987, 937.
Received October 5, 2001;
in revised form January 24, 2002