Determination of the stereochemistry of C-2' and C-3' positions of taxine NA-1 (2'-hydroxytaxine II) by the asymmetric synthesis of the reductive degradation product of its side chain moiety

Article abstract of DOI:10.3987/COM-12-12480

The reductive degradation of taxine NA-1 (2'-hydroxytaxine II) with n-Bu₄NBH₄ gave taxinine A and (-)-3-dimethylamino-3- phenylpropane-1,2-diol (1) in addition to 11,12-dihydrotaxinine A. The relative stereochemistry of (-)-1 was identical with syn-3-dimethylamino-3-phenylpropane- 1,2-diol, (±)-1b, which was synthesized from cis-2,3-epoxy-3- phenylpropan-1-ol, (±)-7. The absolute configuration of (-)-1 was certified by comparison of the specific optical rotation and the spectroscopic data of (-)-1 with those of (+)-1b and (-)-1b, which were enantioselectively synthesized by Sharpless asymmetric epoxidation reaction of cis-cinnamyl alcohol (6), respectively. As the result, the relative and absolute configuration of (-)-1 was same with that of (-)-1b possessing (2R, 3S) configuration. Thus, the absolute configuration of the side chain of taxine NA-1 (2'-hydroxytaxine II) at C-2' and C-3' positions was determined to be (2'R, 3'S).

Full text of DOI:10.3987/COM-12-12480

HETEROCYCLES, Vol. 85, No. 7, 2012
1697
HETEROCYCLES, Vol. 85, No. 7, 2012, pp. 1697 - 1710. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 4th April, 2012, Accepted, 18th May, 2012, Published online, 25th May, 2012
DOI: 10.3987/COM-12-12480
DETERMINATION OF THE STEREOCHEMISTRY OF C-2' AND C-3'
POSITIONS OF TAXINE NA-1 (2'-HYDROXYTAXINE II) BY THE
ASYMMETRIC SYNTHESIS OF THE REDUCTIVE DEGRADATION
PRODUCT OF ITS SIDE CHAIN MOIETY
Wanxia Tang,a,d,* Hiroshi Minato,b Mariko Ando,c and Masayoshi Andod,*
aDepartment of Pharmacy Engineering, College of Chemistry and Chemical
Engineering, Qiqihar University, 42 Wenhuadajie, Qiqihar, Heilongjiang Province,
b
161006, People’s Republic of China. e-mail: twxzlhzlx@yahoo.co.jp; Graduate
School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku,
c
Niigata, 950-2181, Japan; Technical Division, School of Engineering, Tohoku
University, 6-6 Aramaki-aza-Aoba, Aoba-ku, Sendai 980-8579, Japan;
dDepartment of Chemistry and Chemical Engineering, Niigata University, 2-8050
Ikarashi,
Nishi-ku,
Niigata,
950-2181,
Japan.
e-mail:
andomasa@kdp.biglobe.ne.jp
Abstract – The reductive degradation of taxine NA-1 (2'-hydroxytaxine II) with
n-Bu4NBH4 gave taxinine A and ()-3-dimethylamino-3-phenylpropane-1,2-diol
(1) in addition to 11,12-dihydrotaxinine A. The relative stereochemistry of ()-1
was identical with syn-3-dimethylamino-3-phenylpropane-1,2-diol, ()-1b, which
was synthesized from cis-2,3-epoxy-3-phenylpropan-1-ol, (±)-7. The absolute
configuration of ()-1 was certified by comparison of the specific optical rotation
and the spectroscopic data of ()-1 with those of (+)-1b and ()-1b, which were
enantioselectively synthesized by Sharpless asymmetric epoxidation reaction of
cis-cinnamyl alcohol (6), respectively. As the result, the relative and absolute
configuration of ()-1 was same with that of ()-1b possessing (2R, 3S)
configuration. Thus, the absolute configuration of the side chain of taxine NA-1
(2'-hydroxytaxine II) at C-2' and C-3' positions was determined to be (2'R, 3'S).
Paclitaxel (taxol®) was originally isolated from the stem bark of Taxus brevifolia Nutt.1 Because of its
excellent anticancer activity2 and low content in natural plant resources, numerous attempts of its

1698
HETEROCYCLES, Vol. 85, No. 7, 2012
synthesis were reported until now.3 Because of the difficulty of stereo- and enantio-selective construction
of taxane ring and the side chain moiety, the total synthesis of paclitaxel and its analogs needed complex
steps and their overall yields were very low. Thus, the partial syntheses of the biologically active taxoids
from naturally abundant taxoids are more practical method. In the course of our study to find new
biologically active taxoids and the precursors for the syntheses of biologically active taxoids from Taxus
cuspidata, taxine NA-1 (2'-hydoxytaxine II, A) was isolated in 0.043% from the fresh needles of this
plant as the most abundant basic taxoid.4 The stereochemistry of the N,N-dimethyl-3-phenylisoseryl side
chain at C-5 of A was deduced to be syn by the coupling constant between H-2 and H-3 (J = 9.5 Hz) in
its 1H NMR spectrum, which was good agreement with the dihedral angle between H-2 and H-3 (180°)
of the most stable conformation of syn-N,N-dimethyl-3-phenylisoseryl side chain based on MM 2
calculation. Considering the co-occurrence of A and paclitaxel in the same plant and their common
biosynthetic pathway, the C-5 side chain moiety of
A
was deduced to be
(2'R,3'S)-N,N-dimethyl-3-phenylisoseryl.4
In general, it is difficult to decide the relative- and absolute-stereochemistry of the vicinal substituents of
acyclic compounds according to the spectroscopic analysis. In this manuscript, we want to report the
determination of the stereochemistry at C-2' and C-3' of A through enantioselective synthesis of the side
chain derivative (1), which will be derived by reductive cleavage5 of the ester bonding between taxinine
A6 and N,N-dimethyl-3-phenylisoseryl moiety as shown in Figure 1.
Figure 1. Reductive cleavage of taxine NA-1 (2-hydroxytaxine II, A)
Reduction of taxine NA-1 (2-hydroxytaxine II) (A) with n-Bu4NBH4 in CH2Cl2 at room temperature
gave ()-3-dimethylamino-3-phenylpropane-1,2-diol (1) ([]20 36.0) in 32.3% yield together with
D
taxinine A (B) and 11,12-dihydrotaxinine A (C) as a 1:3 mixture in 27.7% yield (Scheme 1).
Scheme 1

HETEROCYCLES, Vol. 85, No. 7, 2012
1699
The structure of compound B was confirmed to be taxinine A by the comparison of the physical and
spectral data with those reported in the literature.6 The structure of compound C was deduced to be
spectral data with those reported in the literature.6 The structure of compound C was deduced to be
1
13
11,12-dihydrotaxinine A by the analyses of the H and C NMR spectra of C. The stereochemistry of
H-11 and H-12 was determined to be - and -configurations, respectively by NOESY correlations as
shown on the structure C (Scheme 1). Detailed spectral data of compounds of B and C were shown in
experimental section.
The structure of ()-1 was deduced to be 3-dimethylamino-3-phenylpropane-1,2-diol (1) by the analyses
of spectral data as shown in experimental section. In 1H NMR spectra, the coupling constant between H-2
and H-3 (J2,3 =10.5 Hz) of ()-1 was in good accordance with that of H-2' and H-3' (J2',3' = 9.5 Hz) of
taxine NA-1 (A). Thus, the stereochemical relationship at C-2' and C-3' of A was kept in that of C-2 and
C-3 in ()-1. In order to determine the stereochemistry at C-2' and C-3' positions of A, we decided to
synthesize ()-1 by the stereo- and enantio-selective manner. First of all, we attempted the synthesis of
anti-stereoisomer, ()-1a (Scheme 2). Epoxidation of cinnamyl alcohol 2 with t-BuO2H (TBHP) in the
presence of VO(acac)2 in benzene7 gave trans-epoxide ()-3 in 91.8% yield. Treatment of ()-3 with
aqueous 40% Me2NH in the presence of KOH afforded anti-isomer, ()-1a in a quantitative yield. 1H and
13C NMR spectral data of (±)-1a was different from ()-1. The coupling constant between H-2 and H-3 in
1H NMR spectra of (±)-1a was J2,3 = 8.1 Hz, which was different from J2,3 = 10.5 Hz of ()-1.
Scheme 2
Subsequently, we attempted the synthesis of syn-stereoisomer, ()-1b (Scheme 3). Phenylacetylene 4 was
treated with paraformaldehyde in the presence of n-BuLi in THF to give 3-phenyl-2-propyn-1-ol (5) in
92.8% yield. The selective hydrogenation of triple bond of 5 in the presence of Lindlar catalyst afforded
cis-cinnamyl alcohol (6) in 87.7% yield.8 Epoxidation of 6 with m-chloroperoxybenzoic acid (m-CPBA)
in the presence of sodium acetate in dichloromethane gave cis-epoxide ()-7 in 84.7% yield. Protection
of the hydroxyl group of ()-7 by treatment with 2-methoxyethoxymethyl chloride (MEMCl) in the
presence of N,N-diisopropylethylamine (DIPEA) and 4-dimethylaminopyridine (DMAP)9 gave ()-8 in
79.7% yield. Treatment of ()-8 with aqueous 40% Me2NH in the presence of KOH afforded
1-(MEM)oxy-3-dimethylamino-3-phenylpropan-2-ol, ()-9 in 80.2% yield. The syn-stereochemistry of
hydroxyl group at C-2 and dimethylamino group at C-3 in ()-9 is apparent considering the reaction

1700
HETEROCYCLES, Vol. 85, No. 7, 2012
Scheme 3
mechanism of ()-8 to ()-9 in reaction conditions. 2-Methoxyethoxymethyl (MEM) protecting group of
()-9 was removed by treatment with ZnBr2 in boiling chlorobenzene to give syn-isomer, ()-1b 67.9%
yield. The 1H and 13C NMR, IR, and HRMS data of ()-1b were identical with those of ()-1, which was
obtained from taxine NA-1 (2-hydroxytaxine II) (A). The coupling constant of H-2 and H-3 in 1H NMR
spectrum of ()-1b (J2,3 = 10.5 Hz) was in good accordance with that of ()-1. Thus, the stereochemistry
at C-2 and C-3 of ()-1 is syn.
Then, we decided to synthesize the ()-1b and (+)-1b by Sharpless asymmetric epoxidation reaction of 6
in order to determine the absolute configuration of ()-1 (Scheme 4).
Scheme 4
cis-Cinnamyl alcohol (6) was subjected to Sharpless asymmetric epoxidation.10 Epoxidation of 6 with
ter-Butyl hydroperoxide (TBHP) in the presence of ()-diisopropyl D-tartrate [D-()-DIPT], titanium
isopropoxide [Ti(O-i-Pr)4], and molecular sieves (MS) 4A gave optical active epoxyalcohol, ()-7 in
74.1% yield. Similarly, enantiomeric epoxyalcohol ()-7 was produced from 6 with the participation of
L-()-DIPT in 70.0% yield. Protection of the primary hydroxyl groups of ()-7 and ()-7 by MEMCl in
the presence of DIPEA and DMAP gave MEM protected epoxides, (+)-8 and ()-8, respectively.
Ring-opening reaction of ()-8 and ()-8 with aqueous solution of 40% Me2NH in the presence of KOH
gave MEM protected optically active dimethylaminoalcohols, ()-9 and ()-9, respectively. Deprotection
of MEM protecting group of ()-9 and ()-9 with ZnBr2 in boiling chlorobenzene gave ()-1b ([]20
D
+31.6) and ()-1b ([]20 31.5), respectively. Judging from the reaction modes of Sharpless
D

HETEROCYCLES, Vol. 85, No. 7, 2012
1701
asymmetric epoxidation of 6 and the following ring-opening reaction of resulting optically active
epoxides, ()-8 and ()-8, the absolute configuration of ()-1b is (2S, 3R) and that of ()-1b is (2R, 3S).
1
13
The H NMR, C NMR, IR, and HRMS spectra and melting points of ()-1b and ()-1b are
superimposable with those of ()-1 that was obtained from taxine NA-1 (2-hydroxytaxine II) (A) by
reductive cleavage. The sign of the specific rotation of ()-1 was identical with that of ()-1b but was
opposite with that of ()-1b. Thus, the absolute configuration of ()-1 is (2R, 3S). Therefore, the absolute
configuration of C-2 and C-3 positions of taxin NA-1 (2-hydroxytaxine II) (A) was determined to be
(2R, 3S). The synthetic methodology employed in this report may be applicable to the preparation of
C-13 chain modified taxol analogs and the study of their structure-activity relationship.
EXPERIMENTAL
General Experimental Procedures. Melting points were determined by Yanagimoto micro-melting
point apparatus and are uncorrected. Optical rotations were measured using a Horiba Polarimeter
SEPA-200. IR spectra were recorded on a Hitachi 270-30 spectrometer. 1H NMR (200 or 500 MHz) and
13C NMR (50 or 125 MHz) spectra were run on Varian Gemini 200 or Varian UNITY-PS 500
1
1
13
spectrometer in CDCl3. H NMR assignments were determined by H-1H COSY experiments. C NMR
assignments were determined using DEPT, HMQC, and HMBC experiments. HREIMS was recorded on
a JEOL JMS HX-110 spectrometer. Silica gel (200400) was employed for flash column chromatography.
To describe flash column chromatography conditions, we designated column inside diameter (i.d.), silica
gel weight, and solvent in this order. HPLC separations were performed on a Hitachi L-6200 HPLC
instrument monitored by Hitachi L-7400 UV detector and a Shodex SE-61 RI detector. To describe
HPLC conditions, we designated column, solvent, flow rate (mL/min), detector, and retention time (tR) in
this order. Reactions were run under an atmosphere of N2 or Ar. THF was distilled from sodium
benzophenone ketyl. Benzene was dried over CaCl2, distilled, and stored in a bottle with Na wire
equipped with a mercury seal. CH2Cl2 was washed with water, dried over CaCl2, and ditilled from CaH2.
Toluene and chlorobenzene were refluxed over CaH2 for 3 h, distilled, and kept in sealed bottles in the
presence of molecular sieves (MS) 4A. 4.71 M CH2Cl2 solution of ter-butyl hydroperoxide (TBHP) was
prepared from commercially available 70% aqueous solution of TBHP as following. 70% Aqueous
solution of TBHP (300 mL) was extracted with CH2Cl2 (3×100 mL). The CH2Cl2 solution of TBHP was
refluxed for 10 h in a flask equipped with a Dean-Stark column packed with MS 3A.
Reductive Cleavage of Taxine NA-1 (2-Hydroxytaxine II) (A). A mixture of taxine NA-1
(2-hydroxytaxine II ) (A, 41.4 mg, 0.062 mmol), n-Bu4NBH4 (26.0 mg, 0.101 mmol) and CH2Cl2 (0.7
mL) was stirred at room temperature for 7 h. The reaction was quenched by addition of EtOAc (350 L)

1702
HETEROCYCLES, Vol. 85, No. 7, 2012
and the solution was concentrated under reduced pressure to give a pale yellow oily residue (147.4 mg),
which was separated by reversed-phase HPLC [Inertsil prep-ODS 250  10 mm i.d. stainless column
(column A), MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN (1:1:2), 5.0 mL/min, UV (254
nm)]. The first fraction (tR 2.3 min, 7.5 mg) was further purified by reversed-phase HPLC [colum A,
MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN (1:16:2), 5.0 mL/min, UV (254 nm)] to give
spectroscopically pure ()-1 (tR 4.4 min, 3.9 mg, 32.3%) as colorless needles: mp 8586 C; []20D 36.0
1
(CHCl3, c 0.30); H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m, C6H5), 4.09 (1H,
ddd, J = 10.5, 3.9, 2.9 Hz, H-2), 3.66 (1H, dd, J = 11.7, 2.9 Hz, H-1), 3.59 (1H, d, J = 10.5 Hz, H-3), 3.24
13
(1H, dd, J = 11.7, 3.9 Hz, H-1), 2.18 (6H, s, NMe2); C NMR (125 MHz)  132.4 (s, C6H5), 129.8 (d,
C6H5), 128.2 (d, C6H5), 128.0 (d, C6H5), 69.1 (d, C-3), 68.6 (d, C-2), 63.0 (t, C-1), 40.7 (q, NMe2); IR
(CHCl3) νmax 3396, 1498, 1458 cm-1; HREIMS m/z 195.1280 ([M]+, calcd for C11H17NO2 195.1259).
The second fraction [tR 4.6 min, yellow oil, 8.2 mg (27.7%)] was deduced to be 1:3 mixture of taxinine A
1
(B) and 11,12-dihydrotaxinine A (C) by the analyses of H NMR spectra. The 1:3 mixture of B and C
was separated with normal-phase HPLC [Inertsil prep-sil 250  10 mm i.d. stainless column (column B),
EtOAchexane (3:7), 5.0 mL/min, UV (254 nm) detector]. The first peak (tR 26 min) gave
spectroscopically pure C (5.8 mg) as colorless prisms: mp 196198 °C; []20D 9.1 (CHCl3, c 0.15); 1H
NMR (500 MHz)  5.87 (1H, d, J = 10.5 Hz, H-9), 5.74 (1H, br d, J = 2.4 Hz, H-2), 5.45 (1H, t, J = 1.6
Hz, H-20), 5.25 (1H, dd, J= 10.5, 1.2 Hz, H-10), 5.20 (1H, br s, H-20), 4.21 (1H, br t, J = 2.7 Hz, H-5),
3.06 (1H, br s, H-3), 2.93 (1H, qd, J = 6.84, 4.20 Hz, H-12), 2.55 (1H, dd, J = 20.3, 8.1 Hz, H-14), 2.45
(1H, d, J = 20.3 Hz, H-14), 2.08 (3H, s, OAc), 2.03 (3H, s, OAc), 2.02 (3H, s, OAc), 1.96 (1H, dd, J =
13.5, 4.5 Hz, H-7), 1.86 (1H, br d, J = 8.1 Hz, H-1), 1.80 (1H, d, J = 4.2 Hz, H-11), 1.80 (1H, m, H-6),
1.66 (1H, m, H-6), 1.57 (1H, m, H-7), 1.53 (3H, s, H-16), 1.35 (3H, d, J = 6.8 Hz, H-18), 0.95 (3H, s,
H-17), 0.90 (3H, s, H-19); 13C NMR (125 MHz)  214.7 (s, C-13), 169.7 (s, OAc), 169.4 (s, OAc), 169.3
(s, OAc), 146.4 (s, C-4), 115.5 (t, C-20), 76.8 (d, C-10), 76.6 (d, C-5), 72.4 (d, C-9), 71.2 (d, C-2), 56.7 (d,
C-11), 50.9 (d, C-1), 45.7 (d, C-12), 42.8 (s, C-8), 40.4 (d, C-3), 37.3 (t, C-14), 35.6 (s, C-15), 33.0 (q,
C-17), 29.6 (t, C-6), 25.9 (q, C-16), 25.7 (t, C-7), 21.4 (q, OAc), 21.2 (q, OAc), 21.1 (q, OAc), 20.8 (q,
C-18), 17.7 (q, C-19); IR (CHCl3) νmax 3480, 1742, 1698 cm1; HREIMS m/z 478.2573 ([M]+, calcd for
C26H38O8 478.2567). The second peak (tR 44 min) gave spectroscopically pure B (1.9 mg) as colorless
prisms, mp 255257 °C; []20D +82.5 (CHCl3, c 0.87); 1H NMR (500 MHz)  6.09 (1H, d, J = 10.2 Hz,
H-10), 5.86 (1H, d, J = 10.2 Hz, H-9), 5.54 (1H, dd, J = 6.2, 2.0 Hz, H-2), 5.15 (1H, br s, H-20), 4.78 (1H,
br d, J = 1.5 Hz, H-20), 4.19 (1H, br t, J = 2.0 Hz, H-5), 3.59 (1H, br d, J = 6.2 Hz, H-3), 2.77 (1H, dd, J
= 20.0, 6.9 Hz, H-14), 2.36 (1H, d, J = 20.0 Hz, H-14), 2.23 (3H, s, H-18), 2.18 (1H, dd, J = 6.9, 2.0 Hz,
H-1), 2.073 (3H, s, OAc), 2.067 (3H, s, OAc), 2.05 (3H, s, OAc), 1.85 (1H, m, H-7), 1.79 (1H, m, H-6),

HETEROCYCLES, Vol. 85, No. 7, 2012
1703
13
1.76 (3H, s, H-17), 1.68 (1H, m, H-7), 1.60 (1H, m, H-6), 1.13 (3H, s, H-16), 0.88 (3H, s, H-19); C
NMR (125 MHz)  199.7 (s, C-13), 170. 0 (s, OAc), 169.7 (s,OAc), 169.4 (s, OAc), 149.6 (s, C-11),
147.0 (s, C-4), 138.6 (s, C-12), 114.1 (t, C-20), 76.1 (d, C-9), 76.0 (d, C-5), 73.3 (d, C-10), 70.1 (d, C-2),
48.5 (d, C-1), 44.7 (s, C-8), 40.9 (d, C-3), 37.7 (s, C-15), 37.3 (q, C-16), 36.1 (t, C-14), 30.5 (t, C-6), 26.6
(t, C-7), 25.2 (q, C-17), 21.4 (q, OAc), 20.9 (q, OAc), 20.7 (q, OAc), 17.3 (q, C-19), 14.0 (q, C-18); IR
(CHCl3) νmax 3616, 1744, 1676 cm-1.
trans-2,3-Epoxy-3-phenylpropan-1-ol ()-(3). Into a solution of cinnamyl alcohol (499.3 mg, 3.721
mmol) in benzene (37.2 mL) was added VO(acac)2 (99.8 mg, 0.372 mmol). After VO(acac)2 was
dissolved completely, 4.71 M CH2Cl2 solution of TBHP (869.0 L, 4.093 mmol) was added. The mixture
was stirred at rt for 140 min. The reaction was terminated by addition of 0.1 M KI (81 mL) and a
saturated aqueous solution of NaHCO3 (81 mL). The mixture was extracted with EtOAc (4  30 mL). The
combined extracts were washed with 0.1 M Na2S2O3 (4  30 mL), a saturated aqueous solution of
NaHCO3 (3  30 mL), and a saturated aqueous solution of NaCl (3  30 mL), dried (Na2SO4), and
concentrated to give yellow oil (565.7 mg), which was purified by flash column chromatography [3.0 cm
i.d., 27 g, EtOAcHexane (3:7)] to give ()-3 (513.2 mg, 91.8%) as a yellow oil: 1H NMR (200 MHz) 
7.207.40 (5H, m, C6H5), 4.03 (1H, ddd, J = 12.8, 6.3, 2.2 Hz, H-1), 3.92 (1H, d, J = 2.2 Hz, H-3), 3.77
(1H, ddd, J = 12.8, 6.3, 4.1 Hz, H-1), 3.22 (1H, ddd, J = 6.3, 4.1, 2.2 Hz, H-2), 2.502.80 (1H, br s, OH);
13C NMR (50 MHz)  136.6 (s, C6H5), 128.4 (d, C6H5), 128.2 (d, C6H5), 125.66 (d, C6H5), 62.5 (d, C-2),
61.2 (t, C-1), 55.6 (d, C-3); IR (neat) νmax 3428, 1502, 1466 cm-1; HREIMS m/z 150.0677 ([M]+, calcd for
C9H10O2 150.0681).
anti-3-Dimethylamino-3-phenylpropane-1,2-diol ()-(1a). A solution of ()-3 (10.0 mg, 0.067 mmol)
in Me2NH/KOH solution [40% Me2NH (479 L), KOH (6.72 mg)] was stirred at rt for 1.5 h. The reaction
was quenched by adding a saturated aqueous solution of NaCl (2 mL). The solution was saturated with
NaCl by further addition of solid NaCl, and extracted continuously for 12 h with CHCl3. The extract was
dried (Na2SO4) and concentrated to give yellow crystalline residue (15.3 mg), which was purified by
reversed-phase HPLC [column A, MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN (1:16:2), 5.0
mL/min, UV (254 nm) , tR 4.7 min] to give ()-1a (13.0 mg, 100%) as colorless needles: mp 99101 °C;
1H NMR (500 MHz)  7.207.40 (5H, m, C6H5), 4.31 (1H, ddd, J = 8.1, 6.4, 5.6 Hz, H-2), 3.68 (1H, dd, J
= 10.5, 5.6 Hz, H-1), 3.66 (1H, dd, J = 10.5, 6.4 Hz, H-1), 3.49 (1H, d, J = 8.1 Hz, H-3), 2.21 (6H, s,
NMe2); 13C NMR (125 MHz)  133.6 (s, C6H5), 130.9 (d, C6H5), 128.4 (d, C6H5), 128.2 (d, C6H5), 74.3 (d,
C-3), 68.3 (d, C-2), 67.0 (t, C-1), 42.4 (q, NMe2); IR (CHCl3) νmax 3384, 1498, 1458 cm-1; HREIMS m/z
195.1250 ([M]+, calcd for C11H17O2N 195.1259).
3-Phenyl-2-propyn-1-ol (5). Into a solution of phenylacetylene (4.0 mL, 36.421 mmol) in THF (18.0

1704
HETEROCYCLES, Vol. 85, No. 7, 2012
mL) was added 1.51 M hexane solution of BuLi (24.1 mL, 36.421 mmol) at 78 °C. The mixture was
stirred at 78 °C for 2 h and then warmed to 0 °C. Paraformaldehyde (2.19 g, 72.84 mmol) was added
into the mixture, which was stirred at 0 °C for 5 min and at rt for 2.5 h, quenched by adding water, kept
for 30 min at rt, and extracted with ether (4  30 mL). The combined extracts were washed with a
saturated aqueous solution of NaHCO3 (2  30 mL) and a saturated aqueous solution of NaCl (2  30 mL),
dried (Na2SO4), and concentrated to give yellow oily residue (4.832 g), which was purified by flash
column chromatography [5.5 cm i.d., 150 g, EtOAcHexane (2:8)] to give 5 (4.466 g, 92.8%) as a pale
yellow oil: 1H NMR (200 MHz)  7.207.50 (5H, m, C6H5), 4.49 (2H, d, J = 5.2 Hz, H-1), 2.21 (1H, br s,
13
OH); C NMR (50 MHz)  131.6 (d, C6H5), 128.4 (d, C6H5), 128.2 (d, C6H5), 122.4 (s, C6H5), 87.2 (s,
C-2 or C-3), 85.6 (s, C-2 or C-3), 51.5 (t, C-1); IR (neat) νmax 3368, 2196, 1496, 1446 cm-1; HREIMS m/z
132.0590 ([M]+, calcd for C9H8O 132.0575).
cis-Cinnamyl Alcohol (6). Into Lindlar catalyst which was prepared from 5% Pd/BaSO4 (100.7 mg)
and quinoline (500 L) by stirring overnight, 5 (1.001 g, 7.57 mmol) and toluene (75.7 mL) was added.
The mixture was stirred under an atmosphere of H2 for 40 min and filtered through Celite. The filtrate was
washed with 2 M HCl (3 × 30 mL), a saturated aqueous solution of NaCl (2 × 30 mL), dried (Na2SO4)
and concentrated to give an oily crude product (1.040 g), which was subsequently purified by flash
column chromatography [4.0 cm i.d., 50 g, EtOAchexane (3:7)] to give pale yellow oil (948.1 mg). This
was further separated by normal-phase HPLC [Inertsil prep-sil 250  10 mm i.d. stainless column
(column B), EtOAchexane (2:8), 5.0 mL/min, UV (254 nm)]. The peak (tR 11.3 min) gave
spectroscopically pure 6 (890.6 mg, 87.7%) as a pale yellow oil: 1H NMR (200 MHz)  7.107.40 (5H, m,
C6H5), 6.58 (1H, br d, J = 11.7 Hz, H-3), 5.88 (1H, dt, J = 11.7, 6.4 Hz, H-2), 4.44 (2H, dd, J = 6.4, 1.6
13
Hz, H-1), 1.56 (1H, br s, OH); C NMR (50 MHz)  136.5 (s, C6H5), 131.08 (d, C-2), 131.05 (d, C-3),
128.8 (d, C6H5), 128.2 (d, C6H5), 127.2 (d, C6H5), 59.7 (t, C-1); IR (neat) νmax 3344, 1498, 1452 cm-1;
HREIMS m/z 134.0741 ([M]+, calcd for C9H10O 134.0732).
cis-2,3-Epoxy-3-phenylpropan-1-ol ()-(7). Into a solution of 6 (158.3 mg, 1.180 mmol) in CH2Cl2
(11.8 mL) was added m-CPBA (307.9 mg, 1.420 mmol) at 0 °C. The mixture was stirred for 4 h,
quenched by adding a mixture of 0.1 M KI (28.4 mL) and a saturated aqueous solution of NaHCO3 (28.4
mL), and extracted with EtOAc (4  40 mL). The combined extracts were washed with 0.1 M Na2S2O3 (4
 40 mL), a saturated aqueous solution of NaHCO3 (3  40 mL), and a saturated aqueous solution of
NaCl (3  40 mL), dried (Na2SO4), and concentrated to give an oily crude product (176.5 mg), which was
purified by flash column chromatography [2.0 cm i.d., 9.0 g, EtOAcHexane (3:7)] to give ()-7 (150.2
mg, 84.7%) as a pale yellow oil: 1H NMR (500 MHz)  7.207.40 (5H, m, C6H5), 4.19 (1H, d, J = 4.0 Hz,

HETEROCYCLES, Vol. 85, No. 7, 2012
1705
H-3), 3.503.60 (1H, m, H-1), 3.403.50 (2H, m, H-1, H-2), 1.70 (1H, br s, OH); 13C NMR (125 MHz) 
134.6 (s, C6H5), 128.3 (d, C6H5), 127.9 (d, C6H5), 126.2 (d, C6H5), 60.5 (t, C-1), 58.5 (d, C-2), 57.0 (d,
C-3); IR (neat) νmax 3412, 1502, 1458 cm-1; HREIMS m/z 150.0673 ([M]+, calcd for C9H10O2 150.0681).
1-(MEM)oxy-3-phenylpropane-cis-2,3-epoxide ()-(8). Into a solution of ()-7 (110.8 mg, 0.738
mmol) in CH2Cl2 (7.4 mL) was added N,N-diisopropylethylamine (1005 L, 5.909 mmol),
4-dimethylaminopyridine (DMAP, 9.1 mg, 0.0745 mmol), and MEMCl (336.1 L, 2.944 mmol). The
mixture was stirred for 24.5 h at rt and quenched by the addition of a saturated aqueous solution of
NaHCO3 (15 mL). The mixture was extracted by EtOAc (3  15 mL). The combined extracts were treated
in the usual manner to give a crude oily product (217.7 mg), which was purified by flash column
chromatography [2.0 cm i.d., 13.6 g, EtOAcHexane (2:8)] to give ()-8 (140.2 mg, 79.7%) as a pale
yellow oil: 1H NMR (500 MHz)  7.307.40 (5H, m, C6H5), 4.65 (1H, d, J = 6.8 Hz, H-1), 4.61 (1H, d, J
= 6.8 Hz, H-1), 4.15 (1H, d, J =3.9 Hz, H-3), 3.403.60 (7H, m, H-1, H-2, H-2, H-3), 3.35 (3H, s,
H-4); 13C NMR (125 MHz)  134.6 (s, C6H5), 128.1 (d, C6H5), 127.7 (d, C6H5), 126.2 (d, C6H5), 95.5 (t,
C-1), 71.6 (t, C-3), 66.6 (t, C-1), 65.2 (t, C-2), 58.9 (q, C-4), 56.9 (d, C-2), 56.3 (d, C-3); IR (neat) νmax
1502, 1458 cm-1; HREIMS m/z 238.1200 ([M]+, calcd for C13H18O4 238.1205). Numbering of (MEM)oxy
group for assignment of 1H and 13C NMR spectra: [C4'H3OC3'H2C2'H2OC1'H2O-].
syn-1-(MEM)oxy-3-dimethylamino-3-phenylpropan-2-ol ()-(9). A solution of ()-8 (6.5 mg, 0.0273
mmol) in Me2NH/KOH solution [40% Me2NH (212 L), KOH (2.97 mg)] was stirred at rt for 20 h. The
reaction was quenched by the addition of a saturated aqueous solution of NaCl (1 mL). The aqueous layer
was extracted continuously for 6 h with CHCl3. The organic layer was dried (Na2SO4) and concentrated
to give an oily residue (7.3 mg), which was purified by reversed-phase HPLC [column A, MeOH0.05 M
NH4OAc buffer solution (pH 4.8)MeCN (1:5:2), 5.0 mL/min, UV (254 nm), tR 3.5 min] to give ()-9
(6.2 mg, 80.2%) as a pale yellow oil: 1H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m,
C6H5), 4.66 (1H, d, J = 6.6 Hz, H-1), 4.62 (1H, d, J = 6.6 Hz, H-1), 4.19 (1H, ddd, J = 10.7, 4.9, 2.2 Hz,
H-2), 3.58 (1H, d, J = 10.7 Hz, H-3), 3.303.60 (6H, m, H-1, H-2, H-3), 3.30 (3H, s, H-4), 2.18 (6H, s,
NMe2); 13C NMR (125 MHz)  132.6 (s, C6H5), 129.6 (d, C6H5), 128.1 (d, C6H5), 127.9 (d, C6H5), 95.6 (t,
C-1), 71.6 (t, C-2 or C-3), 69.5 (d, C-3), 68.7 (t, C-1), 67.9 (d, C-2), 66.4 (t, C-2 or C-3), 58.8 (q, C-4),
40.6 (q, NMe2); IR (neat) νmax 3420, 1498, 1458 cm-1; HREIMS m/z 283.1775 ([M]+, calcd for
C15H25NO4 283.1784).
syn-3-Dimethylamino-3-phenylpropane-1,2-diol ()-(1b). Into a solution of ()-9 (11.1 mg, 0.0392
mmol) in chlorobenzene (400 L) was added ZnBr2 (48.3 mg, 0.214 mmol). The mixture was stirred at
130 °C for 40 h and quenched by addition of a saturated aqueous solution of NaHCO3 (5 mL). The

1706
HETEROCYCLES, Vol. 85, No. 7, 2012
obtained solution was saturated with NaCl by adding solid NaCl and then extracted continuously for 4 h
with CHCl3. The organic layer was dried (Na2SO4) and concentrated to give a yellow oil, which was
purified by reversed-phase HPLC [column A, MeOH0.05 M NH4OAc buffer solution (pH 4.8) MeCN
(1:16:2), 5.0 mL/min, UV (254 nm) detector, tR 4.3 min] to give ()-1b (5.2 mg, 67.9%) as colorless
microcrystals, mp 8485 °C; 1H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m, C6H5),
4.09 (1H, ddd, J = 10.5, 3.9, 2.9 Hz, H-2), 3.67 (1H, dd, J = 11.7, 2.9 Hz, H-1), 3.64 (1H, d, J = 10.5 Hz,
13
H-3), 3.24 (1H, dd, J = 11.7, 3.9 Hz, H-1), 2.21 (6H, s, NMe2); C NMR (125 MHz)  132.3 (s, C6H5),
129.8 (d, C6H5), 128.24 (d, C6H5), 128.16 (d, C6H5), 69.2 (d, C-3), 68.7 (d, C-2), 62.0 (t, C-1), 40.7 (q,
NMe2); IR (CHCl3) νmax 3392, 1498, 1458 cm-1; HREIMS m/z 195.1252 ([M]+, calcd for C11H17NO2
195.1259).
(2R,3S)-2,3-Epoxy-3-phenylpropan-1-ol ()-(7). Into a mixture of MS 4A (290.2 mg) and CH2Cl2
(10.0 mL) were added Ti(O-i-Pr)4 (320.9 L, 1.087 mmol) and ()-diisopropyl D-tartrate (D-()-DIPT,
277.0 L, 1.304 mmol) at 23 °C. The mixture was stirred for 40 min and 6 (145.9 mg, 1.087 mmol) in
CH2Cl2 (2.0 mL) and 4.71 M CH2Cl2 solution of TBHP (461.6 L, 2.174 mmol) were added. The
reaction mixture was stirred at 23 °C for 2 h and kept in freezer at 23 °C for 47.5 h. The reaction
mixture was quenched by stirring in water for 1 h, extracted with CHCl3 (3  10 mL), and worked up as
usual to give a yellow oil (449.3 mg), which was passed through flash column chromatography [3.5 cm
i.d., 28.6 g, EtOAcHexane (2:8)] to give a pale yellow oil (148.3 mg). This was further purified by
normal-phase HPLC [column B, EtOAcHexane (2:8), 5.0 mL/min, RI, tR 19.9 min] to give ()-7 (121.1
1
mg, 74.1%) as a colorless oil: []25 +49.3 (CHCl3, c 1.63); H NMR (500 MHz)  7.207.40 (5H, m,
D
C6H5), 4.19 (1H, d, J = 3.9 Hz, H-3), 3.503.60 (1H, m, H-1), 3.403.50 (2H, m, H-1, H-2), 1.85 (1H, br
s, OH); 13C NMR (125 MHz)  134.6 (s, C6H5), 128.3 (d, C6H5), 127.9 (d, C6H5), 126.1 (d, C6H5), 60.5 (t,
C-1), 58.6 (d, C-2), 57.0 (d, C-3); IR (neat) νmax 3416, 1502, 1458 cm-1; HREIMS m/z 150.0685 ([M]+,
calcd for C9H10O2 150.0681).
(2R,3S)-1-(MEM)oxy-3-phenylpropan-2,3-epoxide ()-(8). Into a solution of ()-7 (96.3 mg, 0.641
mmol) in CH2Cl2 (6.4 mL) were added N,N-diisopropylethylamine (872.1 L, 5.128 mmol), DMAP (8.2
mg, 0.0671 mmol), and MEMCl (292.8 L, 2.564 mmol). The mixture was stirred at rt for 4.7 h,
quenched by adding a saturated aqueous solution of NaHCO3 (5 mL), and extracted with EtOAc (3  5
mL). The combined extracts were worked up as usual to give an oily crude product (221.8 mg), which
was purified by flash column chromatography [2.2 cm i.d., 9.5 g, EtOACHexane (2:8)] to give ()-8
1
(124.8 mg, 81.7%) as a pale yellow oil: []20 +13.0 (CHCl3, c 1.69); H NMR (500 MHz)  7.307.40
D
(5H, m, C6H5), 4.65 (1H, d, J = 6.8 Hz, H-1), 4.61 (1H, d, J = 6.8 Hz, H-1), 4.16 (1H, d, J = 3.9 Hz,

HETEROCYCLES, Vol. 85, No. 7, 2012
1707
H-3), 3.403.60 (7H, m, H-1, H-2, H-2, H-3), 3.35 (3H, s, H-4); 13C NMR (125 MHz)  134.7 (s, C6H5),
128.2 (d, C6H5), 127.8 (d, C6H5), 126.2 (d, C6H5), 95.5 (t, C-1), 71.6 (t, C-3), 66.6 (t, C-1), 65.2 (t, C-2),
58.9 (q, C-4), 57.0 (d, C-2), 56.3 (d, C-3); IR (neat) νmax 1502, 1458 cm-1; HREIMS m/z 238.1203 ([M]+,
calcd for C13H18O4 238.1205).
(2S,3R)-1-(MEM)oxy-3-dimethylamino-3-phenylpropan-2-ol ()-(9). A solution of ()-8 (101.8 mg,
0.427 mmol) in Me2NH/KOH solution [40% Me2NH (3.1 mL), KOH (43.5 mg, 0.78 mmol)] was stirred
at rt for 35 h. The reaction was quenched by adding a saturated aqueous solution of NaCl (10 mL) and
solid NaCl was further added to saturate the aqueous solution. The aqueous solution was extracted
continuously for 5 h with CHCl3. The organic layer was dried (Na2SO4) and concentrated to give an oily
crude product (138.5 mg), which was purified by reversed-phase HPLC [column A, MeOH0.05 M
NH4OAc buffer solution (pH 4.8)MeCN (1:16:2), 5.0 mL/min, UV (254 nm), tR 8.6 min] to give ()-9
1
(98.7 mg, 81.5%) as a pale yellow oil: []20 +25.2 (CHCl3, c 2.12); H NMR (500 MHz)  7.307.40
D
(3H, m, C6H5), 7.107.20 (2H, m, C6H5), 4.65 (1H, d, J = 6.6 Hz, H-1), 4.61 (1H, d, J = 6.6 Hz, H-1),
4.18 (1H, ddd, J = 10.5, 4.9, 2.2 Hz, H-2), 3.56 (1H, d, J = 10.5 Hz, H-3), 3.303.60 (6H, m, H-1, H-2,
13
H-3), 3.29 (3H, s, H-4), 2.16 (6H, s, NMe2); C NMR (125 MHz)  132.6 (s, C6H5), 129.6 (d, C6H5),
128.1 (d, C6H5), 127.9 (d, C6H5), 95.6 (t, C-1), 71.5 (t, C-2 or C-3), 69.6 (d, C-3), 68.6 (t, C-1), 67.8 (d,
C-2), 66.4 (t, C-2 or C-3), 58.8 (q, C-4), 40.6 (q, NMe2); IR (neat) νmax 3420, 1498, 1458 cm-1;
HREIMS m/z 283.1789 ([M]+, calcd for C15H25NO4 283.1784).
(2S,3R)-3-Dimethylamino-3-phenylpropane-1,2-diol ()-(1b). Into a solution of ()-9 (69.6 mg,
0.246 mmol) in chlorobenzene (2.5 mL) was added ZnBr2 (285.0 mg, 1.266 mmol). The mixture was
stirred at 130 °C for 24 h and quenched by adding saturate aqueous solution of NaHCO3 (5 mL). The
solution was saturated by adding solid NaCl and extracted continuously for 5 h with CHCl3. The organic
layer was dried (Na2SO4) and concentrated to give a yellow oily residue (49.9 mg), which was purified by
reversed-phase HPLC [column A, MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN (1:16:2), 5.0
mL/min, UV (254 nm) , tR 6.8 min] to give ()-1b (30.2 mg, 63.0%) as colorless needles: mp 8586 °C;
[]20D +31.6 (CHCl3, c 2.23); 1H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m, C6H5),
4.09 (1H, ddd, J = 10.5, 3.9, 2.9 Hz, H-2), 3.67 (1H, dd, J = 11.7, 2.9 Hz, H-1), 3.64 (1H, d, J = 10.5 Hz,
13
H-3), 3.24 (1H, dd, J = 11.7, 3.9 Hz, H-1), 2.21 (6H, s, NMe2); C NMR (125 MHz)  132.3 (s, C6H5),
129.8 (d, C6H5), 128.24 (d, C6H5), 128.16 (d, C6H5), 69.2 (d, C-3), 68.7 (d, C-2), 62.0 (t, C-1), 40.7 (q,
NMe2); IR (CHCl3) νmax 3384, 1498, 1458 cm-1; HREIMS m/z 195.1252 ([M]+, calcd for C11H17NO2
195.1259).
(2S,3R)-2,3-Epoxy-3-phenylpropan-1-ol ()-(7). Into a stirring mixture of MS 4A (300 mg) and dry

1708
HETEROCYCLES, Vol. 85, No. 7, 2012
CH2Cl2 (10.0 mL) were added Ti(O-i-Pr)4 (330.0 L, 1.118 mmol) and ()-diisopropyl L-tartrate
(L-()-DIPT, 285.0 L, 1.342 mmol) at 23 °C. After stirring for 40 min at this temperature, 6 (150.0 mg,
1.118 mmol) in CH2Cl2 (2 mL) and 4.71 M CH2Cl2 solution of TBHP (475.0 L, 2.236 mmol) were
added to the mixture. The reaction mixture was stirred at 23 °C for 2 h and kept in freezer at 23 °C for
28 h. The reaction was quenched by water and stirred for 1h and extracted with CHCl3 (3  10 mL). The
extracts were worked up as usual to give yellow oily residue (546.3 mg), which was purified by flash
column chromatography [3.5 cm i.d., 31.7 g, EtOAcHexane (2:8)] and normal-phase HPLC [column B,
EtOAcHexane (2:8), 5.0 mL/min, RI detector, tR 19.0 min] to give ()-7 (112.5 mg, 70.0%) as a yellow
1
oil: []25 51.5 (CHCl3, c 1.45); H NMR (500 MHz)  7.207.40 (5H, m, C6H5), 4.19 (1H, d, J = 3.7
D
13
Hz, H-3), 3.503.60 (1H, m, H-1), 3.403.50 (2H, m, H-1, H-2), 1.77 (1H, br s, OH); C NMR (125
MHz)  134.6 (s, C6H5), 128.3 (d, C6H5), 127.9 (d, C6H5), 126.1 (d, C6H5), 60.5 (t, C-1), 58.6 (d, C-2),
57.0 (d, C-3); IR (neat) νmax 3424, 1502, 1458 cm-1; HREIMS m/z 150.0677 ([M]+, calcd for C9H10O2
150.0681).
(2S,3R)-1-(MEM)oxy-3-phenylpropan-2,3-epoxide ()-(8). DIPEA (843.5 L, 4.960 mmol), DMAP
(8.0 mg, 0.0655 mmol), and MEMCl (292.8 L, 2.480 mmol) were added dropwise to a solution of ()-7
(93.1 mg, 0.620 mmol) in CH2Cl2 (6.2 mL). The mixture was stirred at rt for 5.8 h, quenched by adding a
saturate aqueous solution of NaHCO3 (5 mL), and extracted with EtOAc (3  5 mL). The combined
extracts were worked up as usual to give yellow oily residue (177.7 mg), which was purified by flash
column chromatography [2.2 cm i.d., 9.5 g, EtOACHexane (2:8)] to give ()-8 (124.7 mg, 84.4%) as a
pale yellow oil: []20D 13.4 (CHCl3, c 1.92); 1H NMR (500 MHz)  7.307.40 (5H, m, C6H5), 4.66 (1H,
d, J = 6.8 Hz, H-1), 4.61 (1H, d, J = 6.8 Hz, H-1), 4.16 (1H, d, J = 3.9 Hz, H-3), 3.403.60 (7H, m, H-1,
13
H-2, H-2, H-3), 3.35 (3H, s, H-4); C NMR (125 MHz)  134.6 (s, C6H5), 128.1 (d, C6H5), 127.8 (d,
C6H5), 126.2 (d, C6H5), 95.5 (t, C-1), 71.6 (t, C-3), 66.6 (t, C-1), 65.2 (t, C-2), 58.9 (q, C-4), 56.9 (d,
C-2), 56.3 (d, C-3); IR (neat) νmax 1502, 1458 cm-1; HREIMS m/z 238.1207 ([M]+, calcd for C13H18O4
238.1205).
(2R,3S)-1-(MEM)oxy-3-dimethylamino-3-phenylpropan-2-ol ()-(9). A solution of ()-8 (92.9 mg,
0.390 mmol) in Me2NH/KOH solution [40% Me2NH (2.8 mL), KOH (39.3 mg, 0.70 mmol)] was stirred
at rt for 27 h. The reaction was quenched by adding a saturated NaCl solution (10 mL). The aqueous
solution was saturated by further addition of solid NaCl and extracted continuously for 9 h with CHCl3.
The CHCl3 layer was dried (Na2SO4) and concentrated to give yellow oily residue (115.3 mg), which was
purified by reversed-phase HPLC [column A, MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN
(1:16:2), 5.0 mL/min; UV (254 nm), tR 8.2 min] to give ()-9 (89.9 mg, 81.3%) as a pale yellow oil:

HETEROCYCLES, Vol. 85, No. 7, 2012
1709
[]20D 24.8 (CHCl3, c 1.63); 1H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m, C6H5),
4.66 (1H, d, J = 6.6 Hz, H-1), 4.62 (1H, d, J = 6.6 Hz, H-1), 4.19 (1H, ddd, J = 10.5, 5.1, 2.2 Hz, H-2),
3.58 (1H, d, J = 10.5 Hz, H-3), 3.303.60 (6H, m, H-1, H-2, H-3), 3.30 (3H, s, H-4), 2.17 (6H, s,
NMe2); 13C NMR (125 MHz)  132.6 (s, C6H5), 129.6 (d, C6H5), 128.1 (d, C6H5), 127.9 (d, C6H5), 95.6 (t,
C-1), 71.5 (t, C-2 or C-3), 69.6 (d, C-3), 68.6 (t, C-1), 67.8 (d, C-2), 66.4 (t, C-2 or C-3), 58.8 (q, C-4),
40.6 (q, NMe2); IR (neat) νmax 3428, 1498, 1458 cm-1; HREIMS m/z 283.1783 ([M]+, calcd for
C15H25NO4 283.1784).
(2R,3S)-3-Dimethylamino-3-phenylpropane-1,2-diol ()-(1b). Into a solution of ()-9 (66.1 mg,
0.233 mmol) in chlorobenzene (2.3 mL) was added ZnBr2 (263.0 mg, 1.168 mmol). The mixture was
stirred at 130 C for 19 h. The reaction was quenched by adding a saturate aqueous solution of NaHCO3
(5 mL) and worked up as usual to give a yellow oily residue (46.0 mg), which was purified by
reversed-phase HPLC [column A, MeOH0.05 M NH4OAc buffer solution (pH 4.8)MeCN (1:16:2), 5.0
mL/min, UV (254 nm), tR 6.8 min] to give ()-1b (20.7 mg, 45.4%) as colorless needles: mp 8586 C;
[]20D 31.5 (CHCl3, c 1.59); 1H NMR (500 MHz)  7.307.40 (3H, m, C6H5), 7.107.20 (2H, m, C6H5),
4.09 (1H, ddd, J = 10.5, 3.9, 2.9 Hz, H-2), 3.65 (1H, dd, J = 11.7, 2.9 Hz, H-1), 3.60 (1H, d, J = 10.5 Hz,
13
H-3), 3.24 (1H, dd, J = 11.7, 3.9 Hz, H-1), 2.18 (6H, s, NMe2); C NMR (125 MHz)  132.4 (s, C6H5),
129.7 (d, C6H5), 128.1 (d, C6H5), 128.0 (d, C6H5), 69.1 (d, C-3), 68.6 (d, C-2), 63.0 (t, C-1), 40.7 (q,
NMe2); IR (CHCl3) νmax 3400, 1498, 1458 cm-1; HREIMS m/z 195.1274 ([M]+, calcd for C11H17NO2
195.1259).
ACKNOWLEDGEMENTS
This work was supported by Natural Science Foundation for the Return of the Students Studied in
Foreign Country from Heilongjiang Province of China (LC201029), Start Research Fundation Projects for
the Return of the Students Studied in Foreign Country from Ministry of Education of China, Foundation
for University Key Teacher of Heilongjiang Province of China (1251G069), and the Program for Young
Teachers Scientific Research in Qiqihar University (2010K-Z06). This work was also supported by a
Grant-in-Aid for Scientific Research (B) No.1055320 from the Ministry of Education, Science, Sports
and Culture of Japan and Kobe Natural Products and Chemicals Co., Ltd.
REFERENCES
1.
M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon, and A. T. McPhail, J. Am. Chem. Soc., 1971,
93, 2325.
2.
P. B. Schiff, J. Fant, and S. B. Horwitz, Nature, 1979, 277, 665.

1710
HETEROCYCLES, Vol. 85, No. 7, 2012
3.
4.
Y. Qian, X. Xu, L. Jiang, D. Prajapati, and W. Hu, J. Org. Chem., 2010, 75, 7483, and references
cited therein.
M. Ando, J. Sakai, S. Zhang, Y. Watanabe, K. Kosugi, T. Suzuki, and H. Hagiwara, J. Nat. Prod.,
1997, 60, 499; L. Wang, L. Bai, D. Tokunaga, Y. Watanabe, T. Hasegawa, J. Sakai, W. Tang, Y.
Bai, K. Hirose, T. Yamori, A. Tomida, T. Tsuruo, and M. Ando, J. Wood Sci., 2008, 54, 390.
N. F. Magri, D. G. I. Kingston, C. Jitrangsri, and T. Piccariello, J. Org. Chem., 1986, 51, 3239.
H. C. Chiang, M. C. Woods, Y. Nakadaira, and K. Nakanishi, Chem. Comm., 1967, 1201.
C. H. Behrens, S. Y. Ko, K. B. Sharpless, and F. J. Walker, J. Org. Chem., 1985, 50, 5687.
J. Denis, A. E. Greene, A. A. Serra, and M. Luche, J. Org. Chem., 1986, 51, 46.
E. J. Corey, J. Gras, and P. Ulrich, Tetrahedron Lett., 1976, 809.
5.
6.
7.
8.
9.
10. Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, and K. B. Sharpless, J. Am.
Chem. Soc., 1987, 109, 5765.