Organocatalytic approach to (s)-1-arylpropan-2-ols: Enantioselective synthesis of the key intermediate of antiepileptic agent (-)-talampanel

Article abstract of DOI:10.1080/00397910903221753

An efficient organocatalytic route for the preparation of enantioselective synthesis of (S)-1-arylpropan-2-ols derivatives, including the key intermediate of antiepileptic agent (-)-talampanel is described. The key steps involved are L-proline-catalyzed a

Full text of DOI:10.1080/00397910903221753

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Organocatalytic Approach to (S)-1-
Arylpropan-2-ols: Enantioselective
Synthesis of the Key Intermediate of
Antiepileptic Agent (-)-Talampanel
Rajiv T. Sawant a & Suresh B. Waghmode a
a Department of Chemistry , University of Pune, Ganeshkhind ,
Pune, Maharashtra, India
Published online: 07 Jul 2010.
To cite this article: Rajiv T. Sawant & Suresh B. Waghmode (2010) Organocatalytic Approach to
(S)-1-Arylpropan-2-ols: Enantioselective Synthesis of the Key Intermediate of Antiepileptic Agent
(-)-Talampanel, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:15, 2269-2277, DOI: 10.1080/00397910903221753
To link to this article: http://dx.doi.org/10.1080/00397910903221753
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Synthetic Communications1, 40: 2269–2277, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903221753
ORGANOCATALYTIC APPROACH TO
(S)-1-ARYLPROPAN-2-OLS: ENANTIOSELECTIVE
SYNTHESIS OF THE KEY INTERMEDIATE OF
ANTIEPILEPTIC AGENT (ꢀ)-TALAMPANEL
Rajiv T. Sawant and Suresh B. Waghmode
Department of Chemistry, University of Pune, Ganeshkhind, Pune,
Maharashtra, India
An efficient organocatalytic route for the preparation of enantioselective synthesis of (S)-1-
arylpropan-2-ols derivatives, including the key intermediate of antiepileptic agent (ꢀ)-
talampanel is described. The key steps involved are L-proline-catalyzed asymmetric
a-aminooxylation of aldehydes and regioselective tosylation of diols followed by reduction.
Keywords: Asymmetric a-aminooxylation; enantioselective synthesis; L-proline; organocatalysis;
(S)-1-arylpropan-2-ols
Over the past few decades, asymmetric synthesis of enantiomerically pure compounds
has emerged as one of the most important areas of organic synthesis because a single
enantiomer is biologically active in most of the chiral drugs.[1] Enantiomerically pure
(S)-1-arylpropan-2-ols 1 are valuable intermediates in the synthesis of pharmaco-
logically and biologically active compounds. For example, (þ)-(S)-a-methyl-1,3-
benzodioxole-5-ethanol 1c is an important chiral building block used for the synthesis
of potent antiepileptic agent (ꢀ)-talampanel,[2] and (S)-1-(4-methoxyphenyl)propan-2-
ol 1a has been used in the synthesis of adrenergic antagonist (R)-tamsulosin hydrochlor-
ide.[3] Moreover, different oxyfunctionalized (S)-1-arylpropan-2-ols 1a–e are important
chiral building blocks in the synthesis of amphetamines[4] such as (R)-2,5-dimethoxy-4-
bromoamphetamine (DOB), a psychedelic hallucinogenic drug and site-selective 5HT
agonist and antagonist,[4b,c] dihydroisocoumarins,[5] and pyranonapthoquinones[6] such
as HRV 3C-protese inhibitor (ꢀ)-thysanone (Fig. 1).[7]
Because of its wide applications in organic synthesis, several synthetic methods
have been developed to obtain optically pure (S)-1-arylpropan-2-ol 1 derivatives.[8–11]
The reported methods are based on resolution of racemic alcohols,[8] asymmetric
reduction of ketones using both chemical[9] and biological means,[10] or stereospecific
synthesis from chiral building blocks,[4a,6b] whereas organocatalytic asymmetric
methods for the synthesis of functionalized (S)-1-arylpropan-2-ol 1 derivatives are
Received May 14, 2009.
Address correspondence to Suresh B. Waghmode, Department of Chemistry, University of Pune,
Ganeshkhind, Pune 411 007, Maharashtra, India. E-mail: suresh@chem.unipune.ernet.in
2269

2270
R. T. SAWANT AND S. B. WAGHMODE
Figure 1. Structure of (S)-1-arylpropan-2-ol intermediates.
rather rare.[11] These methods suffer from drawbacks such as use of expensive chiral
metal complexes, which create environmental problems, loss of half of the isomer,
poor yield with poor enantioselectivity, and high cost. As part of our ongoing research
program on the L-proline-catalyzed asymmetric a-aminooxylation of aldehyde reac-
tion for the synthesis of biologically active compounds and its chiral intermediates,[7]
we herein report an efficient procedure for the preparation of oxy-functionalized
(S)-1-arylpropan-2-ol 1 derivatives by employing L-proline-catalyzed asymmetric
a-aminooxylation of 3-arylpropanaldhyde and regioselective tosylation followed by
LiAlH4 reduction of tosylate.
RESULTS AND DISCUSSION
Asymmetric organocatalysis has been used to obtain chiral compounds in high
optical purity.[12] Among the different organocatalysts, proline, a readily available
(in both D and L forms) bifunctional amino acid, has been found to be an excellent
organocatalyst.[13] It has also been found to be an versatile organocatalyst for the
asymmetric a-hydroxylation of aldehydes and ketones.[14] We envisaged an efficient
procedure for the synthesis of functionalized (S)-1-arylpropn-2-ols 1 based on
L-proline-catalyzed asymmetric a-aminooxylation[14a] reaction (Scheme 1).
The enantioselective synthesis of (S)-1-arylpropn-2-ols 1 is depicted in Scheme 1.
The required known 3-arylpropanaldehydes 2a–e[15a–e] was prepared by following our
method.[7] Our synthetic sequence commenced with asymmetric a-aminooxylation
of 3-arylpropanaldehydes 2a–e with nitrosobenzene as the oxygen source and
Scheme 1. Reagents and conditions: (a) (i) PhNO, L-proline (25 mol%), CH3CN, ꢀ20 ꢁC, 24 h then
MeOH, NaBH4; (ii) H2 (1 atm), Pd=C (10%), rt, 12 h=CuSO4 (30 mol%), 0 ꢁC MeOH, 10 h; (b) (i) Bu2SnO
(2 mol%), p-TsCl (1.02 equiv), Et3N, CH2Cl2, 0 ꢁC to rt, 2–3 h; (ii) LiAlH4 (3 equiv) THF, 0 ꢁC to rt, 5 h.

ORGANOCATALYTIC APPROACH TO (S)-1-ARYLPROPAN-2-OLS
2271
L-proline (25 mol%) as organocatalyst at ꢀ20 ꢁC in CH3CN to give a-aminooxy
aldehyde, followed by in situ reduction with NaBH4 in MeOH to give crude
a-aminooxy alcohol, which was further reduced with Pd=C (10%) in MeOH under
hydrogen atmosphere (for 2a–d) or with 30 mol% CuSO4 in MeOH (for 2e) to cleave
the O-N bond and furnish corresponding diol 3a–e in good yield (69–73%; Table 1).
Selective tosylation[16] of primary hydroxyl functionality of (þ)-diols 3a–e was
achieved using a catalytic amount of dibutyltinoxide (2 mol%) and p-toluenesulfo-
nylchloride. The crude monotosylate was reduced with LiAlH4 (3 equiv.) in dry tetra-
hydrofuran (THF) to afford the alcohols (S)-1a–e in excellent yield (88–92%; Table 1).
The enantiomeric excesses of (S)-1a–d were determined by comparing their specific
rotation with the literature data,[17,18] and (S)-1e was determined by chiral HPLC
ananlysis.[7]
In conclusion, we have successfully demonstrated L-proline-catalyzed asym-
metric a-aminoxylation of aldehydes in the enantioselective synthesis of the key
intermediate of antiepileptic drug (ꢀ)-talampanel and medicinally important (S)-1-
arylpropan-2-ols in good yields with high optical purity. We believe that the alcohol
(S)-1e will serve as a key intermediate in the synthesis of (R)-DOB.
Table 1. L-Proline-catalyzed enantioselective synthesis of (S)-1-arylpropan-2-ols
3
1
25
½aꢂD
25
½aꢂD
2
(Ar)
Yield (%)
69
Yield (%)
88
Ee
a
12.8 (c 2, CHCl3)
þ19.2 (c 0.73, EtOH)
þ35.9 (c 1.65, CHCl3)
þ32.2 (c 1.1, CHCl3)
>98a
b
c
72
71
91
90
þ26.6 (c 1.85, CH2Cl2)
þ34.4 (c 1.0, CHCl3)
98a
98a
d
72
73
þ10.4 (c 1.0, CHCl3)
92
90
þ14.5 (c 1.0, MeOH)
98a
e
þ20.7 (c 1.0, EtOH)
þ21.0 (c 1.0, CHCl3)
>98b
aee determined from the specific rotation value (see Refs. 17 and 18).
bee determined by chiral HPLC analysis.

2272
R. T. SAWANT AND S. B. WAGHMODE
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Varian Mercury spectrometer at
300 and 75 MHz respectively using CDCl3 as a solvent. Chemical shifts were
reported in d units (ppm) with reference to tetramethylsilane (TMS) as an internal
standard, and coupling constants (J) are given in hertz. Infrared (IR) spectra were
recorded on a Shimadzu Fourier transform (FT)–IR 8400 instrument as a thin film
or KBr pellets and are expressed in centimetersꢀ1. Optical rotations were obtained
on Jasco P-1020 digital polarimeter. Gas chromatography (GC) mass spectra were
obtained on Shimadzu GCMS-QP5050A spectrometer. Elemental analyses were car-
ried out with Thermo-Electron Corporation CHNS analyzer, FLASH-EA 1112, at
the Shimadzu Analytical Centre, University of Pune. Analytical high-performance
liquid chromatography (HPLC) was performed on a chiral AD-H column
(250 mm ꢃ 4.6 mm ꢃ 5 m). Melting points were recorded with Thomas Hoover Capil-
lary melting-point apparatus and are uncorrected. Thin-layer chromatography
(TLC) was performed on Merck 60 F254 silica-gel plates. Crude products were
purified by column chromatography on silica gel of 100–200 mesh.
General Reaction Procedure for the Preparation of (R)-1-Aryl
Propan-1,2-diol
L-proline (0.429 g, 3.738 mmol) was added to a stirred solution of aldehyde 2d
(3.77 g, 19.43 mmol) and nitrosobenzene (1.6 g, 14.95 mmol) in CH3CN (40 mL) at
ꢀ20 ꢁC for 24 h and then diluted with MeOH (15 mL). NaBH4 (1.7 g, 44.85 mmol)
was added to this solution. After 25 min, the reaction mixture was quenched with
saturated aqueous NaHCO3, extracted with ethyl acetate (3 ꢃ 30 mL), dried over
Na2SO4, and concentrated under reduced pressure.
The crude a-aminooxy alcohol was dissolved in methanol (25 mL), and to the
solution was added 10% Pd=C (0.2 g). The reaction mixture was stirred in a hydrogen
atmosphere (120 psi) for 12 h. The reaction mixture was filtered through a Celite pad,
concentrated under reduced pressure to afford crude diol 3d, or the CuSO4 ꢄ 5H2O
(1.12 g, 4.485 mmol) was added at 0 ꢁC to the suspension of crude product in MeOH
(30 mL) and stirred for 10 h. The reaction mixture was quenched with saturated
aqueous NH4Cl solution (40 mL), extracted with ethyl acetate (3 ꢃ 40 mL), washed
with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude
product was purified by silica-gel column chromatography (30–50% ethyl acetate=
hexane) to yield pure (þ)-diol 3d (2.29 g) in 72% yield.
General Reaction Procedure for the Preparation of
(S)-1-Arylpropan-2-ol
Dibutyltin oxide (0.019 mg, 0.079 mmol), triethylamine (0.566 mL, 4.04 mmol),
and p-toluenesulfonyl chloride (0.767 g, 4.04 mmol) were added to a stirred solution
of (þ)-diol 3d (0.84 g, 3.96 mmol) in dry CH2Cl2 (20 mL) at 0 ꢁC. The reaction
mixture was stirred for 2–3 h at room temperature, diluted with water (20 mL),
and extracted with CH2Cl2 (3 ꢃ 25 ml). The combined organic layers were washed
with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure

ORGANOCATALYTIC APPROACH TO (S)-1-ARYLPROPAN-2-OLS
2273
to afford crude monotosylate. The crude monotosylate was used for the next step
without any purification. The solution of crude tosylate (1.45 g, 3.96 mmol) in dry
THF (15 mL) was added dropwise to the cooled (0 ꢁC) suspension of LiAlH4 (0.451 g,
11.88 mmol) in dry THF (20 mL) and stirred for 5 h at room temperature. The reac-
tion mixture was quenched with wet Na2SO4, diluted with ethyl acetate (40 mL), fil-
tered through a pad of Celite under vaccum, and concentrated under reduced
pressure. The crude alcohol was purified by silica-gel column chromatography
(18–20% ethyl acetate=hexane) to afford pure (þ)-alcohol 1d (0.72 g) in 92% yield.
Spectral Data
(R)-3-(4-Methoxyphenyl)propane-1,2-diol (3a). Yield 69%; colorless solid;
25
25
mp: 59–61 ꢁC; ½aꢂD þ 12.8 (c 2, CHCl3) {lit.[17(a)] ½aꢂD þ 12.9 (c 2, CHCl3)}; 1H NMR
(300 MHz, CDCl3): d 2.16 (br s, 2H, OH), 2.73 (m, 2H, ArCH2), 3.48 (dd, J ¼ 6.9,
11.1 Hz, 1H, CH2OH), 3.66 (dd, J ¼ 3.3, 11.1 Hz, 1H, CH2OH), 3.77 (s, 3H,
OMe), 3.88 (m, 1H, CHOH), 6.82 (d, 2H, J ¼ 8.1 Hz, ArH), 7.1 (d, 2H, J ¼ 8.7 Hz,
ArH); 13C NMR (75 MHz, CDCl3): d 38.7, 55.1, 65.6, 73.1, 113.7, 129.8, 130.0,
157.9; IR (KBr): nmax 1028, 1153, 1246, 1458, 1514, 1651, 2924, 3437 cmꢀ1; MS:
m=z 182. Anal. calcd. for C10H14O3: C, 65.91; H, 7.74. Found: C, 65.98; H, 7.70.
(R)-3-3(3,4-Dimethoxyphenyl)propane-1,2-diol (3b). Yield 72%; colorless
25
solid; mp: 84–86 ꢁC (lit.[17(b)] mp: 86.5–87 ꢁC), ½aꢂD þ 19.2 (c 0.7, EtOH) {lit.[17(a)]
25
1
½aꢂD þ 18 (c 0.73, EtOH)}; H NMR (300 MHz, CDCl3): d 2.67 (m, 2H, ArCH2),
2.8 (br s, 2H, OH), 3.44 (dd, J ¼ 7.2, 11.4 Hz, 1H, CH2OH), 3.65 (dd, J ¼ 2.7,
11.1 Hz, 1H, CH2OH), 3.83 (s, 3H,OMe), 3.84 (s, 3H, OMe), 4.08 (m, 1H, CHOH),
6.72–6.81 (m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d 39.2, 55.8, 65.7, 72.9,
111.1, 112.3, 121.0, 130.1, 147.4, 148.7; IR (CH2Cl2): nmax 1028, 1261, 1456, 1514,
3379 cmꢀ1; MS: m=z 212 (Mþ). Anal. calcd. for C11H16O4: C, 62.25; H, 7.60. Found:
C, 71.21; H, 7.89.
(R)-5-(2,3-Dihydroxypropyl)-1,3-benzodioxole (3c). Yield 71%; colorless
25
25
solid; mp: 97–99 ꢁC {lit.[17] 93 ꢁC}; ½aꢂD þ 35.9 (c 1.65, CHCl3) {lit.[17(a)] ½aꢂD þ 32
1
(c 1.65, CHCl3)}; H NMR (300 MHz, CDCl3): d 2.04 (br s, 2H, OH), 2.69 (m,
2H, ArCH2), 3.51 (dd, 1H, J ¼ 6.9, 10.8 Hz, CH2OH), 3.69 (dd, 1H, J ¼ 3.3,
11.4 Hz, CH2OH), 3.87 (m, 1H, CHOH), 5.93 (s, 2H, OCH2O), 6.64–6.76 (m, 3H,
ArH); 13C NMR (75 MHz, CDCl3): d 39.4, 65.7, 72.9, 100.8, 108.2, 109.5, 122.1,
131.2, 144.1, 147.6; IR (CH2Cl2): nmax 1037, 1245, 1442, 1448, 1596, 2922,
3369 cmꢀ1; MS: m=z 196 (Mþ). Anal. calcd. for C10H12O4: C, 61.22; H, 6.16. Found:
C, 61.28; H, 6.08.
(R)-3-(2,5-Dimethoxyphenyl)propane-1,2-diol (3d). Yield 72%; colorless
26
solid; mp: 96–97 ꢁC; ½aꢂD þ 10.4 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3): d
2.44–2.61 (br s, 2H, OH), 2.81 (m, 2H, ArCH2), 3.48 (dd, 1H, J ¼ 6.0, 11.4 Hz,
CH2OH), 3.61 (dd, 1H, J ¼ 2.7, 10.8 Hz, CH2OH), 3.76 (s, 3H, OMe), 3.80 (s, 3H,
OMe), 3.91 (m, 1H, CHOH), 6.73–6.82 (m, 3H, ArH); 13C NMR (75 MHz, CDCl3):
d 34.5, 55.6, 55.9, 65.8, 72.2, 111.3, 111.8, 117.3, 127.1, 151.4, 153.4; IR (KBr): nmax
1037, 1224, 1498, 2929, 3421 cmꢀ1; MS: m=z 212 (Mþ). Anal. calcd. for C11H16O4: C,
62.25; H, 7.60. Found: C, 62.20; H, 7.67.

2274
R. T. SAWANT AND S. B. WAGHMODE
(R)-3-(4-Bromo-2,5-dimethoxyphenyl)-1,2-propanediol
(3e)[7]. Yield
25
1
73%; white solid; mp 123–125 ꢁC; ½aꢂD þ 20.7 (c 1, EtOH); H NMR (300 MHz,
CDCl3): d 2.17 (br s, 1H, OH), 2.35 (br s, 1H, OH), 2.78 (m, 2H, CH2Ar), 3.48
(dd, 1H, J ¼ 6.0, 11.4 Hz, CH2OH), 3.62 (dd, 1H, J ¼ 3.3, 11.4 Hz, CH2OH), 3.80
(s, 3H, OMe), 3.84 (s, 3H, OMe), 3.91 (m, 1H, CHOH), 6.75 (s, 1H, ArH), 7.04
(s, 1H, ArH); 13C NMR (75 MHz, CDCl3): d 34.3, 56.1, 56.8, 65.8, 71.7, 109.1,
115.4, 115.6, 126.4, 149.7, 151.5; IR (KBr): nmax 3319, 2847, 1577, 1496, 1388,
1211, 1080, 1032, 958, 852, 796 cmꢀ1; MS: m=z 292 (Mþ) 81Br, 290 (Mþ) 79Br. Anal.
calcd. for C11H15BrO4: C, 45.38; H, 5.19%. Found: C, 45.31; H, 5.26%.
(S)-1-(4-Methoxyphenyl)propan-2-ol (1a). Yield 88%; colorless oil;
25
24
½aꢂD þ 34.5 (c 1.1, CHCl3) {lit.[3] ½aꢂD þ 32.4 (c 1.0, CHCl3)}; H NMR (300 MHz,
CDCl3): d 1.22 (d, J ¼ 6.3 Hz, 3H, CH3), 1.64 (br s, 1H, OH), 2.60 (dd, J ¼ 8.1,
13.5 Hz, 1H, CH2Ar), 2.73 (dd, J ¼ 4.5, 13.5 Hz, 1H, CH2Ar), 3.78 (s, 3H, OMe),
3.95 (m, 1H, CHOH), 6.83 (dd, J ¼ 8.7 Hz, 2H, ArH), 7.1 (dd, J ¼ 8.1 Hz, 2H,
ArH); 13C NMR (75 MHz, CDCl3): d 22.6, 44.7, 55.1, 68.8, 113.7, 130.1, 130.3,
158.0; IR (CH2Cl2): nmax 1047, 1242, 1452, 2985, 3462 cmꢀ1; MS: m=z 166. Anal.
calcd. for C10H14O2: C, 72.26; H, 8.49%. Found: C, 72.31; H, 8.45%.
1
(S)-1-(3,4-Dimethoxyphenyl)propan-2-ol (1b). Yield 91%; colorless oil;
25
20
½aꢂD þ 26.4 (c 1.85, CH2Cl2) {lit.[5a] ½aꢂD þ 26.8 (c 1.85, CH2Cl2)}; 1H NMR
(300 MHz, CDCl3): d 1.24 (d, 3H, J ¼ 5.7 Hz, CH3), 1.60 (br s, 1H, OH), 2.59 (dd,
J ¼ 7.8, 13.5 Hz, 1H, CH2Ar), 2.74 (dd, J ¼ 4.5, 1H, 13.2 Hz, CH2Ar), 3.85 (s, 3H,
OMe), 3.86 (s, 3H, OMe), 3.98 (m, 1H, CHOH), 6.72–6.82 (m, 3H, ArH); 13C
NMR (75 MHz, CDCl3): d 22.7, 45.3, 55.7, 55.8, 68.8, 111.2, 112.4, 121.1, 130.8,
147.5, 148.7; IR (CH2Cl2): nmax 1031, 1139, 1255, 1514, 2929, 3400 cmꢀ1; MS: m=z
196. Anal. calcd. for C11H16O3: C, 67.32; H, 8.22%. Found: C, 67.28; H, 8.29%.
(S)-1-(Benzo[d][1,3]dioxol-5-yl)propan-2-ol (1c). Yield 90%; colorless oil;
25
20
½aꢂD þ 34.2 (c 1.0, CHCl3) {lit.[8(a)]½aꢂD þ 34.0 (c 1.0, CHCl3)}; 1H NMR
(300 MHz, CDCl3): d 1.15 (d, J ¼ 6.0 Hz, 3H, CH3), 1.54 (br s, 1H, OH), 2.52 (dd,
1H, J ¼ 8.1, 13.5 Hz, CH2Ar), 2.74 (dd, 1H, J ¼ 4.5, 13.5 Hz, CH2Ar), 3.86 (m,
1H, CHOH), 5.84 (s, 2H, OCH2O), 6.53–6.66 (m, 3H, ArH); 13C NMR (75 MHz,
CDCl3): d 22.6, 45.3, 68.6, 100.7, 108.1, 109.5, 122.0, 132.0, 145.9, 147.4; IR
(KBr): nmax 1039, 1245, 1490, 2922, 3460 cmꢀ1; MS: m=z 180. Anal. calcd. for
C10H12O3: C, 66.65; H, 6.71%. Found: C, 66.69; H, 6.64%.
(S)-1-(2,5-Dimethoxyphenyl)propan-2-ol (1d). Yield 92%; white solid; mp
25
23
55–57 ꢁC {lit.[4a] mp 56–57 ꢁC} ½aꢂD þ 14.5 (c 1.0, MeOH) {lit.[4a] ½aꢂD þ 14.8 (c
1
1.01, MeOH)}; H NMR (300 MHz, CDCl3): d 1.20 (d, J ¼ 6.3 Hz, 3H, CH3), 1.58
(br s, 1H, OH), 2.66 (dd, J ¼ 8.1, 13.5 Hz, 1H, CH2Ar), 2.8 (dd, J ¼ 4.2, 13.2 Hz,
1H, CH2Ar), 3.73 (s, 3H, OMe), 3.76 (s, 3H, OMe), 4.0 (m, 1H, CHOH), 6.69–6.78
(m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d 22.9, 40.4, 55.6, 55.8, 67.8, 111.2,
111.5, 117.4, 128.0, 151.5, 153.2; IR (KBr): nmax 1045, 1224, 1500, 2949, 3410 cmꢀ1
;
MS: m=z 196. Anal. calcd. for C11H16O3: C, 67.32; H, 8.22%. Found: C, 67.41; H,
8.16%.
(S)-3-(4-Bromo-2,5-dimethoxyphenyl)-2-propanol (1e)[7]. Yield 90%;
ee 98.7% (determined by chiral HPLC equipped with chiral AD-H column

ORGANOCATALYTIC APPROACH TO (S)-1-ARYLPROPAN-2-OLS
2275
(250 mm ꢃ 4.6 mm ꢃ 5 m) with hexane=EtOH=TFA (90:9.9:0.1 v=v=v) as a eluent
25
1
(flow rate 1.2 mL=min); white solid; mp 111–112 ꢁC. ½aꢂD þ 21.0 (c 1, CHCl3); H
NMR (300 MHz, CDCl3): d 1.21 (d, 2H, J ¼ 6.3 Hz, CH3), 2.02 (br s, 1H, OH),
2.64 (dd, 1H, J ¼ 7.9, 13.4 Hz, CH2Ar), 2.79 (dd, 1H, J ¼ 4.4, 13.4, Hz, CH2Ar),
3.76 (s, 3H, OMe), 3.83 (s, 3H, OMe), 4.01 (m, 1H, CHOH), 6.73 (s, 1H, ArH),
7.02 (s, 1H, ArH); 13C NMR (75 MHz, CDCl3): 23.0, 40.3, 56.0, 56.8, 67.6, 109.1,
115.4, 115.7 127.1, 149.6, 151.7; IR (KBr): tmax 3389, 2935, 2843, 1620, 1496,
1437, 1386, 1118, 1030, 943, 852 cmꢀ1; MS: (m=z) 276 (Mþ) 81Br, 274 (Mþ) 79Br.
Anal. calcd. for C11H15BrO3: C, 48.02; H, 5.50%. Found: C, 49.14; H, 5.42%.
ACKNOWLEDGMENTS
R. T. S. thanks the Council of Scientific and Industrial Research (CSIR), New
Delhi, for a senior research fellowship. The authors are thankful to the Shimadzu
Analytical Centre of the Department of Chemistry, University of Pune, for spectral
analysis.
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