Ozonolysis of ricinolic acid derivatives and transformations of the ozonolysis products under barton reaction conditions

Article abstract of DOI:10.1007/s10600-006-0003-z

The possibility of functionalizing the alkyl part of ricinolic acid using the Barton reaction was investigated.

Full text of DOI:10.1007/s10600-006-0003-z

Chemistry of Natural Compounds, Vol. 41, No. 6, 2005
OZONOLYSIS OF RICINOLIC ACID DERIVATIVES AND
TRANSFORMATIONS OF THE OZONOLYSIS PRODUCTS
UNDER BARTON REACTION CONDITIONS
G. Yu. Ishmuratov, R. Ya. Kharisov, A. Kh. Shayakhmetova,
L. P. Botsman, O. V. Shitikova, and G. A. Tolstikov
UDC 542.85+542.943.5+665.335.5
The possibility of functionalizing the alkyl part of ricinolic acid using the Barton reaction was investigated.
Key words: castor oil, ozonolysis, Barton reaction, ricinolic acid.
Ricinolic acid (1) is a promising substrate for preparing chiral polyfunctional compounds that can in turn act as
convenient building blocks for the synthesis of organic compounds with more complicated structures because of its availability
from castor oil and the presence of asymmetric C-12 with the -configuration.
R
ONO
OH
OR
ONO
(CH ) CO H
2 7
2
4
1
2, 3
2:R = Ac;3: R = CH Ph
2
Herein we report results of investigations on expanding the synthetic potential of 1 by further functionalization of the
chemically stable alkyl part of the molecule (C-12—C-18) using the Barton photochemical rearrangement of nitrites 2-4 in the
key step.
In order to simplify the structure of starting 1, it was fragmented by ozonolysis to produce the desired secondary
monoacetate of diol 6.
Compound 6 was prepared previously by ozonolysis of methyl -12-acetoxyoctadec-9-enoic acid (5) in MeOH [1].
R
Under the conditions described for reduction of the intermediate peroxides (NaBH —MeOH) in the reaction mixture, the
4
product of thermodynamic control, primaryacetate 7 (ratio 6:7, 1:2.5), dominated and was formed as a result of intramolecular
-esterification. Furthermore, an equimolar amount of methyl 9-hydroxynonanoic acid (8), which is difficult to separate
trans
from monoesters 6 and 7, was necessarily formed as a side product.
We investigated ways of optimizing the ozonolysis of ricinolic acid to synthesize secondary acetate 6. The first
approach was based on transformation of the carboxylic acid in 1 to a methyl, for which we used successive hydride reduction
of castor oil 9 (ricinolic acid content ~85%) to diol 10 and subsequent deoxygenation of the primary hydroxyl in it through
monotosylate 11. The resulting chiral homoallyl alcohol 12 was converted to acetate 13 or benzyl ether 14.
Ozonolytic cleavage of the double bond in 13, carried out in CH Cl in the presence ofMeOH(2 equiv.) and subsequent
2
2
treatment of the peroxide products with NaBH , gave a mixture (9:5:1) of acetates 6 and 7 and diol 15 with the desired 6
4
predominating. These were readily freed from the necessary ozonolysis—reduction product 1-nonanol (16) by vacuum
distillation. Replacing NaBH by KBH increased the content of 6 (ratio 6:7:15, 6:1.1:1). The best results (ratio 6:7:15,
4
4
8.6:1.6:1) were obtained for ozonolysis in CH Cl in the presence of two equivalents of AcOH per double bond and with the
2
2
mild reducing agent NaBH(OAc) .
3
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. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 529-534, November-
December, 2005. Original article submitted April 28, 2005.
0009-3130/05/4106-0643 ©2005 Springer Science+Business Media, Inc.
643

R O CH
3
2
2
OH
OAc
OH
R O CH
3
+
+
+
CH (CH )
2 5
OH
OH
OAc
3
R O CH
3
6
7
15
18
OH
R O CH
2
R O CH
1
OH
2
2
2
2
1. Bu1AlH
LiAlH
4
1. Ac O
2
2
CH (CH )
2 5
R O CH
2
R O CH
1
3
(CH ) OT s
2 8
CH (CH )
3
2 5
(CH ) CH
2 7
3
2. TsCl, Et N
3
11
12
BnBr NaH
R O CH
2
R O CH
1
17
9
Ac O
2
OBn
OAc
∆
CH (CH )
CH (CH )
3
2 5
3
2 5
(CH ) CH
2 7
(CH ) CH
2 7
3
3
14
13
OBn
CH (CH ) OH
2 8
CH (CH ) OH
2 8
CH (CH )
OH
3
6
7
15 +
+
3
3
2 5
+
+
19
16
16
OH
20
OAc
OH
O
O
O
CH (CH )
CH (CH )
2 5
9: R
=
17: R
=
2
3
2 5
3
18: R
=
HO(CH ) C
2 8
(CH ) C
2 7
(CH ) C
2 7
1
3
17
In order to extend the results to castor oil, we ozonolyzed , which furthermore enabled the side product of highly
18 6 7 15 13
6
polar triglyceride
to be easily removed. The highest yield of (ratio : : , 17.7:1.5:1) was obtained, like for , for
ozonolysis in CH Cl in the presence of two equivalents of AcOH per one double bond and the use ofNaBH(OAc) as reductant.
2
2
3
14
19
in high yield.
Benzyl ether
was ozonolyzed without any complications to give the other key hydroxyether
20 15
4
Theprecursor ofalkylnitrate , secondaryalcohol , was prepared from diol bydeoxygenation ofthecorresponding
primary tosylate.
2 4
6 19
20
The Barton reaction of nitrites - , which were prepared from alcohols , , and by the standard method [2], was
carried out in an inert atmosphere and an aprotonic medium (benzene).
2
21
6
7
Photolysis of nitrites and , synthesized from a mixture (14:1) of hydroxyacetates and , produced the starting
6
7
15 22
and in addition to diol , which were isolated from the reaction mixture and identified. 1-Acetoxy-3-nonanone ( ), the
product of disproportionation or a "cage radical" reaction between the alkoxyradical and NO [3] that were formed from nitrite
21
, was also observed.
O
ONO
hv
NaNO
2
6
7
2 +
6
7
15
+ +
+
+
CH (CH )
2 5
OAc
CH (CH )
2 5
OAc
3
3
H SO
2
4
21
22
6
19
Because the secondaryacetate in was labile, we used the corresponding benzyl derivative . Photolysisofitsprimary
3
nitrite led to an unusual result. The usual product [4] of 1,5-cleavage was missing among the isolated and identified reaction
products.
OBn
OBn
NaNO
2
hv
19
15 19 +
+
+
CH (CH )
2 5
O
CH (CH )
2 5
ONO
3
H SO
3
2
4
O
O
3
23
CH (CH )
2 5
3
24
24
The principal product was 2-phenyl-4R-hexyl-1,3-dioxane ( ) resulting from 1,6-cleavage in addition to impurities
19 15
23
, and aldehyde . This was confirmed byspectral data. The PMR spectrum had signals at chemical shifts for a phenyl
of
,
644

13
ring (δ 7.25-7.55 ppm) and a singlet for an acetal proton (δ 5.52 ppm). The C NMR spectrum had a doublet (δ 101.09 ppm)
for C-2 and other characteristic signals.
Conversely, photolysis of nitrite 4, prepared from optically pure secondary alcohol 20, followed by chromatography
of the reaction mixture isolated a compound with a modified alkyl chain of the starting material, 6-nitroso-3S-nonanol, existing
primarily [5] as the more stable dimer 26, and 20 and 25 [3].
OH
O
OH
ONO
N
N
O
NaNO
hv
2
CH (CH )
2 5
3
20
+
+
O
CH (CH )
2 5
3
H SO
2
4
25
20
4
OH
OH
26
∆
N
OH
27
Thermolysis of 26 gave quantitatively the -hydroxyoxime 27 as an equal mixture of the syn- and anti-isomers. Two-
13
dimensional CH CORR and double resonance were used in order to assign unambiguously signals in the PMR and C NMR
spectra of the stereoisomers of 27. The signals for C-5 [23.46 (syn-), 29.76 (anti-)] and C-7 [35.88 (syn-), 30.45 (anti-)] and
their protons H-7[2.35(anti-), 2.15 (syn-)] and H -5 [2.40 (syn-), 2.70 (anti-)] were nonequivalent because ofdifferent shielding
a
of the corresponding atoms in this pair of compounds and agreed well with the literature [6] (see Experimental).
EXPERIMENTAL
IR spectra were recorded on a Specord M-82 instrument as thin layers. NMRspectra were obtained on a Bruker AMX-
1
13
300 spectrometer (working frequency 300.13 MHz for H and 75.47 MHz for C) in CDCl with an internal standard of the
3
1
13
CDCl signals ( H δ 7.27 ppm, C δ 77.00 ppm). Chromatography was carried out in a Chrom-5 instrument [column length
3
1.2 m, stationary phase silicone SE-30 (5%) on Chromaton N-AW-DMCS (1.16-0.20 mm), working temperature 50-300°C,
He carrier gas] and in a Shimadzu GC-9A chromatograph (quartz capillary column, 25 m, stationary phase OV-101, working
temperature 80-260°C). Optical rotation was measured in a Perkin—Elmer 241 MC polarimeter. Photolysis was performed
using a mercury lamp OKN-14, TU 64-1-1618-77 (220 V, 950 VA, 1000 W, 50 Hz). The Barton reaction was performed in
a thermostatted Pyrex glass cell ( > 320 nm, 80 mL). TLC monitoring used Sorbfil SiO (Russia). Column chromatography
2
was carried out over SiO (70-230, Lancaster, England) with elution by petroleum ether (40-70°C). The ozonator production
2
was 38 mmol O /h. Elemental analyses agreed with those calculated.
3
Castor Oil Acetate (17). Castor oil (9, 20.00 g) and Ac O (40.29 g, 394.9 mmol) were refluxed for 5 h, washed with
2
hot water (3 × 100 mL), diluted with CH Cl (300 mL), dried over Na SO , and evaporated to afford 17 (22.24 g, 98%).
2
2
2
4
-1
IR spectrum (ν, cm ): 3016 (C=C), 1740 (C=O), 1240, 1164 (C–O–C), 736 (C=C).
R-Octadec-9Z-en-1,12-diol (10). A solution of 9 (10.9 g) in absolute THF (270 mL) and Et O (150 mL) (Ar, -10°C)
2
was treated dropwise with a solution ofi-Bu AlH(23.0 mL, 102.4 mmol, 73%). After the entire amount ofi-Bu AlHwas added,
2
2
the reaction mixture was stirred for 1.5 h at 0°C, treated dropwise with H O (22 mL, 0-5°C), warmed to room temperature, and
2
stirred for another 2 h. The resulting solid was filtered off and washed with Et O. The filtrate was dried over Na SO and
2
2
4
evaporated to afford the product (8.74 g), column chromatography of which (SiO , PE:CH Cl , 2:1) isolated 10 (7.70 g, 94%),
2
2
2
18
[α]
+2.24° (c 0.03, CHCl ).
D
3
-1
IR spectrum (ν, cm ): 3304 (OH), 3010, 1660, (C=C), 1110, 1054, (C–O), 724 (C=C).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.89 (3H, t, J = 6.8, CH ), 1.20-1.45 (18H, m, 9CH ), 1.49 (2H, m, H-13), 1.53
3
3
2
(2H, m, H-2), 1.64 (2H, br.s, 2OH), 2.04 (2H, q, J = 6.7, H-8), 2.22 (2H, t, J = 7.2, H-11), 3.54 (1H, quintet, J = 5.8, H-12), 3.63
(2H, t, J = 6.6, H-1), 5.40 (1H, dt, J = 10.8, 7.4, H-10), 5.55 (1H, dt, J = 10.8, 7.1, H-9).
645

R-Octadec-9Z-en-7-ol (12). A solution of 10 (8.80 g, 30.9 mmol) in dry Et N (7 mL, 128.5 mmol) was stirred (Ar,
3
0°C), treated in portions over 1 h with TsCl (7.05 g, 36.7 mmol), left overnight in a refrigerator, diluted with t-BuOMe
(200 mL), washed successively with H O, aqueous HCl (10%), and saturated NaHCO and NaCl solutions, and dried over
2
3
Na SO to give 11 (13.56 g), which was used without further purification.
2
4
-1
IR spectrum (ν, cm ): 3346 (OH), 3010, 1650 (C=C), 1605 (Ar), 1378, 1185, (S=O), 1110, 1048, (C–O), 724 (C=C).
A solution of 11 (13.56 g, 30.9 mmol) in absolute THF (80 mL) and absolute Et O (80 mL) (Ar, 0°C) was treated with
2
LiAlH (2.65 g, 71.0 mmol), stirred for 3 h at room temperature, cooled to 0 C, diluted with H O (3.3 mL), warmed to room
4
2
temperature, and stirred for another 3 h. The resulting solid was filtered off and washed with t-BuOMe. The filtrate was dried
over Na SO and evaporated to give a product (7.02 g), column chromatography of which (SiO , PE:CH Cl , 2:1, R 0.3)
f
2
4
2
2
2
20
isolated 12 (4.12 g, 50%), [α]
+2.6° (c 0.03, CH Cl ).
2 2
D
-1
IR spectrum (ν, cm ): 3346 (OH), 3010, 1650 (C=C), 1110, 1048 (C–O), 724 (C=C).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.88 (6H, t, J = 6.5, 2CH ), 1.20-1.45 (20H, m, 10CH ), 1.47-1.50 (2H, m, H-6),
3
3
2
1.58 (1H, br.s, OH), 2.05 (2H, q, J = 6.8, H-11), 2.22 (2H, t, J = 6.6, H-8), 3.62 (1H, quintet, J = 5.9, H-7), 5.35-5.65 (2H, m,
H-9, H-10).
13
C NMR spectrum (CDCl , δ, ppm): 14.01 (both q, C-1, C-18), 22.60 (both t, C-2, C-17), 25.68 (t, C-5), 27.40 (t,
3
C-11), 29.27, 29.30, 29.34 (C-12, C-13, C-14), 29.47 (t, C-4), 29.66 (t, C-15), 31.82 (both t, C-3, C-16), 35.32 (t, C-8), 36.82
(t, C-6), 71.47 (d, C-7), 125.10 (d, C-9), 133.37 (d, C-10).
R-7-Acetoxyoctadec-9Z-ene (13). A mixture of12 (2.50 g, 9.3 mmol) and Ac O (20.13 mL, 57.0 mmol) was refluxed
2
for 2 h, washed with hot H O (3 × 20 mL), diluted with CH Cl , dried over Na SO , and evaporated to afford 13 (2.87 g, 99%),
2
2
2
2
4
18
[α]
+25.2° (c 0.02, CHCl ).
IR spectrum (ν, cm ): 1738 (C=O), 3010, 1654 (C=C), 1110, 1048 (C–O), 724 (C=C).
D
3
-1
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.86 (6H, t, J = 6.7, 2CH ), 1.20-1.45 (20H, m, 10CH ), 1.50-1.62 (2H, m, H-6),
3
3
2
2.00-2.10 (4H, m, H-11, AcO), 2.32 (2H, dd, J = 6.7, J = 6.2, H-8), 4.88 (1H, quintet, J = 6.2, H-7), 5.35 (1H, dt, J = 10.8,
J = 7.2, H-9), 5.48 (1H, dt, J = 10.8, J = 7.2, H-10).
R-7-Benzyloxyoctadec-9Z-ene (14). A suspension of NaH (0.56 g, 14.6 mmol, 60% in mineral oil) in DMF (5 mL)
was treated dropwise (Ar, 0°C) with 12 (3.5 g, 13.0 mmol) in DMF (5.5 mL), stirred at 0°C for 1 h, treated with BnBr (2.3 mL,
18.3 mmol), stirred for 6 h at room temperature, left overnight, diluted with t-BuOMe (200 mL), washed with water and
saturated NaCl solution, dried over Na SO , and evaporated. The solid (5.23 g) was chromatographed (SiO , PE) to afford 14
2
4
2
20
(4.06 g, 87%), [α]
+18.1° (c 0.02, CH Cl ).
2 2
D
-1
IR spectrum (ν, cm ): 3010, 1662 (C=C), 1625 (Ar), 1110, 1048 (C–O), 755 (C=C).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.90 (6H, t, J = 6.7, 2CH ), 1.20-1.55 (20H, m, 10CH ), 1.50-1.62 (2H, m, H-6),
3
3
2
2.06 (2H, q, J = 6.3, H-11), 2.25-2.45 (2H, m, H-8), 3.43 (1H, quintet, J = 5.8, H-7), 4.51 (1H, d, J = 11.7, PhCH ), 4.60 (1H,
a
d, J = 11.7, PhCH ), 5.35-5.60 (2H, m, H-9, H-10), 7.25-7.40 (5H, m, Ph).
b
Ozonolysis and reduction of peroxide ozonolysis products: a) An ozone—oxygen mixture was bubbled through a
solution of 13 (1.80 g, 8.8 mmol) in CH Cl (18 mL) and absolute MeOH (0.7 mL, 17.6 mmol) at 0°C at an O :13 mole ratio
2
2
3
of 1:1. The reaction mixture was purged with Ar, diluted with CH Cl (20 mL), stirred (10°C), treated with NaBH (0.44 g,
2
2
4
11.6 mmol), stirred at room temperature for 3 h, treated with AcOH (0.14 mL) and H O (1.4 mL) (10°C), stirred at room
2
temperature for 0.5 h, and washed with saturated NaCl solution. The organic layer was dried over Na SO and evaporated to
2
4
give a product (0.95 g) that contained 6, 7, and 15 in a ratio of 9:5:1, respectively, according to GC.
b) The peroxide ozonolysis product obtained bymethod a) was reduced with KBH (0.63 g, 11.6 mmol), stirred at room
4
temperature for 3 h, treated with AcOH (0.14 mL) and H O (1.4 mL) (10°C), stirred at room temperature for 0.5 h, and washed
2
with saturated NaCl solution. The organic layer was dried over Na SO and evaporated to give a product (0.90 g) that contained
2
4
6, 7, and 15 in a ratio of 6:1.1:1 according to GC.
c) An ozone—oxygen mixture was bubbled through a solution of 13 (0.90 g, 4.4 mmol) in CH Cl (9 mL) and glacial
2
2
AcOH (0.35 mL, 8.8 mmol) at 0°C at an O :13 mole ratio of 1:1. The reaction mixture was purged with Ar, diluted with
3
CH Cl (20 mL), stirred (10°C), treated wth a previously prepared suspension of NaBH(OAc) [addition of glacial AcOH
2
2
3
(3.4 mL, 60.5 mmol) in CH Cl (6 mL) to a suspension of NaBH (0.76 g, 20.17 mmol) in CH Cl (30 mL) with stirring for
2
2
4
2
2
2 h], warmed to room temperature, stirred for 3 h, cooled to 10°C, treated with AcOH (0.24 mL) and H O (2.4 mL), stirred at
2
room temperature for 0.5 h, and washed with saturated NaCl solution. The organic layer was dried over Na SO and evaporated
2
4
to give a product (1.03 g) that contained 6, 7, and 15 in a 8.6:1.6:1 ratio according to GC.
646

d) An ozone—oxygen mixture was bubled through a solution of 17 (5.0 g, 4.7 mmol) in CH Cl (50 mL) and MeOH
2
2
(1.1 mL, 28.3 mmol) at 0°C at an O :17 mole ratio of 3:1. The reaction mixture was purged with Ar, diluted with CH Cl
2
3
2
(30 mL), stirred (10°C), treated with NaBH (1.4 g, 37.2 mmol), stirred at room temperature for 3 h, treated with AcOH
4
(0.44 mL) and H O (4.4 mL) (10°C), stirred at room temperature for 0.5 h, and washed with saturated NaCl solution. The
2
organic layer was dried over Na SO and evaporated to give a product (5.46 g) that contained 6 and 7 in a 1.6:1 ratio according
2
4
to GC.
e) The peroxide ozonolysis product obtained bymethod d) was reduced with KBH (2.0 g, 37.2 mmol), stirred at room
4
temperature for 3 h, treated with AcOH (0.44 mL) and H O (4.4 mL) (10°C), stirred at room temperature for 0.5 h, and washed
2
with saturated NaCl solution. The organic layer was dried over Na SO and evaporated to give a product (4.9 g) that contained
2
4
6, 7, and 15 in a 8.7:1.6:1 ratio according to GC.
f) An ozone—oxygen mixture was bubbled through a solution of 17 (5.00 g, 4.7 mmol) in CH Cl (50 mL) and glacial
2
2
AcOH (1.6 mL, 28.3 mmol) at 0°C at an O :17 mole ratio of 3:1. The reaction mixture was purged with Ar, diluted with
3
CH Cl (20 mL), stirred (10°C), treated with a previously prepared suspension of NaBH(OAc) [glacial AcOH (11.2 mL,
2
2
3
194.7 mmol) and NaBH (2.46 g, 64.9 mmol) in CH Cl (120 mL)], warmed toroom temperature, stired for 3 h, cooled to10°C,
4
2
2
treated with glacial AcOH (0.86 mL) and H O (8.6 mL), stirred at room temperature for 0.5 h, and washed with saturated NaCl
2
solution. The organic layer was dried over Na SO and evaporated to give a product (4.97 g) that contained 6, 7, and 15 in a
2
4
17.7:1.5:1 ratio according toGC. Column chromatographyisolated a mixture of 6 and 7 (1.14 g) in a ratio of 14:1, respectively.
The IR and NMR spectra of 6, 7, and 15 were practically identical to those in the literature [1].
3R-Benzyloxynonan-1-ol (19). Ozonolysis of 14 (4.00 g, 11.2 mmol) by method a) followed by vacuum distillation
20
at 1 mm Hg and 100°C produced 19 (2.66 g, 95%), [α]
-44.07° (c 0.003, CHCl ).
3
D
-1
IR spectrum (ν, cm ): 3420 (OH), 1660 (Ar), 1110, 1048 (C–O).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.91 (3H, t, J = 7.0, CH ), 1.20-1.40 (6H, m, 3CH ), 1.48-1.60 (2H, m, H-5),
3
3
2
1.60-1.73 (2H, m, H-4), 1.70-1.80 (2H, m, H-2), 2.50 (1H, br.s, OH), 3.60-3.65 (1H, m, H-3), 3.65-3.85 (2H, m, H-1), 4.48 (1H,
d, J = 11.5, PhCH ), 4.51 (1H, d, J = 11.5, PhCH ), 7.20-7.50 (5H, m, Ph).
a
b
3S-Nonanol (20). A solution of 15 (5.38 g, 33.6 mmol) in Py (11 mL) at 0°C was stirred, treated in portions with TsCl
(6.90 g, 36.7 mmol), left overnight in a refrigerator, diluted with t-BuOMe (200 mL), washed successivelywith HCl (10%) and
saturated NaHCO and NaCl solutions, dried over Na SO , and evaporated to afford the tosylate (8.83 g, 80%) [IR spectrum
3
2
4
-1
(ν, cm ): 1605 (Ar), 1375, 1180 (S=O), 1112 (C–O)], which was dissolved in absolute t-BuOMe (150 mL). The resulting
solution was cooled to 0°C, treated with LiAlH (2.38 g, 62.7 mmol), warmed to room temperature, stirred for 3 h, cooled to
4
0°C, diluted with H O (5 mL), warmed to room temperature, and stirred for 3 h. The solid was filtered off and washed with
2
t-BuOMe. The filtrate was dried over Na SO and evaporated to give a product (4 g), column chromatographyof which (SiO ,
2
4
20
2
PE:EtOAc, 3:1) gave 20 (3.0 g, 75%), [α]
+8.3° (c 0.05, CH Cl).
3
D
-1
IR spectrum (ν, cm ): 3400 (OH), 1150, 1078 (C–O).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.88 (3H, t, J = 7.0, CH ), 0.94 (3H, t, J = 7.3, CH ), 1.25-1.37 (7H, m, 3CH ,
3
3
3
2
OH), 1.30-1.60 (6H, m, H-2, H-4, H-5), 3.45-3.55 (1H, m, H-3).
13
C NMR spectrum (CDCl , δ, ppm): 9.79 (q, C-1), 13.98 (q, C-9), 22.56 (t, C-8), 25.56 (t, C-5), 29.32 (t, C-6), 30.00
3
(t, C-2), 31.78 (t, C-7), 36.85 (t, C-2), 73.20 (d, C-3).
Nitrite Syntheses. 1. A 3-necked flask equipped with a thermometer, stirrer, and dropping funnel reaching to the
bottom of the flask was charged with NaNO (0.42 g, 6.1 mmol) and H O (1.66 mL) and cooled to 0°C. A cold (0°C) solution
2
2
of a mixture of 6 and 7 (14:1, 1.12 g, 5.5 mmol) prepared as above in H SO (0.28 g, 2.8 mmol) and H O (0.11 mL) was added
2
4
2
through the dropping funnel with stirring at a rate sothat gas was practicallynot evolved and the temperature did not rise. After
the addition the reaction mixture was diluted with t-BuOMe (50 mL), washed with saturated NaCl solution, dried over Na SO ,
2
4
and evaporated to give a mixture of 2 and 21 (1.11 g) that was used without further purification.
-1
IR spectrum (ν, cm ): 1750, 1650, 1620 (N=O), 790, 780, 620 (O–N).
2. Analogously 19 (2.58 g, 10.3 mmol) afforded 3 (2.4 g) that was used without further purification.
-1
IR spectrum (ν, cm ): 1650 (N=O), 1605 (Ar), 1080, 820, 750 (O–N).
3. Analogously 20 (2.20 g, 15.3 mmol) afforded 4 (1.61 g) that was used without further purification.
-1
IR spectrum (ν, cm ): 1645 (N=O), 1085, 820 (O–N).
647

Photolysis of Nitrites. 1. A solution of a mixture of 2 and 21 (0.40 g) in benzene (70 mL) was placed in a
thermostatted Pyrex glass cell and irradiated (Ar, 27°C) for 1.5 h. The solvent was evaporated. The solid (0.36 g) was
chromatographed (PE:t-BuOMe, 15:1) to isolate and identify a mixture of 6 and 7 (0.08 g), 15 (0.20 g), and 22 (0.01 g).
-1
1-Acetoxy-3-nonanone (22). IR spectrum (ν, cm ): 1740 (OC=O), 1714 (C=O).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.90 (3H, t, J = 6.8, CH ), 1.20-1.40 (6H, m, 3CH ), 1.50-1.65 (2H, m, H-5),
3
3
2
2.05 (3H, s, OAc), 2.42 (2H, t, J = 7.4, H-4), 2.72 (2H, t, J = 6.3, H-2), 4.32 (2H, t, J = 6.3, H-1).
13
C NMR spectrum (CDCl , δ, ppm): 13.98 (q, C-9), 20.85 (q, C–CO), 22.44 (t, C-8), 23.53 (t, C-5), 29.00 (t, C-6),
3
31.54 (t, C-7), 41.20 (t, C-2), 43.22 (t, C-4), 59.38 (t, C-1), 170.90 (s, CO ), 208.08 (d, C-3).
2
2. Photolysis of 3 (0.40 g) by the method described above gave a mixture of products (0.40 g), column chromatography
of which isolated and identified 19 (0.13 g), 23 (0.06 g), 15 (0.02 g), and 24 (0.16 g).
-1
3R-Benzyloxynonanal (23). IR spectrum (ν, cm ): 1720 (C=O), 1650 (Ar).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.90 (3H, t, J = 6.7, CH ), 1.20-1.45 (6H, m, 3CH ), 1.50-1.65 (2H, m, H-5),
3
3
2
1.65-1.75 (2H, m, H-4), 2.60 (1H, ddd, J = 16.5, J = 4.9, J = 2.0, H -2), 2.67 (1H, ddd, J = 16.5, J = 7.2, J = 2.6, H -2), 3.95-4.00
a
b
(1H, m, H-3), 4.45-4.60 (2H, m, CH -Ph), 7.25-7.38 (5H, m, Ph), 9.81 (1H, t, J = 2.2, CHO).
2
20
2-Phenyl-4R-hexyl-1,3-dioxane (24), [α]
IR spectrum (ν, cm ): 1640 (Ar), 1155, 1125, 1040 (O–C–O),.
+15.7° (c 0.02, CHCl ).
3
D
-1
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.87 (3H, t, J = 7.02, CH ), 1.25-1.40 (6H, m, 3CH ), 1.40-1.75 (5H, m, H-1′,
3
3
2
H-2′, H -5), 1.82 (1H, dtd, J = 14.0, J = 11.4, J = 4.8, H -5), 3.83 (1H, dddd, J = 11.4, J= 7.1, J = 4.8, J = 2.4, H -4), 3.95 (1H,
e
a
a
td, J = 11.4, J = 2.3, H -6), 4.28 (1H, ddd, J = 11.4, J = 4.8, J = 1.2, H -6), 5.52 (1H, s, H-2), 7.25-7.55 (5H, m, Ph).
a
e
13
C NMR spectrum (CDCl , δ, ppm): 14.04 (q, C-6′), 22.58 (t, C-5′), 24.92 (t, C-2′), 29.23 (t, C-3′), 31.34 (t, C-4′),
3
31.77 (t, C-1′), 36.01 (t, C-5), 67.09 (d, C-6), 77.41 (t, C-4), 101.09 (d, C-2), 125.99, 128.13, 128.56, 138.93 (m, Ph).
3. Photolysis of 4 (0.40 g) by the method descibed above gave a mixture of products (0.27 g), column chromatography
of which isolated and identified 25 (0.02 g), 20 (0.08 g), and 26 (0.15 g).
-1
3-Nonanone (25). IR spectrum (ν, cm ): 1714 (C=O).
PMR spectrum (CDCl , δ, ppm, J/Hz): 0.90 (3H, t, J = 6.6, H-9), 1.15 (3H, t, J = 7.5, H-1), 1.20-1.35 (6H, m, 3CH ),
3
2
1.59 (2H, quintet, J = 7.3, H-5), 2.39 (2H, t, J = 7.4, H-2), 2.42 (2H, q, J = 7.3, H-4).
13
C NMR spectrum (CDCl , δ, ppm): 7.77 (q, C-1), 13.95 (q, C-9), 22.56 (t, C-8), 24.87 (t, C-5), 29.64 (t, C-6), 31.82
3
(t, C-3), 35.76 (t, C-2), 42.37 (t, C-4), 211.85 (s, C-3).
20
Dimer of 6-nitroso-3S-nonanol (26), [α]
+5.5° (c 0.01, CH Cl ).
2 2
D
-1
IR spectrum (ν, cm ): 3400 (OH), 1378, 1240, (N=O), 1174 (C–O).
PMR spectrum (CDCl , δ, ppm): 0.80-1.00 (6H, m, 2CH ), 1.20-2.00 (11H, m, 5CH , OH), 3.40-3.55 (1H, m, H-3),
3
3
2
5.35-5.50 (1H, m, H-6).
13
C NMR spectrum (CDCl , δ, ppm): 9.85 (q, C-1), 13.60 (q, C-9), 19.08 (t, C-8), 28.17 (t, C-5), 29.96 (t, C-2), 32.74
3
(t, C-4), 34.14 (t, C-7), 66.59 (d, C-6), 72.22 (d, C-3).
6-Oximino-3S-nonanol (27). Dimer 26 was heated at 60°C for 48 h to produce in quantitative yield an oily product
20
that was a chromatographically inseparable equal mixture of the syn- and anti-isomers of 27, [α]
-6.2° (c 0.02, CH Cl ).
2 2
D
-1
IR spectrum (ν, cm ): 3500 (OH), 1660 (C=N), 1120 (C–O), 960 (N–O).
PMR spectrum (CDCl , δ, ppm, J/Hz): syn: 0.90-1.00 (6H, m, H-1,9), 1.45-1.60 (4H, m, H-2,8), 3.53 (1H, tdd,
3
3
3
3
3
3
3
2
J = 6.3, J = 3,5, J = 9.5, H-3), 1.60-1.70 (2H, m, H-4), 2.25 (1H, ddd, J = 5.3, J = 7.5, J = 13.0, H -5), 2.70 (1H, td,
a
2
3
J = 8.6, J = 13.0, H -5), 2.15 (2H, t, J = 7.4, H-7), 1.20-1.70 (2H, br.s, OH).
b
3
3
3
anti: 0.90-1.00 (6H, m, H-1,9), 1.45-1.60 (4H, m, H-2,8), 3.42 (1H, tdd, J = 6.3, J = 3.5, J = 9.5, H-3), 1.60-1.70
(2H, m, H-4), 2.25 (1H, ddd, J = 5.3, J = 7.5, J = 13.0, H -5), 2.40 (1H, td, J = 8.6, J = 13.0, H -5), 2.35 (2H, t, J = 7.7,
3
3
2
3
2
3
a
b
H-7), 1.20-1.70 (2H, br.s, OH).
13
C NMR spectrum (CDCl , δ, ppm): syn: 10.04 (C-1), 30.06 (C-2), 72.10 (C-3), 33.04 (C-4), 23.46 (C-5), 161.85
3
(C-6), 35.88 (C-7), 19.04 (C-8), 14.30 (C-9).
anti: 10.11 (C-1), 29.70 (C-2), 71.99 (C-3), 32.68 (C-4), 29.76 (C-5), 161.85 (C-6), 30.45 (C-7), 19.71 (C-8), 13.79
(C-9).
648

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5.
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6.
E. Pretsch, T. Clerc, J. Seibl, and W. Simon, Tables of Spectral Data for Structure Determination of Organic
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649