A general asymmetric synthesis of (R)-Matsutakeol and flavored analogs

Article abstract of DOI:10.3390/molecules22030364

An efficient and practical synthetic route toward chiral matsutakeol and analogs was developed by asymmetric addition of terminal alkyne to aldehydes. (R)-matsutakeol and other flavored substances were feasibly synthesized from various alkylaldehydes in high yield (up to 49.5%, in three steps) and excellent enantiomeric excess (up to >99%). The protocols may serve as an alternative asymmetric synthetic method for active small-molecule library of natural fatty acid metabolites and analogs. These chiral allyl alcohols are prepared for food analysis and screening insect attractants.

Full text of DOI:10.3390/molecules22030364

molecules
Article
A General Asymmetric Synthesis of (R)-Matsutakeol
and Flavored Analogs
Jia Liu , Honglian Li , Chao Zheng , Shichao Lu , Xianru Guo , Xinming Yin , Risong Na 1,4,*,
1
1
2
1
1
1
3
,
4
Bin Yu * and Min Wang
1
Collaborative Innovation Center of Henan Grain Crops, National Key Laboratory of Wheat and Maize Crop
Science, College of Plant Protection, Henan Agricultural University, Wenhua Road No. 95,
Zhengzhou 450002, China; ljia198346@163.com (J.L.); honglianli@sina.com (H.L.);
1
5517151076@163.com (S.L.); guoxianru@126.com (X.G.); xinmingyin@hotmail.com (X.Y.)
2
Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, School of Chemistry and
Chemical Engineering, Hainan Normal University, Haikou 57115, China; zhengchaoustc@163.com
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
School of Sciences, China Agricultural University, Beijing 100193, China; wangmincau@outlook.com
Correspondence: nrs@henau.edu.cn or risongna@163.com (R.N.); zzuyubin@hotmail.com (B.Y.);
Tel.: +86-371-6355-8170 (R.N.)
3
4
*
Academic Editor: Rafael Chinchilla
Received: 18 January 2017; Accepted: 24 February 2017; Published: 27 February 2017
Abstract: An efficient and practical synthetic route toward chiral matsutakeol and analogs was
developed by asymmetric addition of terminal alkyne to aldehydes. (R)-matsutakeol and other
flavored substances were feasibly synthesized from various alkylaldehydes in high yield (up to 49.5%,
in three steps) and excellent enantiomeric excess (up to >99%). The protocols may serve as
an alternative asymmetric synthetic method for active small-molecule library of natural fatty acid
metabolites and analogs. These chiral allyl alcohols are prepared for food analysis and screening
insect attractants.
Keywords: (R)-matsutakeol; general method; asymmetric catalysis; mushrooms; flavored analogs
1
. Introduction
Many natural unsaturated alcohols 1–6 (Figure 1) are very important fatty acid metabolites
derived from fungi [1] and plants [2]. These substances have been found in nutrient, pharmaceutical,
and agricultural use, as their structural diversity and variety of biological activities. For examples,
the chiral allyl alcohols 6a
supplements which are widely used in the food industry [
matsutake [ ], has been found to possess antitumor properties [
spore germination and mushroom and plant development have also been discovered [
R)-matsutakeol 6a and its analogs are widely used in insecticidal compositions as effective attractants
for some harmful hematophagous insects [ ]. In particular, the enantioselectivity and chiral
–
c
(Figure 1) are a class of important flavor substances and dietary
]. (R)-matsutakeol 6a isolated from
]. Effects of inhibition on fungal
]. Recently,
3–5
6
3
7
(
8,9
configuration of the compounds directly determined biological activities such as smell and taste [10].
Inspired by potential applications above, great attention has been paid to preparation of
compounds
6 with high enantioselectivity and structural diversity [11–19]. To take (R)-matsutakeol 6a
as an example, in 1987, 6a and its enantiomer were obtained by Helmchen through the asymmetric
retro Diels-Alder reaction [11]. In the same year, Takano prepared the (R)-matsutakeol by using
the optically active starting material of (R)-epichlorohydrin [12]. In 1988, Kitamura obtained
(R)-matsutakeol (21% ee) via kinetic resolution of racemic allylic alcohols [13]. Oppolzer developed
an enantioseletive synthesis of (R)-matsutakeol (96% ee) by catalytic asymmetric addition of
Molecules 2017, 22, 364; doi:10.3390/molecules22030364
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divinylzinc to hexanal [14]. In 2005, a chiral resolution of racemic matsutakeol was conducted
using (S)-(+)-2-methoxy-2-(1-naphthyl) propionic acid (M NP acid) by Kusuda [15]. In addition,
α
various enzymatic kinetic resolution and enzyme-catalyzed reactions have also been used in
preparation of chiral matsutakeol. In 2010, Bisogno developed an efficient oxidoreductase-catalyzed
system to obtain (R)-matsutakeol in 86% ee [16]. Recently, Rej prepared (S)-matsutakeol as
an important intermediate, by ME-DKR (metal enzyme combined dynamic kinetic resolution) of
(
1
±
)-oct-1-en-3-ol [17
,18]. In 2016, Lee developed a synthetic strategy towards (S)-matsutakeol in
0 steps from inexpensive, natural (2S,3S)-D-tartaric acid with 32% yield [19].
Figure 1. Natural unsaturated alcohols derived from fungi and plant.
In summary, matsutakeol could be prepared by chiral pool synthesis [19], enzymatic kinetic
resolution [17,18], and asymmetric synthesis [14] (Scheme 1). Although, several synthetic routes
have been developed, there is still a lack of efficient method for obtaining a highly enantioselective
allyl alcohols library in screening for flavors or attractants. Compared to asymmetric synthesis
(
(
Scheme 1, method 3), the structural diversity of the reaction products is limited by chiral sources
Scheme 1, method 1) [19], and the effect of enzymatic reaction (Scheme 1, method 2) is constrained
by stability and activity of enzymes [17
,18]. By retro-synthetic analysis, the chiral olefinic alcohol
6
could be formed from propargyl alcohol 12, and chiral propargyl alcohol 12 can be synthesized
from the corresponding methyl propiolate 13 (Scheme 1, method 3). Highly enantioselective methyl
propiolate (S)-13 is obtained by Zn-catalyzed asymmetric addition of terminal alkynes 15 to various
aldehydes 14. This reaction has been widely studied (Scheme 2) [20
ligands are applied, such as (R,R)-ProPhenol 16a 24 39], (R)-BINOL 17a, and its derivatives [28
-Sulfonamide Alcohol 18 31 32], Wolf’s ligand 19 41], and Wang’s ligand 20 (our previous group
–
50], in which numerous chiral
[
,
,
30],
β
[
,
[
research) [33]. Among the numerous catalysts, (R,R)-ProPhenol 16a and (R)-BINOL 17a are readily
available and well-established [20–50].
Scheme 1. Retro-synthetic analysis of matsutakeol and its natural analogs reported in the latest literature.

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Scheme 2. Zn-catalyzed asymmetric direct addition of terminal alkynes to aldehydes.
2
. Results and Discussion
Herein we report the asymmetric synthesis of (R)-matsutakeol and its natural analogs. In our
previous work (Scheme 2) [50], the reaction conditions were optimized for the stereoselective addition
of methyl propiolate to aliphatic aldehydes, and the highest enantiomeric excess values (97%–99% ee)
of (S)-alkynol product 13 were afforded by (R,R)-ProPhenol/Zn complex. It is developed in a general
strategy toward the total synthesis of C17 polyacetylenes such as virol A and virol C [50].
On the basis of previous work [24,25,39,50], we expanded substrate scope of the (S,S)-ProPhenol-
catalyzed direct asymmetric addition, affording the corresponding (R)-configured propargyl alcohols 13
in moderated yields (63%–73%) and with excellent enantioselectivities (97%–99% ee) (Table 1). Thus,
we developed a general method with two steps to obtain highly enantioselective allyl alcohol flavors.
Table 1. Synthesis of chiral alkynol units 13a
methyl propiolate to aliphatic aldehydes .
–
e
of C17 polyacetylenes via the asymmetric addition of
a
a
Unless otherwise noted, the reaction was carried out on a 1.0 mmol scale in toluene (1.0 mL); b Isolated yields;
The ee values were determined by chiral HPLC.
c
As shown in Scheme 3, treatment of compounds 13a–c with LiOH in THF gave the corresponding
carboxylic acid intermediates [38], which were then subjected to the CuCl-catalyzed decarboxylation
directly, producing the chiral propargyl alcohols 12a–c in good yields (83%–86%) and without loss of

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enantio-selectivity (99% ee). Reduction of compounds 12a
–c
with NaBH in the presence of Ni(OAc)
4
2
gave (R)-matsutakeol 6a and its natural analogs 6b and 6c in good yields (82%–85%) [51]. However,
the ee values of (R)-matsutakeol and analogs could not be directly resolved by HPLC on a chiral column
conveniently. Therefore, derivatization of compounds 6a
moiety to the natural molecules, directly afforded compounds 21a
93%–95%) and 99% ee.
–
c
through introducing 3,5-dinitrobenzoyl
–
c
in nearly quantitative yields
(
Scheme 3. Total synthesis of (R)-matsutakeol and its natural analogs 6a
–
c
by using (S,S)-ProPhenol
◦
(
(
Scheme 1, Method 3). Reagents and conditions: (a) (i) LiOH, THF, 0~25 C, 1 h; (ii) CuCl, CH CN,13 h;
3
◦
◦
b) Ni(OAc) , NaBH , EDA, EtOH, 0~25 C; (c) 3,5-Dinitrobenzoyl chloride, Et N, 0~25 C, overnight;
2
4
3
*
The ee value is determined by HPLC on a chiral column after derivatization.
The BINOL-ZnEt -Ti (IV) complex catalyzed asymmetric addition of trimethylsilylacetylene to
2
the aliphatic aldehydes was well developed by Pu’s group [20,22,34]. It is also a practical approach
for providing chiral acetylene alcohols. In the optimization procedure, to increase the catalyst
loading of (R,R)-ProPhenol 16b (entry 1 and 2) and to reduce the temperature (entry 2 and 3) could
0
slightly improve the ee value, of product 13a (Table 2, entry 2, 72% yield, 78% ee). Compared to
◦
addition catalyzed by (R,R)-ProPhenol 16b, almost no product was detected at
entry 4). The reaction yields and optical yields were increased on increasing the amount of BINOL
Table 2, entry 5–7). When the amount of BINOL was increased to 60%, there was no obvious
−
10 C (Table 2,
(
improvement in yield and ee value (entry 7, 67% yield, 81 % ee). Compared to the reaction catalyzed
by (R,R)-ProPhenol 16b (entry 2, 72% yield, 78% ee and entry 3, 74% yield, 76% ee), the asymmetric
addition of trimethylsilylacetylene by using BINOL as chiral ligand could be smoothly carried out at
room temperature, affording higher ee value and almost the same yield (entry 6, 71% yield, 80% ee).
0
Table 2. Screening of reaction conditions and ligands of asymmetric addition of 15 with 14a.
◦
Yield/% c
ee/% d
Entry
Ligand
Ligand/%
Temp/ C
1 a
16b
16b
16b
17b
17b
17b
17b
20
40
40
40
20
40
60
−10
−10
25
70
72
74
–
52
71
67
75
78
76
–
70
80
81
a
2
3
4
5
a
b
−10
b
25
b
6
25
25
b
7
a
The reaction was carried out on a 0.5 mmol scale in toluene (0.5 mL), the organozinc reagent was Me
The reaction was carried out on a 0.5 mmol scale in DCM (6.0 mL), the organozinc reagent was Et
2
2
Zn;
Zn,
b
Et2Zn:Ti(O Pr)4:aldehyde = 4:1:1; Isolated yields; d The ee values were determined by chiral HPLC.
i
c
Herein, we attempted to synthesize the above natural products 6a
–c on gram scale, by employing
the (S)-BINOL 17b as the catalyst. As shown in Scheme 4, (S)-BINOL efficiently catalyzed the

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asymmetric addition of trimethylsilylacetylene with the corresponding aliphatic aldehydes 14a–c,
0
0
affording compounds 13a
–
c
in moderate yields (71%–72%) and enantioselectivities (80%–82% ee),
. K CO -promoted deprotection of trimethyl group
slightly lower than those of compounds 13a
–
c
2
3
0
0
of compounds 13a
Following the same procedures as shown in Scheme 3, compounds 6a
yields (81%–83%) and nearly without loss of enantioselectivities (79%–82% ee, the ee values were
measured by HPLC after derived by 3,5-dinitrobenzoyl chloride). The enantiomeric purity of 21a
could be improved to over 99% ee by slow recrystallization from diethylether/n-hexane (1:5) at a low
temperature. Subsequently, the esters 21a could be quantitatively hydrolyzed to the corresponding
chiral alcohols 6a–c followed in our previous group research [22].
–c
under mild conditions gave compounds 12a
–c
in good yields (87%–89%) [52].
–c
were obtained in moderate
–
c
–c
Scheme 4. Total synthesis of (R)-matsutakeol and its natural analogs 6a
–
c
by using (S)-BINOL
i
(
Scheme 1, Method 3). Reagents and conditions: (a) (i) ZnEt , THF, N , rt; (ii) Ti( PrO) , THF, N ,
2
2
4
2
◦
◦
rt; (b) K CO , MeOH, 0~25 C; (c) Ni(OAc) , NaBH , EDA, EtOH, 0~25 C; (d) 3,5-Dinitrobenzoyl
2
3
2
4
◦
◦
chloride, Et N, 0~25 C, overnight; (e) Recrystallization from diethylether/n-hexane (1/5) at 0~25 C,
3
*
The ee value is determined by HPLC on a chiral column after derivatization.
3
. Materials and Methods
All reactions were performed under an argon atmosphere. Solvents were dried according to
standard procedures and distilled before use. All reagents were purchased commercially and used
1
13
without further purification, unless stated otherwise. H- and C-NMR spectra were recorded at
00 and 75 MHz, respectively. High-resolution mass spectra were recorded on an agilent instrument
3
by the TOF MS technique. Enantiomeric excesses (ee) were determined by chiral HPLC analyses using
a chiral column (Chiralpak OD-H, AD-H, OJ-H), and elution with isopropanol-hexane. The optical
rotations were measured on PERKIN ELMER 341 Polarimeter. 1H-, C-NMR spectra and HPLC
chromatography of the chiral products are in the Supplementary Materials.
13
3
.1. General Procedure of Asymmetric Addition of Methyl Propiolate to Aliphatic Aldehydes (Table 1)
To a stirred solution of methyl propiolate (84 mg, 1 mmol), (S,S)-ProPhenol (128 mg, 0.2 mmol),
triphenylphosphine oxide (111 mg, 0.4 mmol) in toluene (1 mL), dimethylzinc (2.5 mL, 1.2 M in
◦
◦
toluene, 3 mmol) was added slowly at
−
10 C. After stirring for 1.5 h at
−
10 C, aldehyde (1.5 mmol)
◦
in toluene (3 mL) was added via syringe at a slow rate in 24 h at
water (10 mL). The mixture was filtered through a celite pad. The aqueous phase was extracted
with ether. The combined organic phases were washed with saturated brine solution, dried over
−
10 C, and quenched with
anhydrous Na SO , and concentrated under reduced pressure. The residue was purified by silica gel
2
4
chromatography to get the product [25,36].

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3
.1.1. Synthesis of (R)-Methyl-4-hydroxynon-2-ynoate: (R)-13a
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 8:1) to offer (R)-13a (131 mg, 71% yield, 99% ee) as colorless oil. [α] = +5.7
D
1
(c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.57–4.44 (m, 1H), 3.76 (s, 3H), 2.66 (d, J = 4.7 Hz,
2
2
3
13
1
H), 1.80–1.67 (m, 2H), 1.52–1.38 (m, 2H), 1.35–1.25 (m, 4H), 0.88 (t, J = 6.7 Hz, 3H). C-NMR (75 MHz,
+
CDCl3)
δ
(ppm): 153.57, 88.19, 75.78, 61.71, 52.40, 36.46, 30.95, 24.23, 22.08, 13.54. HRMS ESI [M + Na]
+
calcd for C H NaO 207.0992, found 207.0992. Enantiomeric excess was determined by HPLC with
10
16
3
a Chiralcel OD-H column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer
tr = 14.93 min, minor (S)-enantiomer tr = 16.73 min.
3
.1.2. Synthesis of (R)-Methyl-4-hydroxydec-2-ynoate: (R)-13b
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
hexanes/ethyl acetate 8:1) to offer (R)-13b (131 mg, 66% yield, 99% ee) as colorless oil. [α] = +5.8
D
1
(c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.57–4.44 (m, 1H), 3.77 (s, 3H), 2.36 (d, J = 5.7 Hz,
(ppm):
2
2
3
1
1
H), 1.84–1.71 (m, 2H), 1.51–1.24 (m, 8H), 0.87 (t, J = 6.7 Hz, 3H). 13C-NMR (75 MHz, CDCl3)
δ
+
53.51, 88.07, 75.85, 61.76, 52.40, 36.53, 31.25, 28.44, 24.51, 22.16, 13.62. HRMS ESI [M + Na] calcd
for C H NaO 221.1148, found 221.1150. Enantiomeric excess was determined by HPLC with
+
11
18
3
a Chiralcel OD-H column (99:1 n-hexanes:isopropanol, 0.7 mL/min, 210 nm), major (R)-enantiomer
tr = 31.48 min, minor (S)-enantiomer tr = 37.63 min.
3
.1.3. Synthesis of (R)-Methyl-4-hydroxyundec-2-ynoate: (R)-13c
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
(
hexanes/ethyl acetate 8:1) to offer (R)-13c (155 mg, 73% yield, 99% ee) as colorless oil. [α] = +6.7
D
1
c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ (ppm): 4.57–4.44 (m, 1H), 3.76 (s, 3H), 2.67 (d,
2
2
3
1
3
J = 5.8 Hz, 1H), 1.76–1.70 (m, 2H), 1.46–1.42 (m, 2H), 1.35–1.23 (m, 8H), 0.92–0.82 (m, 3H). C-NMR
75 MHz, CDCl3) (ppm): 153.58, 88.22, 75.77, 61.70, 52.41, 36.50, 31.36, 28.75, 28.72, 24.56, 22.23,
3.66. HRMS ESI [M + Na] calcd for C H NaO 235.1305, found 235.1305. Enantiomeric excess
(
1
δ
+
+
1
2
20
3
was determined by HPLC with a Chiralcel OD-H column (99:1 n-hexanes:isopropanol, 1.0 mL/min,
2
10 nm), major (R)-enantiomer tr = 13.97 min, minor (S)-enantiomer tr = 15.47 min.
3
.1.4. Synthesis of (R)-Methyl-4-hydroxypent-2-ynoate: (R)-13d
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
hexanes/ethyl acetate 8:1) to offer (R)-13d (81 mg, 63% yield, 99% ee) as colorless oil. [α] = +3.4
D
1
(c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.57–4.44 (m, 1H), 3.80 (s, 3H), 2.97 (d, J = 5.6 Hz,
(ppm): 153.61, 88.72, 74.99, 57.53, 52.48,
2.85. HRMS ESI [M + Na] calcd for C H NaO 151.0366, found 151.0365. Enantiomeric excess
2
2
3
13
1
2
H), 1.53 (d, J = 6.7 Hz, 3H). C-NMR (75 MHz, CDCl ) δ
3
+
+
6
8
3
was determined by HPLC with a Chiralcel OD-H column (98:2 n-hexanes:isopropanol, 1.0 mL/min,
2
20 nm), major (R)-enantiomer tr = 23.06 min, minor (S)-enantiomer tr = 26.75 min.
3
.1.5. Synthesis of Methyl (R)-Methyl-4-hydroxyhex-2-ynoate: (R)-13e
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
(
(
hexanes/ethyl acetate 8:1) to offer (R)-13e (101 mg, 71% yield, 99% ee) as colorless oil. [α] = +8.2
D
1
c 1.05, CH Cl ), H-NMR (300 MHz, CDCl3)
δ (ppm): 4.57–4.44 (m, 1H), 3.79 (s, 3H), 3.09
d, J = 5.8 Hz, 1H), 1.87–1.75 (m, 2H), 1.04 (t, J = 7.4 Hz, 3H). 13C-NMR (75 MHz, CDCl )
2
2
δ
3
+
+
(
ppm): 153.64, 88.07, 75.76, 62.84, 52.45, 29.64, 8.88. HRMS ESI [M + Na] calcd for C H NaO
7
10
3
165.0522, found 165.0522. Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 220 nm), major (R)-enantiomer t
r
= 20.98 min,
minor (S)-enantiomer tr = 23.86 min.

Molecules 2017, 22, 364
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3
.1.6. Synthesis of (R)-Methyl-4-hydroxyhept-2-ynoate: (R)-13f
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 8:1) to offer (R)-13f (105 mg, 67% yield, 99% ee) as colorless oil. [α] = +5.4
D
1
(c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.57–4.44 (m, 1H), 3.79 (s, 3H), 3.02 (d, J = 5.8 Hz,
2
2
3
13
1
1
1
H), 1.83–1.66 (m, 2H), 1.58–1.41 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H). C-NMR (75 MHz, CDCl )
53.64, 88.29, 75.69, 61.40, 52.45, 38.47, 17.88, 13.22. HRMS ESI [M + Na] calcd for C H NaO
79.0679, found 179.0681. Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
δ
(ppm):
3
+
+
8
12
3
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 220 nm), major (R)-enantiomer t
r
= 24.14 min,
minor (S)-enantiomer tr = 25.45 min.
3
.1.7. Synthesis of (R)-Methyl-4-hydroxyoct-2-ynoate: (R)-13g
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 8:1) to offer (R)-13g (116 mg, 68% yield, 99% ee) as colorless oil. [α] = +2.3
D
1
(c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.55–4.44 (m, 1H), 3.77 (s, 3H), 2.39 (d, J = 5.8 Hz,
2
2
3
13
1
1
1
H), 1.82–1.68 (m, 2H), 1.48–1.31 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H). C-NMR (75 MHz, CDCl )
53.51, 88.06, 75.85, 61.75, 52.40, 36.23, 26.66, 21.88, 13.48. HRMS ESI [M + Na] calcd for C H NaO
93.0835, found 193.0835. Enantiomeric excess was determined by HPLC with a Chiralcel OJ-H
δ
(ppm):
3
+
+
9
14
3
column (95:5 n-hexanes:isopropanol, 1.0 mL/min, 220 nm), major (R)-enantiomer t
minor (S)-enantiomer tr = 8.02 min.
r
= 7.45 min,
3
.1.8. Synthesis of (R)-Methyl-4-hydroxy-5-methylhex-2-ynoate: (R)-13h
Following the general procedure, the residue was purified by silica gel chromatography
25
(
(
(
hexanes/ethyl acetate 8:1) to offer (R)-13h (111 mg, 71% yield, 99% ee) as colorless oil. [α] = +7.2
c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
d, J = 5.9 Hz, 1H), 1.97–1.90 (m, 1H), 1.00 (dd, J = 6.8, 4.4 Hz, 6H). 13C-NMR (75 MHz, CDCl )
D
1
δ (ppm): 4.27 (t, J = 5.9 Hz, 1H), 3.76 (s, 3H), 3.11
2
2
3
δ
3
+
+
(ppm): 153.64, 87.36, 67.05, 52.44, 33.79, 17.58, 17.09. HRMS ESI [M + Na] calcd for C H NaO
8
12
3
179.0679, found 179.0680. Enantiomeric excess was determined by HPLC with a Chiralcel OJ-H
column (95:5 n-hexanes:isopropanol, 1.0 mL/min, 220 nm), major (R)-enantiomer t
minor (S)-enantiomer tr = 10.71 min.
r
= 8.66 min,
3
.1.9. Synthesis of (R)-Methyl-4-hydroxyoct-7-en-2-ynoate: (R)-13i
Following the general procedure, the residue was purified by silica gel chromatography
25
(
(
hexanes/ethyl acetate 8:1) to offer (R)-13i (114 mg, 68% yield, 97% ee) as colorless oil. [α] = −10.1
D
1
c 1.05, CH Cl ), H-NMR (300 MHz, CDCl )
δ (ppm): 5.89–5.75 (m, 1H), 5.12–4.96 (m, 2H), 4.52 (q,
2
2
3
J = 6.4 Hz, 1H), 3.79 (s, 3H), 2.64 (d, J = 5.5 Hz, 1H), 2.26 (dd, J = 14.4, 6.8 Hz, 2H), 1.92–1.81 (m, 2H).
1
3
C-NMR (75 MHz, CDCl )
δ
(ppm): 153.53, 136.64, 115.46, 87.75, 76.03, 61.08, 52.48, 35.48, 28.73.
3
+
+
HRMS ESI [M + Na] calcd for C H NaO 191.0679, found 191.0679. Enantiomeric excess was
9
12
3
determined by HPLC with a Chiralcel OJ-H column (95:5 n-hexanes:isopropanol, 1.0 mL/min, 220 nm),
major (R)-enantiomer tr = 9.01 min, minor (S)-enantiomer tr = 9.75 min.
3
.2. General Procedure for the Synthesis of Chiral Alkynols 12 from Propargyl Alcohols 13
◦
A solution of the chiral alkynol (5 mmol) and THF (60 mL) were cooled to 0 C, 1 M aq LiOH
25 mmol, 5 eq) was added at a slow rate. The solution was warmed to rt and stirred for an additional
h before it was quenched with 1M aq NaHSO (50 mL). The aqueous phase was extracted by ethyl
(
1
4
acetate. The combined organic phases were dried over anhydrous Na SO , and concentrated under
2
4
reduced pressure. The residue was dissolved in acetonitrile (12 mL), CuCl (0.5940 g, 6 mmol, 1.2 eq)
was added in one portion to the mixture. The mixture was allowed to warm to r.t. and stirred for
another 13 h. The aqueous phase was extracted by ether. The combined organic phases were dried

Molecules 2017, 22, 364
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over anhydrous Na SO , and concentrated under reduced pressure. The residue was purified by silica
2
4
gel chromatography to get the product.
3
.2.1. Synthesis of (R)-Oct-1-yn-3-ol: (R)-12a
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
hexanes/ethyl acetate 15:1) to offer (R)-12a (536 mg, 85% yield) as colorless oil. [
α]
= +18.5 (c 1.0,
D
25
1
ethyl ether), lit. [53] [
α]
= +19.3 (c 1.0, ethyl ether), H-NMR (300 MHz, CDCl ) δ (ppm): 4.33–4.27
3
D
(
0
2
m, 1H), 3.10 (s, 1H), 2.40 (d, J = 2.1 Hz, 1H), 1.69–1.60 (m, 2H), 1.46–1.33 (m, 2H), 1.33–1.11 (m, 4H),
.83 (t, J = 7.0 Hz, 3H). 13C-NMR (75 MHz, CDCl )
δ
(ppm): 84.82, 72.31, 61.71, 37.15, 31.03, 24.33,
3
+
+
2.11, 13.53. HRMS ESI [M + Na] calcd for C H NaO 149.0937, found 149.0938.
8
14
3
.2.2. Synthesis of (R)-Non-1-yn-3-ol: (R)-12b
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 15:1) to offer (R)-12b (603 mg, 86% yield) as colorless oil. [
α]
= +5.3 (c 2.0,
D
25
1
CHCl ), lit. [54] [
α]
= +4.6 (c 1.92, CHCl ), H-NMR (300 MHz, CDCl ) δ (ppm): 4.37 (t, J = 5.9 Hz,
3 3
D
3
1
0
2
H), 2.47 (d, J = 5.9 Hz, 1H), 2.38 (s, 1H), 1.75–1.68 (m, 2H), 1.52–1.41 (m, 2H), 1.38–1.27 (m, 6H),
.89 (t, J = 6.7 Hz, 3H). 13C-NMR (75 MHz, CDCl )
δ
(ppm): 84.78, 72.38, 61.90, 37.28, 31.35, 28.53,
3
+
+
4.62, 22.19, 13.66. HRMS ESI [M + Na] calcd for C H NaO Exact Mass: 163.1093, found 163.1093.
9
16
3
.2.3. Synthesis of (R)-Dec-1-yn-3-ol: (R)-12c
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 15:1) to offer (R)-12c (640 mg, 83% yield) as colorless oil. [
α]
= +6.2 (c 1.1,
D
25
1
CHCl ), lit. [55] [
α]
= +4.2 (c 1.1, CHCl ), H-NMR (300 MHz, CDCl ) δ (ppm): 4.35 (dd, J = 6.5,
3 3
D
3
4
0
2
.9 Hz, 1H), 2.44 (d, J = 2.1 Hz, 1H), 2.33 (s, 1H), 1.78–1.60 (m, 2H), 1.50–1.38 (m, 2H), 1.32–1.26 (m, 8H),
.86 (t, J = 6.8 Hz, 3H). 13C-NMR (75 MHz, CDCl )
δ
(ppm): 84.74, 72.41, 61.97, 37.31, 31.40, 29.34,
3
+
+
8.83, 24.66, 22.26, 13.69. HRMS ESI [M + Na] calcd for C H NaO 177.1250, found 177.1250.
10
18
3
.3. General Procedure for the Selective Reduction of the Chiral Alkynols 12
To a stirred solution of nickel acetate tetrahydrate (352 mg, 2 mmol) in ethanol (5 mL) under
◦
hydrogen, sodium borohydride (76 mg, 2 mmol) in ethanol (2 mL) was added at 0 C. After stirring
◦
for 1 h at 25 C, ethylenediamine (481 mg, 8 mmol) was added. The reaction mixture was stirred for
another 10 min before chiral alkynol (2 mmol) in ethanol (2 mL) was added slowly to the reaction
◦
◦
◦
mixture at 0 C. The reaction was allowed to proceed at 25 C under hydrogen for 6 h at 25 C.
The mixture was filtered through a celite pad, diluted with ether, and concentrated under reduced
pressure. The residue was purified by silica gel chromatography to get the product.
3
.3.1. Synthesis of (R)-Oct-1-en-3-ol: (R)-6a
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
hexanes/ethyl acetate 10:1) to offer (R)-6a (210 mg, 82% yield) as colorless oil. [
α
]
=
−
10.8 (c 1.1,
10.0 (c 1.67, CHCl ), H-NMR (300 MHz, CDCl ) δ (ppm): 5.95–5.83 (m, 1H),
3 3
D
25
1
CHCl ), lit. [56] [
5
1
3
α]
=
−
3
D
.27–5.21 (m, 1H), 5.14–5.10 (m, 1H), 4.12 (d, J = 4.8 Hz, 1H), 1.61 (d, J = 2.8 Hz, 1H), 1.58–1.48 (m, 2H),
(ppm): 141.02, 114.12, 72.92,
6.68, 31.40, 24.64, 22.23, 13.64. HRMS ESI [M + Na] calcd for C H NaO 151.1093, found 151.1093.
13
.44–1.25 (m, 6H), 0.91 (t, J = 6.7 Hz, 3H). C-NMR (75 MHz, CDCl )
δ
3
+
+
8
16
3
.3.2. Synthesis of (R)-Non-1-en-3-ol: (R)-6b
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 10:1) to offer (R)-6b (242 mg, 85% yield) as colorless oil. [
α
]
=
−
11.5 (c 1.1,
13.4 (c 1.12, ethanol), H-NMR (300 MHz, CDCl ) δ (ppm): 5.94–5.83
3
D
2
5
1
ethanol), lit. [57] [
α]
=
−
D
(
m, 1H), 5.27–5.20 (m, 1H), 5.14–5.09 (m, 1H), 4.12 (d, J = 5.9 Hz, 1H), 1.67 (d, J = 3.5 Hz, 1H), 1.60–1.49

Molecules 2017, 22, 364
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(
7
m, 2H), 1.40–1.29 (m, 8H), 0.90 (t, J = 6.7 Hz, 3H). 13C-NMR (75 MHz, CDCl )
2.91, 36.72, 31.43, 28.86, 24.93, 22.22, 13.68. HRMS ESI [M + Na] calcd for C H NaO 165.1250,
δ
(ppm): 141.03, 114.10,
3
+
+
9
18
found 165.1250.
3
.3.3. Synthesis of (R)-Dec-1-en-3-ol: (R)-6c
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 10:1) to offer (R)-6c (259 mg, 83% yield) as colorless oil. [
α
]
=
−
16.7 (c 1.1,
18.1 (c 1.22, CHCl ), H-NMR (300 MHz, CDCl ) δ (ppm): 5.92–5.81 (m, 1H),
3 3
D
2
5
1
CHCl ), lit. [58] [
5
α]
=
−
3
D
.32–5.17 (m, 1H), 5.16–5.06 (m, 1H), 4.15–4.05 (m, 1H), 1.91 (d, J = 3.7 Hz, 1H), 1.58–1.46 (m, 2H),
13
1.40–1.22 (m, 10H), 0.89 (t, J = 6.7 Hz, 3H). C-NMR (75 MHz, CDCl )
δ
(ppm): 141.04, 114.04, 72.86,
3
+
+
3
6.70, 31.45, 29.16, 28.88, 24.97, 22.27, 13.68. HRMS ESI [M + Na] calcd for C H NaO 179.1406,
10
20
found 179.1408.
3
.4. General Procedure for the Esterification Reaction and Determination of Enantiomeric Excess by HPLC
Triethylamine (152 mg, 1.5 mmol) and 3,5-dinitrobenzoyl chloride (277 mg, 1.2 mmol) were added
◦
to a stirred solution of the chiral alcohol (1 mmol) in CH Cl (6 mL) at
−
5 C. The mixture was
2
2
◦
◦
stirred for 5 h at 25 C before water (2 mL) was poured into the mixture at 0 C. The aqueous phase
was extracted with ether, and combined organic phases were washed with saturated brine solution,
dried over anhydrous Na SO , and concentrated under reduced pressure. The residue was purified by
2
4
silica gel chromatography to get the product.
3
.4.1. Synthesis of (R)-Oct-1-en-3-yl-3,5-dinitrobenzoate: (R)-21a
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
(
hexanes/ethyl acetate 8:1) to offer (R)-21a (306 mg, 95% yield, 99% ee) as white solid. [α] = −16.2
D
1
c 1.1, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 9.22 (t, J = 2.1 Hz, 1H), 9.16 (d, J = 2.1 Hz,
2
2
3
2
H), 5.92 (m 1H), 5.56 (q, J = 6.9 Hz, 1H), 5.36 (m, 2H), 1.96–1.72 (m, 2H), 1.48–1.26 (m, 6H), 0.89 (t,
J = 6.9 Hz, 3H). 13C-NMR (75 MHz, CDCl3)
δ
(ppm): 161.45, 148.34, 135.09, 134.00, 129.02, 121.92,
+
+
118.05, 77.82, 33.69, 31.09, 24.40, 22.10, 13.57. HRMS ESI [M + Na] calcd for C H N NaO
15 18 2 6
345.1057, found 345.1057. Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
column (99:1 n-hexanes: isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 17.74 min,
minor (S)-enantiomer tr = 14.46 min.
3
.4.2. Synthesis of (R)-Non-1-en-3-yl-3,5-dinitrobenzoate: (R)-21b
Following the general procedure, the residue was purified by silica gel chromatography
25
(
hexanes/ethyl acetate 8:1) to offer (R)-21b (312 mg, 93% yield, 99% ee) as colorless oil. [α] = −18.3
D
1
(c 1.1, CH Cl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 9.21 (t, J = 2.1 Hz, 1H), 9.15 (d, J = 2.1 Hz,
2
2
3
2
H), 6.01–5.84 (m, 1H), 5.56 (d, J = 6.6 Hz, 1H), 5.34 (dd, J = 26.1, 13.8 Hz, 2H), 1.95–1.70 (m, 2H),
13
1
1
.45–1.26 (m, 8H), 0.87 (t, J = 6.7 Hz, 3H). C-NMR (75 MHz, CDCl3)
33.99, 129.02, 121.92, 118.01, 77.81, 33.73, 31.27, 28.59, 24.70, 22.17, 13.63. HRMS ESI [M + Na] calcd
δ
(ppm): 161.45, 148.33, 135.11,
+
+
for C H N NaO 359.1214, found 359.1214. Enantiomeric excess was determined by HPLC with
16
20
2
6
a Chiralcel OD-H column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer
tr = 15.27 min, minor (S)-enantiomer tr = 12.67 min.
3
.4.3. Synthesis of (R)-Dec-1-en-3-yl-3,5-dinitrobenzoate: (R)-21c
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
(
hexanes/ethyl acetate 8:1) to offer (R)-6c (332 mg, 95% yield, 99% ee) as white solid. [
α]
=
−
21.2
D
1
c 1.05, CH Cl ), H-NMR (300 MHz, CDCl ) δ (ppm): 9.23 (t, J = 2.1 Hz, 1H), 9.16 (d, J = 2.1 Hz, 2H),
2
2
3
5
(
.98–5.87 (m, 1H), 5.57 (q, J = 6.8 Hz, 1H), 5.35 (dd, J = 25.1, 13.8 Hz, 2H), 1.99–1.71 (m, 2H), 1.40–1.28
(ppm): 161.45, 148.35, 135.09, 134.02,
m, 10H), 0.88 (t, J = 6.6 Hz, 3H). 13C-NMR (75 MHz, CDCl3)
δ

Molecules 2017, 22, 364
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+
1
29.03, 121.92, 118.08, 77.85, 33.74, 31.37, 28.90, 28.75, 24.76, 22.24, 13.68. HRMS ESI [M + Na] calcd
+
for C H N NaO 373.1370, found 373.1370. Enantiomeric excess was determined by HPLC with
17
22
2
6
a Chiralcel OD-H column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer
tr = 16.89 min, minor (S)-enantiomer tr = 13.50 min.
3
.5. General Procedure of Asymmetric Addition of Ethynyltrimethylsilane to Aliphatic Aldehydes
To a stirred solution of ethynyltrimethylsilane (3922 mg, 40 mmol), (S)-BINOL (1144 mg, 4 mmol),
HMPA (3584 mg, 20 mmol) in methylene chloride (120 mL), diethylzinc (40 mL, 40 mmol) was added
◦
◦
slowly at 0 C. After stirring for 16 h at 25 C, Titanium(IV) isopropoxide (2842 mg, 10 mmol) was
◦
added and the stirring was continued for another 1 h at 25 C. Then an aldehyde (10 mmol) was
added and the reaction was allowed to proceed at 25 C for another 6 h before being quenched with
◦
water (20 mL). The mixture was filtered through a celite pad. The aqueous phase was extracted with
ether. The combined organic phases were washed with saturated brine, dried over anhydrous Na SO ,
2
4
and concentrated under reduced pressure. The residue was purified by silica gel chromatography to
get the product [34,40].
0
3
.5.1. Synthesis of (R)-1-(Trimethylsilyl)oct-1-yn-3-ol: (R)-13a
Following the general procedure, the residue was purified by silica gel chromatography
0
hexanes/ethyl acetate 20:1) to offer (R)-13a (1408 mg, 71% yield, 80% ee) as colorless oil. [α] = +8.2
D
25
(
(
25
1
c 1.1, CHCl ), lit. [56] [
α]
= +13.6 (c 1.1, CHCl ), H-NMR (300 MHz, CDCl ) δ (ppm): 4.38 (dd,
3 3
D
3
J = 12.2, 6.4 Hz, 1H), 1.80 (d, J = 5.5 Hz, 1H), 1.76–1.68 (m, 2H), 1.47 (d, J = 7.3 Hz, 2H), 1.35 (dd,
J = 7.1, 3.5 Hz, 4H), 0.92 (t, J = 6.7 Hz, 3H), 0.20 (s, 9H). 13C-NMR (75 MHz, CDCl )
δ
(ppm): 106.61,
3
+
+
8
2
8.96, 62.61, 37.35, 31.04, 24.41, 22.16, 13.59,
21.1332, found 221.1332. Enantiomeric excess was determined by HPLC with a Chiralcel AD-H
−
0.47. HRMS ESI [M + Na] calcd for C H NaOSi
11
22
column (99:1 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 14.72 min,
minor (S)-enantiomer tr = 13.52 min.
0
3
.5.2. Synthesis of (R)-1-(Trimethylsilyl)non-1-yn-3-ol: (R)-13b
Following the general procedure, the residue was purified by silica gel chromatography
0
25
(
(
1
δ
hexanes/ethyl acetate 20:1) to offer (R)-13b (1529 mg, 72% yield, 82% ee) as colorless oil. [α] = +2.3
D
1
c 1.1, CHCl ), H-NMR (300 MHz, CDCl )
δ
(ppm): 4.38 (dd, J = 12.3, 6.5 Hz, 1H), 1.78–1.68 (m, 3H),
3
3
13
.46 (d, J = 6.5 Hz, 2H), 1.38–1.27 (m, 6H), 0.92 (t, J = 6.7 Hz, 3H), 0.20 (s, 9H). C-NMR (75 MHz, CDCl )
3
(ppm): 106.68, 88.89, 62.54, 37.36, 31.34, 28.52, 24.70, 22.17, 13.67,
−
0.48. HRMS ESI [M + Na]+ calcd
+
for C H NaOSi 235.1489, 235.1490. Enantiomeric excess was determined by HPLC with a Chiralcel
12
24
AD-H column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
minor (S)-enantiomer tr = 12.42 min.
r
= 13.68 min,
0
3
.5.3. Synthesis of (R)-1-(Trimethylsilyl)dec-1-yn-3-ol: (R)-13c
Following the general procedure, the residue was purified by silica gel chromatography
0
25
(
(
1
(
hexanes/ethyl acetate 20:1) to offer (R)-13c (1608 mg, 71% yield, 80% ee) as colorless oil. [α] = +3.2
D
1
c 1.1, CHCl ). H-NMR (300 MHz, CDCl )
δ
(ppm): 4.36 (dd, J = 12.3, 6.5 Hz, 1H), 2.00 (m, 1H),
3
3
1
3
.83–1.61 (m, 2H), 1.53–1.40 (m, 2H), 1.40–1.31 (m, 8H), 0.90 (t, J = 6.7 Hz, 3H), 0.18 (m, 9H). C-NMR
(ppm): 106.70, 88.87, 62.54, 37.36, 31.39, 28.81, 28.79, 24.74, 22.26, 13.70, 0.48.
HRMS ESI [M + Na] calcd for C H NaOSi 249.1645, found 249.1645. Enantiomeric excess was
75 MHz, CDCl3)
δ
−
+
+
13
26
determined by HPLC with a Chiralcel AD-H column (99:1 n-hexanes:isopropanol, 0.9 mL/min, 210 nm),
major (R)-enantiomer tr = 18.90 min, minor (S)-enantiomer tr = 16.94 min.

Molecules 2017, 22, 364
11 of 16
0
3
.6. General Procedure for the Synthesis of chIral Alkynols 12 from Propargyl Alcohols 13
To a stirred solution of chiral alkynol (10 mmol) in methanol (20 mL), potassium carbonate
◦
◦
(
2764 mg, 20 mmol) was added slowly at 0 C. After stirring for 20 h at 25 C, water (20 mL) was added
◦
slowly at 0 C. The reaction mixture was concentrated under reduced pressure. The aqueous phase
was extracted with ether. The combined organic phases were washed with saturated brine solution,
dried over anhydrous Na SO , concentrated under reduced pressure. The residue was purified by
2
4
silica gel chromatography to get the product.
3
.6.1. Synthesis of (R)-Oct-1-yn-3-ol: (R)-12a
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
(
hexanes/ethyl acetate 15:1) to offer (R)-12a (1098 mg, 87% yield) as colorless oil. [
α]
= +16.2
D
25
+
+
c 1.0, ethyl ether), lit. [53] [
α]
= +19.3 (c 1.0, ethyl ether). HRMS ESI [M + Na] calcd for C H NaO
8 14
D
1
49.0937, found 149.0937.
3
.6.2. Synthesis of (R)-Non-1-yn-3-ol: (R)-12b
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 15:1) to offer (R)-12b (1248 mg, 89% yield) as colorless oil. [
α
]
= +4.1 (c 2.0,
D
25
+
+
CHCl ), lit. [54] [
α]
= +4.6 (c 1.92, CHCl ). HRMS ESI [M + Na] calcd for C H NaO Exact mass:
3 9 16
D
3
1
63.1093, found 163.1093.
3
.6.3. Synthesis of (R)-Dec-1-yn-3-ol: (R)-12c
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 15:1) to offer (R)-12c (1373 mg, 89% yield) as colorless oil. [
α
]
= +5.1 (c 1.1,
D
2
5
+
+
CHCl ), lit. [55] [
α]
= +4.2 (c 1.1, CHCl ). HRMS ESI [M + Na] calcd. for C H NaO 177.1250,
3
3
10 18
D
found 177.1250.
3
.7. General Procedure for the Selective Reduction of the Chiral Alkynols 12
To a stirred solution of nickel acetate tetrahydrate (1408 mg, 8 mmol) in ethanol (20 mL) under
◦
hydrogen, sodium borohydride (303 mg, 8 mmol) in ethanol (8 mL) was added at 0 C. After stirring
◦
for 1 h at 25 C, ethylenediamine (481 mg, 8 mmol) was added. The reaction mixture was stirred for
another 10 min before chiral alkynol (8 mmol) in ethanol (8 mL) was added slowly to the reaction
◦
◦
◦
mixture at 0 C. The reaction was allowed to proceed at 25 C under hydrogen for 6 h at 25 C.
The mixture was filtered through a celite pad, diluted with ether, and concentrated under reduced
pressure. The residue was purified by silica gel chromatography to get the product.
3
.7.1. Synthesis of (R)-Oct-1-en-3-ol: (R)-6a
Following the general procedure, the residue was purified by silica gel chromatography
2
5
(
hexanes/ethyl acetate 10:1) to offer (R)-6a (831 mg, 81% yield) as colorless oil. [
α]
=
−
7.3 (c 1.1,
D
25
+
+
CHCl ), lit. [56] [
found 151.1093.
α]
=
−
10.0 (c 1.67, CHCl ). HRMS ESI [M + Na] calcd. for C H NaO 151.1093,
3
3
8
16
D
3
.7.2. Synthesis of (R)-Non-1-en-3-ol: (R)-6b
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 10:1) to offer (R)-6b (944 mg, 83% yield) as colorless oil. [
α
]
=
−
10.5 (c 1.1,
D
2
5
+
+
ethanol), lit. [57] [
found 165.1250.
α]
=
−
13.4 (c 1.12, ethanol). HRMS ESI [M + Na] calcd. for C H NaO 165.1250,
9 18
D

Molecules 2017, 22, 364
12 of 16
3
.7.3. Synthesis of (R)-Dec-1-en-3-ol: (R)-6c
Following the general procedure, the residue was purified by silica gel chromatography
25
(
(
hexanes/ethyl acetate 10:1) to offer (R)-6c (1013 mg, 81% yield) as colorless oil. [
c 1.1, CHCl ), lit. [58] [
α
]
=
−
14.2
D
2
5
+
+
α]
=
−
18.1 (c 1.22, CHCl ). HRMS ESI [M + Na] calcd. for C H NaO
3 10 20
3
D
1
79.1406, found 179.1406.
3
.8. General Procedure for the Esterification Reaction and Determination of Enantiomeric Excess by HPLC
Triethylamine (909 mg, 9 mmol) and 3,5-dinitrobenzoyl chloride (1660 mg, 7.2 mmol) were added
◦
to a stirred solution of the chiral alcohol (6 mmol) in CH Cl (40 mL) at
−
5 C. The mixture was
2
2
◦
◦
stirred for 5 h at 25 C before water (10 mL) was poured into the mixture at 0 C. The aqueous phase
was extracted with ether and combined organic phases were washed with saturated brine solution,
dried over anhydrous Na SO , and concentrated under reduced pressure. The residue was purified by
2
4
silica gel chromatography to get the product.
3
.8.1. Synthesis of (R)-Oct-1-en-3-yl-3,5-dinitrobenzoate: (R)-21a
Following the general procedure, the residue was purified by silica gel chromatography
(
[
hexanes/ethyl acetate 8:1) to offer (R)-21a (1837 mg, 95% yield, 80% ee) as white solid.
25
α] = −14.2 (c 1.1, CH Cl ). Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
2
2
D
column (99:1 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 17.80 min,
minor (S)-enantiomer tr = 14.65 min.
3
.8.2. Synthesis of (R)-Non-1-en-3-yl-3,5-dinitrobenzoate: (R)-21b
Following the general procedure, the residue was purified by silica gel chromatography
hexanes/ethyl acetate 8:1) to offer (R)-21b (1987 mg, 98% yield, 82% ee) as colorless oil.
(
[
25
α] = −15.2 (c 1.1, CH Cl ). Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
2
2
D
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 15.76 min,
minor (S)-enantiomer tr = 12.93 min.
3
.8.3. Synthesis of (R)-Dec-1-en-3-yl-3,5-dinitrobenzoate: (R)-21c
Following the general procedure, the residue was purified by silica gel chromatography
25
(hexanes/ethyl acetate 8:1) to offer (R)-21c (2018 mg, 96% yield, 79% ee) as white solid. [α] = −18.2
D
(c 1.05, CH Cl ). Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
2
2
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 16.58 min,
minor (S)-enantiomer tr = 13.66 min.
3
.9. General Procedure for the Recrystallization to Improve Optical Purity
Dinitrobenzoates (5 mmol) were dissolved in diethyl ether at room temperature, then n-hexane
was added slowly to the mixture until a white precipitate occurred. A small portion of diethyl ether
◦
was added and the white precipitate was dissolved. The mixture was cooled to
−
30 C and stayed for
4
8 h to get a white crystal of the dinitrobenzoate.
3
.9.1. Recrystallization of (R)-Oct-1-en-3-yl-3,5-dinitrobenzoate: (R)-21a
Following the general procedure, the residue was purified by silica gel chromatography
(
[
hexanes/ethyl acetate 8:1) to offer (R)-21a (999 mg, 62% yield, 99% ee) as white solid.
α] = −16.1 (c 1.1, CH Cl ). HRMS ESI [M + Na]+ calcd for C H N NaO
2
5
+
345.1057,
2
2
15 18
2
6
D
found 345.1057.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
column (99:1 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 18.20 min,
minor (S)-enantiomer tr = 14.46 min.

Molecules 2017, 22, 364
13 of 16
3
.9.2. Recrystallization of (R)-Non-1-en-3-yl-3,5-dinitrobenzoate: (R)-21b
Following the general procedure, the residue was purified by silica gel chromatography
(
[
hexanes/ethyl acetate 8:1) to offer (R)-21b (1076 mg, 64% yield, 99% ee) as colorless oil.
α] = −18.7 (c 1.1, CH Cl ). HRMS ESI [M + Na]+ calcd for C H N NaO
2
5
+
359.1214,
2
2
16 20
2
6
D
found 359.1214.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 15.60 min,
minor (S)-enantiomer tr = 12.67 min.
3
.9.3. Recrystallization of (R)-Dec-1-en-3-yl-3,5-dinitrobenzoate: (R)-21c
Following the general procedure, the residue was purified by silica gel chromatography
(
[
hexanes/ethyl acetate 8:1) to offer (R)-6c (1051 mg, 60% yield, 99% ee) as white solid.
α]] = −21.5 (c 1.05, CH Cl ). HRMS ESI [M + Na]+ calcd for C H N NaO 373.1370,
2
5
+
2
2
17 22
2
6
D
found 373.1370.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-H
column (98:2 n-hexanes:isopropanol, 1.0 mL/min, 210 nm), major (R)-enantiomer t
r
= 16.46 min,
minor (S)-enantiomer tr = 13.50 min.
4
. Conclusions
In summary, we developed a general synthetic route toward chiral matsutakeol and its analogs
via the asymmetric catalytic alkynylation. A practical and efficient access was provided to prepare the
R)-matsutakeol (99% ee, total yield up to 50.2%, in three steps) and its highly enantioselective analogs,
(
by utilizing the (S,S)-ProPhenol as chiral catalyst. In addition, the method may allow for gram-scale
synthesis of (R)-matsutakeol and its analogs by using (S)-BINOL as chiral catalyst, thus facilitating
their potential applications. Besides, this strategy has been proven to be practical for obtaining flavored
allyl alcohols with high enantioselectivity in food analysis and screening insect attractants. Biological
evaluation of target molecules is in progress and will be reported in due course.
Supplementary Materials: The following are available online: Figure S1–S43.
Acknowledgments: We thank the Special Fund for Agroscientific Research in the Public Interest (No.201503112),
National Natural Science Foundation of China (No.21602043 and 31601657), the Agricultural Technology System of
Henan (No.S2014-11-G03), Science and Technology Planning Project of Henan Province of China (No.142102110050)
and (No.141PPTGG424), the Educational Commission of Henan Province of China (No.14A210027), Henan Key
Laboratory of the Innovation and Application of Novel Pesticide, Collaborative Innovation Center of Henan Grain
Crops, National Key Laboratory of Wheat and Maize Crop Science for the financial support of this study.
Author Contributions: This research was carried on by all the authors. Chao Zheng, Shichao Lu, Jia Liu,
Risong Na, and Bin Yu performed the experiments; Honglian Li, Xianru Guo, Xinming Yin, and Bin Yu participated
in bio-activity experiment; Jia Liu and Min Wang wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
3.
Negri, R. Polyacetylenes from terrestrial plants and fungi: Recent phytochemical and biological advances.
Fitoterapia 2015, 106, 92–109. [CrossRef] [PubMed]
Konovalov, D.A. Polyacetylene compounds of plants of the Asteraceae Family (Review). Pharm. Chem. J.
2
014, 48, 613–631. [CrossRef]
Finimundy, T.C.; Dillon, A.J.P.; Henriques, J.A.P.; Ely, M.R. A review on general nutritional compounds
and pharmacological properties of the Lentinula edodes mushroom. Food Nutr. Sci. 2014, 5, 1095–1105.
[
CrossRef]
Swift, K.A.D. Current Topics in Flavors and Fragrances: Towards a New Millennium of Discovery; Springer Science
Business Media B.V.: GX Dordrecht, The Netherlands, 1999; p. 235.
4
.
.
+
5
Mizuno, T. Bioactive biomolecules of mushrooms: Food function and medicinal effect of mushroom fungi.
Food Rev. Int. 1995, 11, 7–21. [CrossRef]

Molecules 2017, 22, 364
14 of 16
6.
7.
8.
Murahashi, S. The odor of matsutake (Armillaria matsutake Ito et Imai Agaricaceae). II. Sci. Papers Inst. Phys.
Chem. Res. 1938, 34, 155–172.
Hung, R.; Lee, S.; Bennett, J.W. The effects of low concentrations of the enantiomers of mushroom alcohol
(1-octen-3-ol) on Arabidopsis thaliana. Mycology 2014, 5, 73–80. [CrossRef] [PubMed]
McMeniman, C.J.; Corfas, R.A.; Matthews, B.J.; Ritchie, S.A.; Vosshall, L.B. Multimodal Integration of
Carbon Dioxide and Other Sensory Cues Drives Mosquito Attraction to Humans. Cell 2014, 156, 1060–1071.
[CrossRef] [PubMed]
9
1
1
.
Sikuljak, T.; Mazuir, F.; Arevalo, A.; Menon, A. Pesticidal Mixture Comprising a Carboxamide Compound
and a Biopesticide. WO2016142456 A1, 10 March 2016.
0. Combet, E.; Henderson, J.; Eastwood, D.C.; Burton, K.S. Eight-carbon volatiles in mushrooms and fungi:
Properties, analysis, and biosynthesis. Mycoscience 2006, 47, 317–326. [CrossRef]
1. Helmchen, G.; Ihrig, K.; Schindler, H. EPC-syntheses via asymmetric Diels-Alder reactions/retro Diels-Alder
reactions. I. (R)- and (S)-Matsutake alcohol, (R)- and (S)-sarcomycin methyl ester. Tetrahedron Lett. 1987, 28,
1
83–186. [CrossRef]
1
1
1
1
1
2. Takano, S.; Yanase, M.; Takahashi, M.; Ogasawara, K. Enantiodivergent synthesis of both enantiomers of
sulcatol and matsutake alcohol from (R)-epichlorohydrin. Chem. Lett. 1987, 16, 2017–2020. [CrossRef]
3. Kitamura, M.; Kasahara, I.; Manabe, K.; Noyori, R.; Takaya, H. Kinetic resolution of racemic allylic alcohols
by BINAP-ruthenium(II) catalyzed hydrogenation. J. Org. Chem. 1988, 53, 708–710. [CrossRef]
4. Oppolzer, W.; Radinov, R.N. Enantioselective synthesis of sec-allyl alcohols by catalytic asymmetric addition
of divinylzinc to aldehydes. Tetrahedron Lett. 1988, 29, 5645–5648. [CrossRef]
5. Kusuda, S.; Ueno, Y.; Toru, T. Vinyl anion equivalent V. Asymmetric synthesis of allylic alcohols using chiral
2
-(trialkylsilyl)ethyl sulfoxides. Tetrahedron 1994, 50, 1045–1062. [CrossRef]
6. Bisogno, F.R.; Rioz-Martinez, A.; Rodriguez, C.; Lavandera, I.; de Gonzalo, G.; Torres Pazmino, D.E.;
Fraaije, M.W.; Gotor, V. Oxidoreductases Working Together: Concurrent Obtaining of Valuable Derivatives
by Employing the PIKAT Method. ChemCatChem 2010, 2, 946–949. [CrossRef]
1
7. Rej, R.K.; Nanda, S. Chemoenzymic Asymmetric Total Synthesis of Nonanolide (Z)-Cytospolides D, E and
Their Stereoisomers. Eur. J. Org. Chem. 2014, 2014, 860–871. [CrossRef]
1
8. Rej, R.K.; Kumar, R.; Nanda, S. Asymmetric synthesis of cytospolide C and cytospolide D through successful
exploration of stereoselective Julia-Kocienski olefination and Suzuki reaction followed by macrolactonization.
Tetrahedron 2015, 71, 3185–3194. [CrossRef]
1
2
9. Lee, W.H.; Bae, I.H.; Kim, B.M.; Seu, Y.-B. New Synthetic Approach to Optically Activate Matsutakeol,
the Major Flavor Component of Tricholoma matsutake, from L-Tartaric Acid. Bull. Korean Chem. Soc. 2016
7, 1910–1911. [CrossRef]
,
3
0. Huang, J.; Wei, S.; Wang, L.; Zhang, C.; Li, S.; Liu, P.; Du, X.; Wang, Q. Highly enantioselective catalytic
methyl propiolate addition to both aromatic and aliphatic aldehydes. Tetrahedron Asymmetry 2016, 27,
4
28–435. [CrossRef]
2
1. Funes-Maldonado, M.; Sieng, B.; Amedjkouh, M. Enabling Asymmetric Alkynylation of Azaaryl Aldehydes
with Soai Autocatalyst. Eur. J. Org. Chem. 2015, 2015, 4081–4086. [CrossRef]
2
2. Yang, Y.-Q.; Li, S.-N.; Zhong, J.-C.; Zhou, Y.; Zeng, H.-Z.; Duan, H.-J.; Bian, Q.-H.; Wang, M. Total synthesis
of each enantiomer of falcarinol and panaxjapyne A via asymmetric catalytic alkynylation of an aldehyde.
Tetrahedron Asymmetry 2015, 26, 361–366. [CrossRef]
2
2
3. Trost, B.M.; Quintard, A. Asymmetric Catalytic Alkynylation of Acetaldehyde: Application to the Synthesis
of (+)-Tetrahydropyrenophorol. Angew. Chem. Int. Ed. 2012, 51, 6704–6708. [CrossRef] [PubMed]
4. Trost, B.M.; Burns, A.C.; Bartlett, M.J.; Tautz, T.; Weiss, A.H. Thionium Ion Initiated Medium-Sized Ring
Formation: The Total Synthesis of Asteriscunolide D. J. Am. Chem. Soc. 2012, 134, 1474–1477. [CrossRef]
[PubMed]
2
2
5. Trost, B.M.; Bartlett, M.J.; Weiss, A.H.; von Wangelin, A.J.; Chan, V.S. Development of
Zn-ProPhenol-Catalyzed Asymmetric Alkyne Addition: Synthesis of Chiral Propargylic Alcohols.
Chem. Eur. J. 2012, 18, 16498–16509. [CrossRef] [PubMed]
6. Trost, B.M.; Bartlett, M.J. Transition-Metal-Catalyzed Synthesis of Aspergillide B: An Alkyne Addition
Strategy. Org. Lett. 2012, 14, 1322–1325. [CrossRef] [PubMed]

Molecules 2017, 22, 364
15 of 16
2
2
7. Na, R.; Wang, B.; Liu, H.; Bian, Q.; Zhong, J.; Wang, M.; Guo, H. Synthesis and application of novel dithiane
alcohol ligand based on chiral cyclopropane-backbone for asymmetric ethylation of aromatic aldehydes.
Lett. Org. Chem. 2012, 9, 622–627. [CrossRef]
8. Chen, X.; Chen, W.; Wang, L.; Yu, X.-Q.; Huang, D.-S.; Pu, L. Synthesis of a C1 symmetric BINOL-terpyridine
ligand and highly enantioselective methyl propiolate addition to aromatic aldehydes. Tetrahedron 2010, 66,
1
990–1993. [CrossRef]
2
3
3
9. Ito, J.-I.; Asai, R.; Nishiyama, H. Asymmetric Direct Alkynylation Catalyzed by Chiral
Ru-Bis(oxazolinyl)phenyl Complexes. Org. Lett. 2010, 12, 3860–3862. [CrossRef] [PubMed]
0. Turlington, M.; DeBerardinis, A.M.; Pu, L. Highly Enantioselective Catalytic Alkyl Propiolate Addition to
Aliphatic Aldehydes. Org. Lett. 2009, 11, 2441–2444. [CrossRef] [PubMed]
1. Lin, L.; Zhao, Q.; Li, A.N.; Ren, F.; Yang, F.; Wang, R. Enantioselective synthesis of Anomala osakana
pheromone and Janus integer pheromone: A flexible approach to chiral
009, 7, 3663–3665. [CrossRef] [PubMed]
2. Qiu, L.; Wang, Q.; Lin, L.; Liu, X.; Jiang, X.; Zhao, Q.; Hu, G.; Wang, R. Highly enantioselective addition
of terminal alkynes to aldehydes catalyzed by a new chiral -sulfonamide alcohol/Ti(OiPr)4/Et2Zn/R3N
catalyst system. Chirality 2009, 21, 316–323. [CrossRef] [PubMed]
3. Zhong, J.-C.; Hou, S.-C.; Bian, Q.-H.; Yin, M.-M.; Na, R.-S.; Zheng, B.; Li, Z.-Y.; Liu, S.-Z.; Wang, M. Highly
enantioselective zinc/amino alcohol-catalyzed alkynylation of aldehydes. Chem. Eur. J. 2009, 15, 3069–3071.
γ-butyrolactones. Org. Biomol. Chem.
2
3
3
3
β
[
CrossRef] [PubMed]
0
4. Yue, Y.; Turlington, M.; Yu, X.-Q.; Pu, L. 3,3 -Anisyl-Substituted BINOL, H4BINOL, and H8BINOL Ligands:
Asymmetric Synthesis of Diverse Propargylic Alcohols and Their Ring-Closing Metathesis to Chiral
Cycloalkenes. J. Org. Chem. 2009, 74, 8681–8689. [CrossRef] [PubMed]
3
5. Xu, Z.; Wu, N.; Ding, Z.; Wang, T.; Mao, J.; Zhang, Y. L-Proline-derived tertiary amino alcohol as a new chiral
ligand for enantioselective alkynylation of aldehydes. Tetrahedron Lett. 2009, 50, 926–929. [CrossRef]
6. Yang, F.; Xi, P.; Yang, L.; Lan, J.; Xie, R.; You, J. Facile, Mild, and Highly Enantioselective Alkynylzinc
Addition to Aromatic Aldehydes by BINOL/N-Methylimidazole Dual Catalysis. J. Org. Chem. 2007, 72,
3
5
457–5460. [CrossRef] [PubMed]
7. Lin, L.; Jiang, X.; Liu, W.; Qiu, L.; Xu, Z.; Xu, J.; Chan, A.S.C.; Wang, R. Highly Enantioselective Synthesis
of -Hydroxy- -acetylenic Esters Catalyzed by a -Sulfonamide Alcohol. Org. Lett. 2007, 9, 2329–2332.
CrossRef] [PubMed]
8. Trost, B.M.; Weiss, A.H. Catalytic Enantioselective Synthesis of Adociacetylene B. Org. Lett. 2006, 8,
461–4464. [CrossRef] [PubMed]
3
γ
α,
β
β
[
3
3
4
4
9. Trost, B.M.; Weiss, A.H.; von Wangelin, A.J. Dinuclear Zn-Catalyzed Asymmetric Alkynylation of
Unsaturated Aldehydes. J. Am. Chem. Soc. 2006, 128, 8–9. [CrossRef] [PubMed]
0. Gao, G.; Wang, Q.; Yu, X.-Q.; Xie, R.-G.; Pu, L. Highly enantioselective synthesis of
esters by asymmetric alkyne addition to aldehydes. Angew. Chem. Int. Ed. 2006, 45, 122–125. [CrossRef]
PubMed]
1. Wolf, C.; Liu, S. Bisoxazolidine-catalyzed enantioselective alkynylation of aldehydes. J. Am. Chem. Soc. 2006
28, 10996–10997. [CrossRef] [PubMed]
γ-hydroxy-α,β-acetylenic
[
4
4
4
4
,
1
2. Emmerson, D.P.G.; Hems, W.P.; Davis, B.G. Carbohydrate-Derived Amino-Alcohol Ligands for Asymmetric
Alkynylation of Aldehydes. Org. Lett. 2006, 8, 207–210. [CrossRef] [PubMed]
3. Cozzi, P.G.; Rudolph, J.; Bolm, C.; Norrby, P.-O.; Tomasini, C. Me Zn-Mediated Addition of Acetylenes to
2
Aldehydes and Ketones. J. Org. Chem. 2005, 70, 5733–5736. [CrossRef] [PubMed]
4. Yamashita, M.; Yamada, K.-i.; Tomioka, K. Catalytic asymmetric addition of terminal alkynes to aldehydes
mediated by (1R,2R)-2-(dimethylamino)-1,2-diphenylethanol. Adv. Synth. Catal. 2005, 347, 1649–1652.
[CrossRef]
4
4
4
5. Jiang, B.; Si, Y.-G. The first highly enantioselective alkynylation of chloral: A practical and efficient pathway
to chiral trichloromethyl propargyl alcohols. Adv. Synth. Catal. 2004, 346, 669–674. [CrossRef]
6. Dahmen, S. Enantioselective Alkynylation of Aldehydes Catalyzed by [2.2]Paracyclophane-Based Ligands.
Org. Lett. 2004, 6, 2113–2116. [CrossRef] [PubMed]
7. Stefani, H.A.; Menezes, P.H.; Costa, I.M.; Silva, D.O.; Petragnani, N. Use of chiral sulfoxide in the asymmetric
synthesis of (+)-virol C. Synlett 2002, 8, 1335–1337. [CrossRef]

Molecules 2017, 22, 364
16 of 16
4
4
5
5
5
5
8. Jiang, B.; Chen, Z.; Xiong, W. Highly enantioselective alkynylation of aldehydes catalyzed by a readily
available chiral amino alcohol-based ligand. Chem. Commun. (Camb., UK) 2002, 14, 1524–1525. [CrossRef]
9. Rotticci, D.; Haeffner, F.; Orrenius, C.; Norin, T.; Hult, K. Molecular recognition of sec-alcohol enantiomers
by Candida antarctica lipase B. J. Mol. Catal. B Enzym. 1998, 5, 267–272. [CrossRef]
0. Liu, J.; Li, H.-L.; Guo, X.-R.; Zhou, L.; Wang, Y.; Duan, Y.-N.; Wang, M.-Z.; Na, R.-S.; Yu, B. A general strategy
toward the total synthesis of C17 polyacetylenes virols A and C. Tetrahedron 2016, 72, 6603–6610. [CrossRef]
1. Morandi, S.; Palate, F.; Benvenuti, S.; Prati, F. Total synthesis of a dienynone from Echinacea pallida.
Tetrahedron 2008, 64, 6324–6328. [CrossRef]
2. Zheng, M.; Wu, F.; Chen, K.; Zhu, S. Styrene as 4π-Component in Zn (II)-Catalyzed Intermolecular
Diels–Alder/Ene Tandem Reaction. Org. Lett. 2016, 18, 3554–3557. [CrossRef] [PubMed]
3. Johnson, W.S.; Elliott, R.; Elliott, J.D. Asymmetric synthesis via acetal templates. 4. Reactions with
silylacetylenic compounds. Formation of chiral propargylic alcohols. J. Am. Chem. Soc. 1983, 105, 2904–2905.
[CrossRef]
5
5
5
5
4. Jiang, X.; Fu, C.; Ma, S. Highly stereoselective iodolactonization of 4,5-allenoic acids—An efficient synthesis of
0
0
5
-(1 -iodo-1 (Z)-alkenyl)-4,5-dihydro-2(3H)-furanones. Chemistry 2008, 14, 9656–9664. [CrossRef] [PubMed]
5. Fu, R.; Chen, J.; Guo, L.-C.; Ye, J.-L.; Ruan, Y.-P.; Huang, P.-Q. Asymmetric Total Synthesis of
−)-Awajanomycin. Org. Lett. 2009, 11, 5242–5245. [CrossRef] [PubMed]
6. Nakamura, S.; Nakayama, J.; Toru, T. Asymmetric Reduction of -(Trimethylsilyl)methyl-
with DIBAL under Basic Conditions. J. Org. Chem. 2003, 68, 5766–5768. [CrossRef] [PubMed]
(
α
β-ketosulfoxide
7. Bessodes, M.; Abushanab, E.; Antonakis, K. Enantiospecific synthesis of the immunopotentiators
erythro-9-(2-hydroxy-3-nonyl)hypoxanthines and the threo-diastereomers. Tetrahedron Lett. 1984, 25,
5
899–5902. [CrossRef]
5
8. Gartner, M.; Mader, S.; Seehafer, K.; Helmchen, G. Enantio- and Regioselective Iridium-Catalyzed Allylic
Hydroxylation. J. Am. Chem. Soc. 2011, 133, 2072–2075. [CrossRef] [PubMed]
Sample Availability: Samples of (R)-Matsutakeol and compounds 13a–i are available from the authors.
©
2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
CC BY) license (http://creativecommons.org/licenses/by/4.0/).
(