R. Kubilius et al. / Tetrahedron Letters 52 (2011) 346–348
347
COOCH3
TTN
O
O
O
H+
COOCH3
+
CH3OH
CH3O
O
O
OCH3
4
3
6
5
Scheme 2.
stored overnight at room temperature over molecular sieves. Anal-
ysis of the IR, 1H NMR, and mass spectra proved the formation of
tricyclic acetal 11. Thus formation of 11 occurs with indirect partic-
ipation of thallium(III) nitrate. The unexpected formation of 11
could be accounted for by the proximity of the carbonyl groups
in 9, and transannular cyclization takes place before oxidation. In
addition, the 2,7-diketone 13 with proximate carbonyl groups
gives an analogous cyclic acetal 14 under similar reaction condi-
tions which support the above conclusion.
O
COOCH3
Tl(NO3)3
CH3OH
O
O
R
R
O
O
R'
R'
7a,b
a R,R' = -CH2CH2- 8a,b
b
R=R' =CH3
Scheme 3.
CH3O
O
O
OCH3
O
O
COOCH3
O
COOCH3
OCH3
O
Tl(NO3)3
CH3OH
OCH3
+
+
O
13
14
OCH3
OCH3
10
11
12
9
In conclusion, reaction of enantiomerically pure (+)-2,6-dike-
tone 1 with TTN (molar ratio 1: 2) in methanol proceeds via oxida-
tive rearrangement, exclusively affording methyl (+)-exo,exo-
bicyclo[2.2.1]heptane-2,5-dicarboxylate 2 in good yield. Analogous
transformations of (+)-2,9-dione, 2,7- and 3,7-diketones led not
only to oxidative rearrangement but also to transannular ring clo-
sure into tricyclic products due to the proximity of the carbonyl
groups in the bicyclononane skeleton.
Scheme 4.
undergoes ring-opening in acidic aqueous solution, by way of car-
bon–carbon bond cleavage between atoms C-1 and C-2 leading to
the formation of 3-(2-oxocyclohexyl)propanoic acid.12 Indeed, the
reaction mixture of 3 and TTN in methanol contained methyl 3-
(2-oxocyclohexyl)propanoate (5, 20%). In addition, the spectra of
this compound were identical to those of 5 prepared as follows.
A methanol solution of 3 was acidified with concentrated aqueous
hydrochloric acid and kept overnight at room temperature. The
main component in the mixture (59%) was acetal 6 (Scheme 2).
The synthesis of analogous ethanediol acetal 7 illustrates the ten-
dency of 3 to form acetals at the C-9 carbonyl instead of the C-2
carbonyl.
Acknowledgment
This work was supported by Nordforsk via the Nordic-Baltic
Network Excellent Nordic Chemistry.
References and notes
Acetals of diketone 3 may impede the ring-opening of the bicy-
clic skeleton. In order to verify this observation, oxidative rear-
rangement of spiro[1,3-dioxolane-2,90-bicyclo[3.3.1]nonan]-20-
one13 (7a) was carried out. Treatment of 7a with TTN in methanol
afforded the rearrangement products, diastereomeric esters 8a
(38%) (Scheme 3). Since traces of water are present originating
from Tl(NO3)3ꢀ3H2O, minor amounts of the deprotected diketone
3 (hydrolysis product) and the subsequently rearranged ketoester
4 (3%), respectively, were also present. Since ethanediol acetal 7a
undergoes oxidative rearrangement, analogous behavior of di-
methyl acetal 7b would be expected and diastereomers of acetal
8b were the main products in the reaction mixture. The products
of acetal hydrolysis and Favorskii-like rearrangement were also
identified in this reaction mixture.
1. Ferraz, H. M. C.; Silva, L. F. Quim. Nova 2000, 23, 216–224.
2. McKillop, A.; Taylor, E. C. In Comprehensive Organometallic Chemistry;
Wilkinson, J., Ed.; Pergamon: Oxford, 1982; Vol. 7, pp 465–513.
3. (a) Ferraz, H. M. C.; Vieira, T. O.; Silva, L. F., Jr. Synthesis 2006, 2748–2752; (b)
Takaya, Y.; Terashima, K.; Ito, J.; He, Y. H.; Tateoka, M.; Yamaguchi, N.; Niwa, M.
Tetrahedron 2005, 61, 10285–10290; (c) Ferraz, H. M. C.; Silva, L. F., Jr.; Aguilar,
A. M.; Vieira, T. O. J. Braz. Chem. Soc. 2001, 12, 680–684.
4. Butkus, E. Synlett 2001, 1827.
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Zilinskas, A.; Stoncius, S.; Rozenbergas, R.; Urbanová, M.; Setnicka, V.; Bour, P.;
Volka, K. Tetrahedron: Asymmetry 2002, 13, 633.
6. Wallentin, C. J.; Orentas, E.; Butkus, E.; Warnmark, K. Synthesis 2009, 864.
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ˇ
10. Butkus, E.; Stoncius, A. Synlett 1999, 234.
11. GC–MS spectra were recorded on a Hewlett-Packard 6980 instrument with a
The reaction of bicyclo[3.3.1]nonane-3,7-dione (9) with an
equimolar amount of TTN was carried out in methanol. The dike-
tone 9 showed lower reactivity compared to the 2,6- and 2,9-iso-
mers 1 and 3 under the same reaction conditions.14 The starting
material was still present in the mixture after 24 h at room tem-
perature. Three compounds were formed during this reaction:
the oxidative rearrangement product 10, tricyclic acetal 11, and
the rearranged acetal 12 (Scheme 4). The first two compounds
were separated by flash chromatography.
mass selective detector HP 5973 using a Supelcowax capillary column
(30 m ꢁ 0.25 mm) or on an AEI MS 902S mass spectrometer (FAB in positive
mode).
12. Hargreaves, J. R.; Hickmott, P. W.; Hopkins, B. J. J. Chem. Soc. (C) 1969, 592–595.
13. spiro[1,3-Dioxolane-2,90-bicyclo[3.3.1]nonan]-20-one (7a). P2O5 (0.1 g) was
added to a solution of 3 (0.41 g, 2.7 mmol) and ethanediol (0.17 g, 2.7 mmol)
in dry toluene (10 mL). The mixture was refluxed with azeotropic removal of
H2O, cooled, and residual P2O5 was quenched with H2O. The product was
extracted with benzene (3 ꢁ 5 mL); the extracts were combined, washed with
saturated NaHCO3 (2 ꢁ 10 mL) solution and H2O (10 mL), dried over Na2SO4,
and concentrated under reduced pressure. The product was distilled in vacuo
to afford 0.19 g (37%) of an oily liquid, bp 112–115 °C/2 mmHg. IR, kmax: 1715,
1112, 1100 cmꢂ1
.
1H NMR (300 MHz, CDCl3): 3.9 (m, 4H, O(CH2)2O), 2.54 (m,
In order to prove the structure of 11, a methanolic solution of 9
was acidified with a catalytic amount of p-toluenesulfonic acid and
2H), 2.32–1.77 (m, 8H), 1.74–1.6 (m, 2H). 13C NMR (75 MHz, CDCl3): 212.2