Adamantylation of β-dicarbonyl compounds

Article abstract of DOI:10.1007/s11172-012-0239-7

Reactions of adamantan-1-ol with β-dicarbonyl compounds in 1,2-dichloroethane in the presence of In(OTf)₃, Ga(OTf)₃, Sc(OTf)₃, or Cu(OTf)₂ give the corresponding adamantylated derivatives in 45-93% yields.

Full text of DOI:10.1007/s11172-012-0239-7

Russian Chemical Bulletin, International Edition, Vol. 61, No. 9, pp. 1733—1735, September, 2012
1733
Adamantylation of ꢀdicarbonyl compounds
A. A. Turmasova, E. S. Spesivaya, Dzh. N. Konshina, and V. V. Konshin
Kuban State University,
1
49 ul. Stavropol´skaya, 350040 Krasnodar, Russian Federation.
Fax: +7 (861) 219 9571. Eꢀmail: organotin@mail.ru
Reactions of adamantanꢀ1ꢀol with ꢀdicarbonyl compounds in 1,2ꢀdichloroethane in the
presence of In(OTf) , Ga(OTf) , Sc(OTf) , or Cu(OTf) give the corresponding adamantylꢀ
3
3
3
2
ated derivatives in 45—93% yields.
Key words: ꢀdicarbonyl compounds, adamantanꢀ1ꢀol, adamantylation, Lewis acids,
indium(III) triflate.

ꢀDicarbonyl compounds take an important role in
The reaction conditions were optimized for adamanꢀ
tylation of acetylacetone (2a) with an equimolar amount
of adamantanꢀ1ꢀol; the concentration of the catalyst was
5 mol.% (Table 1). The use of FeCl on silica gel or ZnI as
1
organic synthesis. In the last few years, methods for benzꢀ
ylation,2 allylation, and especially propargylation of
ꢀdicarbonyl compounds with appropriate alcohols in the
3
4

3
2
presence of Lewis acids have been under active developꢀ
ment. This method is suitable for alcohols easily generatꢀ
ing the corresponding carbocations.
catalysts failed: product 3a was not detected even in trace
amounts. Adamantylation in toluene did not afford the
target product; instead, we obtained 1ꢀ(4ꢀtolyl)adamanꢀ
tane in a nearly quantitative yield. The highest yield of
compound 3a was achieved in boiling 1,2ꢀdichloroethane
with indium(III) triflate as a catalyst. The use of scandium,
gallium, and copper(II) triflates provided close yields.
Dibenzoylmethane (2b), ethyl acetoacetate (2c), and
ethyl benzoylacetate (2d) were also efficiently adamantylꢀ
We found it interesting to study the possibility of obꢀ
taining adamantylated ꢀdicarbonyl compounds because
they can further be used as starting materials for the synꢀ
5
thesis of biologically active heterocycles. Known routes
to such compounds involve reactions of cobalt(II), copꢀ
per(II), and zinc ꢀdiketonates with 1ꢀbromoadamantane,6
reactions of 1,3ꢀdehydroadamantane with ꢀdicarbonyl
7
compounds, or acidꢀcatalyzed alkylation of the latter
8
,9
with adamantanꢀ1ꢀol in nitromethane
acetic acid.1
or trifluoroꢀ
Table 1. Adamantylation of ꢀdicarbonyl compounds
0
In the present work, we propose a simple and efficient
procedure for adamantylation of various ꢀdicarbonyl
compounds with adamantanꢀ1ꢀol in the presence of
such Lewis acids as Sc(OTf) , Ga(OTf) , In(OTf) , or
ꢀDicarbonyl
compound
Catalyst
Solvent
Product
Yield
(%)
2
a
In(OTf)3
CH Cl
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
2f
14
93
0
54
0b
89
91
90
0
2
2
3
3
3
1
,2ꢀDCE
Cu(OTf) (Scheme 1).
a
2
1,2ꢀDCE
MeNO2
PhCH3
Scheme 1
Ga(OTf)3
Sc(OTf)3
Cu(OTf)2
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
MeNO2
FeCl /SiO
3
2
ZnI2
0
2
2
2
2
2
b
c
d
e
f
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
92
83
80
45
7
i. M(OTf) (5 mol.%), Cl(CH ) Cl.
n
2 2
2f
85
1
2
1
2
1
2
2
, 3: R = R = Me (a); R = R = Ph (b); R = Me, R = OEt (c);
1
2
1
2
a At ~20 C.
R = Ph, R = OEt (d); R = OEt, R = OEt (e);
1
2
b
R + R = —CH C(Me )CH — (f)
The reaction product is 1ꢀ(4ꢀtolyl)adamantane.
2
2
2
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1717—1719, September, 2012.
066ꢀ5285/12/6109ꢀ1733 © 2012 Springer Science+Business Media, Inc.
1

1734
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
Turmasova et al.
ated in 1,2ꢀdichloroethane with indium(III) triflate as
a catalyst (see Table 1). The moderate yield of the target
product in the adamantylation of diethyl malonate (2e) is
explained by the low content of its enol form.11 In conꢀ
trast, adamantylation of dimedone (2f) was efficient only
in nitromethane: the yield of compound 3f was 85% against
its 7% yield in 1,2ꢀdichloroethane. This fact confirms that
the reaction mechanism involves addition of the carbocaꢀ
tion to an enolized ꢀdicarbonyl compound.12
The target products can easily be isolated by flash chroꢀ
matography; the reaction mixtures should first be treated
with dilute HCl and concentrated.
(m, 3 H, CH); 5.41 (s, 1 H, CH); 7.35—7.39 (m, 4 H); 7.47—7.51
13
(
m, 2 H); 7.88—7.90 (m, 4 H). C NMR (100.52 MHz, CDCl ),
3

: 29.13 (CH), 39.86 (CH ), 40.30 (CH ), 45.53 (C), 63.61 (CH),
2 2
128.47, 128.84, 133.19, 138.38 (Ph), 194.20 (C=O). MS (EI,
+
7
0 eV), m/z (Irel (%)): 340 [M] (21), 253 (21), 135 (6), 105 (100).
Ethyl 2ꢀ(1ꢀadamantyl)ꢀ3ꢀoxobutanoate (3c) was obtained
as described for compound 3a from adamantanꢀ1ꢀol (1 g,
.57 mmol) and ethyl acetoacetate (2c) (0.86 g, 6.57 mmol) in
6
the presence of In(OTf) (0.185 g, 0.33 mmol). Compound 3c
3
was isolated by flash chromatography with hexane—ethyl aceꢀ
tate (10 : 3) as an eluent. Yield 1.44 g (83%), yellowish oil. IR
(
1
1
thin film), /cm– : 2978, 2904, 2848 (C —H), 1745, 1737,
1
sp3
1
732, 1714, 1703 (C=O). H NMR (399.78 MHz, CDCl ), :
.25 (t, 3 H, J = 7 Hz); 1.60—1.79 (m, 12 H, CH ); 1.96 (m, 3 H,
3
2
To sum up, we proposed a convenient atom economiꢀ
cal preparation of adamantylated ꢀdicarbonyl comꢀ
pounds. The procedure meets "green chemistry" philosoꢀ
phy: the catalyst used in the reaction can be recovered
without considerable loss in its activity1 and water is the
only secondary product.
CH); 2.21 (s, 3 H); 3.17 (s, 1 H, CH); 4.12—4.17 (m, 2 H, CH ).
2
13
C NMR (100.52 MHz, CDCl ), : 14.28 (Me), 28.64 (CH),
3
3
6
2.21 (Me), 36.70 (CH ), 37.05 (CH ), 40.13 (C), 60.82 (CH),
2
2
9.95 (CH ), 168.75 (C=O), 203.45 (C=O). MS (EI, 70 eV),
2
3
+
m/z (Irel (%)): 264 [M] (2), 222 (10), 135 (100), 119 (8), 105 (5).
Ethyl 2ꢀ(1ꢀadamantyl)ꢀ3ꢀoxoꢀ3ꢀphenylpropanoate (3d) was
obtained as described for compound 3a from adamantanꢀ1ꢀol
(
1 g, 6.57 mmol) and ethyl benzoylacetate (2d) (1.26 g, 6.57 mmol)
Experimental
in the presence of In(OTf) (0.185 g, 0.33 mmol). Compound 3d
3
was isolated by flash chromatography with hexane—ethyl aceꢀ
1H and 13C NMR spectra were recorded on a JEOL ECA400
tate (10 : 3) as an eluent. Yield 1.71 g (80%), yellowish oil.
IR (thin film), /cm– : 3061 (Csp
1
—H), 2978, 2904, 2848
instrument in CDCl (Aldrich) with reference to the signals for
2
3
the residual protons of the solvent. IR spectra were recorded on
a Shimadzu IR Prestige instrument. The course of the reactions
was monitored by GCꢀMS on a Shimadzu GCꢀ2010 instrument
equipped with a Shimadzu QPꢀ2010 Plus massꢀselective detecꢀ
tor (Supelko SLBꢀ5ms column (30 m), programmed heating from
(Csp
3
—H), 1745, 1732, 1693, 1681 (C=O), 1595, 1446
—Csp ). H NMR (399.78 MHz, CDCl ), : 1.18 (t, 3 H,
2
3
1
(Csp
2
J = 7 Hz); 1.62—1.87 (m, 12 H, CH ); 1.96 (m, 3 H, CH);
4.09—4.14 (m, 2 H, CH ); 4.20 (s, 1 H, CH); 7.43—7.47
(m, 2 H); 7.53—7.57 (m, 1 H); 7.94—7.96 (m, 2 H). C NMR
(100.52 MHz, CDCl ), : 14.23 (Me), 28.72 (CH), 36.81 (CH ),
37.55 (C), 40.38 (CH ), 60.93 (CH), 62.85 (CH ), 167.97 (C=O),
2 2
195.02 (C=O). MS (EI, 70 eV), m/z (Irel (%)): 326 [M] (8), 308
(7), 252 (17), 235 (23), 135 (14), 105 (100).
Diethyl (1ꢀadamantyl)malonate (3e) was obtained as described
for compound 3a from adamantanꢀ1ꢀol (1 g, 6.57 mmol) and
diethyl malonate (2e) (1.26 g, 6.57 mmol) in the presence of
2
2
13
6
0 to 265 C at a rate of 30 deg min–1).
ꢀDicarbonyl compounds 2a,c—e (Aldrich) were distilled
3
2

+
in vacuo before use; adamantanꢀ1ꢀol (1) (Aldrich) was used as
purchased. Solvents were prepared using standard laboratory proꢀ
cedures.14 Metal triflates were prepared as described earlier.15
3
ꢀ(1ꢀAdamantyl)pentaneꢀ2,4ꢀdione (3a). A flask equipped
with a reflux condenser was charged with 1,2ꢀdichloroethane
10 mL) and In(OTf) (0.185 g, 0.33 mmol). Then a solution of
(
In(OTf) (0.185 g, 0.33 mmol). Compound 3e was isolated by
3
3
adamantanꢀ1ꢀol (1 g, 6.57 mmol) and acetylacetone (2a) (0.65 g,
.57 mmol) in 1,2ꢀdichloroethane (25 mL) was added. The reacꢀ
tion mixture was refluxed with stirring for 2 h and transferred to
a separatory funnel containing 2 M HCl (20 mL). The organic
layer was separated and the product from the aqueous phase was
flash chromatography with hexane—ethyl acetate (10 : 3) as an
–
1
6
eluent. Yield 0.86 g (45%), colorless oil. IR (thin film), /cm :
1
2980, 2906, 2848 (Csp3—H), 1755, 1728 (C=O). H NMR (399.78
MHz, CDCl ), : 1.20 (t, 6 H, J = 7 Hz); 1.57—1.72 (m, 12 H,
3
CH ); 1.92 (m, 3 H, CH); 3.01 (s, 1 H, CH); 4.08—4.15 (m, 4 H,
2
13
extracted with CHCl (3×10 mL). The combined organic exꢀ
CH ). C NMR (100.52 MHz, CDCl ), : 14.21 (Me), 28.59
3
2
3
tracts were concentrated on a rotary evaporator and the residue
(CH), 35.95 (C), 36.72 (CH ), 39.87 (CH ), 60.74 (CH), 62.53
2 2
(CH ), 167.82 (C=O). MS (EI, 70 eV), m/z (I (%)): 294 [M]+
was sublimed in vacuo. Yield 1.32 g (86%), m.p. 53 C. IR (KBr),
2
rel
–
1

/cm : 2974, 2910, 2893, 2846 (Csp
3
—H), 1697, 1687 (C=O).
(4), 220 (7), 135 (100), 105 (5).
1
H NMR (399.78 MHz, CDCl ), : 1.59—1.70 (m, 12 H, CH );
2ꢀ(1ꢀAdamantyl)ꢀ5,5ꢀdimethylcyclohexaneꢀ1,3ꢀdione (3f) was
obtained as described for compound 3a from adamantanꢀ1ꢀol
(1 g, 6.57 mmol) and dimedone (2f) (0.92 g, 6.57 mmol) in
nitromethane (20 mL) in the presence of In(OTf)3 (0.185 g,
0.33 mmol). Compound 3f was isolated by flash chromatography
with hexane—ethyl acetate (10 : 4) as an eluent. Yield 1.53 g
(85%), colorless crystals, m.p. 160 C (cf. Ref. 7c: m.p. 113 C).
3
2
1
.96 (m, 3 H, CH); 2.18 (s, 6 H, Me); 3.51 (s, 1 H, CH).
1
3
C NMR (100.52 MHz, CDCl ), : 28.64 (CH), 33.21 (Me),
3
3
6.60 (CH ), 40.45 (CH ), 45.35 (C), 78.25 (CH), 204.61 (C=O).
2
2
+
MS (EI, 70 eV), m/z (Irel (%)): 234 [M] (4), 192 (16), 135 (100).
ꢀ(1ꢀAdamantyl)ꢀ1,3ꢀdiphenylpropaneꢀ1,3ꢀdione (3b) was
obtained as described for compound 3a from adamantanꢀ1ꢀol
1 g, 6.57 mmol) and dibenzoylmethane (2b) (1.47 g, 6.57 mol)
2
–1
(
IR (KBr), /cm : 2956, 2945, 2906, 2881, 2848 (Csp3—H), 1710,
1
in the presence of In(OTf) (0.185 g, 0.33 mmol). Compound 3b
1691 (C=O). H NMR (399.78 MHz, CDCl ), : 0.81 (s, 3 H,
3
3
was recrystallized from methanol. Yield 2.17 g (92%), m.p.
Me); 1.13 (s, 3 H, Me); 1.57—1.68 (m, 12 H, CH ); 1.99 (m, 3 H,
2
11 C. IR (KBr), /cm–1: 3064 (Csp
—H), 2906, 2891, 2843
13
2
2
CH); 2.42—2.52 (m, 4 H, CH ); 2.70 (s, 1 H, CH). C NMR
2
1
(
(
Csp
3
—H), 1697, 1653 (C=O), 1593, 1446 (Csp
2
—Csp
2
). H NMR
(100.52 MHz, CDCl ), : 26.96 (Me), 29.03 (CH), 30.40 (C),
3
399.78 MHz, CDCl ), : 1.53—1.94 (m, 12 H, CH ); 2.04
30.72 (Me), 36.39 (CH ), 38.27 (C), 41.90 (CH ), 56.00 (CH ),
3
2
2
2
2

Adamantylated ꢀdicarbonyl compounds
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1735
7
6.89 (CH), 207.98 (C=O). MS (EI, 70 eV), m/z (I (%)): 274
lenko, Tetrahedron Lett., 1983, 24, 613; (c) B. I. No, G. M.
Butov, V. M. Mokhov, G. Yu. Parshin, Zh. Org. Khim., 2002,
rel
+
[
M] (6), 190 (4), 135 (100), 105 (3).
3
(
8, 1428 [Russ. J. Org. Chem. (Engl. Transl.), 2002, 38, 1377];
d) B. I. No, G. M. Butov, V. M. Mokhov, G. Yu. Parshin,
Zh. Org. Khim., 2003, 39, 1737 [Russ. J. Org. Chem.
Engl. Transl.), 2003, 39, 1668]; (e) G. M. Butov, V. M.
References
(
1
2
. (a) W. A. Smit, A. D. Dilman, Osnovy sovremennogo organꢀ
icheskogo sinteza [Basics of Modern Organic Synthesis],
BINOM, Laboratoriya Znanii, Moscow, 2009, 750 pp.
Mokhov, G. Yu. Parshin, R. U. Kunaev, S. A. Shevelev,
I. L. Dalinger, I. A. Vatsadze, Zh. Org. Khim., 2008, 44, 1171
[
Russ. J. Org. Chem. (Engl. Transl.), 2008, 44, 1157].
(
2
in Russian); (b) A. V. Kel´in, A. Maioli, Curr. Org. Chem.,
003, 7, 1855.
8
9
. Yu. N. Klimochkin, T. S. Tilli, I. K. Moiseev, Zh. Org. Khim.,
1
2
988, 24, 1780 [J. Org. Chem. USSR (Engl. Transl.), 1988,
4, 1605].
. (a) M. Yasuda, T. Somyo, A. Baba, Angew. Chem., Int. Ed.
Engl., 2006, 45, 793; (b) M. Rueping, B. Nachtsheim,
A. Kuenkel, Org. Lett., 2007, 9, 825; (c) M. Noji, Y. Konno,
K. Ishii, J. Org. Chem., 2007, 72, 5161; (d) W. Huang,
J. Wang, Q. Shen, X. Zhou, Tetrahedron Lett., 2007, 48, 3969.
. P. Kothandaraman, W. Rao, X. Zhang, P. W. H. Chan, Tetraꢀ
hedron, 2009, 65, 1833.
. (a) W. H. W. Lunn, P. D. Podmore, S. S. Szinai, J. Chem.
Soc. C, 1968, 1657; (b) J. P. Jonak, S. F. Zakrzewski, L. H.
Mead, M. T. Hakala, J. Med. Chem., 1970, 13, 1170;
(
c) S. Landa, J. Burkhard, J. Vais, Collect. Czech. Chem. Comꢀ
3
4
mun., 1973, 38, 1445; (d) J. P. Jonak, L. H. Mead, Y. K. Ho,
S. F. Zakrzewski, J. Med. Chem., 1973, 16, 724.
. (a) W. Huang, J. Wang, Q. Shen, X. Zhou, Tetrahedron,
1
0. (a) E. Shokova, Tasoulla Mousoulou, Y. Luzikov, V. Kovaꢀ
lev, Synthesis, 1997, 1034; (b) A. Shmailov, L. Alimbarova,
E. Shokova, V. Tafeenko, I. Vatsuro, V. Kovalev, Tetraꢀ
hedron, 2010, 66, 3058; (c) Z. Kazimierczuk, A. Orzeszko,
Helv. Chim. Acta, 1999, 82, 2020.
1. A. Gero, J. Org. Chem., 1954, 19, 1960.
2. P. Boldt, H. Militzer, W. Thielecke, L. Schulz, Liebigs Ann.
Chem., 1968, 718, 101.
3. G. K. S. Prakash, P. Yan, B. Torok, I. Bucsi, M. Tanaka,
G. A. Olah, Catal. Lett., 2003, 85, 1.
4. W. Armarego, C. Chai, Purification of Laboratory Chemicals,
ElsevierꢀScience, Oxford, 2003, 608 pp.
5. S. Kobayashi, I. Hachiya, M. Araki, H. Ishitani, Tetrahedron
Lett., 1993, 34, 3755.
2
007, 63, 11636; (b) J. Fan, C. Wan, G. Sun, Z. Wang,
J. Org. Chem., 2008, 73, 8608; (c) X. Feng, Z. Tan, D. Chen,
Y. Shen, C.ꢀC. Guo, J. Xiang, C. Zhu, Tetrahedron Lett.,
2
008, 49, 4110; (d) J. S. Yadav, B. V. Subba Reddy, K. V.
Raghavendra Rao, R. Narender, Tetrahedron Lett., 2009,
0, 3963; (e) Y. Pan, S. Zhao, W. Ji, Z. Zhan, J. Comb.
1
1
5
Chem., 2009, 11, 103.
. E. A. Shokova, V. V. Kovalev, Russ. Chem. Rev., 2011,
5
6
1
1
1
8
0, 927.
. (a) A. Ganzales, F. Guell, J. Marquet, M. MorenoꢀManas,
Tetrahedron Lett., 1985, 26, 3755; (b) A. Ganzales, J. Marꢀ
quet, M. MorenoꢀManas, Tetrahedron, 1986, 4253; (c) J. Marꢀ
quet, M. MorenoꢀManas, P. Pacheco, A. Vallribera, Tetraꢀ
hedron Lett., 1988, 29, 1465.
7
. (a) B. E. Kogay, W. A. Sokolenko, Izv. Akad. Nauk SSSR,
Ser. Khim., 1982, 222 [Bull. Acad. Sci. USSR, Div. Chem. Sci.
Received July 9, 2012;
(
Engl. Transl.), 1982, 31, 213]; (b) B. E. Kogay, W. A. Sokoꢀ
in revised form September 10, 2012