Asymmetric syntheses of the sex pheromones of pine sawflies, their homologs and stereoisomers

Article abstract of DOI:10.1002/hlca.201200341

We describe efficient and flexible enantioselective syntheses of the active enantiomers of the pheromones of pine sawflies, including the species Diprion jingyuanensis, their homologs and, stereoisomers, as well as those identified from the Chinese species Diprion jingyuanensis, i.e., 126. A total of 48 compounds, including acetates 78-101 and propanoates 102-125, have been synthesized. Our general approach towards these compounds originated from the commercially available chirons diethyl (S)- and (R)-malates, as well as ethyl (R)-3-hydroxybutanoate. The Seebach asymmetric methylation was employed in a key step to control additional configuration. Copyright

Full text of DOI:10.1002/hlca.201200341

Helvetica Chimica Acta – Vol. 95 (2012)
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Asymmetric Syntheses of the Sex Pheromones of Pine Sawflies, Their
Homologs and Stereoisomers
by Jian-Feng Zhenga), Hong-Qiao Lana), Rui-Feng Yanga), Qi-Long Penga), Zhen-Hua Xiaoa),
Shi-Chuan Tuoa), Kong-Zhen Hua), Yong-Gang Xianga), Zhen Weia), Zhen Zhangb), and
Pei-Qiang Huang*a)
a) Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P.R. China
(e-mail: pqhuang@xmu.edu.cn)
b) The Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry,
Key Laboratory of Forest Protection of State Forestry Administration, Beijing 100091, P.R. China
Dedicated to Professor Dieter Seebach on the occasion of his 75th birthday
We describe efficient and flexible enantioselective syntheses of the active enantiomers of the
pheromones of pine sawflies, including the species Diprion jingyuanensis, their homologs and,
stereoisomers, as well as those identified from the Chinese species Diprion jingyuanensis, i.e., 126. A
total of 48 compounds, including acetates 78 – 101 and propanoates 102 – 125, have been synthesized. Our
general approach towards these compounds originated from the commercially available chirons diethyl
(S)- and (R)-malates, as well as ethyl (R)-3-hydroxybutanoate. The Seebach asymmetric methylation was
employed in a key step to control additional configuration.
Introduction. – Pine sawflies (Hymenoptera: Diprionidae) are common insects
found in the coniferous forests of Europe, Asia, and North America. Consisting of
more than 120 species, many of them are severe pests on conifers. Since the
identification of the acetate 1A and the propanoate 1P of 3,7-dimethylpentadecan-2-ol
(diprionol; 1; Fig.) as the sex pheromones of Neodiprion lecontei (North American
species) and Diprion similes (European species introduced to North America),
respectively [1], intensive studies have been devoted to the pheromones of pine
sawflies [2]. While only the free alcohol has been found in the females [3], the males
are attracted to the corresponding acetate or propanoate, which leads to the
assumption that the alcohol is stored as the sex pheromone precursor and then
esterified just before emission [1]. These precursors are basically long-chain 2-alcohols
with configurational, chain length, and Me-branching variations. Remarkable impact of
chirality and chain length on the behavioral activity was also noted as a common
phenomenon in the pheromones [4]. For example, while Neodiprion species use
(2S,3S,7S)-1A (acetate) or 1P (propionate) as the main pheromones, and (2S,3R,7R)-
1A or 1P as a synergist or inhibitor [2], Diprion similis contains (2S,3R,7R)-1P as the
main pheromone [5]. The shorter-chain homolog (2S,3R,7R)-dimethyltridecan-2-ol (2)
was found in the female European species Diprion pini and Microdiprion pallipes
[6a][6b], and in the Chinese species Diprion jingyuanensis as well [6c]. An even
shorter homolog, (2S,3R,9S)-3,9-dimethylundecan-2-ol (3), was isolated from the
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Figure. Structures of compounds 1 – 8. erythro-(2S,3S,7S)-1 and threo-(2S,3R,7R)-1 from Neodiprion
spp. and Diprion similis, threo-(2S,3R,7R)-2 from Neodiprion pini, threo-(2S,3R,9S)-3 from Diprion
nipponica, threo-(2S,3S,7S,11R)-4 from Microdiprion pallipes, threo-(2S,3R,7R,9S)-5 from Macrodiprion
nemoralis, threo-(2S,3R,7R)-6 and threo-(2S,3R,7R)-7 from G. pallida and N. sertifer, and 8 from N.
sertifer.
Japanese pine sawfly Diprion nipponica (Rohwer) [7]. The additional Me-branched
(2S,3S,7S,11R)-3,7,11-trimethyltridecan-2-ol (4) was found in Microdiprion pallipes
¤
(Fallen) [8], while (2S,3R,7R,9S)-3,7,9-trimethyltridecan-2-ol (5) was isolated from
the pine sawfly macrodiprion nemoralis (Hymenoptera: Diprionidae) [9]. In addition,
from female extracts of the pine sawflies N. sertifer and Diprion pini, 3,7-dimethylhex-
adecan-2-ol (6), 3,7-dimethyltetradecan-2-ol (7), and 3,7-dimethyldodecan-2-ol (8)
were identified as minor pheromone components [6b][10]. Incidentally, Me-branched
long-chain 2-alcohol substructure is also present in some bioactive natural products
such as cytotoxic butenolides [11].
In view of structural elucidation, identification of active components, and develop-
ment of selective methods for monitoring and controlling the populations of pine
sawflies, the enantioselective synthesis of the sex pheromones of pine sawflies has
attracted considerable attention. A number of methods [4 – 6] have been developed for
the asymmetric synthesis of diprionol (1) [6][12], its stereoisomers [7][13], and
homologs, which are due largely to Hedenstrçm and co-workers [3][6a][6b][8][9]
[10a][10b][12h][13c][13g][13i][13j][14a][14b], Tai and co-workers [5][7][12e][13a]
[13b], and Mori and co-workers [4][12b][12c][13d]. In a program aiming at the
monitoring of pine sawflies, we needed some homologs and all stereoisomers of pine
sawfly pheromones as diprionol esters. Consequently, we undertook the asymmetric
syntheses of these compounds as well as the pheromone identified from the Chinese
species Diprion jingyuanensis [15], and we report the results herein.
Results and Discussion. – Our synthetic plan is outlined in Scheme 1, which involves
the use of diethyl (S)-malate ((S)-9), diethyl (R)-malate ((R)-9), and ethyl (R)-3-

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Scheme 1
hydroxybutanoate ((R)-10) as the chirons for the construction of all stereogenic centers
of all target pheromone components, their homologs and stereoisomers 78 – 125.
erythro-Segment A, (2S,3S)-11, was synthesized from diethyl (S)-malate according
to our previously established method [16], which was based on the Seebach asymmetric
methylation method [17]. Following the same procedure, (2R,3R)-11 was prepared in
five steps and 41% overall yield from diethyl (R)-malate (Scheme 2).
Scheme 2
For the syntheses of threo-diastereoisomers (2S,3R)-11 and (2R,3S)-11, inexpensive
and easily available C4 building block ethyl (R)-hydroxybutanoate ((R)-10; Scheme 3)
was used as the only starting enantiomer. Thus, successive treatment of (R)-10 with
lithium diisopropylamide (LDA) and MeI gave the desired C(2)-methylated product

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(2R,3R)-18 and its diastereoisomer in a 23 :1 ratio. The OH group in (2R,3R)-18 was
protected (3,4-dihydro-2H-pyran (DHP), TsOH, CH2Cl2), and the resulting tetrahy-
dropyran-2-yl (THP)-protected hydroxy ester was reduced with LiAlH4 (LAH) to give
compound (2S,3R)-19 in 79% overall yield. Tosylation of (2S,3R)-19 (TsCl, Et3N,
CH2Cl2, ꢀ 208, 3 h; r.t., 36 h) gave (2S,3R)-11 in 86% yield (Scheme 3).
Scheme 3
To prepare the other enantiomer, (2R,3S)-11, (R)-10 was converted to (S)-10 by a
two-step procedure, which involved mesylation (MsCl, Et3N, CH2Cl2, 96%) and a SN2
reaction (CaCO3, H2O) [18] leading to an inversion of configuration. Following the
procedure described for its enantiomer (R)-10, (S)-10 was converted to (2R,3S)-11 (via
the intermidates (2S,3S)-18 and (2R,3S)-19) in four steps with an overall yield of 50%
(Scheme 4).
Scheme 4
After securing the synthesis of all four stereoisomers of fragment A [14], we next
focused on the syntheses of six homologs of BC fragments: namely both enantiomers of
three BC fragments, 1-bromo-3-methylheptane (12), 1-bromo-3-methylnonane (13),
and 1-bromo-3-methylundecane (14). Previously, we synthesized BC fragments
starting from diethyl (S)- and (R)-malate [16]. As an alternative approach, (R)-10
was used as a chiral starting material for the synthesis of BC fragments. Thus, (R)-10
was transformed to toluene-4-sulfonate (R)-23 by reduction with LAH (yield 97%),
t
which, upon chemoselective protection of the primary OH group with BuMe2SiCl
(TBSCl) (1H-imidazole, THF, 24 h), followed by tosylation (TsCl, pyridine (Py),
CH2Cl2), afforded (R)-23 in 60% yield from (R)-21a. CuI-Promoted C,C coupling
reactions of (R)-23 with butyl, hexyl, and octyl magnesium bromide, gave, via the SN2
reaction, (R)-24, (R)-25, and (R)-26 in 86, 86, and 86% yield, respectively. Silyl ethers

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(R)-24, (R)-25, and (R)-26 were converted to the corresponding bromides (R)-12, (R)-
13, and (R)-14 (Ph3P, Br2, CH2Cl2, r.t.) in one pot. The overall yields from (R)-10 (five
steps) were 38, 43, and 46%, respectively (Scheme 5).
Scheme 5
The syntheses of (S)-enantiomers of 12 – 14 started with (S)-10, which was
converted to (S)-12, (S)-13, and (S)-14, respectively, according to a similar procedure
described for their (R)-enantiomers (Scheme 5).
We next turned our attention to the coupling reaction between fragments A and
BC. Thus, Cu-catalyzed coupling of the Grignard reagent (S)-27, prepared in situ from
bromide (S)-12, with toluene-4-sulfonate (2S,3S)-11, furnished the desired coupling
product 30. The crude product, without purification, was subjected to acidic conditions
to give the alcohol 54 in 50% yield. Following the procedure described for alcohol 54,
alcohols 55 – 77 were obtained in 50 – 77% yields. The alcohols 54 – 77 were then
converted to acetates 78 – 101 and propionates 102 – 125, respectively, by acylation
(Scheme 6).
Finally, we set out to synthesize C(7)-epimeric mixture of the sex pheromone of
Diprion jingyuanensis ((2S,3R,7R,S)-3,7-dimethylpentadecan-2-yl propanoate; 126)
(Scheme 7). The syntheses of the two diastereoisomers, (2S,3R,7R)-102 and
(2S,3R,7S)-108, have been described in Scheme 6. In light of the finding that both
diastereoisomers were the sex pheromonal components of Diprion jingyuanensis, it is
desirable to adopt a simpler method to prepare the diastereoisomer mixture 126
starting from the racemic butane-1,3-diol ((ꢁ)-21). To this end, racemic (ꢁ)-13 was
synthesized in five steps and 50% overall yield from (ꢁ)-21 (Scheme 5). The racemic
bromide (ꢁ)-13 was converted to its corresponding Grignard reagent (ꢁ)-28
(Scheme 6), which was coupled with (2S,3R)-11 to yield the desired C-atom skeleton.
The coupled product was then converted to 126 via successive deprotection and

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Scheme 6
Scheme 7
esterification. The overall yield of 126 from (2S,3R)-11 was ca. 60%, and the purity of
the product was > 95%.
Conclusions. – In summary, we developed an efficient and flexible methodology for
the total syntheses of 48 pheromone related compounds, including active enantiomers
of the pheromones of pine sawflies, their homologs, and stereoisomers. The general
approach utilizes commercially available chirons diethyl (S)- and (R)-malate, as well as
ethyl (R)-3-hydroxybutanoate, to assemble the required stereogenic centers. Sex
pheromone identified from the Chinese species Diprion jingyuanensis, (2S,3R,7R,S)-
3,7-dimethylpentadec-2-yl propanoate (126), was also synthesized from racemic
butane-1,3-diol (21) and ethyl (R)-3-hydroxybutanoate.
Experimental Part
General. THF was distilled prior to use from sodium benzophenone ketyl under N2. CH2Cl2 was
distilled over P2O5 under N2. Silica gel (SiO2; 300 – 400 mesh) was used for flash column chromatography

Helvetica Chimica Acta – Vol. 95 (2012)
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(FC), eluting (unless otherwise stated) with AcOEt/petroleum ether (PE, 60 – 908) mixtures. Optical
rotations: Perkin-Elmer 341 automatic polarimeter. IR Spectrum: Nicolet Avatar 360 FT-IR spectro-
photometer; ˜n in cmꢀ1. NMR Spectra: Bruker 400 spectrometer in CDCl3 (1H: 400 and 13C: 100 MHz); d
in ppm rel. to Me4Si as internal standard, J in Hz. MS: Bruker Dalton Esquire 3000 plus LC/MS apparatus
(ESI, direct injection); in m/z. HR-MS: Shimadzu LC/MS-IT-TOF apparatus; in m/z.
Synthesis of Sex Pheromone 126 of Chinese Species Diprion jingyuanensis. Ethyl (2S,3S)-3-Hydroxy-
2-methylbutanoate ((2S,3S)-18). To a soln. of LDA (prepared under N2 by addition of BuLi (93 ml of
2.5m in hexane, 232.5 mmol) to a soln. of (i-Pr)2NH (32.5 ml, 232.5 mmol) in anh. THF (70 ml; at ꢀ 788
and stirred at 08 for 30 min) was added hydroxy ester (S)-10 (13.99 g, 105.7 mmol) within 10 min at
ꢀ 508. After stirring for 30 min, MeI (45.01 g, 317.1 mmol) and hexamethylphosphoramide (HMPA)
(30 ml, 169.1 mmol) were added. After stirring at ꢀ 508 for another 10 min and at 08 for 10 min, the
reaction was quenched with sat. aq. NH4Cl soln., and the aq. layer was extracted with AcOEt (3 ꢂ 50 ml).
The combined org. phases were washed with brine, dried (Na2SO4), filtered, and concentrated under
reduced pressure. The residue was purified by FC (SiO2; AcOEt/PE 1:8) to afford (2S,3S)-18 (11.4 g,
73%). Colorless oil. [a]2D0 ¼ þ19.4 (c ¼ 1.0, CHCl3) ([19a]: [a]2D0 ¼ þ14.8 (c ¼ 1.83, CHCl3); [19b]: [a]2D0
¼
þ23.3 (c ¼ 1.24, CHCl3)). IR (film): 3436, 2971, 2930, 1731, 1458, 1375, 1184, 1109, 1042. 1H-NMR
(400 MHz, CDCl3): 1.19 (d, J ¼ 7.2, 3 H); 1.23 (d, J ¼ 6.4, 3 H); 1.28 (t, J ¼ 7.2, 3 H); 2.40 – 2.42 (m, 1 H);
2.81 (s, 1 H); 3.90 (qd, J ¼ 6.4, 6.4, 1 H); 4.1 (q, J ¼ 7.2, 2 H). 13C-NMR (100 MHz, CDCl3): 14.2; 14.3;
20.9; 47.2; 61.0; 69.8; 177.0. ESI-MS: 169 ([M þ Na]þ).
(2R,3S)-2-Methyl-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)butan-1-ol ((2R,3S)-19) [20]. To a soln. of
(2S,3S)-18 (8.59 g, 58.8 mmol) and TsOH (cat.) in anh. CH2Cl2 (50 ml) was added dropwise
dihydropyran (14.8 g, 176.4 mmol) with stirring at r.t. After stirring for 4 h, the mixture was washed
successively with sat. aq. NaHCO3 soln. and brine, and dried (anh. Na2SO4). After filtering and
concentrated under reduced pressure, the crude product was employed for the next step without further
purification. To a stirred and ice-cooled suspension of LiAlH4 (4.40 g, 118 mmol) in anh. THF (150 ml)
was added dropwise the above-mentioned ester in anh. THF (20 ml). The mixture was stirred overnight
at 408, cooled to r.t., and the reaction was quenched by successive addition of H2O (4.4 ml), a 10% NaOH
aq. soln. (6.6 ml), and H2O (12 ml). The resulting mixture was filtered through Celite. The residue was
refluxed for 3 h in EtOH (100 ml), and then filtered through Celite. The combined filtrates were
concentrated, and the residue purified by FC (AcOEt/PE 1:1) to afford (2R,3S)-19 (8.85 g, 75%).
Colorless oil. [a]D20 ¼ þ32.4 (c ¼ 1.0, CHCl3). IR (film): 3439, 2941, 1453, 1379, 1116, 1076, 1024. ESI-MS:
188 ([M þ H]þ), 210 ([M þ Na]þ).
(2R,3S)-2-Methyl-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)butyl 4-Methylbenzenesulfonate ((2R,3S)-
11) [7b]. To a soln. of (2R,3S)-19 (8.30 g, 44.1 mmol) and 4-(dimethylamino)pyridine (DMAP) in anh.
CH2Cl2 (2 ml) was added dropwise pyridine (7.1 ml, 88.2 mmol), then a soln. of TsCl (12.6 g, 66.2 mmol)
in anh. CH2Cl2 was added dropwise on an ice bath. After stirring at r.t. for 16 h, the reaction was
quenched by adding H2O on an ice bath until the solid dissolved. The aq. layer was extracted with CH2Cl2
(3 ꢂ 20 ml). The combined org. phases were washed with brine (5 ml), dried (anh. Na2SO4), filtered, and
concentrated under reduced pressure. The residue was purified by FC (AcOEt/PE 1:8) to afford
(2R,3S)-11 (12.4 g, 86%). Pale yellow oil. [a]2D0 ¼ þ14.5 (c ¼ 1.1, CHCl3). IR (film): 2941, 1598, 1495,
1454, 1361, 1033. ESI-MS: 365 ([M þ Na]þ).
4-{[(tert-Butyl)(dimethyl)silyl]oxy}butan-2-ol ((ꢁ)-22) [21]. To an ice-bath cooled soln. of butane-
1,3-diol ((ꢁ)-21; 20.4 g, 226 mmol), 1,4-imidazole (37.0 g, 543 mmol), and DMAP (cat.) in anh. THF
(300 ml) was added a soln. of tBuMe2SiCl (TBSCl; 34.0 g, 226 mmol) in anh. THF (100 ml). The mixture
was stirred at r.t. for 24 h and then concentrated under reduced pressure. The resulting mixture was
diluted with H2O (20 ml) and extracted with CH2Cl2 (3 ꢂ 20 ml). The combined org. phases were washed
with brine and dried (Na2SO4). After filtration and concentration under reduced pressure, the residue
was directly used in next reaction. A sample was purified by FC (AcOEt/PE 1:20) to give (ꢁ)-22.
Colorless oil. IR (film): 3415, 2957, 2930, 2858, 1470, 1256, 1089, 836, 776. 1H-NMR (400 MHz, CDCl3):
0.07 (s, 6 H); 0.89 (s, 9 H); 1.20 (d, J ¼ 6.4, 3 H); 1.58 – 1.77 (m, 2 H); 3.41 (s, 1 H); 3.81 – 3.88 (m, 2 H);
4.00 – 4.20 (m, 1 H). 13C-NMR (100 MHz, CDCl3): ꢀ 5.6; ꢀ 5.5; 18.1; 23.3; 25.7; 25.8; 40.0; 62.8; 68.3.
ESI-MS: 205 ([M þ H]þ), 227 ([M þ Na]þ).

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4-{[(tert-Butyl)(dimethyl)silyl]oxy}butan-2-yl 4-methylbenzenesulfonate ((ꢁ)-23) [22]. To a soln. of
crude (ꢁ)-22 and DMAP (cat.) in pyridine (33 ml, 410 mmol) was added slowly TsCl (47.0 g, 246 mmol)
at 08. After stirring overnight at r.t., 1H-imidazole (12.0 g, 176 mmol) was added. Then, an aq. HCl soln.
(2n, 70 ml) was added, and the mixture was extracted with CH2Cl2 (4 ꢂ 60 ml). The org. layers were
washed successively with a sat. aq. soln. of NaHCO3 (5 ml) and brine (5 ml), dried (anh. Na2SO4),
filtered, and concentrated under reduced pressure. The residue was purified by FC (AcOEt/PE 1:20) to
give (ꢁ)-23 (56.6 g, 70% over two steps). Colorless oil. IR (film): 2954, 2930, 2884, 2851, 1599, 1470, 1360,
1177, 1099. 1H-NMR (400 MHz, CDCl3): 0.05 (s, 6 H); 0.86 (s, 9 H); 1.24 (d, J ¼ 6.4, 3 H); 1.70 – 1.88 (m,
2 H); 2.48 (s, 3 H); 3.62 – 3.77 (m, 2 H); 4.84 – 4.92 (m, 1 H); 7.37 (d, J ¼ 8.0, 2 H); 7.83 (d, J ¼ 8.0, 2 H).
13C-NMR (100 MHz, CDCl3): ꢀ 5.6; ꢀ 5.5; 18.1; 21.0; 21.6; 25.8; 25.8; 25.8; 39.5; 58.8; 78.1; 127.7; 129.7;
134.5; 144.4. ESI-MS: 359 ([M þ H]þ), 381 ([M þ Na]þ).
(tert-Butyl)(dimethyl)[(3-methylnonyl)oxy]silane ((ꢁ)-25). A soln. of hexyl magnesium bromide in
THF was prepared from hexyl bromide (40 ml, 371 mmol) and Mg (9.80 g, 408 mmol) in dry THF
(146 ml). The soln. was chilled to ꢀ 788, to which a soln. of (ꢁ)-23 (18.0 g, 50.2 mmol) in THF (200 ml)
and CuI (500 mg) were added. The mixture was gradually warmed to r.t. After stirring overnight at r.t.,
the mixture was poured into an ice-cooled aq. NH4Cl soln. (40 ml) and extracted with CH2Cl2 (4 ꢂ
100 ml). The Et2O soln. was successively washed with aq. NaHCO3 soln. and brine, dried (anh.
Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by FC (PE) to give
(ꢁ)-25 (11.8 g, 86%). Colorless oil. IR (film): 2956, 2928, 2857, 1462, 1379, 1254, 1100. 1H-NMR
(400 MHz, CDCl3): 0.05 (s, 6 H); 0.84 – 0.91 (m, 15 H); 1.09 – 1.12 (m, 1 H); 1.21 – 1.34 (m, 10 H); 1.47 –
1.58 (m, 2 H); 3.58 – 3.68 (m, 2 H). 13C-NMR (100 MHz, CDCl3): ꢀ 5.3; ꢀ 5.3; 14.1; 18.3; 19.8; 22.7;
26.0; 26.0; 26.0; 26.9; 29.5; 29.6; 31.9; 37.1; 40.0; 61.6. HR-ESI-MS: 295.2432 ([M þ Na]þ, C16H36NaOSiþ;
calc. 295.2432).
1-Bromo-3-methylnonane ((ꢁ)-13) [23]. To a freshly prepared suspension of Ph3P/Br2 in CH2Cl2
(180 ml) was added (ꢁ)-25 (10.5 g, 43.1 mmol) in CH2Cl2 (50 ml). After stirring at r.t. for 24 h, a sat. aq.
soln. of NaHCO3 (20 ml) and a sat. aq. soln. of Na2S2O4 (10 ml) were added successively. The mixture was
extracted with CH2Cl2 (3 ꢂ 30 ml). The org. layers were washed with a sat. aq. soln. of NaHCO3 (5 ml)
and brine (5 ml), dried (anh. Na2SO4), filtered, and concentrated under reduced pressure to get a mash.
The mixture was filtered through Celite (PE). The org. layer was concentrated under reduced pressure.
The residue was purified by FC (PE) to give (ꢁ)-13 (8.2 g, 86%). Colorless oil. IR (film): 2957, 2926,
1
2856, 1462, 1379, 1254, 1213. H-NMR (400 MHz, CDCl3): 0.86 – 0.93 (m, 6 H); 1.10 – 1.30 (m, 10 H);
1.60 – 1.71 (m, 2 H); 1.83 – 1.92 (m, 1 H); 3.37 – 3.49 (m, 2 H). 13C-NMR (100 MHz, CDCl3): 14.1; 19.0;
22.7; 26.8; 29.5; 31.7; 31.9; 32.2; 36.5; 40.1.
(2S,3R,7R,S)-3,7-Dimethyltridecan-2-ol (127) [12i]. Grignard reagent (ꢁ)-28 was prepared from Mg
(962 mg, 40.1 mmol) and (ꢁ)-13 (4.05 g, 18.4 mmol) in THF (18 ml). To a cold soln. (ꢀ 788) of the above-
mentioned Grignard reagent (4.5 ml) was added a soln. of (2R,3S)-11 (550 mg, 1.61 mmol) in THF (2 ml)
and CuI (cat.). The mixture was allowed to warm up to 08 and kept at this temp. for 3 h. After stirring
overnight at r.t., the reaction was quenched with a sat. aq. soln. of NH4Cl (2 ml) and H2O (2 ml). The org.
layer was separated, and the aq. layer was extracted with Et2O (3 ꢂ 3 ml). The combined org. layers were
washed with brine, dried (anh. Na2SO4), filtered, and concentrated under reduced pressure. The residue
was treated with TsOH (cat.) in MeOH (20 ml) at 508. After stirring for 1.5 h, the mixture was
concentrated under reduced pressure. The residue was purified by FC (SiO2; AcOEt/PE 1:15) to
afford 127 (282 mg, 77%). Colorless oil. [a]2D0 ¼ þ13.1 (c ¼ 2.29, hexane). IR (film): 3360, 2959, 2926,
2857, 1587, 1463, 1378, 1096, 1001. 1H-NMR (400 MHz, CDCl3): 0.82 – 0.92 (m, 9 H); 1.02 – 1.54 (m,
22 H); 3.63 – 3.72 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 14.1; 14.5; 14.5; 19.3; 19.4; 19.6; 19.8; 22.7;
24.7; 24.7; 27.0; 27.1; 29.7; 32.0; 32.7; 32.8; 32.8; 32.9; 37.0; 37.2; 37.3; 37.4; 40.0; 40.1; 71.8; 71.8. ESI-MS:
251 ([M þ Na]þ).
(2S,3R,7R,S)-3,7-Dimethyltridecan-2-yl Propanoate (126) [12i]. Propanoic anhydride (208 mg,
1.6 mmol) was added to an ice-cooled soln. of 127 (273 mg, 1.2 mmol) in anh. pyridine (0.5 ml). The
mixture was left overnight at r.t. and diluted with Et2O (5 ml). The soln. was washed successively with a
5% aq. soln. of HCl, H2O, sat. NaHCO3 (aq.), and brine, dried (MgSO4), filtered, and concentrated
under reduced pressure. The residue was purified by FC (AcOEt/PE 1:30) to give 126 (327 mg, 95%).
Colorless oil. [a]2D0 ¼ þ4.9 (c ¼ 2.43, hexane). IR (film): 2958, 2927, 2857, 1738, 1463, 1378, 1274, 1193,

Helvetica Chimica Acta – Vol. 95 (2012)
1807
1083. 1H-NMR (400 MHz, CDCl3): 0.80 – 0.93 (m, 9 H); 1.00 – 1.42 (m, 23 H); 1.61 – 1.71 (m, 1 H); 2.30
(q, J ¼ 7.6, 2 H); 4.77 – 4.87 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 9.3; 14.1; 14.6; 14.6; 15.8; 15.9; 19.6;
19.7; 22.7; 24.5; 27.0; 27.0; 28.0; 29.7; 32.0; 32.7; 32.7; 32.9; 32.9; 37.0; 37.1; 37.2; 37.3; 74.0; 74.1; 174.1. ESI-
MS: 307 ([M þ Na]þ).
The authors are grateful to the National Basic Research Program (973 Program) of China (Grant No.
2010CB833200), the NSF of China (20832005, 21072160), and the Natural Science Foundation of Fujian
Province of China (No. 2011J01054) for financial support. We are grateful to Prof. Dr. L.-F. Xie for
valuable discussion.
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Received July 3, 2012