Stereoselective total synthesis of phenolic nonadecanediol

Article abstract of DOI:10.1002/hlca.201300221

A simple and highly efficient synthetic route has been developed for synthesis of 1-(4-hydroxyphenyl)nonadecane-3,5-diol (1). The two stereogenic centers were generated by employing proline asymmetric α-hydroxylation (MacMillan α-hydroxylation), Jacobsen's hydrolytic kinetic resolution (HKR), and, finally, Yamaguchi oxirane opening as key steps (Scheme 2). Copyright

Full text of DOI:10.1002/hlca.201300221

Helvetica Chimica Acta – Vol. 97 (2014)
613
Stereoselective Total Synthesis of Phenolic Nonadecanediol
by Baggu Chinnababu, Sudina Purushotham Reddy, Kunuru Venkatesham, Dasireddi Chandra Rao, and
Yenamandra Venkateswarlu*†1)
Division of Natural Products Chemistry, Natural Products Laboratory Indian Institute of Chemical
Technology, Hyderabad – 500 007, India
(phone: þ 91-40-27191881; fax: þ 91-40-27160512; e-mail: suresh@iict.res.in)
A simple and highly efficient synthetic route has been developed for synthesis of 1-(4-hydroxy-
phenyl)nonadecane-3,5-diol (1). The two stereogenic centers were generated by employing proline
asymmetric a-hydroxylation (MacMillan a-hydroxylation), Jacobsenꢀs hydrolytic kinetic resolution
(HKR), and, finally, Yamaguchi oxirane opening as key steps (Scheme 2).
Introduction. – Phenolic compounds are an important group of natural antioxidants
with possible beneficial effects on human health, and they are widely distributed in the
medicinal plants, spices, vegetables, fruits, grains, pulses, and other seeds. Their
antioxidant activity [1] is based on their ability to donate H-atoms to free-radical
scavengers by the formation of stable phenoxyl radicals. Moreover, phenolic com-
pounds also have a broad spectrum of other biological features such as antimutagenic,
antibacterial, antiviral, anticarcinogenic, anti-inflammation, antiallergic activities, as
well as the ability to modify gene expression [2][3]. The resinous exudates of
Heliotropium sinuatum possess very good antioxidant capacity due to the presence of
phenolic compounds [4]. (3S,5R)-1-(4-Hydroxyphenyl)nonadecane-3,5-diol was iso-
lated from Heliotropium sinuatum (family Boraginaceae) [5]. Recently, Chen et al.
synthesized and determined the absolute configuration of both isomers of 1 on the basis
of spectroscopic data and optical rotation [6]. Considering the structure as well as its
activity, in continuation of our interest in the synthesis of biologically active natural
products [7], herein we report a simple and facile route for the preparation of 1 using
proline asymmetric a-hydroxylation (MacMillan a-hydroxylation), Jacobsenꢀs hydro-
lytic kinetic resolution (HKR) as chirality-introducing steps, and, finally, Yamaguchi
oxirane opening. The retrosynthesis of structure 1 is depicted in Scheme 1 starting from
4-(2-hydroxyethyl)phenol (2).
Results and Discussion. – The synthesis of 1 started from commercially available
4-(2-hydroxyethyl)phenol 2. The known intermediates 3 – 9 were prepared as follows
[8]: selective protection of the phenolic OH group of 2 with BnBr afforded the
corresponding benzyl ether 3 in 98% yield, which was oxidized with 2-iodoxybenzoic
1
)
Deceased July 17, 2013; correspondence should be addressed to Dr. K. Suresh Babu (phone: þ 91-
40-27191881; e-mail: suresh@iict.res.in)
ꢁ 2014 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Scheme 1. Retro synthetic Analysis
acid (IBX) in DMSO to give the corresponding aldehyde. The crude aldehyde was
subjected to C2-homologation with methyl 2-(triphenylphosphorylidene)acetate to
furnish an unsaturated ester ((E)/(Z) 85 :15) in 92% yield. The latter was reduced by
using NiCl2 · 6 H2O/NaBH4 to the saturated ester 4 in 95% yield [8g]. Ester 4 was
reduced with DIBAL in CH2Cl2 at ꢀ 788 to afford the corresponding aldehyde in 92%
yield, which was subjected to proline-catalyzed a-hydroxylation (MacMillan a-
hydroxylation) using d-proline and PhNO in DMSO at 08, followed by in situ
reduction of the resulting anilinoxy aldehyde with NaBH4 in EtOH, and, subsequently,
treatment with CuSO4 · 5 H2O in MeOH at 08 provided the diol 5 in 65% yield [9][10].
The primary OH group in 5 was selectively tosylated with TsCl/Et3N/Bu2SnO/CH2Cl2
(88% yield). The intermediate tosylate was then transformed to the chiral epoxide
6 by treatment with K2CO3/MeOH in 90% yield. Opening of epoxide 6 with vinyl-
magnesium bromide furnished the homoallylic alcohol 7 in 85% yield. The result-
ing OH group in 7 was protected as its silyl ether 8 with TBSCl/1H-imidazole in 94%
yield.
Compound 8 was subjected to epoxidation using mCPBA in CH2Cl2 to afford an
inseparable diastereoisomer mixture of epoxides in 98% yield, which was subjected to
Jacobsenꢀs hydrolytic kinetic resolution (HKR) using (S,S)-salen-Co(OAc) complex
(0.5 mol-%) and H2O (0.55 equiv.) at room temperature to afford pure epoxide 9 in
48% yield and diol 9a in 48% yield [11]. Then, employing the Yamaguchi procedure
[12], oxirane 9 was treated with the Li salt of tridec-1-ynate in dry THF at ꢀ 788 to
furnish 10 in 95% yield. The TBS group in 10 was removed by using Bu4NF in THF to
give syn-1,3-diol 11 in 93% yield. Finally, hydrogenation of the CꢁC bond and
debenzylation of compound 11 by treatment with Pd/C (10 mol-%) afforded the
natural phenolic nonadecanediol 1 in 65% yield.
In conclusion, we have achieved the asymmetric total synthesis of the phenolic diol
1 from the readily available starting material 2 in ten distinct steps with an overall yield
of 8.75%. The synthesis involves proline-catalyzed a-hydroxylation (MacMillan a-
hydroxylation), Jacobsenꢀs hydrolytic kinetic resolution, and finally, the Yamaguchi
oxirane opening as key steps.
The authors are grateful to CSIR, New Delhi, India, for the financial support, and to the Director,
CSIR-Indian Institute of Chemical Technology (CSIR-IICT), for constant encouragement.

Helvetica Chimica Acta – Vol. 97 (2014)
615
Scheme 2
a) K2CO3, BnBr, DMF, 08 to r.t., overnight; 98%. b) 1) 2-iodoxybenzoic acid, DMSO, CH2Cl2, 4 h. 2)
Ph3PCHCOOMe, CH2Cl2, r.t., 6 h; 92% (over two steps). 3) NiCl2 · 6 H2O, NaBH4, MeOH, r.t., 1 min;
95%. c) 1) Diisobutylaluminium hydride (DIBAL), CH2Cl2, ꢀ 788, 1 h; 92%. 2) PhNO, d-proline,
DMSO, 08, 0.5 h, then NaBH4, EtOH, 08, 2 h, then CuSO4 · 5 H2O in MeOH, r.t., overnight; 65%. d) 1)
TsCl, Bu2SnO, Et3N, 08 to r.t., 4 h; 88%. 2) K2CO3, MeOH, 08 to r.t., 1 h; 90%. e) Vinylmagnesium
bromide (1.0 m soln. in THF), THF, CuI, ꢀ 208, 1 h; 85%. f) (tBu)Me2SiCl (TBSCl), 1H-Imidazole, dry
CH2Cl2, 4 h; 94%. g) 1) meta-Chloroperbenzoic acid (mCPBA), CH2Cl2, r.t., 4 h, 98%. 2) (S,S)-(salen)-
CoII · OAc (0.5 mol-%), dist. H2O (0.55 equiv), 08 to r.t., 16 h; 48% for 9, 48% for 9a. h) Tridec-1-yne,
BuLi, BF3 · Et2O, THF, ꢀ 788, 4 h; 95%. i) Bu4NF (TBAF) (1.0 m soln. in THF), THF, r.t., 2 h; 93%. j)
Pd/C (10 mol-%), H2, AcOEt, r.t., overnight; 65%.
Experimental Part
General. All the reagents and solvents were of reagent grade and used without further purification
unless otherwise stated. Technical-grade AcOEt and hexanes used for column chromatography (CC)
were distilled before use. THF, when used as solvent for the reactions, was freshly distilled from Na
benzophenone ketyl. All the reactions were performed under N2 in flame or oven dried glassware with
magnetic stirring. Column chromatography (CC): silica gel (SiO2, 60 – 120 mesh). Optical rotations:
Anton Paar MLP 200 modular circular digital polarimeter by using a 2-ml cell with a path length of 1 dm.
FT-IR Spectra: PerkinElmer 683 IR spectrophotometer; neat or as thin films in KBr optics; ˜n in cmꢀ1. 1H-
and 13C-NMR spectra: Bruker-Avance 300 instrument (300 and 75 MHz resp.) at r.t.; in CDCl3; d in ppm
rel. to Me4Si as internal standard, J in Hz. Low-resolution (LR) MS: Agilent Technologies LC-MSD trap
SL spectrometer; in m/z.
2-[4-(Benzyloxy)phenyl]ethanol (3). To a stirred soln. of 2 (5 g, 36.23 mmol) and K2CO3 (14.99 g,
108.6 mmol) in dry DMF (40 ml) was added BnBr (36.23 mmol, 4.3 ml) at 08 under N2, the mixture was
and stirred at r.t. for overnight. After completion of the reaction (TLC), the reaction was quenched with
H2O (50 ml) and the mixture was extracted with 50% AcOEt and hexane (3 ꢂ 30 ml), and the combined
org. extract was washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The
residue was purified by CC (AcOEt/hexane 2 :8) to afford pure 3 (8.09 g, 98%). White solid.

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Methyl 4-[4-(Benzyloxy)phenyl]butanoate (4). To a stirred soln. of 2-iodoxybenzoic acid (11.15 g,
39.82 mmol) in dry DMSO (8 ml) was added a soln. of 3 (6 gm, 26.54 mmol) in dry CH2Cl2 (50 ml) at r.t.,
and the mixture was stirred for 4 h. After completion of the reaction (TLC), the mixture was filtered
through Celite and diluted with H2O (25 ml) and extracted into CH2Cl2 (2 ꢂ 30 ml). The combined org.
layer was washed with brine (20 ml), dried (Na2SO4), and concentrated to give crude aldehyde, which
was used directly for the next step. To a stirred soln. of the aldehyde (4 g, 17.69 mmol) in dry CH2Cl2
(50 ml) was added Ph3PCHCOOMe (8.86 g, 26.54 mmol) at r.t., and the mixture was stirred for 6 h. After
completion of the reaction (TLC), the mixture was diluted with H2O (40 ml) and extracted with CH2Cl2
(3 ꢂ 25 ml). The combined org. extract was washed with brine, dried (Na2SO4), and concentrated in
vacuo. The residue was purified by CC (AcOEt/hexane 1:9) to afford an (E)/(Z)-mixture (85 :15; 4.59 g,
92%) as a colorless solid. To a cooled (08) soln. of the unsat. esters (3 g, 10.63 mmol) and NiCl2 · 6 H2O
(0.25 g, 1.063 mmol) in MeOH was added NaBH4 (0.4 g, 10.63 mmol) portionwise in open air (color
changed from turbid white to black), immediately checked by TLC. The reaction was complete within a
1 min and was quenched by addition of crushed ice, MeOH was evaporated in vacuo, and the residue was
extracted with AcOEt (2 ꢂ 15 ml). The combined org. extract was washed with brine, dried (Na2SO4) and
concentrated, and the residue was purified by CC (hexane/AcOEt 8 :2) to afford pure 4 (2.87 g, 95%).
Colorless solid. IR (neat): 2935, 2851, 1733, 1609, 1510, 1219, 1016. 1H-NMR (300 MHz, CDCl3): 7.49 –
7.30 (m, 5 H); 7.12 (d, J ¼ 8.3, 2 H); 6.93 (d, J ¼ 8.3, 2 H); 5.06 (s, 2 H); 3.68 (s, 3 H); 2.62 (t, J ¼ 7.5, 2 H);
2.35 (t, J ¼ 7.5, 2 H); 2.02 – 1.88 (m, 2 H).13C-NMR (75 MHz, CDCl3): 173.8; 157.0; 137.1; 133.6; 129.2;
128.4; 127.7; 127.3; 114.6; 69.9; 51.3; 34.1; 33.2; 26.5. ESI-MS: 285 ([M þ 1]þ).
(2S)-4-[4-(Benzyloxy)phenyl]butane-1,2-diol (5). To a cooled (ꢀ 788) soln. of 4 (2 g, 7.04 mmol) in
dry CH2Cl2 (20 ml) was added slowly DIBAL (25% in toluene, 4 ml, 7.04 mmol) for 10 min., and the soln.
was stirred for 1 h at the same temp. After completion of the reaction (TLC), the reaction was quenched
with sodium potassium tartrate soln. (10 ml) at ꢀ 788 and diluted with CH2Cl2, and the mixture was
stirred for 0.5 h. Then, the separated org. layer was concentrated under reduced pressure, and the residue
was purified by CC (hexane/AcOEt 8 :2) to afford pure aldehyde (1.64 g, 92%) as colorless liquid. To a
cooled (08) soln. of PhNO (0.42 g, 3.93 mmol) and d-proline (0.18 g, 1.57 mmol) in dry DMSO (10 ml)
was added the aldehyde (1 g, 3.93 mmol) in dry DMSO (15 ml). The mixture was stirred at r.t. for 0.5 h,
followed by the addition of EtOH (20 ml) and NaBH4 (0.59 g, 15.72 mmol) at r.t., and the mixture was
stirred for 2 h. After completion (TLC), the reaction was quenched with crushed ice, EtOH was
evaporated, and the resulting mixture was extracted with Et2O (3 ꢂ 10 ml). The combined org. phases
were dried (Na2SO4) and concentrated to give the crude aminooxy alcohol, which was directly used for
the next step without purification. To a cooled (08) soln. of the crude aminooxy alcohol in MeOH (15 ml)
was added CuSO4 · 5 H2O (0.29 g, 1.17 mmol), and the mixture was stirred at r.t. for overnight. After
completion of the reaction (TLC), MeOH was evaporated in vacuo, and then the mixture was filtered
through Celite and concentrated. The residue was purified by CC (hexane/AcOEt 7:3) gave 5 (0.696 g,
65%). Light-gray semisolid.
(2S)-2-{2-[4-(Benzyloxy)phenyl]ethyl}oxirane (6). To a cooled (0o) soln. of 5 (0.6 g, 2.20 mmol), a
cat. amount of Bu2SnO (5 mg), Et3N (0.91 ml, 6.61 mmol) in CH2Cl2 (20 ml), and TsCl (0.42 g,
2.20 mmol) were added and the mixture was stirred at r.t. for 4 h. After completion of reaction (TLC),
the mixture was diluted with H2O and extracted with CH2Cl2 (3 ꢂ 5 ml). The org. layer was washed with
brine and dried (Na2SO4), and the combined org. layer was concentrated. The residue was purified by CC
(hexane/AcOEt 7:3) to afford the tosylated compound as a viscous liquid (0.82 g, 88%). To a soln. of this
Ts compound (0.5 g, 1.17 mmol) in MeOH (10 ml) was added K2CO3 (0.34 g, 2.46 mmol) at r.t., and the
mixture was stirred for 1 h. After completion of the reaction (TLC), MeOH was evaporated, diluted with
H2O, and the mixture was extracted with Et2O (3 ꢂ 10 ml). The combined org. layer was dried (Na2SO4)
and concentrated, and the residue was purified by CC (hexane/AcOEt 8 :2) to give 6 (0.268 g, 90%).
Colorless oil.
(3S)-1-[4-(Benzyloxy)phenyl]hex-5-en-3-ol (7). CuI (0.17 g, 0.94 mmol) was gently heated under
vacuum and slowly cooled under N2, then dry THF (10 ml) was added. The resulting suspension was
cooled to ꢀ 208 and vinyl magnesium bromide (1m in THF, 1.8 ml, 1.88 mmol) was added at the same
temp. A soln. of 6 (0.24 g, 0.94 mmol) in dry THF (15 ml) was added, and the mixture was stirred at
ꢀ 208 for 1 h. After completion (TLC), the reaction was quenched with sat. aq. NH4Cl at ꢀ 208, and the

Helvetica Chimica Acta – Vol. 97 (2014)
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mixture was extracted with AcOEt (3 ꢂ 5 ml). The combined org. layer was washed with brine, dried
(Na2SO4) and concentrated, and the residue was purified by CC (hexane/AcOEt 8/2 (v/v)) to afford 7
(0.22 g, 85%). Colorless liquid.
({(3S)-1-[4-(Benzyloxy)phenyl]hex-5-en-3-yl}oxy)(tert-butyl)(dimethyl)silane (8). To a cooled (08)
soln. of 7 (0.2 g, 0.70 mmol) and 1H-imidazole (0.1 g, 1.48 mmol) in dry CH2Cl2 (5 ml) was added TBSCl
(0.117 g, 0.78 mmol), and the mixture was stirred at r.t. for 4 h. After completion of the reaction (TLC),
the mixture was diluted with H2O (10 ml) and extracted with CH2Cl2 (3 ꢂ 5 ml). The combined org. layer
was dried (Na2SO4) and concentrated, and the residue was purified by CC (hexane/AcOEt 9.5 :0.5) to
furnish pure 8 (0.26 g, 94%). [a]2D5 ¼ ꢀ8.0 (c ¼ 0.2, CHCl3). IR (neat): 2945, 2930, 1611, 1511, 1245, 1073,
773. 1H-NMR (300 MHz, CDCl3): 7.45 – 7.29 (m, 5 H); 7.09 (d, J ¼ 8.5, 2 H); 6.89 (d, J ¼ 8.6, 2 H); 5.87 –
5.77 (m, 1 H); 5.08 – 5.01 (m, 4 H); 3.78 – 3.72 (m, 1 H); 2.69 – 2.61 (m, 1 H); 2.56 – 2.49 (m, 1 H); 2.26 (t,
J ¼ 7.0, 2 H); 1.79 – 1.65 (m, 2 H); 0.91 (s, 9 H); 0.06 (s, 3 H); 0.06 (s, 3 H). 13C-NMR (75 MHz, CDCl3):
156.8; 137.1; 135.0; 134.9; 129.1; 128.4; 127.8; 127.4; 116.8; 114.6; 71.5; 69.9; 41.8; 38.8; 30.8; 25.8; 18.1; ꢀ
4.33; ꢀ 4.54. ESI-MS: 414 ([M þ NH4]þ).
({(2S)-4-[4-(Benzyloxy)phenyl]-1-[(2S)-oxiran-2-yl]butan-2-yl}oxy)(tert-butyl)dimethylsilane (9).
To a cooled (08) soln. of 8 (0.2 g, 0.50 mmol) in CH2Cl2 (5 ml) was added mCPBA (70%) (0.10 g,
0.60 mmol) and the mixture was stirred at r.t. for 4 h. The reaction was quenched by addition of sat.
Na2SO3 soln., and the mixture was extracted with CH2Cl2, washed with sat. aq. NaHCO3 soln., and dried
(Na2SO4). The org. phase was concentrated, and the residue was purified by CC (hexane/AcOEt 8 :2) to
give a recemic epoxide as an inseparable mixture (0.20 g, 98%). Colorless liquid. A mixture of (S,S)-
(salen)-CoII (0.004 g, 0.0072 mmol) and AcOH (0.012 ml, 0.001 mmol) in toluene (1 ml) was stirred in
open air at r.t. for 1 h. The solvent was removed under reduced pressure, and the brown residue was dried
in high vacuum. The racemic epoxide (0.15 g, 0.36 mmol) was added in one portion to the above residue
at 08 and H2O (0.03 ml, 0.20 mmol) was slowly added, and the mixture was stirred at r.t. for 16 h. After
completion of the reaction (TLC), the mixture was concentrated, and the residue was purified by CC to
afford 9 (0.072 g, 48%) and 9a (0.078 mg, 48%). Colorless liquids.
(3S,5R)-1-[4-(Benzyloxy)phenyl]-3-{[(tert-butyl)(dimethyl)silyl]oxy}nonadec-7-yn-5-ol (10). To a
cooled (ꢀ 788) soln. of 9 (0.05 g, 0.12 mmol) in dry THF (5 ml) was added BF3 · Et2O (0.03 ml,
0.26 mmol) dropwise, and the mixture was stirred for 0.5 h, followed by addition of BuLi in hexane
(2.5 m, 0.06 ml, 0.18 mmol) at ꢀ 788 and stirring for 4 h at same temp. After completion (TLC), the
reaction was quenched at ꢀ 788 by addition of sat. aq. NH4Cl soln., and the mixture was extracted with
Et2O (3 ꢂ 3 ml). The combined org. extract was washed with brine, dried (MgSO4), and concentrated,
and the residue was purified by CC (AcOEt/hexane 2 :8) to provide pure 10 (0.068 g, 95%). Colorless
liquid. [a]2D5 ¼ ꢀ25.0 (c ¼ 0.4, CHCl3). IR (neat): 3467, 3032, 2928, 2856, 1611, 1511, 1244, 1078. 1H-NMR
(300 MHz, CDCl3): 7.46 – 7.28 (m, 5 H); 7.08 (d, J ¼ 8.3, 2 H); 6.89 (d, J ¼ 8.6, 2 H); 5.04 (s, 2 H); 4.10 –
3.99 (m, 1 H); 3.99 – 3.91 (m, 1 H); 2.64 – 2.49 (m, 2 H); 2.39 – 2.28 (m, 2 H); 2.21 – 2.10 (m, 2 H); 1.86 –
1.46 (m, 4 H); 1.45 – 1.09 (m, 18 H); 0.97 – 0.82 (m, 12 H); 0.08 (s, 6 H). 13C-NMR (75 MHz, CDCl3):
157.0; 137.1; 134.4; 129.1; 128.5; 127.9; 127.4; 114.8; 82.9; 82.7; 70.0; 69.4; 67.4; 41.8; 40.6; 31.9; 31.0; 30.2;
29.3; 29.2; 29.0; 27.9; 27.7; 25.8; 22.7; 18.7; 17.9; 14.1; ꢀ 4.0; ꢀ 4.6. ESI-MS: 594 ([M þ 1]þ).
(3S,5R)-1-[4-(Benzyloxy)phenyl]nonadec-7-yne-3,5-diol (11). To a cooled (08) soln. of 10 ( 0.06 g,
0.10 mmol) in THF (2 ml) was added Bu4NF (0.03 ml, 0.15 mmol, 1.0 m soln. in THF) dropwise and the
mixture was stirred at r.t. for 2 h. The reaction was quenched with sat. aq. NH4Cl soln. (5 ml), and the
mixture was extracted with AcOEt (2 ꢂ 5 ml). The combined org. layer was washed with brine (10 ml),
dried (Na2SO4), and concentrated, and the residue was purified by CC (hexanes/AcOEt 70 :30) to give
pure 11 (0.044 g, 93%). Colorless white solid. [a]2D5 ¼ ꢀ23.7 (c ¼ 0.4, CHCl3). IR (KBr): 3379, 3072, 2952,
2931, 1612, 1513, 1249, 1092. 1H-NMR (300 MHz, CDCl3): 7.46 – 7.29 (m, 5 H); 7.12 (d, J ¼ 8.3, 2 H); 6.90
( d, J ¼ 8.6, 2 H); 5.04 (s, 2 H); 3.98 – 3.85 (m, 2 H); 2.76 – 2.59 (m, 4 H); 2.37 – 2.32 (m, 2 H); 2.16 (t, J ¼
7.1, 2 H); 1.85 – 1.68 (m, 3 H); 1.64 – 1.55 (m, 1 H); 1.52 – 1.44 (m, 2 H); 1.41 – 1.20 (m, 12 H); 0.89 ( t, J ¼
6.8, 3 H). 13C-NMR (75 MHz, CDCl3): 156.9; 137.0; 134.2; 129.2; 128.4; 127.8; 127.4; 114.7; 83.5; 75.5;
71.6; 71.4; 69.9; 41.9; 39.7; 31.8; 30.7; 29.6; 29.5; 29.5; 29.3; 29.1; 28.9; 28.8; 28.2; 22.6; 18.6; 14.1. ESI-MS:
501 ([M þ Na]þ).
(3S,5R)-1-(4-Hydroxyphenyl)nonadecane-3,5-diol (1). To a stirred soln. of 11 (0.02 g, 0.04 mmol) in
dry AcOEt (5 ml) was added Pd/C (10 mol-%; 0.0004 g, 0.004 mmol) at r.t., and the mixture was stirred

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Helvetica Chimica Acta – Vol. 97 (2014)
overnight. After completion of the reaction (TLC), the mixture was filtered on Celite, the emulsion was
concentrated, and the residue was purified by CC (AcOEt/hexane 6 :4) to afford pure 1 (0.010 g, 65%).
Colorless white solid. [a]2D5 ¼ ꢀ4.8 (c ¼ 0.25, MeOH). IR (KBr): 3334, 2931, 2863, 1644, 1219, 1072.
1H-NMR (300 MHz, CDCl3): 7.05 (d, J ¼ 7.5, 2 H); 6.75 (d, J ¼ 8.3, 2 H); 3.94 – 3.78 (m, 2 H); 2.76 – 2.57
(m, 2 H); 2.56 – 2.29 (br. s, 2 H); 1.85 – 1.67 (m, 2 H); 1.66 – 1.55 (m, 2 H); 1.54 – 1.40 (m, 2 H); 1.25 (s,
24 H); 0.87 (t, J ¼ 6.7, 3 H). 13C-NMR (75 MHz, CDCl3): 153.8; 133.8; 129.4; 115.2; 73.3; 72.4; 42.8; 39.8;
38.3; 31.9; 30.7; 29.68; 29.64; 29.59; 29.3; 25.3; 22.6; 14.1. HR-EI-MS: 415.3342 ([M þ Na]þ, C25H44NaO3þ ;
calc. 415.3329).
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Received June 14, 2013