Catalytic Reductive β-Metalloethylation in the Synthesis of 6-Methylnonan-3-One and 3-Methylheptanoic Acid, Racemic Analogs of Hesperophylax occidentalis and Coleoptera scarabaeidae Pheromones

Full text of DOI:10.1007/s10600-018-2282-6

DOI 10.1007/s10600-018-2282-6
Chemistry of Natural Compounds, Vol. 54, No. 1, January, 2018
CATALYTIC REDUCTIVE ꢀ-METALLOETHYLATION
IN THE SYNTHESIS OF 6-METHYLNONAN-3-ONE AND
3-METHYLHEPTANOIC ACID, RACEMIC ANALOGS OF
Hesperophylax occidentalis AND Coleoptera scarabaeidae
PHEROMONES
*
R. M. Sultanov, I. F. Khafizov, N. V. Shutov,
I. V. Ozden, and F. Sh. Khafizov
Previously, the syntheses of 4-methyloctanoic acid, an aggregation pheromone component of an Oryctes rhinoceros
beetle [1], and 6-methyloctan-3-one, a racemic analog of an alarm pheromone of a Crematogaster ant [2], were used as
examples to demonstrate the potential of the reductive ꢀ-metalloethylation of 1-alkenes in the presence of tantalum (Ta)
complexes that was discovered by us [3–7].
Herein, this synthetic approach is expanded to the syntheses of 6-methylnonan-3-one (1), a racemic analog of the sex
pheromone of the caddisfly Hesperophylax occidentalis, and 3-methylheptanoic acid (2), a racemic analog of the aggregation
pheromone of the beetle Coleoptera scarabaeidae. The sex pheromone of H. occidentalis was first isolated by Bjostad et al.
[8] and identified as 6-methylnonan-3-one. Multistep syntheses of this compound as a racemate and enantiomers are known [8–10].
An effective synthetic pathway to the racemic analog of pheromone 1 was based on the new regioselective reductive
ꢀ-zinc-ethylation of 1-alkenes using Et Zn and TaCl as a catalyst that was recently discovered by us [4].
2
5
Thus, the reaction of pent-1-ene with Et Zn in the presence of TaCl (Et Zn–pent-1-ene–TaCl , 110:100:5, 20°C, 5 h)
2
5
2
5
formed organozinc compound 3. For this, pent-1-ene (1.4 mL, 20 mmol) was added to hexane (20 mL) cooled to 0°C, treated
with Et Zn (22 mmol, 22.0 mL) and TaCl (0.4 g, 1 mmol), heated gradually to room temperature, stirred for 5 h, cooled
2
5
to –5°C, and treated dropwise with propionyl chloride (4, 1.74 mL, 20 mmol) in hexane (10 mL). All these manipulations
were performed under dry Ar. After 4 was added, the mixture was stirred for 2 h at room temperature and treated with HCl
solution (10%). The resulting 1 was extracted with Et O (3 ꢁ 50 mL), dried over anhydrous MgSO , and evaporated.
2
4
The solid was chromatographed (SiO , hexane–Et O, 6:1) to afford 1 (2.95 g, 99% pure by GC) in 95% yield from 4 (Scheme 1).
2
2
ZnEt
b
a
Et Zn
2
+
O
1
3
a. TaCl , hexane, 5 h; b. 1. C H COCl (4), 2. HCl/H O
5
2
5
2
Scheme 1
Catalytic ꢀ-metalloethylation was used in the key step of a synthesis of 3-methylheptanoic acid (2).
The reaction of hex-1-ene with EtMgCl in the presence of TaCl –Ph P (1:1) catalyst (EtMgCl–hex-1-ene–TaCl +Ph P,
5
3
5
3
150:100:5, 1 mM EtMgCl, THF, 20°C, 4 h) formed organomagnesium compound 5 (Scheme 2). For this, a solution of EtMgCl
(37.5 mL, 37.5 mmol) in THF (37.5 mL) at 0°C was stirred and treated with hex-1-ene (2.1 g, 25 mmol), Ph P (0.33 g,
3
1.25 mmol), and TaCl (0.45 g, 1.25 mmol). The temperature was increased to 20°C. Stirring continued for 4 h. The mixture
5
was oxidized in a glass thermostatted reactor by passing pure O through the reaction mixture at 8–10°C for 2 h. Then, the
2
mixture was poured into HCl solution (5%). The resulting alcohol 6 was extracted with Et O (3 ꢁ 70 mL). The extract was
2
dried over MgSO and evaporated in vacuo to isolate 3-methylheptan-1-ol (6, 2.93 g, 99% pure by GC, based on starting
4
hex-1-ene), which had the reported spectral characteristics [11].
Ufa State Petroleum Technological University, 1 Kosmonavtov St., Ufa, 450062, Russia, fax: 8 (347) 243 18 13,
e-mail: sultanov55@mail.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 1, January–February, 2018, pp. 136–137.
Original article submitted May 12, 2017.
©
0009-3130/18/5401-0161 2018 Springer Science+Business Media, LLC
161

MgEt
c
b
a
Et Mg
2
OH
+
6
5
O
d
OH
O
7
2
a. TaCl -PhP , THF, 4 h; b. O , HCl/H O; c. PCC, CH Cl ; d. H O–AgNO (catalyst), MeCN
5
3
2
2
2
2
2
3
Scheme 2
Alcohol 6 was oxidized to aldehyde 7 as follows. A suspension of pyridinium chlorochromate (PCC, 5.9 g,
27.5 mmol) in anhydrous CH Cl (35 mL) was stirred (20°C, Ar), treated in one portion with a solution of 6 (2.93 g,
2
2
22.5 mmol) in CH Cl (10 mL), stirred for 1.5 h, diluted with anhydrous Et O (35 mL), and filtered through a layer of Al O
2
2
2
2 3
(5 cm). The solid was rinsed with anhydrous Et O (50 mL). The solvents were evaporated to afford 7 (2.51 g, 87.7%).
2
–1
IR spectrum (ꢂ, cm ): 2730, 2950, 1725, 1470, 1390. Aldehyde 7 was oxidized to acid 2 as follows. A solution of AgNO
3
(0.32 g, 0.19 mmol) and 7 (2.51 g, 19.6 mmol) in MeCN (40 mL) was stirred, treated dropwise with H O (11.2 mL, 98 mmol,
2
2
30%), heated to 50°C and held there for 10 h, decomposed at 5°C by Na S O solution (10%, 10 mL), and extracted with
2 2
3
CH Cl (2 ꢁ 50 mL). The solvent was evaporated. The solid was chromatographed over SiO (CHCl ) to isolate 2 (2.83 g,
2
2
2
3
63% based on starting hex-1-ene, Scheme 2), which was >98% pure by GC [12].
13
The structures of 1 and 2 were confirmed by IR, PMR, and C NMR spectra, mass spectrometry, and comparisons
with the literature [8, 9, 13, 14].
Thus, new synthetic capabilities of catalytic reductive ꢀ-metalloethylation were demonstrated.
The isolated products were analyzed on a Shimadzu GC-2014 chromatograph in a He stream using a column
(2,000 ꢁ 3 mm, 5% SE-30 on Chromaton N-AW-HMDS, 0.125–0.160 mm) at operating temperature 50–300°C. One- (PMR,
13
C NMR) and two-dimensional (COSY, HSQC, HMBC) NMR spectra were recorded in CDCl on a Bruker Avance-400
3
13
1
spectrometer (100 MHz for C, 400 MHz for H) at 25°C. Chemical shifts were given vs. TMS. Mass spectra were measured
on a Shimadzu GCMS-QP 2010 (Supelco SLB™-5ms, glass capillary column, 60,000 ꢁ 0.25 mm ꢁ 0.25 ꢃm, He carrier gas,
temperature programmed from 50 to 260°C at 5°C/min, ion-source temperature 260°C, 70 eV). Elemental analyses were
determined on a Carlo Erba Model No. 1106 analyzer. Chromatograms of reaction mixtures were calculated using an internal
standard. IR spectra were taken on a Bruker VERTEX 70V spectrometer.
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