Prilezhaev dihydroxylation of (R)-octadec-9Z-en-7-0l

Article abstract of DOI:10.1007/s10600-009-9441-8

Formation of new asymmetric centers with primarily the (S)-configuration was induced by the optically active center of (R)-octadec-9Z-en-7-ol upon Prilezhaev dihydroxylation. This was proved by cyclization of a 1,3-glycol system (de 26%) into the correspo

Full text of DOI:10.1007/s10600-009-9441-8

Chemistry of Natural Compounds, Vol. 45, No. 5, 2009
PRILEZHAEV DIHYDROXYLATION OF(R)-OCTADEC-9Z-EN-7-0L
R. R. Muslukhov, A. Kh. Shayakhmetova, O. O. Shakhanova,
M. P. Yakovleva,* G. Yu. Ishmuratov, and A. G. Tolstikov
UDC 547.475.124
Formation of new asymmetric centers with primarily the (S)-configuration was induced by the optically
active center of (R)-octadec-9Z-en-7-ol upon Prilezhaev dihydroxylation. This was proved by cyclization of
a 1,3-glycol system (de 26%) into the corresponding 1,3-dioxane stereoisomers.
Key words: (R)-octadec-9Z-en-7-ol, Prilezhaev dihydroxylation, asymmetric induction.
We have previously shown that the hydroxyl at the optically active center of (R)-ricinoleic acid had a slight influence
on the regioselectivity during hydroboration and oxidation of its derivatives [1]. This was indicated by the predominance by
6–10% of the 1,3-diol over its 1,4-isomer. However, the hydroxyl did induce formation of new asymmetric centers of primarily
the (S)-configuration. This was demonstrated by cyclization of 1,3-glycols (up to 32–50%) into the corresponding stereoisomeric
1,3-dioxanes; 1,4-diols (up to 22–40%), into 2,5-dialkyl-substituted tetrahydrofurans.
Our goal was to study Prilezhaev dihydroxylation (asymmetric induction due to the influence of the homoallyl hydroxyl)
of (R)-octadec-9Z-en-7-ol (1), which is available from castor oil [2].
OH OH
OH
c
a, b
10 (CH ) Me
2 7
9
Me(CH )
2 5
Me(CH )
2 5
7
(CH ) Me
2 7
OH
2
1
Ph
Ph
Ph
2'
2'
2'
O
O
O
O
O
O
+
+
Me(CH )
2 4
1
Me(CH )
2 4
1
Me(CH )
2 4
(CH ) Me
2 7
(CH ) Me
2 7
1
(CH ) Me
2 7
6'
4'
6'
4'
6'
4'
1''
1''
1''
OH
OH
OH
3a
3b
3c
a. H O , HCOOH; b. NaOH, H O; c. PhCHO, ZnCl , Na SO
4
2
2
2
2
2
Prilezhaev oxidation of non-terminal olefins is known to occur exclusively with formation of cis-epoxides [3]. This
was demonstrated earlier using ricinoleic acid methyl ester as an example [4]. Further opening of the epoxide ring occurs
under both acidic and basic conditions [5] with complete inversion of only one of the C atoms to form trans-diols.
Prilezhaev dihydroxylation of homoallyl alochol 1 was performed using H O (30%) in the presence of formic acid
2
2
with subsequent treatment by NaOH solution [3].
The configuration of the newly formed asymmetric centers on C-9 and C-10 of the product triol 2 was determined by
cyclization using benzaldehyde of the 1,3-diol system into stereoisomeric 2,4,6-tri-substituted 1,3-dioxanes 3. The cyclization
to form a benzylidene group is known to occur quantitatively without inversion of the optically active center [6–8]. Alkyl-
substituted 1,3-dioxanes in neutral media have a stable chair conformation with an equatorially oriented phenyl group in both
stereoisomers [7]. Triol 2 produced a mixture of dialkylphenyl-substituted 1,3-dioxanes 3 that was separated by chromatography
13
into three diastereoisomers 3a, 3b, and 3c in high (>90%) purity. They were identified by NMR spectroscopy. The C NMR
spectrum of the reaction mixture from benzylation contained a set of resonances corresponding to three of the four possible
diastereomers with the (R)-configuration at the dioxane C-6′ atom. The contents of the diastereomers were dominated by one
13
of them (63.0, 23.5, and 13.5% according to quantitative C NMR spectroscopy).
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Russian Federation, 450054,
Ufa, prosp. Oktyabrya, 71, fax: 3472 35 60 66, e-mail: insect@anrb.ru. Translated from Khimiya Prirodnykh Soedinenii,
No. 5, pp. 537–539, September–October, 2009. Original article submitted May 11, 2009.
©
0009-3130/09/4505-0637 2009 Springer Science+Business Media, Inc.
637

Overlap of methylene proton resonances at 1.50–1.80 ppm and unresolved multiplets and overlap of resonances of
the three protons on C-4′, C-6′, and C-1 in addition to the α-methylenes of substituents and C-5′ protons made it practically
impossible to analyze and assign the stereochemistry of resonances in PMR spectra of 3a-c. Nevertheless, analysis of COSY
(C–H) and COSY (H–H) one- and two-dimensional spectra enabled resonances of C atoms and the C-6′, C-4′, and C-1 protons
to be assigned, the mutual orientation of the substituents on C-6′ and C-4′ of the ring to be established, and the configuration
of C-4′ of 3a-c to be determined for the known (R)-configuration at C-6′.
NMR resonances of stereoisomers were assigned using literature data [9, 10] for stereoisomeric 2,4,6-trialkyl-
1,3-dioxanes and proton spectra of 2-ethynyl-1,3-dioxane conformers.
13
Of three doublets in the range 67.0–83.0 ppm, the one at weakest field in C spectra of 3a-c was assigned to C-4′ of
the ring. The proton resonance on this C atom in spectra of 3a-c was a resolved doublet of doublets of doublets and was
determined from COSY (C–H) and COSY (H–H) correlation spectra. The proton–proton SSCC were determined using double
resonance of three protons in the range 3.5–4.0 ppm. Similar chemical shifts of C-6′ and C-1′′ α-methylene protons and the
3
large J SSCC (H -6′–H -5′) (12.3 Hz) indicated that the alkyl substituent on C-6′ had the equatorial orientation.
a
a
3
The J SSCC (H -4′–H -5′) (11.7 Hz) and the weak-field shift of the resonance for C-1 (72.51 ppm) in the PMR
a
a
spectrum for the dominant diastereomer 3a compared with those for 3b and 3c (67.66 and 67.70, respectively) indicated that
the substituent on C-4′ also had the equatorial orientation. Asymmetric C-4′ had the (S)-configuration for the diequatorial
orientation of the substituents and the known (R)-configuration of asymmetric C-6′ in the cis,cis-(eee)-diastereomer. Resonances
13
for C-1 in C spectra of 3b and 3c were located at stronger field. This indicated that the substituent on C-4′ had the axial
3
orientation. The vicinal SSCC ( J = 5.7, 4.2, and 3.1 Hz) also were consistent with the equatorial orientation of proton H-4′
and, therefore, the axial orientation of the C-4′ substituent. Chiral C-4′ in trans-(ea)-(C-6′,C-4′) diastereomers 3b and 3c had
the (R)-configuration because of the known (R)-configuration of optically active C-6′.
13
The similar chemical shifts for the heterocyclic C atoms in C NMR spectra of 3b and 3c with a small strong-field
shift for C-4′ of 3c (81.43 ppm) compared with 3b (82.61 ppm) and a noticeable weak-field shift of the C-2′ proton (5.84 ppm)
in the spectrum of 3c indicated that the Ph group was oriented axially and, therefore, asymmetric center C-2′ of 3c had the
(S)-configuration. Similar chemical shifts for the C-2′ protons of 3a and 3b (5.51 and 5.54, respectively), which appeared at
stronger field compared with 3c, indicated that the Ph group was oriented equatorially and, therefore, that asymmetric center
C-2′ had the (R)-configuration.
Considering the (S)-configuration of C-4′ in the dominant diastereomer 3a that was determined from spectra of the
1,3-dioxanes, it can be concluded that the dominant diastereomer triol 2a had the (7R,9S,10S)-configuration.
EXPERIMENTAL
IR spectra were recorded as thin layers using a Specord M-82 instrument; NMR spectra, in (CD ) C=O solution on a
3 2
1
13
Bruker AM-300 spectrometer (operating frequency 300.13 MHz for H and 75.47 MHz for C) with TMS internal standard.
Resonances were assigned using two-dimensional COSY (C–H) and (H–H) correlation spectroscopy. The quantitative ratio
of diastereomers was determined from NMR spectra recorded with a delay of 10 sec between pulses. HPLC was carried out
on a Du Pont (USA) liquid chromatograph with a refractive-index detector, stainless steel column (300 × 3.9), μ-Porasil
(Waters, 5 μm), and mobile phase hexane:isopropanol (92:8) at room temperature. TLC monitoring used Sorbfil (Russia)
SiO .
2
Octadecan-7(R),9,10-triol (2). A cooled mixture that was prepared by adding H O (30%, 1.1 mL, 10.5 mmol) to
2
2
HCOOH (88%, 4.5 mL, 102.8 mmol) was treated over 30 min with 1 (2.00 g, 7.5 mmol) at a rate such that the temperature
remained below 40°C. The resulting mixture was held at 40°C for 1 h and 20°C for 12 h. HCOOH was distilled at reduced
pressure. The remainder was diluted with an ice-cold NaOH solution (0.60 g, 15.0 mmol) in H O (1.1 mL) at a rate such that
2
the temperature remained below 45°C. The organic layer was separated. The aqueous layer was extracted with methyl-
–1
t-butylether (MTBE, 3 × 50 mL), dried over Na SO , and evaporated to afford 2 (2.14 g, 95%). IR spectrum (ν, cm ): 1110
2
4
(C–O), 3304 (OH).
PMR spectrum (δ, ppm): 0.90 (6H, m, H-1, H-18), 1.20–1.38 (20H, m, H-2–H-5, H-12–H-17), 1.40–1.68 (6H, m,
H-6, H-8, H-11), 3.30–3.45 (1H, m, H-10), 3.60–3.73 (1H, m, H-9), 3.72–3.85 (1H, m, H-7), 3.80 (3H, br.s, OH).
638

13
C NMR spectrum: 14.28 (q, C-1, C-18), 23.07 (t, C-2, C-17), 25.19 (t, C-12), 25.46 (t, C-5), 29.07-29.61 (all t,
C-4, C-13–C-15), 32.33 (t, C-3, C-16), 33.89 (33.74) (t, C-11), 38.66 (38.05) (t, C-6), 39.98 (39.71) (t, C-8), 72.62 (69.39),
(d, C-7), 75.16 (72.24) (d, C-9), 75.49 (74.95) (d, C-10).
1-(6R-Hexyl-2-phenyl-1,3-dioxan-4-yl)nonan-1-ols (3a-c). A mixture of octadecan-7R,9,10-triol (2, 1.50 g,
5.0 mmol), freshly distilled benzaldehyde (1.5 mL, 15.0 mmol), anhydrous ZnCl (0.45 g, 3.3 mmol), and anhdyrous Na SO
4
2
2
(0.45 g, 3.0 mmol) was stirred under Ar at room temperature until the reaction was finished (TLC monitoring), diluted with
aqueous Na CO solution (7.3 mL), and stirred for 10 min. The precipitate of Zn(OH) was filtered off and washed with Et O.
2
3
2
2
The aqueous layer was extracted with Et O (3 × 50 mL). The combined extracts were washed with H O, dried over MgSO ,
2
2
4
and evaporated to afford a mixture (1.63 g, 86%) of two stereoisomers in a 63:37 ratio that were separated by column
chromatography (SiO , PE:EtOAc, 20:1).
2
20
1-(6R-Hexyl-2R-phenyl-1,3-dioxan-4S-yl)nonan-1S-ol (3a). [α] +1.6° (c 3.5, CH Cl ).
D
2
2
PMR spectrum (δ, ppm, J/Hz): 0.83 (6H, t, CH ), 1.20–1.41 (22H, m, H-3–H-8, H-1″–H-5″), 1.43-1.60 (3H, m, H-2,
3
2
3
H -5′), 1.64 (1H, dt, J = 12.1, J = 2.4, H -5′), 2.80 (1H, br.s, OH), 3.51–3.62 (1H, m, H-1), 3.73 (1H, ddd, J = 6.9, 2.4, 11.7,
a
e
H -4′), 3.78–3.86 (1H, m, H-6′), 5.51 (s, H -2′), Ph: 7.30–7.43 (3H, m), 7.51 (2H, d, J = 7.1).
a
a
13
C NMR spectrum: 13.15 (q, C-9, C-6″), 22.05 (t, C-8, C-5″), 24.55 (t, C-2″), 25.19 (t, C-3), 28.04-29.38 (all t,
C-4–C-6, C-3″), 31.37 (t, C-7, C-4″), 31.77 (t, C-2), 35.62 (t, C-1″), 38.63 (t, C-5′), 72.51 (d, C-1), 75.93 (d, C-6′), 79.52 (d,
C-4′), 99.91 (d, C-2′), Ph: 125.85, 127.32, 127.76 (all d), 139.21 (s).
20
1-(6R-Hexyl-2R-phenyl-1,3-dioxan-4R-yl)nonan-1R-ol (3b). [α] –15.5° (c 5.5, MTBE).
D
PMR spectrum (δ, ppm, J/Hz): 0.91 (6H, t, CH ), 1.19–1.50 (16H, m, H-3–H-7, H-2′′–H-4″), 1.40–1.51 (4H, m,
3
H-8, H-5″), 1.52–1.61 (4H, m, H-2, H-1″), 1.60–1.81 (2H, m, H-5′), 3.10 (1H, br.s, OH), 3.55–3.85 (2H, m, H-1, H-6′), 4.01
3
(1H, ddd, J = 5.7, 4.2, 3.2, H -4′), 5.54 (s, H -2′), Ph: 7.35–7.42 (3H, m), 7.52 (2H, d, J = 7.9).
e
a
13
C NMR spectrum: 13.35 (q, C-9, C-6″), 22.30 (t, C-8, C-5″), 25.32 (t, C-2″), 25.83 (t, C-3), 28.06-29.60 (all t,
C-4–C-6, C-3″), 31.61 (t, C-7, C-4″), 32.38 (t, C-2), 38.28 (t, C-1″), 40.73 (t, C-5′), 78.39 (d, C-6′), 67.66 (d, C-1), 82.61 (d,
C-4′), 102.16 (d, C-2′), Ph: 126.14, 127.87, 128.66 (all d), 139.25 (s).
20
1-(6R-Hexyl-2S-phenyl-1,3-dioxan-4R-yl)nonan-1R-ol (3c). [α] –4.0° (c 1.5, MTBE).
PMR spectrum (δ, ppm, J/Hz): 0.88 (6H, t, CH ), 1.21–1.48 (16DH, m, H-3–H-7, H-2″–H-4″), 1.40–1.51 (4H, m,
3
H-8, H-5″), 1.52–1.61 (4H, m, H-2, H-1″), 1.63–1.80 (m, 2H, H-5′), 2.90 (1H, br.s, OH), 3.54–3.85 (2H, m, H-1, H-6′), 4.05
3
(1H, ddd, J = 5.8, 4.3, 3.2, H -4′), 5.84 (s, H -2′), Ph: 7.30–7.39 (3H, m), 7.45 (2H, d, J = 7.8).
e
e
13
C NMR spectrum: 13.37 (q, C-9, C-6″), 22.30 (t, C-8, C-5″), 25.31 (t, C-2″), 25.85 (t, C-3), 28.57-29.61 (all t,
C-4–C-6, C-3″), 31.61 (t, C-7, C-4″), 32.38 (t, C-2), 38.24 (t, C-1″), 40.67 (t, C-5′), 67.70 (d, C-1), 79.81 (d, C-6′), 81.43 (d,
C-4′), 102.25 (d, C-2′), Ph: 126.60, 127.91, 128.89 (all d), 139.12 (s).
ACKNOWLEDGMENT
The work was supported financially by RFBR Grant No. 09-03-00831.
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