CuI-catalyzed N,N’-diarylation of diamines of adamantane series

Article abstract of DOI:10.1007/s11172-016-1481-1

A copper(I) complex-catalyzed N,N’-diarylation of diamines based on 1,3-disubstituted adamantane, using aryl iodides bearing electron-donating and electron-withdrawing substituents, was studied. In the case of 2,2’-(adamantane-1,3-diyl)ethanediamine, the optimal catalyst system is CuI—2-(isobutyryl)cyclohexanone—Cs₂CO₃—DMF. The highest yield of diarylation product was reached in the case of 4-methoxyiodobenzene (79%). In the case of more spatially hindered adamantane-1,3-diyldimethanamine, 1,1’-binaphthalene-2,2’-diol (BINOL) should be used, with the highest yield of the target product (84%) being reached in the reaction with iodobenzene.

Full text of DOI:10.1007/s11172-016-1481-1

Russian Chemical Bulletin, International Edition, Vol. 65, No. 6, pp. 1550—1555, June, 2016
1550
CuIꢀcatalyzed N,N´ꢀdiarylation of diamines of adamantane series
S. P. Panchenko,a A. C. Abel,a A. D. Averin,a O. A. Maloshitskaya,a E. N. Savelyev,b B. S. Orlinson,b
I. A. Novakov,b and I. P. Beletskayaa
aM. V. Lomonosov Moscow State University, Department of Chemistry,
Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation.
Fax: +7 (495) 939 3618. Eꢀmail: averin@org.chem.msu.ru
bVolgograd State Technical University,
28 prosp. Lenina, 400131 Volgograd, Russian Federation.
Fax: +7 (844 2) 23 8787
A copper(I) complexꢀcatalyzed N,N´ꢀdiarylation of diamines based on 1,3ꢀdisubstituted
adamantane, using aryl iodides bearing electronꢀdonating and electronꢀwithdrawing substituꢀ
ents, was studied. In the case of 2,2´ꢀ(adamantaneꢀ1,3ꢀdiyl)ethanediamine, the optimal cataꢀ
lyst system is CuI—2ꢀ(isobutyryl)cyclohexanone—Cs2CO3—DMF. The highest yield of diarylꢀ
ation product was reached in the case of 4ꢀmethoxyiodobenzene (79%). In the case of more
spatially hindered adamantaneꢀ1,3ꢀdiyldimethanamine, 1,1´ꢀbinaphthaleneꢀ2,2´ꢀdiol (BINOL)
should be used, with the highest yield of the target product (84%) being reached in the reaction
with iodobenzene.
Key words: amination, catalysis, copper(I) complexes, adamantane, amines, aryl iodides.
Nꢀ(Hetero)aryl derivatives of adamantaneꢀcontaining
mantane with iodopyridine11 and studied N,N´ꢀdiarylaꢀ
tion of diꢀ and polyamines with a number of aryl iodides
and halopyridines.12—14 It was found that depending on
the structure of polyamines, the relative reactivities of aryl
iodides containing electronꢀdonating and electronꢀwithꢀ
drawing substituents noticeably differ. In this connection,
in the present work we study two diamines based on 1,3ꢀdiꢀ
substituted adamantane, 2,2´ꢀ(adamantaneꢀ1,3ꢀdiyl)ꢀ
ethanediamine (1) and adamantaneꢀ1,3ꢀdiyldimethanꢀ
amine (2), in the reactions of CuIꢀcatalyzed arylation.
The arylating agents were iodobenzene, its derivatives
with electronꢀwithdrawing substituents (4ꢀiodobiphenyl,
4ꢀiodofluorobenzene, and 4ꢀ(trifluoromethyl)iodobenzꢀ
ene) and electronꢀdonating groups (4ꢀiodotoluene and
4ꢀiodoanisole). Initially, we carried out the reactions with
diamine 1 bearing more spatially available amino groups
(Scheme 1). Proceeding from the earlier obtained data on
the N,N´ꢀdiarylation of diamines, we used the catalytic
system CuI—2ꢀ(isobutyryl)cyclohexanone (L1) (10 and
20 mol.%), the reactions were carried out at the molar
ratio diamine : aryl iodide 1 : 2.5 in DMF at 110 °C and
a concentration of diamine 0.5 mol L–1; cesium carbonate
was used as a base. The obtained compounds were isolated
by chromatography on silica gel, the yields are given in
Table 1. The reaction of diamine 1 with iodobenzene gives
the target product 3 in a moderate yield (entry 1), while in
the case of electronꢀdeficient 4ꢀiodobiphenyl and 4ꢀiodoꢀ
fluorobenzene, the product yields were much better (enꢀ
tries 4 and 5). The best yields were observed in the case of
amines are of great interest as compounds exhibiting
various biological activity. Some of them, for example,
chlodantan (immunopotentiator)1 and ladasten (neuroꢀ
stimulating agent),2 are already used as pharmaceutical
agents. A great role in the development of new medicines
belongs to compounds containing in the (hetero)aromatic
rings such substituents as fluorine and trifluoromethyl
group. About 20—25% of modern drugs contain fluorine
in the composition,3 most frequently as a substituent in
the aromatic or heteroaromatic ring (for example, sitaꢀ
gliptin, atorvastatin, ciproflaxin) or trifluoromethyl group
(fluoxetin, sensipar, sustiva). The fluorine atoms present
in the molecule of a potential pharmaceutical agent modꢀ
ulate its acidity,4 stabilize certain conformations,5 modify
hydrophobic interactions and hydrogen bonds,6 lipoꢀ
philicity,7 solubility,8 which leads to the changes in the
binding ability with the site of interest and can lead to the
improvement of binding selectivity. At the same time,
physiological activity of adamantane diamino derivatives
is a subject of modern studies. Thus, for example, adaꢀ
mantaneꢀ1,3ꢀdiyldimethanamine dihydrochloride is patꢀ
ented as an antiviral agent for home animals.9,10 In this
connection, development of versatile methods for the inꢀ
troduction of (hetero)aryl substituents in the adamantaneꢀ
containing amines and diamines seems an actual problem.
One of such methods is the copper complexꢀcatalyzed
(hetero)arylation of amines. Recently, we studied a CuIꢀ
catalyzed heteroarylation of various amines based on adaꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1550—1555, June, 2016.
1066ꢀ5285/16/6506ꢀ1550 © 2016 Springer Science+Business Media, Inc.

Arylation of adamantane diamines
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 6, June, 2016
1551
Scheme 1
Compound
R
—
—
H
Ph
F
n
1
0
1
1
1
Compound
6
7
8
9
10
R
CF3
Me
OMe
H
n
1
1
1
0
0
Compound
R
F
CF3
Me
OMe
Ph
n
0
0
0
0
Compouns
R
CF3
Me
Me
OMe
OMe
n
1
2
3
4
5
11
12
13
14
15
16
17
18
19
20
—
—
—
—
—
Ph
—
i. CuI/L/DMF, Cs2CO3, 110—140 °C.
electronꢀenriched 4ꢀiodotoluene and 4ꢀiodoanisole (70
and 79%, respectively, entries 8 and 9). The activity of 4ꢀ(triꢀ
fluoromethyl)iodobenzene turned out to be unexpectedly
the lowest (entry 6). An attempt to improve the result by
using another ligand, Lꢀproline (L2), was unsuccessful
(entry 2).
An increase in the reaction temperature to 140 °C did
not lead to a noticeable improvement of the result, as it
was inferred from the NMR data of the reaction mixture.
Yet another O,O´ꢀbidentate ligand, racꢀBINOL (L3), has
proved more efficient when used at 140 °C (entry 3), which
allowed us to obtain the target compound 3 in 66% yield.
This ligand also facilitated the preparation of derivative 6
containing trifluoromethyl substituents in 52% yield (entry 7).
The reactions with diamine 2 containing more spatially
hindered amino groups due to their closer position from
the adamantane framework were carried out exclusively in
the presence of ligand L3 and at 140 °C, since in the
preliminary experiment with iodobenzene in the presence
of the system CuI—L1, even at 140 °C the conversion of
the starting compounds was low. When catalyzed with the
system CuI—L3, N,N´ꢀdiphenyl derivative 9 was isolated
in 84% yield (entry 10), however, in the reactions with
other iodoarenes the yields were considerably lower. Thus,
out of electron deficient aryl iodides only reaction with
4ꢀiodofluorobenzene gave diarylation product 11 in a modꢀ
erate yield of 41% (entry 12), whereas with electronꢀenꢀ
riched iodoarenes the yields were 28% in the case of
4ꢀiodotoluene (entry 14) and 35% in the case of 4ꢀiodoꢀ
anisole (entry 15). In the latter case, to increase the conꢀ
version of the starting compounds we had to increase the
amount of the catalyst to 20 mol.%. Apart from that, in
a number of cases the formation of imines 17 and 19 was
observed as a result of the catalytic reduction of the C—I
bond accompanied by the βꢀhydride elimination from the
copper amide complex. In the reaction with 4ꢀiodobiꢀ
phenyl, imine 15 was the only compound isolated in the
individual state (entry 11). The chromatographic separaꢀ

1552
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 6, June, 2016
Panchenko et al.
Table 1. Synthesis of N,N´ꢀdiaryl derivatives of adamantaneꢀ
containing diamines 3—14
and 13C NMR spectra are given in δ scale relative to Me4Si as an
internal standard. MALDI mass spectra of positive ions were
recorded on a Bruker Autoflex II instrument using 1,8,9ꢀtriꢀ
hydroxyanthracene as a matrix and poly(ethylene glycols) as
internal standards. Preparative column chromatography was
carried out using Merck silica gel (40/60). The starting iodoareꢀ
nes, 2ꢀisobutyrylcyclohexanone, Lꢀproline, racꢀBINOL, and ceꢀ
sium carbonate from SigmaꢀAldrich were used without purifiꢀ
cation. Amines 1 and 2 were synthesized according to the proceꢀ
dure described earlier.15
Entry Diamine
R
Ligand T/°C Products Yield (%)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
2
2
H
H
H
Ph
F
CF3
CF3
Me
OMe
H
L1
L2
L3
L1
L1
L1
L3
L1
L1
L3
L3
110
110
140
110
110
110
140
140
110
140
140
3
3
3
4
5
6
6
7
8
33
27
66
50
57
21
52
70
79
84
Traces
12
41
20
23
28
10
10
Synthesis of Nꢀarylꢀsubstituted adamantaneꢀcontaining amines
(general procedure). A corresponding iodoarene (1.25—2.5 mmol),
CuI (10 mol.%, 9.5—19 mg), a corresponding ligand (20 mol.%),
cesium carbonate (1.25—2.5 mmol, 408—916 mg), DMF
(1—2 mL), and adamantaneꢀcontaining diamine 1 or 2
(0.5—1 mmol, 111—222 or 97—194 mg, respectively) were placed
in a oneꢀneck flask equipped with a magnetic stirrer and a reflux
condenser and filled with anhydrous argon. The reaction mixꢀ
ture was stirred at 110 or 140 °C for 24 h. After the reaction
reached completion, the mixture was cooled to room temperaꢀ
ture and diluted with dichloromethane (5 mL), a precipitate was
filtered off and washed additionally with dichloromethane
(5 mL), the combined organic fractions were concentrated
in vacuo, the residue was analyzed by NMR spectroscopy and
subjected to chromatography on silica gel using the following
sequence of eluents: light petroleum ether—CH2Cl2
(10 : 1)→(1 : 4), CH2Cl2, CH2Cl2—MeOH (100 : 1)→(3 : 1).
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]dianiline (3)
was obtained from diamine 1 (222 mg) and iodobenzene (510 mg)
in the presence of CuI (19 mg) and 2ꢀisobutyrylcyclohexanone
(33 mg) in DMF (2 mL). Eluent CH2Cl2 → CH2Cl2—MeOH
(50 : 1). The yield was 124 mg (33%), a white crystalline powder,
m.p. 85—87 °C. When racꢀBINOL (28.5 mg, 20 mol.%) was
used as the ligand, diamine 1 (111 mg, 0.5 mmol) and iodobenzꢀ
ene (255 mg, 1.25 mmol) gave the yield of 123 mg (66%). The
spectral data are given in the work.16
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]bis(biphenꢀ
ylꢀ4ꢀamine) (4) was obtained from diamine 1 (222 mg), 4ꢀiodoꢀ
biphenyl (700 mg) in the presence of CuI (19 mg) and 2ꢀisoꢀ
butyrylcyclohexanone (33 mg) in DMF (2 mL). Eluent light
petroleum ether—CH2Cl2 (1 : 4), CH2Cl2. The yield was 265 mg
(50%), a yellow crystalline powder, m.p. 150—152 °C. 1H NMR
(CDCl3), δ: 1.38 (br.s, 2 H, HAd); 1.45—1.49 (m, 4 H, CH2—Ad);
1.50—1.54 (m, 4 H, HAd); 1.57—1.62 (m, 4 H, HAd); 1.66 (br.s,
2 H, HAd); 2.10 (br.s, 2 H, HCAd); 3.16—3.20 (m, 4 H, CH2NPh);
3.61 (br.s, 2 H, NH); 6.69 (d, 4 H, HAr, 3Jobs = 8.5 Hz); 7.27 (t, 2 H,
HAr, 3J = 7.3 Hz); 7.40 (t, 4 H, HAr, 3Jobs = 7.8 Hz); 7.47 (d, 4 H,
HAr, 3Jobs = 8.5); 7.53—7.57 (m, 4 H, HAr). 13C NMR (CDCl3),
δ: 28.9 (2 C, HCAd); 32.7 (2 C, CAd); 36.4 (1 C, H2CAd); 38.7
(2 C, CH2—Ad); 42.0 (4 C, H2CAd); 43.7 (2 C, CH2NPh); 47.8
(1 C, H2CAd); 112.9 (4 C, HCAr); 126.0 (2 C, HCAr); 126.2 (4 C,
HCAr); 127.9 (4 C, HCAr); 128.6 (4 C, HCAr); 130.0 (2 C, CAr);
141.3 (2 C, CAr); 147.9 (2 C, NCAr). MS (MALDI), found: m/z
527.3403 [M + H]+. C38H43N2. Calculated: 527.3426.
9
10
11
9
Ph
10
15
11
12
16
13
17
18
14
19
20
12
13
2
2
F
CF3
L3
L3
140
140
14
15
2
2
Me
L3
140
140
OMe
L3*
35
22
9
* CuI/L3 (20/40 mol.%)was used.
tion of the reaction products was accompanied by partial
hydrolysis of imines to the corresponding aldehydes, which
also were isolated and characterized (compounds 16, 18,
and 20), with their yields being comparable with the yields
of the target N,N´ꢀdiarylation products. In a number of
cases, the formation of monoarylation products was obꢀ
served, however, they were not isolated in the individual
state because of the difficulties of separation from the uniꢀ
dentified impurities by chromatography. All the new tarꢀ
get compounds 4—8 and 10—14 were characterized by
1H and 13C NMR spectroscopy (except for the product 12
because of the technical difficulties arising upon acquisiꢀ
tion of quaternary carbon atoms in the trifluoromethylꢀ
phenyl fragment) and high resolution MALDI mass
spectrometry. The side compounds 15—20 were also charꢀ
acterized by NMR spectroscopy and MALDI.
In conclusion, using the N,N´ꢀdiarylation reactions of
adamantaneꢀcontaining diamines as an example it was
shown that under conditions of the catalysis by copper(I)
complexes, a thorough selection of the ligand is required
for determination of reagent pairs, whereas the reactivity
of aryl iodides in the indicated process is not unambiguꢀ
ously determined by the presence of electronꢀdonating or
electronꢀwithdrawing substituents.
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]bis(4ꢀfluoroꢀ
aniline) (5) was obtained from diamine 1 (222 mg), 4ꢀiodofluoroꢀ
benzene (555 mg) in the presence of CuI (19 mg) and 2ꢀisoꢀ
butyrylcyclohexanone (33 mg) in DMF (2 mL). Eluent CH2Cl2,
CH2Cl2—MeOH (100 : 1)→(50 : 1). The yield was 271 mg (66%),
a colorless dense oil. 1H NMR (CDCl3), δ: 1.33 (br.s, 2 H, HAd);
1.39—1.44 (m, 4 H, CH2—Ad); 1.45—1.50 (m, 4 H, HAd);
1.52—1.58 (m, 4 H, HAd); 1.63 (br.s, 2 H, HAd); 2.07 (br.s, 2 H,
Experimental
1
H and 13C NMR spectra were recorded on a Bruker Avanceꢀ
400 spectrometer (400 MHz) at 298 K. Chemical shifts in the 1H

Arylation of adamantane diamines
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 6, June, 2016
1553
HAd); 3.05—3.09 (m, 4 H, CH2N); 3.34 (br.s, 2 H, NH); 6.50—6.55
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(methanediyl)]dianiline (9) was
obtained from diamine 2 (97 mg) and iodobenzene (255 mg) in
the presence of CuI (9.5 mg) and racꢀBINOL (28.5 mg) in DMF
(1 mL). Eluent light petroleum ether—CH2Cl2 (1 : 1)→(1 : 2).
The yield was 145 mg (84%), a white crystalline powder, m.p.
101—103 °C. The spectral data are given in the work.16
4
(d, 4 H, HPh(2), HPh(2´), JH,F = 4.3 Hz); 6.86—6.93 (d, 4 H,
3
H
Ph(3), HPh(3´), JH,F = 8.8 Hz). 13C NMR (CDCl3), δ: 28.9
(2 C, HCAd); 32.6 (2 C, CAd); 36.4 (1 C, H2CAd); 39.2 (2 C,
CH2—Ad); 41.9 (4 C, H2CAd); 43.6 (2 C, CH2N); 47.8 (1 C,
H2CAd); 113.4 (d, 4 C, CPh(2), CPh(2), 3JC,F = 7.6 Hz); 115.6 (d,
2
4 C, CPh(3), CPh(3´), JC,F = 21.9 Hz); 144.9 (2 C, CPh(1));
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(methanediyl)]bis(4ꢀfluoroꢀ
aniline) (11) was obtained from diamine 2 (97 mg) and 4ꢀfluoroꢀ
iodobenzene (278 mg) in the presence of CuI (9.5 mg) and racꢀ
BINOL (28.5 mg) in DMF (1 mL). Eluent light petroleum
ether—CH2Cl2 (1 : 1)→(1 : 2). The yield was 78 mg (41%),
1
155.5 (d, 2 C, CPh(4), JC,F = 234.4 Hz). MS (MALDI),
found: m/z 409.2481 [M – H2 + H]+. C26H31F2N2. Calculated:
409.2455.
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]bis(4ꢀtriꢀ
fluoromethylaniline) (6) was obtained from diamine 1 (222 mg),
4ꢀtrifluoromethyliodobenzene (680 mg) in the presence of CuI
(19 mg) and 2ꢀisobutyrylcyclohexanone (33 mg) in DMF (2 mL).
Eluent light petroleum ether—CH2Cl2 (2 : 1)→(1 : 1). The yield
was 107 mg (21%), a white crystalline powder, m.p. 107—109 °C.
When racꢀBINOL (28.5 mg, 20 mol.%) was used as the ligand,
diamine 1 (111 mg, 0.5 mmol) and 4ꢀtrifluoromethyliodobenzꢀ
ene (340 mg, 1.25 mmol) gave the yield of 134 mg (52%). 1H NMR
(CDCl3), δ: 1.41—1.45 (m, 4 H, CH2—Ad); 1.46—1.51 (m, 4 H,
1
a yellow dense oil. H NMR (CDCl3), δ: 1.41 (br.s, 2 H, HAd);
1.49—1.59 (m, 8 H, HAd); 1.66 (br.s, 2 H, HAd); 2.12 (br.s, 2 H,
HCAd); 2.80 (s, 4 H, CH2N); 3.57 (br.s, 2 H, NH); 6.56 (dd, 4 H,
3
4
HPh(2), HPh(2´), Jobs = 8.6 Hz, JH,F = 4.0 Hz); 6.86 (dd,
H
3
Ph(3), HPh(3´), Jobs =
3JH,F = 8.6 Hz). 13C NMR (CDCl3),
δ: 28.4 (2 C, HCAd); 34.5 (2 C, CAd); 36.4 (1 C, H2CAd); 40.2 (4 C,
H2CAd); 43.7 (1 C, H2CAd); 57.0 (2 C, CH2N); 113.6 (4 C,
C
Ph(2), CPh(2´)); 115.6 (d, 4 C, CPh(3), CPh(3´), 2JC,F = 22.8 Hz);
1
145.3 (2 C, CPh(1)); 155.7 (d, 2 C, CPh(4), JC,F = 234.4 Hz).
MS (MALDI), found: m/z 383.2324 [M + H]+. C24H29F2N2.
Calculated: 383.2299.
H
Ad); 1.54—1.60 (m, 4 H, HAd); 1.64 (br.s, 4 H, HAd); 2.08 (br.s,
2 H, HCAd); 3.12—3.16 (m, 4 H, CH2NPh); 3.82 (br.s, 2 H,
NH); 6.57 (d, 4 H, HPh(2), HPh(2´), 3Jobs = 8.6 Hz); 7.39 (d, 4 H,
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(methanediyl)]bis(4ꢀtrifluoroꢀ
methylaniline) (12) was obtained from diamine 2 (97 mg) and
4ꢀ(trifluoromethyl)iodobenzene (340 mg) in the presence of CuI
(9.5 mg) and racꢀBINOL (28.5 mg) in DMF (1 mL). Eluent light
petroleum ether—CH2Cl2 (10 : 1). The yield was 48 mg (20%),
3
H
Ph(3), HPh(3´), Jobs = 8.6 Hz). 13C NMR (CDCl3), δ: 28.8
(2 C, HCAd); 32.7 (2 C, CAd); 36.3 (1 C, H2CAd); 38.2 (2 C,
CH2—Ad); 41.9 (4 C, H2CAd); 43.4 (2 C, CH2NPh); 47.8 (1 C,
H2CAd); 111.7 (4 C, CPh(2), CPh(2´)); 118.5 (q, 2 C, CPh(4),
2JC,F = 32.6 Hz); 125.1 (q, 2 C, CF3, 1JC,F = 270.2 Hz); 126.6 (4 C,
CPh(3), CPh(3´)); 150.8 (2 C, CPh(1)). MS (MALDI), found:
m/z 491.2510 [M – F]+. C28H32F5N2. Calculated: 491.2486.
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]bis(4ꢀmethꢀ
ylaniline) (7) was obtained from diamine 1 (111 mg), 4ꢀiodotoluꢀ
ene (273 mg) in the presence of CuI (9.5 mg) and 2ꢀisobutyrylꢀ
cyclohexanone (17 mg) in DMF (1 mL). Eluent CH2Cl2. The
yield was 141 mg (70%), a beige crystalline powder, m.p. 86—88 °C.
1H NMR (CDCl3), δ: 1.33 (br.s, 2 H, HAd); 1.38—1.44 (m, 4 H,
Ad—CH2); 1.44—1.56 (m, 8 H, HAd); 1.62 (br.s, 2 H, HAd); 2.06
(br.s, 2 H, HCAd); 2.25 (s, 6 H, CH3); 3.08—3.12 (m, 4 H,
CH2N); 3.46 (br.s, 2 H, NH); 6.55 (d, 4 H, HPh(2), HPh(2´),
1
a light yellow dense oil. H NMR (CDCl3), δ: 1.41 (br.s, 2 H,
HAd); 1.47—1.59 (m, 8 H, HAd); 1.65 (br.s, 2 H, HAd); 2.12 (br.s,
2 H, HCAd); 2.88 (s, 4 H, CH2N); 4.05 (br.s, 2 H, NH);
6.63 (br.s, 4 H, HPh(2), HPh(2´)); 7.37 (d, HPh(3), HPh(3´), 3Jobs
=
= 8.3 Hz). MS (MALDI), found: m/z 463.2120 [M – F]+.
C26H28F5N2. Calculated: 463.2173.
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(methanediyl)]bis(4ꢀmethylꢀ
aniline) (13) was obtained from diamine 2 (97 mg) and 4ꢀiodoꢀ
toluene (273 mg) in the presence of CuI (9.5 mg) and racꢀBINOL
(28.5 mg) in DMF (1 mL). Eluent light petroleum ether—CH2Cl2
(1 : 2). The yield was 53 mg (28%), a beige crystalline powder,
1
m.p. 132—134 °C. H NMR (CDCl3), δ: 1.42 (br.s, 2 H, HAd);
3
3Jobs = 8.3 Hz); 6.99 (d, 4 H, HPh(3), HPh(3´), Jobs = 8.3 Hz).
1.51—1.62 (m, 8 H, HAd); 1.67 (br.s, 2 H, HAd); 2.13 (br.s, 2 H,
13C NMR (CDCl3), δ: 20.4 (2 C, CH3); 28.9 (2 C, HCAd); 32.7
(2 C, CAd); 36.5 (1 C, H2CAd); 39.1 (2 C, Ad—CH2); 42.0 (4 C,
H2CAd); 43.7 (2 C, CH2N); 47.8 (1 C, H2CAd); 113.1 (4 C,
HCAd); 2.25 (s, 6 H, CH3); 2.84 (s, 4 H, CH2N); 3.50 (s, 2 H,
3
NH); 6.57 (d, 4 H, HPh(2), HPh(2´), Jobs = 8.2 Hz); 6.99
3
(d, 4 H, HPh(3), HPh(3´), Jobs = 8.2 Hz). 13C NMR (CDCl3),
C
Ph(2), CPh(2´)); 126.5 (2 C, CPh(4)); 129.7 (4 C, CPh(3),
δ: 20.3 (2 C, CH3); 28.5 (2 C, HCAd); 34.6 (2 C, CAd); 36.5 (1 C,
H2CAd); 40.2 (4 C, H2CAd); 43.8 (1 C, H2CAd); 56.4 (2 C,
CH2N); 112.6 (4 C, CPh(2), CPh(2´)); 126.1 (2 C, CPh(4));
129.7 (4 C, CPh(3), CPh(3´)); 146.8 (2 C, CPh(1)). MS
(MALDI), found: m/z 375.2767 [M + H]+. C26H35N2. Calcuꢀ
lated: 375.2800.
CPh(3´)); 146.1 (2 C, CPh(1)). MS (MALDI), found: m/z
403.3089 [M + H]+. C28H39N2. Calculated: 403.3113.
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(ethaneꢀ2,1ꢀdiyl)]bis(4ꢀmethꢀ
oxyaniline) (8) was obtained from diamine 1 (222 mg), 4ꢀiodoꢀ
anisole (585 mg) in the presence of CuI (19 mg) and 2ꢀisobuꢀ
tyrylcyclohexanone (33 mg) in DMF (2 mL). Eluent CH2Cl2—
MeOH 10 : 1. The yield was 346 mg (79%), a brown dense oil.
1H NMR (CDCl3), δ: 1.31 (br.s, 2 H, HAd); 1.37—1.42 (m, 4 H,
CH2—Ad)); 1.43—1.48 (m, 4 H, HAd); 1.52—1.56 (m, 4 H, HAd);
1.61 (br.s, 2 H, HAd); 2.04 (br.s, 2 H, HCAd); 3.03—3.07 (m, 4 H,
CH2NPh); 3.32 (br.s, 2 H, NH); 3.73 (s, 6 H, OCH3); 6.57 (d, 4 H,
HPh(2), HPh(2´), 3Jobs = 8.8 Hz); 6.77 (d, 2 H, HPh(3), HPh(3´),
3Jobs = 8.8 Hz). 13C NMR (CDCl3), δ: 28.8 (2 C, HCAd); 32.5
(2 C, CAd); 36.3 (1 C, H2CAd); 39.4 (2 C, CH2—Ad); 41.8 (4 C,
H2CAd); 43.6 (2 C, CH2NPh); 47.6 (1 C, H2CAd); 55.6 (2 C,
OCH3); 113.9 (4 C, HCPh); 114.7 (4 C, HCPh); 142.7 (2 C,
N,N´ꢀ[Adamantaneꢀ1,3ꢀdiylbis(methanediyl)]bis(4ꢀmethoxyꢀ
aniline) (14) was obtained from diamine 2 (97 mg) and 4ꢀiodoꢀ
anisole (293 mg) in the presence of CuI (19 mg) and racꢀBINOL
(57 mg) in DMF (1 mL). Eluent CH2Cl2, CH2Cl2—MeOH
1
(100 : 1). The yield was 71 mg (35%), a brown oil. H NMR
(CDCl3), δ: 1.42 (br.s, 2 H, HAd); 1.50—1.60 (m, 8 H, HAd); 1.65
(br.s, 2 H, HAd); 2.11 (br.s, 2 H, HCAd); 2.79 (s, 4 H, CH2N);
3.47 (br.s, 2 H, NH); 3.74 (s, 6 H, OCH3); 6.60 (d, 4 H, HPh(2),
3
H
Ph(2´), Jobs = 8.7 Hz); 6.76 (d, 4 H, HPh(3), HPh(3´), 3Jobs
=
= 8.7 Hz). 13C NMR (CDCl3), δ: 28.5 (2 C, HCAd); 34.5 (2 C,
CAd); 36.5 (1 C, H2CAd); 40.3 (4 C, H2CAd); 43.8 (1 C, H2CAd);
55.8 (2 C, CH2N); 57.4 (2 C, CH3O); 114.1 (4 C, CPh(2),
C
Ph(1)); 151.8 (2 C, CPh(4)). MS (MALDI), found: m/z 435.3052
[M + H]+. C28H39N2O2. Calculated: 435.3012.
C
Ph(2´)); 114.9 (4 C, CPh(3), CPh(3´)); 143.2 (2 C, CPh(1));

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 6, June, 2016
Panchenko et al.
151.9 (2 C, CPh(4)). MS (MALDI), found: m/z 407.2752 [M + H]+.
C26H35N2O2. Calculated: 407.2699.
H
Ph(2), HPh(2´), 3Jobs = 8.2 Hz); 6.98 (d, 2 H, HPh(3), HPh(3´),
3Jobs = 8.2 Hz); 9.36 (s, 1 H, CHO). 13C NMR (CDCl3), δ: 20.3
(1 C, CH3); 27.6 (2 C, HCAd); 34.4 (1 C, CAd); 35.5 (2 C, H2CAd);
36.2 (1 C, H2CAd); 38.8 (1 C, H2CAd); 39.8 (2 C, H2CAd); 45.5
(1 C, CAd); 56.1 (1 C, CH3O); 112.9 (2 C, CPh(2), CPh(2´)); 126.2
(1 C, CPh(4)); 129.6 (2 C, CPh(3), CPh(3´)); 146.6 (1 C, CPh(1));
205.4 (1 C, CHO). MS (MALDI), found: m/z 284.22 [M + H]+.
C19H26NO. Calculated: 284.20.
Nꢀ({3ꢀ[(Biphenylꢀ4ꢀylamino)methyl]ꢀ1ꢀadamantyl}methylꢀ
idene)biphenylꢀ4ꢀamine (15) was obtained in the attempt to synꢀ
thesize compound 10 from diamine 2 (97 mg) and 4ꢀiodobiꢀ
phenyl (350 mg) in the presence of CuI (9.5 mg) and racꢀBINOL
(28.5 mg) in DMF (1 mL). Eluent light petroleum ether—CH2Cl2
1
1 : 2. The yield was 30 mg (12%), a yellow dense oil. H NMR
(CDCl3), δ: 1.63—1.89 (m, 12 H, HAd); 2.24 (br.s, 2 H, HCAd);
Nꢀ({3ꢀ[(4ꢀMethoxyphenylamino)methyl]ꢀ1ꢀadamantyl}meꢀ
thylidene)ꢀ4ꢀmethoxyphenylamine (19) was obtained as a second
product in the synthesis of compound 14. Eluent CH2Cl2. The
2.98 (s, 2 H, CH2N); 3.80 (br.s, 1 H, NH); 6.72 (d, 2 H, HAr
,
3Jobs = 8.5 Hz); 7.10 (d, 2 H, HAr, Jobs = 8.3 Hz); 7.24—7.48
(m, 8 H, HAr); 7.53—7.63 (m, 6 H, HAr); 7.66 (s, 1 H, CH=N).
13C NMR (CDCl3), δ: 28.1 (2 C, HCAd); 34.5 (1 C, CAd); 36.1 (1 C,
H2CAd); 38.9 (2 C, H2CAd); 39.6 (1 C, CAd); 39.9 (2 C, H2CAd);
42.0 (1 C, H2CAd); 55.8 (1 C, CH2N); 112.8 (2 C, HCAr);
121.0 (2 C, HCAr); 125.9 (1 C, HCAr); 126.2 (2 C, HCAr); 126.4
(1 C, HCAr); 126.9 (2 C, HCAr); 127.6 (2 C, HCAr); 127.9 (2 C,
HCAr); 128.6 (2 C, HCAr); 128.7 (2 C, HCAr); 131.5 (1 C,
CAr); 138.2 (1 C, CAr); 140.7 (1 C, CAr); 141.3 (1 C, CAr); 148.5
(1 C, NCAr); 151.8 (1 C, NCAr); 172.3 (1 C, CH=N). MS
(MALDI), found: m/z 497.2930 [M + H]+. C36H37N2. Calcuꢀ
lated: 497.2957.
3
1
yield was 36 mg (18%), a brown dense oil. H NMR (CDCl3),
δ: 1.52—1.82 (m, 12 H, HAd); 2.19 (br.s, 2 H, HCAd); 2.85 (s, 2 H,
CH2N); 3.74 (s, 3 H, OCH3); 3.79 (s, 3 H, OCH3´); 6.60 (d, 2 H,
HPh(2), HPh(2´), 3Jobs = 8.7 Hz); 6.77 (d, 2 H, HPh(3), HPh(3´),
3
3Jobs = 8.7 Hz); 7.00 (d, 2 H, HPh(3), HPh(3´), Jobs = 8.7 Hz);
3
7.59 (d, 2 H, HPh(2), HPh(2´), Jobs = 8.7 Hz); 7.59 (s, 1 H,
CH=N), the proton of the NH group was not found. 13C NMR
(CDCl3), δ: 28.1 (2 C, HCAd); 34.2 (1 C, CAd); 36.2 (1 C, H2CAd);
38.8 (1 C, CAd); 38.9 (2 C, H2CAd); 40.0 (2 C, H2CAd); 42.1 (1 C,
H2CAd); 55.4 (1 C, CH2N); 57.0 (1 C, OCH3); 57.3 (1 C,
OCH3´); 114.0 (2 C, CPh(2), CPh(2´)); 114.9 (4 C, CPh(3),
CPh(3´), CPh(3), CPh(3´)); 121.7 (2 C, CPh(2), CPh(2´)); 143.3
(1 C, CPh(1)); 145.6 (1 C, CPh(1´)); 151.8 (1 C, CPh(4)); 157.6
(1 C, CPh(4´)); 170.9 (1 C, CH=N). MS (MALDI), found: m/z
405.23 [M + H]+. C26H33N2O2. Calculated: 405.25.
3ꢀ[(4ꢀTrifluoromethylphenylamino)methyl]adamantaneꢀ1ꢀ
carbaldehyde (16) was obtained as a second product in the synꢀ
thesis of compound 12. Eluent light petroleum ether—CH2Cl2
1 : 1—1 : 2. The yield was 39 mg (23%), a colorless dense oil.
1H NMR (CDCl3), δ: 1.52—1.56 (m, 4 H, HAd); 1.59—1.65 (m,
4 H, HAd); 1.68—1.77 (m, 4 H, HAd); 2.20 (br.s, 2 H, HCAd);
2.93 (s, 2 H, CH2N); 6.64 (d, 2 H, HPh(2), HPh(2´), 3Jobs = 8.4 Hz);
3ꢀ{[(4ꢀMethoxyphenyl)amino]methyl}adamantaneꢀ1ꢀcarbꢀ
aldehyde (20) was obtained as a second product in the synthesis
of compound 14. Eluent CH2Cl2. The yield was 13 mg (9%),
3
1
7.37 (d, 2 H, HPh(3), HPh(3´), Jobs = 8.4 Hz); 9.35 (s, 1 H,
a brown dense oil. H NMR (CDCl3), δ: 1.52—1.83 (m, 12 H,
CHO); the proton of the NH group was not found. 13C NMR
(CDCl3), δ: 27.5 (2 C, HCAd); 34.6 (1 C, CAd); 35.4 (2 C, H2CAd);
35.8 (1 C, H2CAd); 38.7 (1 C, H2CAd); 39.7 (2 C, H2CAd); 45.4
(1 C, CAd); 55.3 (1 C, CH2N); 112.0 (2 C, CPh(2), CPh(2´)); 126.6
(2 C, CPh(3), CPh(3´)); 205.2 (1 C, CHO), three quaternary
carbon atoms were not found. MS (MALDI), found: m/z 338.18
[M + H]+. C19H23F3NO. Calculated: 338.17.
Nꢀ({3ꢀ[(4ꢀMethylphenylamino)methyl]ꢀ1ꢀadamantyl}methylꢀ
idene)ꢀ4ꢀmethylphenylamine (17) was obtained as a second prodꢀ
uct in the synthesis of compound 13. Eluent light petroleum
ether—CH2Cl2 1 : 4. The yield was 18 mg (10%), a pale yellow
dense oil. 1H NMR (CDCl3), δ: 1.55—1.83 (m, 12 H, HAd); 2.20
(br.s, 2 H, CH(Ad)); 2.24 (s, 3 H, CH3); 2.34 (s, 3 H, CH3); 2.88
HAd); 2.19 (br.s, 2 H, HCAd); 2.84 (s, 2 H, CH2N); 3.74 (s, 3 H,
CH3O); 6.60 (d, 2 H, HPh(2), HPh(2´), 3Jobs = 8.7 Hz); 6.77 (d, 2 H,
HPh(3), HPh(3´), 3Jobs = 8.7 Hz); 9.35 (s, 1 H, CHO); the proton
of the NH group was not found. 13C NMR (CDCl3), δ: 27.6 (2 C,
HCAd); 34.0 (1 C, CAd); 35.5 (2 C, H2CAd); 36.0 (1 C, H2CAd);
39.3 (1 C, H2CAd); 39.8 (2 C, H2CAd); 45.5 (1 C, CAd); 55.8 (1 C,
CH2N); 56.9 (1 C, OCH3); 113.9 (2 C, CPh(2), CPh(2´)); 114.9
(2 C, CPh(3), CPh(3´)); 143.3 (1 C, CPh(1)); 151.8 (1 C, CPh(4));
205.4 (1 C, CHO). MS (MALDI), found: m/z 300.22 [M + H]+.
C19H26NO2. Calculated: 300.20.
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 13ꢀ03ꢀ00572
and 16ꢀ03ꢀ00349).
(s, 2 H, CH2N); 3.60 (br.s, 1 H, NH); 6.56 (d, 2 H, HPh(2),
3
HPh(2´), 3Jobs = 8.2 Hz); 6.92 (d, 2 H, HPh(3), HPh(3´), Jobs
=
3
= 8.2 Hz); 6.98 (d, 2 H, HPh(3), HPh(3´), Jobs = 8.2 Hz); 7.13
(d, 2 H, HPh(2), HPh(2´)); 7.58 (s, 1 H, CH=N). 13C NMR
(CDCl3), δ: 20.3 (1 C, CH3); 20.8 (1 C, CH3); 28.1 (2 C, HCAd);
34.1 (1 C, CAd); 36.0 (1 C, H2CAd); 38.9 (2 C, H2CAd); 39.4 (1 C,
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Received March 28, 2016;
in revised form April 20, 2016