Synthesis of optically pure 3R-methylcyclopentan-1-one from L-(-)-menthol

Article abstract of DOI:10.1007/s10600-005-0203-y

Synthesis of optically pure 3R-methylcyclopentan-1-one using in the key step Dieckmann cyclization of diisopropyl 3R-methylhexan-1,6-dioate, which is accessible from L-(-)-menthol, was proposed. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10600-005-0203-y

Chemistry of Natural Compounds, Vol. 41, No. 5, 2005
SYNTHESIS OF OPTICALLY PURE 3 -METHYLCYCLOPENTAN-
R
1-ONE FROM L-(-)-MENTHOL
G. Yu. Ishmuratov,1 M. P. Yakovleva,1 V. A. Ganieva,2
G. R. Gareeva,2 R. R. Muslukhov,1 and G. A. Tolstikov1
UDC 547.461.6+547.514.472.1+
547.514.482.2'26+547.596.2
Synthesis of optically pure 3R-methylcyclopentan-1-one using in the key step Dieckmann cyclization of
diisopropyl 3R-methylhexan-1,6-dioate, which is accessible from L-(-)-menthol, was proposed.
Key words: L-(-)-menthol, diisopropyl 3 -methylhexan-1,6-dioate, isopropyl 4 -methyl-2-oxocyclopentan-1-
R
R
carboxylate, 3 -methylcyclopentan-1-one, Dieckmann cyclization.
R
3 -Methylcyclopentan-1-one (8) has been used to synthesize oil components of marigold
R
, e.g.,
Tagetes glandulifera
(+)-dihydrotagetone [1], and Bulgarian rose oil, e.g., 4 -rosoxide [2-(2,2-dimethylvinyl)-4 -tetrahydropyran] [2].
R
R
Optically active 8 has been prepared previously starting from -pulegone [3] using cyclization of 3 -methyl-1,6-
R
R
hexanedicarboxylic acid in thekeystepandusingdecarbalkoxylation ofmethyl andethyl esters of 4 -methyl-2-oxocyclopentan-
R
1-carboxylic acid [2, 4-6].
We proposed a new approach to the synthesis of optically pure 3 -methylcyclopentan-1-one (8) that is based on the
R
available monoterpenoid L-(-)-menthol (1), which gave mentholactone (2) as before [7]. Subsequent transesterification using
isopropanol and H SO produced isopropyl-3 ,7-dimethyl-6 -hydroxyoctanoate (3). Successive Corey and then
R
S
2
4
Bayer—Villager (usingMCPBA, which proceeds regiospecifically)oxidationsaffordeddiisopropyl 3 -methylhexan-1,6-dioate
R
(4), Dieckmann cyclization of which was performed by several methods. Using sodium isopropylate as the base produced a
mixture that was inseparable by column chromatography. According to GC and PMR spectra, the ratio of integrated intensities
of a doublet at 1.15 ppm for CH -4 and a doublet at 1.19 ppm for CH -5, which belong to the isopropyl esters of 4 -methyl-2-
R
3
3
oxo- (6) and 5 -methyl-2-oxo- (7) cyclopentan-1-carboxylic acids, respectively, was 3.5:1. Decarboxylation of the mixture of
R
esters (6 and 7) by heating in DMSO in the presence of NaCl [8] gave a single product, 3 -methyl-cclopentan-1-one (8). An
R
attempt to increase the regioselectivity of the cyclization of 5 by using sodium amide as the base, which was used previously
[9] for the dimethyl ester of 3-methylhexan-1,6-dioic acid, was unsuccessful. The starting compound was obtained. Cyclization
of 5 in the presence of Na, which was also used to cyclize diesters [10], led to decarboxylation and formation of a single
product, 8.
i
i
CO Pr
2
i
CO Pr
CO Pr
2
2
i
[7]
Pr OH/H SO
MCPBA
PCC
2
4
O
O
OH
O
i
CO Pr
2
OH
5
4
2
3
1
Na/C H CH
3
6
5
NaCl,
DMSO - H O
i
CO Pr
2
i
Pr ONa / PhMe
∆
2
+
∆
∆
O
O
O
i
Pr O C
2
6
7
8
1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71; 2) Birsk State Social-Pedagogical Academy, 452320, Birsk, ul. Internatsional′naya, 10. Translated from Khimiya
Prirodnykh Soedinenii, No. 5, pp. 448-450, September-October, 2005. Original article submitted August 18, 2005.
0009-3130/05/4105-0549 ©2005 Springer Science+Business Media, Inc.
549

Thus, a synthetic scheme for the valuable intermediate 3R-methylcyclopentan-1-one that is used to synthesize several
biologicallyactive compounds was developed basedon theaccessible monoterpenoid L-(-)-menthol (1) and gave an overall yield
of 30% calculated for 1.
EXPERIMENTAL
IR spectra were recorded on a UR-20 instrument in thin layers. NMR spectra were recorded on a Bruker AM-300
13
spectrometer (working frequency 300.13 MHz for PMR and 75.47 MHz for C NMR) in CDCl . The internal standard for
3
13
PMR was the proton impurity in CDCl at δ 7.27 ppm; for C NMR, the average CDCl signal at δ 77.00 ppm. GC was
3
3
performed on Chrom-5 [column length 1.2 m, stationary phase silicon SE-30 (5%) on Chromaton N-AW-DMCS (0.16-
0.20 mm), working temperature 50-300°] and Chrom-41 [column length 2.4 m, stationary phase PEG-6000, working
temperature 50-200°] instruments with He carrier gas. Column chromatography was carried out on silica gel L (40-100 µm)
(Czech Rep.). TLC was performed on Silufol UV-254 plates (Czech Rep.). Optical rotation was measured on a Perkin—Elmer
241-MC polarimeter. Elemental analyses of all compounds agreed with those calculated.
Isopropyl 3R,7-Dimethyl-6S-hydroxyoctanoate (3). A solution of 2 (2.5 g, 14.7 mmol) obtained from 1 as before
[7] in dry isopropanol (19 mL) was acidified with conc. H SO (2 drops) and stirred on a magnetic stirrer for 72 h. The
2
4
isopropanol was evaporated. The solid was dissolved in ethylacetate, washed successively with saturated solutions of NaCl,
20
NaHCO , and NaCl, dried over MgSO , and evaporated to afford 3 (2.87 g, 85%), [α]
-13.3° (c 0.90, CHCl ).
3
3
4
D
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.82 (6H, d, J = 6.8, H-8, CH -7), 0.84 (3H, d, J = 6.8, CH -3), 1.19 [6H, d,
3
3
3
J = 6.8, (CH ) CH], 1.93 (8H, m, H-2—H-5, H-7), 3.25 (1H, m, H-6), 3.97 (1H, br.s, OH).
3 2
13
C NMR spectrum (CDCl ): 18.73 (q, C-8, CH -7), 19.64 (q, CH -3), 21.68 [q, CH(CH ) ], 30.42 (d, C-3), 31.24
3
3
3
3 2
(t, C-4), 32.86 (t, C-5), 33.22 (d, C-7), 41.83 (t, C-2), 67.19 [d, CH(CH ) ], 76.63 (d, C-6), 172.67 (s, C-1).
3 2
Isopropyl 3R,7-Dimethyl-6S-oxooctan-1-oate (4). A suspension of PCC (4.18 g, 19.4 mmol) in dryCH Cl (75 mL)
2
2
was treated dropwise with a solution of 3 (2.87 g, 12.4 mmol) in dry CH Cl (5 mL), stirred for 3 h, diluted with Et O (80 mL),
2
2
2
20
filtered through a layer of Al O , and evaporated to afford 4 (2.50 g, 83%), [α]
+2.8° (c 2.82, CHCl ).
3
2
3
D
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.91 (3H, d, J = 6.1, CH -3), 1.07 (6H, d, J = 6.8, CH -7, H-8), 1.19 [6H, d,
3
3
3
J = 6.1, (CH ) CH], 1.50 (3H, m, H-3, H-4), 2.22 (5H, m, H-2, H-5, H-7), 4.97 [1H, septet, J = 6.1, (CH ) CH].
3 2
3 2
13
C NMR spectrum (CDCl ): 18.21 (q, C-8, CH -7), 19.41 (q, CH -3), 23.86 [q, (CH ) CH], 30.01 (d, C-3), 30.26
3
3
3
3 2
(t, C-4), 37.74 (t, C-5), 40.76 (d, C-7), 41.86 (t, C-2), 67.38 [d, (CH ) CH], 172.35 (s, C-1), 214.38 (d, C-6).
3 2
Diisopropyl 6R-Methylhexan-1,6-dioate (5). A suspension of MCPBA (3.10 g, 8.9 mmol) in dry CHCl (30 mL) at
3
room temperature was treated dropwise with a solution of 4 (1.40 g, 6.2 mmol) in dry CHCl (10 mL), stirred for 48 h, diluted
3
with CH Cl (100 mL), washed successivelywith saturated solutions of NaHCO , Na S O , and NaCl, dried over MgSO , and
2
2
3
2 2
3
4
20
evaporated to afford 5 (1.25 g, 83%), [α]
+3.1° (c 3.20, CHCl ).
3
D
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.93 (3H, d, J = 6.1, CH -3), 1.19 [12H, d, J = 6.1, (CH ) CH], 4.97 [2H, septet,
3
3
3 2
J = 6.1, (CH ) CH], 2.06 (m, H-2—H-5).
3 2
13
C NMR spectrum (CDCl ): 19.18 (q, CH -3), 21.72 [q, (CH ) CH], 30.32 (d, C-3), 30.64 (t, C-4), 41.92, 42.47 (both
3
3
3 2
t, C-2, C-5), 67.39, 67.44 [both d, (CH ) CH], 172.26 (s, C-6), 173.02 (s, C-1).
3 2
Isopropyl 4R-Methyl-2-oxo- (6) and 5R-Methyl-2-oxo- (7) cyclopentan-1-carboxylates. A solution of sodium
isopropylate that was prepared from Na (0.05 g, 2.05 mg-at) and isopropanol (0.13 g, 2.1 mmol) in dry toluene (3 mL) was
treated dropwise (Ar) with a solution of 5 (0.50 g, 2.1 mmol) in dry toluene (2 mL). The mixture was boiled for 8 h, cooled to
room temperature, and poured into cold water (25 mL) containing CH COOH (8.5 mL). The aqueous layer was extracted with
3
ether (3×40 mL), washed successively with saturated solutions of NaHCO and NaCl, dried over Na SO , and evaporated to
3
2
4
afford a mixture (3.5:1) of 6 and 7 (0.30 g, 79%) according to GC.
Isopropyl 4R-Methyl-2-oxocyclopentan-1-carboxylate (6). PMR spectrum (CDCl , δ, ppm, J/Hz): 1.15 (3H, d,
3
J = 6, CH ), 1.19 [6H, d, J = 6, CH(CH ) ], 2.22 (5H, m, CH , CHCH ), 3.26 (1H, t, J = 6.4, CHCO ), 5.35 [1H, septet, J = 6.1,
3
3 2
2
3
2
CH(CH ) ].
3 2
Isopropyl 5R-Methyl-2-oxocyclopentan-1-carboxylate (7). PMR spectrum (CDCl , δ, ppm, J/Hz): 1.19 (3H, d,
3
J = 6, CH ), 1.19 [6H, d, J = 6, CH(CH ) ], 1.46 and 2.15 (4H, both m, CH ), 2.75 (1H, m, CHCH ), 3.15 (1H, d, J = 9.1,
3
3 2
2
3
CHCO ), 5.35 [1H, septet, J = 6.1, CH(CH ) ].
2
3 2
550

3R-Methylcyclopentane (8): a) A suspension ofNa (0.04 g, 1.9 mg-at) in drytoluene (3 mL) (Ar) was heated to 90°C,
treated dropwise with a solution of 5 (0.47 g, 1.9 mmol) in dry toluene (4 mL), boiled for 1 h, diluted with hexane, and filtered
20
20
through a layer of Al O (2 cm) to afford 8 (0.15 g, 81%), [α]
+152.5° (c 1.20, CHCl ) {[α]
D
+154° (c 0.6, MeOH) [6]}.
2
13
3
D
3
The IR, PMR, and C NMR spectra were identical to those published previously [11];
b) A solution of 6 and 7 (0.50 g, 2.5 mmol) in DMSO (21 mL) and H O (3 mL) was treated with NaCl (0.70 g,
2
12 mmol), held at 165° for 2 h, and cooled. The aqueous layer was extracted with petroleum ether, dried over Na SO , and
2
4
evaporated to afford 8 (0.16 g, 65%) that was identical to that obtained in a).
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