L-(-)-menthol in the synthesis of key synthons for optically active methyl-branched insect pheromones

Article abstract of DOI:10.1007/s10600-006-0019-4

A synthesis of optically active 4S-methylhexanal, 1-bromo-3S-methylheptane, and 1-bromo-3S-methylundecane, which are key synthons for several methyl-branched insect pheromones, that is based on chemically selective transformations of 6-tosyloxy- and 6-iodoisopropyl-4R-methylhexanoates that are available from L-(-)-menthol was proposed. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10600-006-0019-4

Chemistry of Natural Compounds, Vol. 41, No. 6, 2005
L-(-)-MENTHOL IN THE SYNTHESIS OF KEY SYNTHONS
FOR OPTICALLY ACTIVE METHYL-BRANCHED
INSECT PHEROMONES
G. Yu. Ishmuratov,1 M. P. Yakovleva,1 V. A. Ganieva,2
D. V. Amirkhanov,1 and G. A. Tolstikov1
UDC 547.223+547.281+547.323
+547.295.226+547.596.2
A synthesis of optically active 4S-methylhexanal, 1-bromo-3S-methylheptane, and 1-bromo-3S-
methylundecane, which are key synthons for several methyl-branched insect pheromones, that is based on
chemically selective transformations of 6-tosyloxy- and 6-iodoisopropyl-4R-methylhexanoates that are
available from L-(-)-menthol was proposed.
Key words: L-(-)-menthol, 6-tosyloxy- and 6-iodoisopropyl-4 -methylhexanoates, 4 -methylhexanal, 1-bromo-3 -
R
S
S
methylheptane, 1-bromo-3 -methylundecane, insect pheromones, synthon, synthesis.
S
We previouslyreported the synthesis ofchiral synthons 6-tosyloxy- (2) and 6-iodo- (3) isopropyl-4 -methylhexanoates
R
from L-(-)-menthol (1) [1]. These wereusedin the present work tosynthesize opticallypure 4 -methylhexanal (5), 1-bromo-3 -
S
S
methylheptane (11), and 1-bromo-3 -methylundecane (12), which are keyintermediates for the alarm pheromone of ants of the
S
and
genera (6), sex pheromones of the peach leafminer
(13), and pine sawflies of
Lyonetia clerkella
Cremotogaster
Myrmica
genera (14), respectively. The syntheses of these were also reported [2].
Neodiprion
the and
Diprion
[1]
X
O
OH
O
1
2, 3
X = OTs (2), I (3)
In order to prepare 4 -methylhexanal (5), tosyloxyester 2 was converted by hydride reduction, which occurred at both
S
esters, into 4 -methylhexan-1-ol (4), which was oxidized further by the Corey method. The resulting aldehyde (5) was
S
transformed into the pheromone (6) by the literature method [3].
Compounds 11 and 12 were synthesized using catalyzed cross-coupling of the iodoester (3) with Grignard reagents 7
and 8, which were generated from ethyl- or -hexylbromides, to give the isopropyl ester of 4 -methyloctanoic (9) or
n
S
4 -methyldodecanoic (10) acid, respectively. Alkaline hydrolysis of esters 9 and 10 with subsequent Hunsdiecker reaction of
S
the resulting acids produced 1-bromo-3 -methylheptane (11), which was converted tothe sex pheromone ofthe peach leafminer
S
(13) as before [4], and 1-bromo-3 -methylundecane (12), a key synthon for the sex pheromone of pine sawflies (14) [5],
S
respectively.
Thus, the proposed synthesis of optically pure 4 -methylhexanal, 1-bromo-3 -methylheptane, and 1-bromo-3 -
S
S
S
methylundecane, which are key synthons for several methyl-branched insect pheromones, is based on chemically selective
transformations of 6-tosyloxy- and 6-iodoisopropyl-4 -methylhexanoates, which are available from L-(-)-menthol.
R
1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, fax (3472) 35 60 66, e-mail: kharis@anrb.ru; 2) Birsk State Social-Pedagogical Academy, 452320, RF, Birsk, ul.
Internatsional naya, 10. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 592-593, November-December, 2005.
Original article submitted July 29, 2005.
0009-3130/05/4106-0719 ©2005 Springer Science+Business Media, Inc.
719

[3]
LiAlH
PCC
4
HO
O
2
CH Cl
2
Et O
2
2
4
O
5
6
(CH )
2 11
[4]
13
RMgBr ( ,
)
7 8
1. KOH/H O
2
R
Br
R
3
Li CuCl
2. Ag O
2
2
4
i
CO Pr
[5]
11, 12
2
3. Br
2
(CH ) CH
2 7
9, 10
3
OAc
R = Et
; 8, 10, 12:
R
Me(CH )
7, 9, 11:
=
14
2 5
EXPERIMENTAL
General comments have been published [1].
4S-Methylhexan-1-ol (4). A solution of 2 (4.00 g, 11.7 mmol), which was prepared as before [1], in absolute Et O
2
(24 mL, Ar, 0°C) was treated with LiAlH (1.32 g, 34.7 mmol), stirred at the same temperature for 1 h, decomposed with H O
4
2
(4 mL), diluted with Et O (120 mL), and filtered. The filtrate was washed with saturated NaCl solution, dried over MgSO ,
2
4
20
20
and evaporated to afford 4 (0.98 g, 72%), [α]
+8.54° (c 5.3, CDCl ), lit. [6] [α]
+8.62° (c 3.7, CDCl ). IR and PMR
D
3
D
3
spectra were identical to those in the literature [7].
4S-Methylhexanal (5). A suspension of PCC (2.89 g, 13.4 mmol) in dry CH Cl (31 mL, Ar, 20°C) was treated in
2
2
one portion with a solution of 4 (0.95 g, 9.1 mmol) in dry CH Cl (7 mL), held at the same temperature for 1.5 h, diluted with
2
2
Et O (40 mL), and filtered through a layer of Al O (5 cm). The filtrate was evaporated to afford 5 (0.86 g, 92%). The IR and
2
2 3
NMR spectra were identical to those in the literature [3].
Isopropyl-4S-methyloctanoate (9). A solution of 3 (7.70 g, 25.8 mmol), prepared as before [1], was treated
(Ar, -10°C) with Li CuCl in absolute THF (10 mL, 0.1 M) and Grignard reagent 7, which was generated from EtBr (5.30 g,
2
4
49 mmol) and Mg (1.30 g, 54 mg-at) in absolute THF (90 mL), held at the same temperature for 6 h, decomposed by saturated
NH Cl solution (50 mL), extracted with Et O (3 × 70 mL), washed with saturated NaCl solution, dried over MgSO , and
4
2
4
20
evaporated. The solid was chromatographed over SiO (PE:MTBE 20:1) to afford 9 (2.18 g, 54%), [α]
+4.13° (c 2.6,
2
D
CHCl ).
3
-1
IR spectrum (KBr, ν, cm ): 1740 (C=O).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.84 (3H, t, J = 6, H-8), 0.90 (3H, d, J = 6, CH -4), 1.19 [6H, d, J = 6,
3
3
CH(CH ) ], 1.50 (9H, m, H-3—H-7), 2.25 (2H, m, H-2), 4.97 [1H, septet, J = 6.3, CH(CH ) ].
3 2
13
3 2
C NMR spectrum (CDCl ): 19.10 (q, C-8), 21.03 (q, CH -4), 21.67 [q, CH(CH ) ], 29.53 (d, C-4), 31.28, 31.85,
3
3
3 2
32.33, 35.22 (all t, C-3, C-5—C-7), 62.73 (t, C-2), 67.51 [d, CH(CH ) ], 173.30 (s, C-1).
3 2
1-Bromo-3S-methylheptane (11). A solution of 9 (2.40 g, 12.0 mmol) and KOH (1.60 g, 29.0 mmol) in MeOH
(10 mL) and H O (2 mL) was boiled and evaporated. The solid was dissolved in H O (23 mL) and treated with a solution of
2
2
AgNO (2.04 g, 12.0 mmol) in hot H O (60°C, 8 mL). The solid was filtered off and dried in vacuo (10-15 mm Hg) at 100°C
3
2
to produce the silver salt (2.52 g), which was suspended in CCl (15 mL), treated dropwise with stirring with Br (1.82 g,
4
2
11.5 mmol) in CCl (4 mL), held at room temperature for 2 h, and then boiled (until CO evolution was complete). The solid
4
2
was filtered off. The filtrate was evaporated. The solid was chromatographed (SiO , hexane) to afford 11 (1.66 g, 83%),
2
21
21
[α]
+7.42° (c 3.7, CHCl ), lit. [4] [α]
+3.71° (c 3.3, CHCl ) (ee ~50%). IR and PMR spectra were identical to those in
3
D
3
D
the literature [4].
Isopropyl-4S-methyldodecanoate (10). A solution of 3 (5.77 g, 15 mmol), which was prepared as before [1], was
treated (Ar, -10°C) with Li CuCl in absolute THF (0.8 mL, 0.1 M) and Grignard reagent, which was generated from n-
2
4
hexylbromide (6.06 g, 37 mmol) and Mg (0.98 g, 40 mg-at) in absolute THF (67 mL), held at the same temperature for 6 h,
decomposed with saturated NH Cl solution (40 mL), extracted with Et O (4 × 50 mL), washed with saturated NaCl solution,
4
2
dried over MgSO , and evaporated. The solid was chromatographed over SiO (PE:MTBE 20:1) to afford 10 (1.61 g, 42%),
4
2
20
[α]
+2.50° (c 0.4, CHCl ).
D
3
720

-1
IR spectrum (KBr, ν, cm ): 1745 (C=O).
PMR spectrum (C D , δ, ppm, J/Hz): 0.69 (6H, m, CH -4, H-12), 1.06 [6H, d, J = 6, CH(CH ) ], 1.31 (17H, m,
6
6
3
3 2
H-3—H-11), 2.13 (2H, m, H-2), 5.20 [1H, septet, J = 6.2, CH(CH ) ].
3 2
13
C NMR spectrum (C D ): 19.02 (q, C-12), 20.55 (q, CH -4), 21.83 [q, CH(CH ) ], 23.55 (t, C-11), 27.77 (t, C-6),
6
6
3
3 2
28.72, 29.32, 29.62 (all t, C-7—C-9), 29.82 (d, C-4), 31.72, 32.04, 32.30 (all t, C-2, C-3, C-10), 35.45 (t, C-5), 67.27 [d,
CH(CH ) ], 173.85 (s, C-1).
3 2
1-Bromo-3S-methylundecane (12). A solution of 10 (1.60 g, 6.3 mmol) and KOH (0.85 g, 15 mmol) in MeOH
(10 mL) and H O (1 mL) was boiled for 4 h and evaporated. The solid was dissolved in H O (16 mL) and treated with AgNO
3
2
2
(1.07 g, 6.3 mmol) in hot water (60°C, 7 mL). The solid was filtered off and dried in vacuo (10-15 mm Hg) at 100°C to produce
the silver salt (1.80 g), which was suspended in CCl (11 mL), treated dropwise with stirring with Br (0.90 g, 6.0 mmol) in
4
2
CCl (3 mL), and worked up as above for 11. The solid was chromatographed (SiO , hexane) to afford 12 (1.18 g, 85%),
4
2
23
21
[α]
+4.02° (c 4.4, hexane), lit. [5] [α]
+4.04° (c 4.5, hexane). IR and PMR spectra were identical to those in the
D
D
literature [5].
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