The first one-pot synthesis of 1,3-dicarbonyl adamantanes from 1-bromoadamantanes

Article abstract of DOI:10.1016/j.mencom.2011.09.009

Treatment of 1-bromoadamantane and 1-bromo-3,5-dimethyladamantane with CBr₄·2AlBr₃ under carbon monoxide atmosphere followed by quenching with nucleophiles affords 1,3-dicarbonyl adamantanes.

Full text of DOI:10.1016/j.mencom.2011.09.009

Mendeleev
Communications
Mendeleev Commun., 2011, 21, 259–261
The first one-pot synthesis of 1,3-dicarbonyl
adamantanes from 1-bromoadamantanes
Irena S. Akhrem,* Dzhul’etta V. Avetisyan, Lyudmila V. Afanas’eva, Evgenii I. Goryunov,
Irina M. Churilova, Pavel V. Petrovskii and Nikolai D. Kagramanov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085; e-mail: cmoc@ineos.ac.ru
DOI: 10.1016/j.mencom.2011.09.009
Treatment of 1-bromoadamantane and 1-bromo-3,5-dimethyladamantane with CBr ·2AlBr under carbon monoxide atmosphere followed
4
3
by quenching with nucleophiles affords 1,3-dicarbonyl adamantanes.
Replacement of labile atoms or groups by other functionalities is
a powerful synthetic approach in modern organic chemistry.
Meanwhile, selective one-pot bifunctionalization involving the
Br
COY
1
CBr3, CO, :YH
R
R
COY
cleavage of both labile C–X and poorly reactive Csp –H bonds
3
with the formation of compounds containing two new functional
groups is a considerable challenge. Principally, depending on the
type of the initiating system, these transformations should pro-
ceed either through biradical (A) or dication (B) intermediates
R
R
1
1
a R = H
b R = Me
:YH = H2O, alcohol, amine,
arene, heteroarene
(Scheme 1).
Scheme 2
2
E
proceeded selectively under very mild conditions and afforded
the target dicarbonyl adamantanes in high yields (Scheme 2).
Carbonylation of 1a was carried out in CH Br at 0°C under
C
X
(CH2)n
C
H
C
C
(CH2)n
C
C
–
–
EX, – EH
A
2
2
1
atm of CO in the presence of 20–50% excess of superelectro-
2
E
phile CBr ·2AlBr (E) for 3 h. The process can also be performed
C
X
(CH2)n
C
H
(CH2)n
4
3
EX, – EH
at room temperature for 45 min, however, in this case the selec-
tivity is lower. The resulting carbonylation product was then treated
with 1.5–4-fold molar excess of a nucleophile with respect to E
strictly under CO atmosphere at 0°C for ca. 30 min, with the
exception of the reaction with water, which required a longer
time. In case of various alcohols, the corresponding diesters 3a–i
were obtained (Scheme 3).According to GC, as a rule, conversion
of 1a was close to 100%. The product yields were determined by
GC and NMR (with mesitylene as an internal standard), the
yields of isolated products in the Schemes 3–5 are marked by
asterisk.
B
Scheme 1
Radical transformations can hardly be expected to be selective.
At the same time, generation of species bearing two carbocationic
centers would require the use of potent superelectrophiles. How-
ever, in their presence, cracking, isomerizations, and other by-
processes are also difficult to be avoided.
Herein, we report a new approach to one-pot transformations
of 1-bromoadamantanes which produce bifunctional derivatives
with two new carbonyl-containing groups at the bridged-head
position via cleavage of both C–Br and Csp
–H bonds.
Our strategy was based on the use of superelectrophile
CBr ·2AlBr , which, as we found, can easily generate carbo-
Surprisingly, we found that if water and then solvent, such
as diethyl ether or chloroform, were added to the product of
carbonylation of 1a, dimethyl or diethyl adamantane-1,3-car-
boxylates, respectively, were formed in good yields instead of
the target diacid. Although the content of MeOH and EtOH
impurities in Et O and CHCl , respectively, was no higher than
3
4
3
2
3,4
cations from alkanes or even from monofunctionalized alkanes
leaving a functional group unaffected. Under CO atmosphere,
these cations are converted into the corresponding acylium inter-
mediates, which, in turn, upon in situ treatment with nucleo-
philes afford monofunctional or bifunctional products, respec-
tively.
We found that carbonylation of 1-bromoadamantane 1a
and 1-bromo-3,5-dimethyladamantane 1b in the presence of
CBr ·2AlBr followed by the in situ treatment of the resulting
2
3
0.3–0.5%, and water was used in 50–100-fold molar excess with
2
3,4
†
Typical procedure. At 0°C under CO atmosphere (1 atm) bromo-
adamantane 1a or 1b (0.83 mmol) was added to the stirred solution of the
complex CBr4·2AlBr3 (E), freshly prepared from AlBr3 (2.50 mmol) and
CBr (1.25 mmol) in anhydrous CH Br (1.3 ml) at room temperature.
4
2
2
A molar ratio [E]:[1a] = 1.2:1; [E]:[1b] = 1.5:1. After 3 h stirring at 0°C
under CO atmosphere, a nucleophileYH (molar ratio [YH]:[E] = 4:1) was
added to the in situ prepared carbonylation intermediate. The mixture was
left to warm up to 0°C for 20–30 min. After that, 10 ml of water and 20 ml
4
3
1
,3-dicarbonylation products with nucleophiles provides a con-
venient synthetic route to dicarbonyl adamantanes with two new
†
functional groups at the bridged-head position. In contrast to
of CHCl were carefully added under stirring, and organic layer was separated.
the reactions previously described,3 where the original func-
tionalities interacted with the superelectrophile reversibly and
finally remained intact, the here studied labile Br atom was
replaced by the carbonyl moiety either. These one-pot reactions
,4
3
The remaining aqueous layer was extracted with CHCl (2×20 ml), com-
3
bined organic extracts were dried over Na SO , the solvent was removed
2
4
under reduced pressure and the residue was purified by crystallization or
precipitation.
©
2011 Mendeleev Communications. All rights reserved.
– 259 –

Mendeleev Commun., 2011, 21, 259–261
COOH
Br
COOR
Br
COOH
+CBr3,
CO
+CBr3,
CO
+CBr3, CO
Me
Me
COOH
2
H O
ROH
COOR
2
H O
COOH
Me
Me
7, 60%*
2
, 80%*
1a
3a–i
1
b
+
3
3
3
3
a R = Me, 83% 3e R = (CH2)3Br, 75%
b R = Et, 81%
c R = Pr , 97%
d R = Bu , 84% 3h R = CH2CH(Me)CF3, 94%
CBr , CO
3
3f R = CH2CºCH, 74%
3g R = CH2CF3, 92%
+
i
CBr , CO ROH
YH
O
Y
3
s
3
i R = CH2(CF2)2H, 90%
COOR
Me
Y
O
Scheme 3
Me
Me
COOR
respect to the alcohols, the carbonylation product absorbed
alcohols much quicker even from very diluted solutions. The
9
a Y = NEt2, 75%*
‡
Me
9b Y = NHPh, 88%*
8
8
a R = Me, 65%*
b R = Pr , 79%
desired diacid was obtained only when quenching of the car-
bonylation intermediate with water was performed at room tem-
perature for several hours (up to 48 h) in the solvent-free manner
or at least with the use of alcohol-free solvent. Under these con-
ditions, adamantane-1,3-dicarboxylic acid was isolated in 70–80%
yield. These results show that the reactions of the carbonyla-
tion product with water proceeded much slower than those with
alcohols.
The use of diethylamine, morpholine and aniline led to the
corresponding dicarboxamides 4a–c. In the case of anisole, di-
ketone 5 was obtained in 69% yield, while very active furan pro-
vided only 42% yield of diketone 6 together with 1-bromo-
i
9c Y =
N
O , 85%*
1
0 Y = 4-MeOC6H4, 73%*
Scheme 5
The suggested reaction path for 1a,b (Scheme 6) involves the
elimination of the Br atom by the superelectrophile. Evidently,
this step occurs catalytically. The Ad (or 1,3-Me Ad ) adds CO
to form more stable AdCO (or 1,3-Me AdCO ). The latter, in
turn, undergoes the abstraction of hydride to give under CO atmo-
sphere diacylium species which is a precursor for the formation of
the final products.
+
+
2
+
+
2
3
-(2-furylcarbonyl)adamantane as a by-product (Scheme 4).
Br
CO
O
E, CO
O
NEt2
O
NHPh
O
N
E, CO
R
R
–
EH
O
R
R
R
NEt2
NHPh
N
COBr
E
CO
O
O
4b, 84%*
O
4
a, 75%*
4c, 86%*
R
COBr
E
COBr
E
OMe
R
R
R
Br
O
O
CO
COY
O
OMe
R
:YH
CO
COY
1
a
O
R
R
O
O
R = H, Me
E = CBr3 Al2Br7
5
, 69%*
6, 42%
Scheme 6
Scheme 4 Reagents: CBr ·2AlBr , CO, Et NH (for 4a), PhNH (for 4b),
4
3
2
2
morpholine (for 4c), anisol (for 5) or furan (for 6).
A great body of evidence accumulated in the last few decades
shows that positively charged species are capable of further inter-
action with strong protic or aprotic superelectrophiles to produce
highly active ditonic dications, i.e., the species containing two
cationic centers separated by one or several atoms, and even
gistonic dications with two cationic centers located at two adjacent
1
-Bromo-3,5-dimethyladamantane 1b behaved similarly to
form the corresponding dicarbonyl compounds (Scheme 5). The
reactions with 1b required somewhat higher excess of E than
those with 1a to achieve good selectivity and high yields of the
products. It seems likely that the carbonylation product generated
from 1b is less stable in comparison with that prepared from 1a,
because donor methyl groups in acylium cations facilitate their
7
carbon atoms. The ditonic 1,3-adamantanediyl dication con-
taining two tertiary carbenium centers separated by a methylene
group was shown by B3LYP/6-31G* quantum chemical calcula-
6
decarbonylation.
8
tion to have a minimum on the potential energy surface, although
‡
In a special experiment, 1a (1.07 mmol) was carbonylated in the pres-
ence of CBr ·2AlBr (1.29 mmol) in CH Br (1.4 ml) at 0°C over 3 h.
In situ treatment of the carbonylation product with 30 ml of hexane, con-
taining 0.162 g (2.19 mmol) of Bu OH afforded the Ad(COOBu ) in
attempts to prepare it in the superacid solution were unsuccess-
4
3
2
2
9
ful. Elucidation of the nature of the carbonylation products of
1
-bromoadamantane will be the subject of our future work.
Many derivatives of adamantane carboxylic acids display
s
s
2
6
8% yield.
5
,10
For experimental details, analytical and spectroscopic ( H, 13C, 19F NMR
1
promising biological activities.
Incorporation of the AdCO
and MS) data for obtained compounds, see Online Supplementary
Materials.
into polymers such as polyesters and polyamides enhances their
1
1
thermal and chemical stability. Other fields of application of
–
260 –

Mendeleev Commun., 2011, 21, 259–261
1
2(a),(b)
AdCO-containing compounds involve crown ethers,
peptide
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P. V. Petrovskii and A. V. Orlinkov, Tetrahedron Lett., 2010, 51, 907.
1
2(c)
13
ionophores,
etc.
4
5
A. V. Orlinkov, N. D. Kagramanov, P. V. Petrovskii and I. S. Akhrem,
Tetrahedron Lett., 2010, 51, 259.
E. I. Bagrii, Adamantany: poluchenie, svoistva, primenenie (Adamantanes:
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Important, carbonyl-containing groups in the prepared pro-
ducts can be easily transformed into a broad variety of other
functionalities. Therefore, one may expect that a new approach
5
to selective one-pot synthesis of various bifunctional adaman-
tanes from available bromoadamantanes would provide new ways
to biological active compounds, polymers, and other valuable
products.
Until now, one-pot synthesis of 1,3-dicarbonyl adamantanes
has not been known. Previously reported syntheses1 of such
compounds are based on poorly available adamantane-1,3-di-
carboxylic acid as the starting material and the use of oleum as
the reaction medium, and do not provide good yields of the
products.
The herein developed method seems to be rather common for
the preparation of various 1,3-dicarbonyl adamantanes by using
nucleophiles which are reluctant to superelectrophiles. In the
case of very active nucleophiles, the corresponding compounds
can be prepared by the known multi-step reactions starting from
adamantanedicarboxylic acids, which could be obtained by our
method using water as a nucleophile.
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Many of the products prepared in this work are new. Their
1
13
structures are consistent with H and C NMR, mass spectra and
elemental analyses, which are available in Online Supplementary
Materials.
In summary, the use of powerful superelectrophilic complex
CBr ·2AlBr allowed us to achieve selective one-pot bifunction-
1
1
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1
This work was supported by the Russian Foundation for
Basic Research (project no. 09-03-00110) and the RAS Presidium
Foundation (program 7P).
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Online Supplementary Materials
1
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Received: 21st March 2011; Com. 11/3702
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