Enantioselective synthesis of 2- and 3-benzofuryl β-amino alcohols

Article abstract of DOI:10.3987/COM-00-9143

Enantioselective reduction of 2- and 3-bromoacetylbenzofurans with (-)-B-chlorodiisopinocampheylborane produced the corresponding bromohydrins which were transformed into (S)-(benzofuran-2-yl)oxirane of 70% ee and (S)-(benzofuran-3-yl)oxirane of 71% ee, respectively. The epoxides treated with primary alkylamines gave the corresponding (S)-1-(benzofuran-2- and -3-yl)-2-(alkylamino) ethanols.

Full text of DOI:10.3987/COM-00-9143

HETEROCYCLES, Vol. 55, No. 3, pp. 569 - 577, Received, 12th December, 2000
ENANTIOSELECTIVE SYNTHESIS OF 2- AND 3-BENZOFURYL
β-AMINO ALCOHOLS
Marek Zaidlewicz*, Aldona Chechłowska, Andrzej Prewysz-Kwinto, and Andrzej
Wojtczak
E-mail: zaidlevi@chem.uni.torun.pl
Faculty of Chemistry, Nicolaus Copernicus University, 87–100 Toruń, Poland
Abstract – Enantioselective reduction of 2- and 3-bromoacetylbenzofurans with
(–)-B-chlorodiisopinocampheylborane produced the corresponding bromohydrins
which were transformed into (S)-(benzofuran-2-yl)oxirane of 72% ee and (S)-
(benzofuran-3-yl)oxirane of 71% ee, respectively. The epoxides treated with
primary alkylamines gave the corresponding (S)-1-(benzofuran-2- and -3-yl)-2-
(alkylamino)ethanols.
In spite of a long history of studies on the synthesis of benzofuran derivatives, enantioselective
approaches to these compounds and preparation of enantiomers via resolution of racemates is the subject
of current interest, justified by their diverse pharmacological activity.1-5 Among these derivatives, amino
alcohols play an important role showing antiarrhythmic,6,7 enzyme inhibitiory,5,7 antihypertensive,8 and
β-adrenoacceptor blocking activity.9 For example, bufuralol, a derivative of 1 proved effective for
treatment of hypertension,10 is a potent nonselective β-adrenergic receptor antagonist with partial β2
agonist preperties,9,11 and an inhibitor of testosterone 6β-hydroxylase.5
The aim of this study was an enantioselective synthesis of β-amino alcohols (1) and (2) using as a key
reaction the reduction of the corresponding bromo ketones with (−)-B-chlorodiisopinocampheylborane
((–)-DIP-Cl).12,13
OH
NHR
O
NHR
O
OH
1; R = alkyl
2; R = alkyl

A readily available 2-acetylbenzofuran (3) was the starting material for the synthesis of β-amino alcohols
(1a, 1b) (Scheme 1). Bromination of 3 with bromine / aluminum chloride gave bromo ketone (4) in good
yield. Enantioselective reduction of 4 with (−)-DIP-Cl afforded bromohydrin (5) which was transformed
into epoxide (6) of 70% ee. The (S)–configuration of the epoxide was correlated with (S)-1-(benzofuran-
2-yl)ethanol (7)14 by the reduction of 6 with lithium aluminum hydride and comparison of the sign of
rotation. Alcohol (7) of 91% ee was independently prepared by the reduction of 3 with (−)-DIP-Cl. The
X-Ray analysis of its p-nitrobenzoate (7a) is shown on Scheme 1. Epoxide (6) was treated with n-butyl-
and tert-butylamine to give the corresponding amino alcohols ((S)-1a, (S)-1b).15
(–)-DIP-Cl
CH3
THF
CH3
OH
O
O
O
3
7
Br2/AlCl3,
CH2Cl2
LiAlH4,
Et2O
The X–Ray structure of 7a
Crystal data: orthorhombic, P212121, a = 5.861(1),
b = 8.708(1), c = 28.725(2) Å, V = 1466.1(3) Å3, Z = 4,
Dx-ray = 1.410 Mg/m3, F(000) = 648, µ = 0.881 mm-1,
R1 = 0.0426, wR2 = 0.1163, the Flack parameter
x =0.03(26).
O
Br
O
4
1. (–)-DIP-Cl, THF
2. (HOCH2CH2)2NH, Et2O
RNH2
3M NaOH
H2O
O
Br
O
O
NHR
O
OH
OH
5
6
(S)-1a ; R = n-Bu
(S)-1b ; R = t-Bu
Scheme 1
3-Acetylbenzofuran (10), the starting material for the synthesis of 1-(benzofuran-3-yl)-2-(isopropyl-
amino)ethanol (Scheme 2), is not so readily available as its isomer (3). The literature procedures involve
several steps and the overall yield of 10 is low.16 Considering other possibilities we focused on 3-formyl-
benzofuran (9) as an intermediate. Since the reported syntheses of 9 require several steps, we decided to
study the oxidation of a readily available 3-methylbenzofuran (8) with selenium dioxide. Surprisingly, no

oxidation product was formed after refluxing the reagents in ethanol for several hours. Fortunately, in
dioxane 9 was produced cleanly in 77% yield. Treatment with methylmagnesium iodide followed by
oxidation of the crude product alcohol with pyridinium chlorochromate afforded 10 in 60% yield.
O
CH3
CHO
SeO2
1,4 - Dioxane
1. MeMgI
2. PCC
77 %
O
O
O
Acetic acid 60 %
Pyridine
Ethanol
40 %
no reaction
8
9
10
Bromination of 10 with pyridinium tribromide proceeded regioselectively to give bromo ketone (11) with
no competing substitution at the 2-position (Scheme 2).
OH
(–)-DIP-Cl
THF
CH3
10
O
14
C5H5NHBr3,
AcOH
O
The X–Ray structure of 14a
Br
Crystal data: monoclinic, C2, a = 31.389(6), b = 7.173(1),
LiAlH4,
Et2O
c = 6.937(1) Å, β = 98.56(3)°, V = 1544.5(4) Å3, Z = 4,
O
D
x-ray = 1.339 Mg/m3, F(000) = 648, µ = 0.836 mm-1,
11
R1 = 0.0483, wR2 = 0.1301, the Flack parameter
x = –0.27(38).
1. (–)-DIP-Cl, THF
2. (HOCH2CH2)2NH, Et2O
OH
OH
O
i
Br
NHPr
i-PrNH2
NaH
THF
O
O
O
12
13
(S)-2a
Scheme 2
The bromo ketone was reduced with (−)-DIP-Cl to bromohydrin (12), which was treated with sodium
hydride in tetrahydrofuran to give (S)-epoxide (13) of 71% ee. Its configuration was correlated with (S)-1-

(benzofuran-3-yl)ethanol (14) prepared by the reduction of 10 with (−)-DIP-Cl. The absolute
configuration of 14 was established by the X-Ray analysis of its p-nitrobenzoate (14a). Epoxide (13) was
treated with isopropylamine to give amino alcohol ((S)-2a). A small amount of its regioisomer (~5 %)
present in the crude reaction product was removed by crystallization.
In conclusion, the enantioselective reduction of α-bromo ketones (4) and (11) with (−)-DIP-Cl provides a
convenient access to the corresponding β-amino alcohols. The reaction sequence leading to these
products employs simple reagents, does not require tedious separations, and can be scaled up to larger
quantities. Convenient syntheses of 3-formyl- and 3-acetylbenzofuran, which in general are more difficult
to prepare as compared to the corresponding 2-substituted derivatives, have been developed. These
compounds can serve as useful intermediates in transformations leading to other 3-substituted
benzofurans.
EXPERIMENTAL
1H, 13C, and 11B NMR spectra were recorded on a Varian Gemini 200 instrument. IR spectra were
recorded on a Perkin Elmer 200 spectrophotometer. X-Ray structures were determined using a Kuma
KM4 diffractometer with Cu Kα radiation. GC analyses were performed on a Chrom 5 chromatograph
provided with a flame ionisation detector and two columns: 2 m x 4 mm, OV-17 on Chromosorb G AW
DMCS 80-100 mesh, and 3 m x 4 mm, 15% Carbowax 20M on Chromosorb W NAW 80-100 mesh.
A Hewlett-Packard chromatograph was provided with a flame ionisation detector and two capillary
columns: SPB-5, 30 m x 0.32 mm, and Supelcowax-10, 30 m x 0.32 mm. Preparative GC separations
were carried out using a GCHF 18.3 chromatograph provided with a column 1 m x 10 mm, 20%
Carbowax 20M on Chromosorb W 60-80 mesh. HPLC analyses were carried out with a liquid
chromatography system model LC-5B, Laboratorni Pristroje, Praha, equipped with a Daicel Chiralcel OJ
column 25 cm x 4.6 mm and a precolumn 5 cm x 4.6 mm. Rotations were measured on a Lot-Oriel S-2
automatic polarimeter. Tetrahydrofuran was freshly distilled from sodium benzophenone ketyl.
2-Acetylbenzofuran (3),17 2-bromoacetylbenzofuran (4)18 and 3-methylbenzofuran (8)19 were prepared
according to the literature. (−)-B-Chlorodiisopinocampheylborane ((–)-DIP-Cl) was a commercial product
(Aldrich).
(S)-(−)-(Benzofuran-2-yl)oxirane (6)
A mixture of (−)-DIP-Cl (8.71 g, 27.1 mmol) and tetrahydrofuran (40 mL) was cooled to –30 °C under
nitrogen and a solution of 4 (5.88 g, 24.6 mmol) in tetrahydrofuran (15 mL) was slowly added. The
mixture was stirred at this temperature for 3 h, and then at –5 °C for 24 h. The 11B NMR spectrum
indicated no signal at δ 32 corresponding to DIP-Cl. The solvent was removed under vacuum and ether

(30 mL) was added, followed with diethanolamine (5.65 g, 53.7 mmol). The mixture was stirred for 2 h at
rt. The precipitated solid was filtered off and washed with ether (2x10 mL). The combined ether solution
was dried over magnesium sulfate. Solvent was removed under vacuum and crude 5 (11.60 g) was
obtained. A mixture of 3M sodium hydroxide (87 mmol, 29 mL), ether–pentane (1 : 1) (150 mL) and the
crude 5 was stirred for 3 h at rt. The organic layer was separated, and the aqueous phase was extracted
with ether (3x10 mL). The combined ether solution was dried over magnesium sulfate. Solvent was
removed and 6 was isolated by distillation, bp 81–84 °C/0.6 mmHg, (1.67 g, 42%). An analytical sample
was isolated by preparative GC, [α]D20 –31.86° (c 25.24, CHCl3). 1H NMR (CDCl3) δ: 3.21 (1H, dd, J=5.4
Hz, J=4.0 Hz, CH), 3.36 (1H, dd, J=5.4 Hz, J=2.6 Hz, CH), 4.00 (1H, dd, J=4.0 Hz, J=2.6 Hz, CH), 6.80 (1H, s,
CHAr), 7.15–7.35 (2H, m, CHAr), 7.40–7.60 (2H, m, CHAr).13C NMR (CDCl3) δ: 46.51 (CH), 48.17(CH2),
106.40, 111.25, 120.91, 122.89, 124.65, 127.91, 152.80, 154.80. Anal. Calcd for C10H8O2: C, 74.99; H, 5.03.
Found: C, 74.68; H, 5.00.
For determining the enantiomeric excess, a solution of 6 (0.40 g, 2.5 mmol) in ether (2 mL) was added
dropwise to a solution of lithium aluminum hydride (0.10 g, 2.6 mmol) in ether (3 mL). The mixture was
stirred for 0.5 h at rt. Water (1 mL) was slowly added and the mixture was stirred for 0.5 h. Precipitated
solid was filtered off and washed with ether (10 mL). The ether solution was dried over magnesium
20
sulfate, and 7 was isolated by distillation (0.36 g, 90%), bp 109–110 °C/ 1 mmHg, [α]D –25.40°
(c 10.38, CHCl3), 70% ee (by comparison of the sign of rotation with a sample of 7 prepared as described
below).
(S)-(–)-1-(Benzofuran-2-yl)ethanol (7)
A solution of 3 (3.20 g, 20.0 mmol) in THF (20 mL) was slowly added to a mixture of (–)-DIP-Cl (7.70 g,
24.0 mmol) and THF (25 mL) at –30 °C under nitrogen. The mixture was stirred at this temperature for
11
3 h and then at rt for 24 h. The B NMR spectrum indicated no signal at δ 32 corresponding to DIP-Cl.
The solvent was removed under vacuum and ether (20 mL) was added, followed with diethanolamine
(5.01 g, 47.6 mmol). The mixture was stirred for 2 h at rt. The precipitated solid was filtered off and
washed with ether (2x10 mL). The combined ether solution was dried over magnesium sulfate. The
product was isolated by distillation, (1.48 g, 46%), bp 106–108 °C/1.2 mmHg. An analytical sample was
20
purified by preparative GC, [α]D –33.27° (c 10.17, CHCl3). HPLC analysis, Daicel Chiralcel OJ
20
1
column, n–hexane/isopropanol (9 : 1) showed 91% ee. lit.14 (R)-7, [α]D +19.99° (c 1.21, CHCl3). H
NMR (CDCl3) δ: 1.64 (3H, d, J=4.4 Hz, CH3), 2.92 (1H, br s, OH), 5.00 (1H, q, J=4.4 Hz, CH), 6.60 (1H,
13
s, CHAr), 7.20–7.35 (2H, m, CHAr), 7.45–7.55 (2H, m, CHAr). C NMR (CDCl3) δ: 21.28 (CH3), 63.97
(CH), 101.66, 111.08, 120.95, 122.64, 124.01, 128.06, 154.65, 160.19. Anal. Calcd for C10H10O2: C,
74.06; H, 6.20. Found: C, 74.02; H, 6.18. p-Nitrobenzoate (7a), mp 59–60 °C (from n-hexane). 1H NMR

(CDCl3) δ: 1.85 (3H, d, J=4.4 Hz, CH3), 6.38 (1H, q, J=4.4 Hz, CH), 6.80 (1H, s, CHAr), 7.20–7.35 (2H,
13
m, CHAr), 7.45–7.60 (2H, m, CHAr), 8.21–8.29 (4H, m, CHAr). C NMR (CDCl3) δ: 18.21 (CH3), 67.03
(CH), 104.93, 111.42, 121.36, 123.01, 123.50 (2CH), 124.85, 127.68, 130.88 (2CH), 135.46, 150.63,
154.92, 155.11, 163.84 (C=O). Anal. Calcd for C17H13 NO5: C, 65,59; H, 4.21; N, 4.49. Found: C, 65.38;
H, 4.10; N, 4.45. The crystal data and the X-Ray structure are given on Scheme 1.
(S)-(–)-1-(Benzofuran-2-yl)-2-(n-butylamino)ethanol ((S)-1a). Typical procedure
A solution of 6 (1.00 g, 6.25 mmol) in n–butylamine (5 mL) was placed in an autoclave and kept at 100 °C for
3 h. Excess of n–butylamine was removed and the product was crystallized from cyclohexane (1.20 g, 83%),
20
1
mp 51–53 °C, [α]D –30.88° (c 10.00, THF). H NMR (CDCl3) δ: 0.90 (3H, t, J=7.0 Hz, CH3), 1.25–1.55
(4H, m, CH2), 2.65 (2H, t, J=6.8 Hz, CH2), 2.75 (2H, br s, OH, NH), 3.02 (1H, dd, J=12.0 Hz, J=4.8 Hz,
CH2N), 3.10 (1H, dd, J=12.0 Hz, J=6.8 Hz, CH2N), 4.87 (1H, dd, J=6.8 Hz, J=4.8 Hz, CH-O), 6.70 (1H, s,
CHAr), 7.15–7.30 (2H, m, CHAr), 7.40–7.60 (2H, m, CHAr). 13C NMR (CDCl3) δ: 13.89 (CH3), 20.29 (CH2),
32.06 (CH2), 49.24 (CH2), 53.29 (CH2), 66.02 (CH), 102.89, 111.09, 120.86, 122.63, 123.88, 128.09, 154.73,
158.40. Anal. Calcd for C14H19 NO2: C, 72.07; H, 8.21; N, 6.00. Found: C, 72.00; H; 8.02, N; 5.89.
(S)-(–)-1-(Benzofuran-2-yl)-2-(tert-butylamino)ethanol ((S)-1b)
20
1
Yield (0.91 g, 61%), mp 149–151 °C (from cyclohexane). [α]D –30.36° (c 10.00, THF). H NMR
(CDCl3) δ: 1.07 (9H, s, CH3), 2.70 (2H, br s, OH, NH), 2.98 (1H, dd, J=11.6 Hz, J=6.2 Hz, CH2), 3.05
(1H, dd, J=11.6 Hz, J=4.8 Hz, CH2), 4.80 (1H, dd, J=6.2 Hz, J=4.8 Hz, CH), 6.70 (1H, s, CHAr), 7.15–
7.30 (2H, m, CHAr), 7.40–7.60 (2H, m, CHAr). 13C NMR (CDCl3) δ: 29.13 (CH3), 46.40 (CH2), 50.32 (C),
66.74 (CH), 102.88, 111.08, 120.81, 122.62, 123.79, 128.27, 154.89, 158.76. Anal. Calcd for C14H19 NO2: C,
72.07; H, 8.21; N, 6.00. Found: C, 72.00; H, 8.20; N, 5.89.
3-Formylbenzofuran (9)
A mixture of 8 (10.02 g, 75.8 mmol) and selenium dioxide (9.70 g, 87.4 mmol) in dry 1,4-dioxane (100
mL) was refluxed for 48 h. Black precipitate was filtered off and the product was isolated by distillation,
(8.62 g, 77%), bp 68–69 °C/0.4 mmHg, mp 37–38 °C. lit.,20 bp 72–74 °C/2 mmHg, mp 38–39 °C.
1H NMR (CDCl3) δ: 7.30–7.50 (2H, m, CHAr), 7.50–7.60 (1H, m, CHAr), 8.15–8.22 (1H, m, CHAr), 8.26
(1H, s, CHAr), 10.17 (1H, s, CHO). 13C NMR (CDCl3) δ: 111.66, 122.60, 122.94, 123.01, 124.86, 126.28,
155.31, 155.48, 184.77 (C=O).
3-Acetylbenzofuran (10)
A solution of 9 (8.50 g, 58.2 mmol) in ether (25 mL) was slowly added with stirring at 0 °C to a solution
of methylmagnesium iodide, prepared from magnesium (1.70 g, 69.9 mmol) and iodomethane (9.94 g,
70.0 mmol), in ether (40 mL). The mixture was left overnight at rt and a saturated ammonium chloride
solution (15 mL) was slowly added. The organic layer was separated and the aqueous layer was extracted

with ether (3x20 mL). The combined ether solution was washed with brine (10 mL) and dried over
magnesium sulfate. Solvent was removed, dichloromethane (50 mL) was added, and the solution was
slowly added to PCC (21.39 g, 99.2 mmol) in dichloromethane (75 mL) at 20–25 °C. The mixture was
stirred at rt for 10 h, diluted with ether (100 mL), and stirred for 1 h. Precipitated solid was filtered off
and washed with ether (2x25 mL). The combined solution was dried over magnesium sulfate. Solvent
was removed and the product was isolated by distillation, (6.80 g, 77%), bp 78–80 °C/0.5 mmHg. lit.,16 bp
60–70 °C/0.3 mmHg. 1H NMR (CDCl3) δ: 2.50 (3H, s, CH3), 7.30–7.40 (2H, m, CHAr), 7.45–7.52 (1H, m,
13
CHAr), 8.17 (1H, m, CHAr), 8.20–8.25 (1H, m, CHAr). C NMR (CDCl3) δ: 27.86 (CH3), 111.30, 122.46,
122.69, 124.04, 124.36, 125.46, 151.16, 155.50, 192.78 (C=O).
3-Bromoacetylbenzofuran (11)
To a solution of 10 (6.09 g, 38.0 mmol) in acetic acid (60 mL), pyridinium tribromide (14.58 g, 45.6
mmol) was slowly added at 45–50 °C. The mixture was stirred at this temperature for 0.5 h and then at rt
for 1 h. Precipitated solid was filtered off and dissolved in ether (50 mL). The solution was washed with
saturated bicarbonate solution (3x10 mL) and dried over magnesium sulfate. Solvent was removed and
the product was crystallized from carbon tetrachloride, (3.59 g, 60%), mp 135–136 °C. 1H NMR (CDCl3)
δ: 4.32 (2H, s, CH2), 7.35–7.46 (2H, m, CHAr), 7.50–7.60 (1H, m, CHAr), 8.15–8.30 (1H, m, CHAr), 8.39
(1H, s, CHAr). 13C NMR (CDCl3) δ: 31.35 (CH2), 111.58, 119.55, 122.82, 124.02, 124.85, 126.04, 151.72,
155.60, 186.50 (C=O). Anal. Calcd for C10H7 O2Br: C, 50.24; H, 2.95. Found: C, 50.00, H, 2.89.
(S)-(+)-(Benzofuran-3-yl)oxirane (13)
A mixture of (–)-DIP-Cl ( 8.45 g, 26.0 mmol) and tetrahydrofuran (30 mL) was cooled to –30 °C under
nitrogen and a solution of 11 (5.03 g, 21.0 mmol) in tetrahydrofuran (20 mL) was slowly added. The
mixture was stirred at this temperature for 2 h and then at rt for 24 h. The 11B NMR spectrum indicated no
signal at δ 32 corresponding to DIP-Cl. Workup carried out as described for 5 gave 9.37 g of crude 12. To
a mixture of sodium hydride (4.37 g, 182.1 mmol) and tetrahydrofuran (50 mL), a solution of the crude 12
(9.20 g, 38.2 mmol) was slowly added with vigorous stirring at rt. Stirring was continued for 3 h, and the solid
material was filtered off, and 13 was isolated by distillation, (2.63 g, 78%), bp 70–74 °C/0.3 mmHg. An
analytical sample was isolated by preparative GC, [α]D20 +12.26° (c 36.5, CHCl3). 1H NMR (CDCl3) δ: 3.16–
3.19 (2H, m, CH2), 4.05 (1H, dd, J=3.2 Hz, J=3.0 Hz, CH), 7.20–7.40 (2H, m, CHAr), 7.47–7.55 (1H, m,
CHAr), 7.55–7.70 (1H, m, CHAr), 7.65 (1H, s, CHAr). 13C NMR (CDCl3) δ: 46.32 (CH), 48.26 (CH2), 111.62,
118.23, 120.12, 122.89, 124.72, 126.02, 142.95, 155.63. Anal. Calcd for C10H8O2: C, 74.99; H, 5.03. Found:
C, 74.90; H, 5.00.
For determining the enantiomeric excess, a solution of 13 (0.45 g, 2.8 mmol) in ether (2 mL) was reduced
with lithium aluminum hydride (0.12 g, 3.2 mmol) in ether (2 mL), as described above for 6, to give 14

20
isolated by distillation, (0.40 g, 89%), bp 81–82 °C/0.1 mmHg, [α]D –20.28° (c 11.34, CHCl3), 71% ee
(by comparison of the sign of rotation with 14 prepared as described below).
(S)-(–)-1-(Benzofuran-3-yl)-2-(isopropylamino)ethanol ((S)-2a)
A solution of 13 (1.00 g, 6.25 mmol) in isopropylamine (10 mL) was placed in an autoclave and kept at
100 °C for 3 h. Excess of isopropylamine was removed and the product was crystallized from
20
1
cyclohexane, (0.75 g, 55%), mp 92–93 °C, [α]D –46.27° (c 10.15, CHCl3). H NMR (CDCl3) δ: 1.09
(6H, dd, J=6.2 Hz, J=1.0 Hz, CH3), 2.10–2.65 (2H, br s, NH, OH), 2.87 (1H, septet, J=6.2 Hz, CH), 2.93
(1H, dd, J=12.0 Hz, J=8.0 Hz, CH2), 3.10 (1H, dd, J=12.0 Hz, J=4.0 Hz, CH2), 4.94 (1H, ddd, J=8.2 Hz,
J=4.0 Hz, J=1.0 Hz, CH), 7.18–7.37 (2H, m, CHAr), 7.46–7.55 (1H, m, CHAr), 7.60 (1H, d, J=1.0 Hz,
CHAr), 7.62–7.70 (1H, m, CHAr). 13C NMR (CDCl3) δ: 23.09 (CH3), 23.28 (CH3), 48.73(CH), 52.49 (CH2),
65.66 (CH), 111.64, 120.39, 122.44, 122.54, 124.40, 126.25, 141.66, 155.78. Anal. Calcd for C13H17 NO2: C,
71.21; H, 7.81; N, 6.39. Found: C, 71.11; H, 7.68; N, 6.25.
(S)-(–)-1-(Benzofuran-3-yl )ethanol (14)
A solution of 10 (1.62 g, 10.1 mmol) in tetrahydrofuran (10 mL) was slowly added to a mixture of
(–)-DIP-Cl (3.88 g, 12.1 mmol) and tetrahydrofuran (10 mL) at –30 °C under nitrogen. The mixture was
stirred at this temperature for 24 h. 11B NMR spectrum indicated no signal at δ 32 corresponding do DIP-Cl.
Workup carried as described for 7 gave the product which was isolated by distillation, (1.14 g, 69.5%), bp
20
80–82 °C/0.1 mmHg. An analytical sample was further purified by preparative GC, [α]D
–20.76° (c 10.91, EtOH). HPLC analysis, Daicel Chiralcel OJ column, n–hexane/isopropanol (9 : 1)
showed 90% ee. 1H NMR (CDCl3) δ: 1.64 (3H, d, J=4.4 Hz, CH3), 2.10 (1H, s, OH), 5.14 (1H, q, J=4.4
Hz, CH), 7.22–7.34 (2H, m, CHAr), 7.47–7.50 (1H, m, CHAr), 7.55 (1H, m, CHAr), 7.69–7.72 (1H, m,
CHAr).13C NMR (CDCl3) δ: 23.25 (CH3), 62.96 (CH), 111.50, 120.40, 122.48, 124.36, 125.06, 126.02,
140.66, 155.62. Anal. Calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 74.00, H, 6.10. p-Nitrobenzoate
(14a) mp 81–83 °C (from ethanol). 1H NMR (CDCl3) δ: 1.86 (3H, d, J=4.4 Hz, CH3), 6.47 (1H, q, J=4.4
Hz, CH), 7.24–7.40 (2H, m, CHAr), 7.48–7.54 (1H, m, CHAr), 7.69–7.74 (1H, m, CHAr), 7.72 (1H, s,
CHAr), 8.19–8.29 (4H, m, CHAr). 13C NMR (CDCl3) δ: 20.30 (CH3), 66.82 (CH), 111.87, 120.20, 120.73,
123.00, 123.53 (2CH), 124.80, 125.76, 130.75 (2CH), 135.65, 142.36, 150.58, 155.67, 164.00 (C=O).
Anal. Calcd for C17H13 NO5: C, 65,59; H, 4.21; N, 4.49. Found: C, 65.38; H, 4.10; N, 4.33. The crystal
data and the X-Ray structure are shown on Scheme 2.
ACKNOWLEDGMENT
Financial support from the State Committee for Scientific Research, Warsaw, grant K009/T09/1999, is
acknowledged.

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