Supporting Information

An Improved Bouveault-Blanc Ester Reduction with Stabilized

Alkali Metals

Brian S. Bodnar* and Paul F. Vogt

SiGNa Chemistry, Inc., 1 Deer Park Drive, Suite C, Monmouth Junction, NJ 08852
bsbodnar@signachem.com

Table of Contents

Experimental Section………………………………………………………………….. S1

General Methods……………………………………………………………… S1

Preparation of Methyl Esters…………………………………………………. S2

Reduction of Esters Using Na-SG(I)………………………………………….. S5

Presentation of NMR Spectra…………………………………………………………. S11

Experimental Section

General Methods

Stage I sodium silica gel, Na-SG(I), is available from Sigma-Aldrich (#660167).

Commercially available esters used for Bouveault-Blanc reductions were purchased and used
directly or were prepared according to the general procedure provided. Reactions were carried
out under an inert atmosphere of argon or nitrogen unless otherwise specified in the experimental
procedure and were monitored by TLC and/or HPLC for consumption of starting material.
Glass-backed silica gel 60 F254 plates were used for thin layer chromatography.
Analytical HPLC data was collected at 1.5 mL/min using a water/acetonitrile gradient
through a Microsorb-MV 100-5 C18 250 x 4.6 mm column. Melting points are uncorrected. All
NMR spectra were recorded under ambient temperatures unless otherwise noted. Chemical shift
values for NMR spectra are reported as δ in ppm relative to TMS. MS data is reported with the
relative intensity of ions compared to the base peak (100%). EI and CI mass spectra were
collected using internal ionization mode and methanol was used as the CI gas. APCI mass
spectra were collected through direct infusion of samples.

S1
Preparation of Methyl Esters

O SOCl2 O

R OH MeOH R OMe

General procedure for the preparation of methyl esters. Anhydrous methanol (70
mL) was added to a flame-dried single-necked 250-mL round-bottomed flask. The methanol
was cooled in an ice/H2O bath as thionyl chloride (1.10 mL, 15.1 mmol) was added. After 15
min, the carboxylic acid (6 mmol) was added in one portion. The ice/H2O bath was removed and
the solution was stirred at RT overnight. The solution was concentrated and the crude material
was concentrated from toluene (3x) to yield the pure methyl ester.

CO2Me

NC
Methyl 4-cyanophenylacetate (1i). Ester 1i was prepared according to the general
procedure for the preparation of methyl esters using thionyl chloride (1.10 mL, 15.1 mmol) and
4-cyanophenylacetic acid (0.98 g, 6.1 mmol) in 70 mL of methanol. After 23 h, pure compound
1i was obtained as a light yellow oil that solidified upon standing (1.07 g, >99% yield). 1H NMR
(500 MHz, CDCl3) δ 7.63 (d, J = 8.5 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 3.72 (s, 3H), 3.71 (s, 2H)
ppm. 13C NMR (125 MHz, CDCl3) δ 170.7, 139.1, 132.2, 130.1, 118.6, 111.0, 52.3, 40.9 ppm.
EI-MS m/z: M+ 175 (21.9%), 131 (17.5%), 116 (100%).

CO2Me

F
Methyl 4-fluorophenylacetate (1k). Ester 1k was prepared according to the general
procedure for the preparation of methyl esters using thionyl chloride (1.30 mL, 17.9 mmol) and
4-fluorophenylacetic acid (1.10 g, 7.14 mmol) in 70 mL of methanol. After 24 h, pure ester 1k
was obtained as a light yellow oil (1.07 g, 89.2% yield). 1H NMR (500 MHz, CDCl3) δ 7.24 (dd,
J = 8.0, 5.5 Hz, 2H), 7.01 (t, J = 8.5 Hz, 2H), 3.69 (s, 3H), 3.60 (s, 2H) ppm. 13C NMR (125
MHz, CDCl3) δ 171.9, 161.9 (d, J = 244 Hz), 130.8 (d, J = 7.9 Hz), 129.6 (d, J = 3.3 Hz), 115.4
(d, J = 21.4 Hz), 52.1, 40.2 ppm. EI-MS m/z: M+ 168 (17.1%), 109 (100%).

CO2Me

F3 C
Methyl 4-trifluoromethylphenylacetate (1l). Ester 1l was prepared according to the
general procedure for the preparation of methyl esters using thionyl chloride (0.80 mL, 11.0
mmol) and 4-trifluoromethylphenylacetic acid (0.95 g, 4.7 mmol) in 50 mL of methanol. After
16 h, pure ester 1l was obtained as a pale yellow oil (0.96 g, 95% yield). 1H NMR (500 MHz,
CDCl3) δ 7.59 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 3.71 (s, 3H), 3.70 (s, 2H) ppm. 13C

S2
NMR (125 MHz, CDCl3) δ 171.2, 137.8, 129.7, 125.5 (q, J = 3.8 Hz), 52.3, 40.8 ppm. EI-MS
m/z: M+ 218 (35.8%), 199 (19.0%), 159 (100%), 140 (21.6%), 109 (54.9%), 105 (39.6%).

CO2Me

Methyl 2-(4-isobutylphenyl)propanoate (1m). Ester 1m was prepared according to the

general procedure for the preparation of methyl esters using thionyl chloride (2.00 mL, 27.5
mmol) and (±)-Ibuprofen (2.33 g, 11.3 mmol) in 110 mL of methanol. After 17 h, pure ester 1m
was obtained as a pale yellow liquid (2.46 g, 99% yield). 1H NMR (500 MHz, CDCl3) δ 7.20 (d,
J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.70 (q, J = 7.0 Hz, 1H), 3.65 (s, 3H), 2.44 (d, J = 7.0
Hz, 2H), 1.89 – 1.78 (m, 1H), 1.48 (d, J = 7.0 Hz, 3H), 0.89 (d, J = 6.5 Hz, 6H) ppm. 13C NMR
(125 MHz, CDCl3) δ 175.2, 140.5, 137.7, 129.3, 127.1, 52.0, 44.99, 44.96, 30.2, 22.4, 18.6 ppm.
EI-MS m/z: [M+H]+ 221 (25.1%), 220 (27.2%), 161 (100%), 117 (25.4%), 91 (13.0%).

CO2Me

Methyl 1-phenylcyclopropanecarboxylate (1n). Ester 1n was prepared according to

the general procedure for the preparation of methyl esters using thionyl chloride (1.40 mL, 19.2
mmol) and 1-phenyl-1-cyclopropanecarboxylic acid (1.20 g, 7.40 mmol) in 80 mL of methanol.
After 16 h, pure ester 1n was obtained as a colorless oil (1.19 g, 92% yield). 1H NMR (500
MHz, CDCl3) δ 7.36 – 7.30 (m, 4H), 7.28 – 7.25 (m, 1H), 3.62 (s, 3H), 1.60 (q, J = 3.9 Hz, 2H),
1.20 (q, J = 3.9 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3) δ 175.2, 139.5, 130.5, 128.1, 127.2,
52.4, 29.0, 16.7 ppm. EI-MS m/z: M+ 176 (58.2%), 144 (36.6%), 115 (100%), 91 (22.6%).

CO2Me

Methyl 1-phenylcyclopentanecarboxylate (1o). Ester 1o was prepared according to the

general procedure for the preparation of methyl esters using thionyl chloride (1.40 mL, 19.2
mmol) and 1-phenyl-1-cyclopentanecarboxylic acid (1.40 g, 7.36 mmol) in 80 mL of methanol.
After 17 h, pure ester 1o was obtained as a deep brown oil (1.46 g, 97% yield). 1H NMR (500
MHz, CDCl3) δ 7.41 – 7.35 (m, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.23 (m, 1H), 3.60 (s, 3H), 2.65
(m, 2H), 1.90 (m, 2H), 1.73 (m, 4H) ppm. 13C NMR (125 MHz, CDCl3) δ 176.5 (C), 143.2 (C),
128.2 (CH), 126.74 (CH), 126.65 (CH), 59.0 (C), 52.3 (CH3), 36.1 (CH2), 23.5 (CH2) ppm. EI-
MS m/z: [M+H]+ 205 (48.9%), 145 (100%), 128 (12.4%), 115 (15.2%), 91 (51.5%).

S3
 OMe

CO2Me

Methyl (S)-2-methoxy-2-phenylacetate (1q). Ester 1q was prepared according to the

general procedure for the preparation of methyl esters using thionyl chloride (1.10 mL, 15.1
mmol) and S-(+)-α-methoxyphenylacetic acid (1.01 g, 6.08 mmol) in 50 mL of methanol. After
17 h, pure ester 1q was obtained as a pale yellow oil (1.02 g, 93% yield). 1H NMR (500 MHz,
CDCl3) δ 7.45 – 7.43 (m, 2H), 7.40 – 7.34 (m, 3H), 4.78 (s, 1H), 3.72 (s, 3H), 3.41 (s, 3H) ppm.
13
C NMR (125 MHz, CDCl3) δ 171.1, 136.0, 128.8, 128.6, 127.2, 82.4, 57.3, 52.3 ppm. EI-MS
m/z: M+ 180 (0.4%), 149 (2.6%), 121 (100%), 105 (5.0%), 91 (14.3%).

CO2Me

MeO
Methyl 4-methoxycinnamate (8). Ester 8 was prepared according to the general
procedure for the preparation of methyl esters using thionyl chloride (2.60 mL, 35.7 mmol) and
4-methoxycinnamic acid (2.51 g, 14.1 mmol) in 100 mL of methanol. After 19 h, ester 8 was
obtained as a white crystalline solid (2.68 g, 99% yield). 1H NMR (500 MHz, CDCl3) δ 7.66 (d,
J = 15.97 Hz, 1H), 7.48 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 6.32 (d, J = 15.96 Hz, 1H),
3.84 (s, 3H), 3.80 (s, 3H) ppm. 13C NMR (125 MHz, CDCl3) δ 167.8 (C), 161.3 (C), 144.5
(CH), 129.7 (CH), 127.0 (C), 115.2 (CH), 114.3 (CH), 55.4 (CH3), 51.6 (CH3) ppm. EI-MS m/z:
M+ 192 (79.6%), 161 (100%), 133 (36.6%), 118 (12.7%), 103 (6.6%), 90 (9.7%).

CO2Me
Methyl 1-adamantanecarboxylate (18). Ester 18 was prepared according to the general
procedure for the preparation of methyl esters using thionyl chloride (2.00 mL, 27.4 mmol) and
1-adamantanecarboxylate (2.03 g, 11.3 mmol) in 115 mL of methanol. After 20 h, ester 18 was
obtained as light yellow crystals (2.13 g, 97% yield). 1H NMR (500 MHz, CDCl3) δ 3.65 (s,
3H), 2.01 (m, 3H), 1.89 (m, 6H), 1.71 (m, 6H) ppm. 13C NMR (125 MHz, CDCl3) δ 178.1 (C),
51.5 (CH3), 40.6 (C), 38.8 (CH2), 36.4 (CH2), 27.9 (CH) ppm. CI-MS m/z: [M+H]+ 195 (100%),
161 (3.5%), 135 (10.5%).

CO2Me

OMe
Methyl 2-methoxybenzoate (25). Ester 25 was prepared according to the general
procedure for the preparation of methyl esters using thionyl chloride (1.20 mL, 16.5 mmol) and
o-anisic acid (1.01 g, 6.64 mmol) in 70 mL of methanol. After 18 h, ester 25 was obtained as a
pale yellow oil (1.09 g, 99% yield). 1H NMR (500 MHz, CDCl3) δ 7.80 (dd, J = 7.5, 1.5 Hz,
1H), 7.47 (ddd, J = 8.5, 7.5, 2.0 Hz, 1H), 6.98 (m, 2H), 3.91 (s, 3H), 3.89 (s, 3H) ppm. 13C NMR
(125 MHz, CDCl3) δ 166.7 (C), 159.1 (C), 133.5 (CH), 131.6 (CH), 120.1 (CH), 119.9 (C),
111.9 (CH), 55.9 (CH3), 52.0 (CH3) ppm. EI-MS m/z: [M+H]+ 167 (47.4%), 135 (100%), 105
(10.7%), 92 (16.0%).

S4
 CO2Me

MeO
Naproxen methyl ester (29). Ester 29 was prepared according to the general procedure
for the preparation of methyl esters using thionyl chloride (1.50 mL, 20.6 mmol) and naproxen
(2.00 g, 8.69 mmol) in 85 mL of methanol. After 16 h, ester 29 was obtained as a white solid
(2.12 g, >99% yield). mp = 89-90 °C. 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 8.5 Hz, 2H),
7.66 (s, 1H), 7.40 (dd, J = 8.5, 1.5 Hz, 1H), 7.13 (dd, J = 9.0, 2.5 Hz, 1H), 7.10 (d, J = 2.0 Hz,
1H), 3.90 (s, 3H), 3.85 (q, J = 7.0 Hz, 1H), 3.66 (s, 3H), 1.57 (d, J = 7.0 Hz, 3H) ppm. 13C NMR
(125 MHz, CDCl3) δ 175.1, 157.5, 135.6, 133.6, 129.2, 128.8, 127.1, 126.1, 125.9, 119.0, 105.4,
55.2, 52.0, 45.3, 18.6 ppm. EI-MS m/z: M+ 244 (38.6%), 185 (100%), 170 (20.9%), 153
(10.5%), 141 (16.1%), 115 (12.0%).

CO2Me
N O
Methyl 3-methyl-5-isoxazoleacetate (32). Ester 32 was prepared according to the
general procedure for the preparation of methyl esters using thionyl chloride (1.25 mL, 17.2
mmol) and 3-methyl-5-isoxazoleacetic acid (1.10 g, 7.80 mmol) in 50 mL of methanol. After 26
h, ester 32 was obtained as a brown oil (0.88 g, 73% yield). 1H NMR (500 MHz, CDCl3) δ 6.11
(s, 1H), 3.80 (s, 2H), 3.76 (s, 3H), 2.30 (s, 3H) ppm. 13C NMR (125 MHz, CDCl3) δ 168.1,
164.6, 160.0, 104.1, 52.6, 32.4, 11.4 ppm. EI-MS m/z: [M+H]+ 156 (100%), 114 (44.1%), 96
(42.6%).

Ph O CO2Me

N
Methyl 5-phenyloxazole-2-propionate (33). Ester 33 was prepared according to the
general procedure for the preparation of methyl esters using thionyl chloride (0.85 mL, 11.7
mmol) and 5-phenyloxazole-2-propionic acid (1.05 g, 4.83 mmol) in 50 mL of methanol. After
26 h, ester 33 was obtained as an off-white solid (1.12 g, >99% yield). 1H NMR (500 MHz,
CDCl3) δ 7.65 (d, J = 7.5 Hz, 2H), 7.52 (s, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.41 (t, J = 7.5 Hz, 1H),
3.72 (s, 3H), 3.38 (t, J = 6.5 Hz, 2H), 3.06 (t, J = 6.5 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3)
δ 171.8, 163.8, 152.4, 129.6, 129.1, 125.9, 124.4, 117.1, 52.2, 30.2, 23.1 ppm. CI-MS m/z:
[M+H]+ 232 (100%), 200 (6.1%).

Reduction of Esters Using Na-SG(I)

1) Na-SG(I)
O THF, 0 °C
R OH
R OR' 2) MeOH
General procedure for the reduction of esters using Na-SG(I). Stage I sodium silica
gel (3.56 g, 27.1 wt% stage I, 42 mmol Na) was added to a flame-dried 3-necked 100-mL round-
bottomed flask with a stir bar. The flask was fitted with an addition funnel and a temperature
probe, and anhydrous THF (40 mL) was added. The mixture was cooled in an ice/H2O bath to 0

S5
°C under Ar. The ester (3.00 mmol) was added, followed immediately by the addition of
methanol (3.00 mL, 74.2 mmol) dropwise over 2-5 min. Some bubbling was observed and the
temperature of the mixture rose to 20-25 °C before falling. The ice/H2O bath was removed and
the mixture was quenched by adding H2O (30 mL, bubbling and exothermic) after the ester was
completely consumed (typically immediately after methanol addition). The aqueous layer was
extracted with ether or EtOAc (2 x 50 mL), and the combined organic layers were washed with
H2O (40 mL) and brine (40 mL), dried, filtered, and concentrated.

OH

Phenethyl alcohol (2a) from reduction of methyl phenylacetate (1b). Alcohol 2a was
prepared according to the general procedure using methyl phenyl acetate (1b, 0.425 mL, 3.02
mmol) and Na-SG(I) (3.54 g, 27.1 wt% stage I, 41.7 mmol). Alcohol 2a was obtained as a pale
yellow liquid (0.327 g, 89% yield). 1H NMR (500 MHz, CDCl3) δ 7.32 (m, 2H), 7.24 (m, 3H),
3.85 (t, J = 6.5 Hz, 2H), 2.86 (t, J = 6.5 Hz, 2H), 1.66 (br, 1H) ppm. 13C NMR (125 MHz,
CDCl3) δ 138.4, 129.0, 128.5, 126.4, 63.6, 39.1 ppm. EI-MS m/z: M+ 122 (11.7%), 104 (10.2%),
92 (49.7%), 91 (100%).

Phenethyl alcohol (2a) from reduction of methyl 4-chlorophenylacetate (1j). Alochol

2a was prepared according to the general procedure using methyl 4-chlorophenylacetate (1j,
0.553 g, 3.00 mmol) and Na-SG(I) (3.57 g, 27.1 wt% stage I, 42.1 mmol). Alcohol 2a was
obtained a light orange oil (0.258 g, 71% yield).

OH

Me
2-(4-Methylphenyl)ethanol (2c) from reduction of methyl 4-methylphenylacetate
(1c). Alcohol 2c was prepared according to the general procedure using methyl 4-
methylphenylacetate (1c, 0.53 mL, 3.01 mmol) and Na-SG(I) (3.56 g, 27.1 wt% stage I, 42.0
mmol). Alcohol 2c was obtained as a yellow oil (0.345 g, 84% yield). 1H NMR (500 MHz,
CDCl3) δ 7.12 (m, 4H), 3.81 (t, J = 6.5 Hz, 2H), 2.82 (t, J = 6.5 Hz, 2H), 2.32 (s, 3H), 1.63 (br,
1H) ppm. 13C NMR (125 MHz, CDCl3) δ 135.9 (C), 135.2 (C), 129.2 (CH), 128.9 (CH), 63.7
(CH2), 38.6 (CH2), 21.0 (CH3) ppm. EI-MS m/z: M+ 136 (68.8%), 119 (18.9%), 106 (17.8%),
105 (100%), 91 (19.8%).

2-(4-Methylphenyl)ethanol (2c) from reduction of methyl 4-

trifluoromethylphenylacetate (1l). Alcohol 2c was prepared according to the general
procedure using ester 1l (0.665 g, 3.05 mmol) and Na-SG(I) (3.56 g, 27.1 wt% stage I, 42.0
mmol). Alcohol 2c was obtained as a yellow oil (0.267 g, 64% yield).

OH

2-(4-tert-Butylphenyl)ethanol (2d). Alcohol 2d was prepared according to the general

procedure using methyl 4-tertbutylphenylacetate (1d, 0.63 mL, 3.01 mmol) and Na-SG(I) (3.56

S6
g, 27.1 wt% stage I, 42.0 mmol). Alcohol 2d was obtained as a yellow oil (0.507 g, 94% yield).
1
H NMR (500 MHz, CDCl3) δ 7.34 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 3.85 (t, J = 6.5
Hz, 2H), 2.84 (t, J = 6.5 Hz, 2H), 1.52 (br, 1H), 1.31 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3)
δ 149.3 (C), 135.3 (C), 128.7 (CH), 125.5 (CH), 63.7 (CH2), 38.6 (CH2), 34.4 (C), 31.1 (CH3)
ppm. EI-MS m/z: M+ 178 (8.2%), 163 (100%), 145 (15.3%), 117 (25.8%), 105 (11.6%), 91
(6.9%).

OH

HO
4-(2-Hydroxyethyl)phenol (2e). Alcohol 2e was prepared according to the general
procedure using methyl 4-hydroxyphneylacetate (1e, 0.499 g, 3.00 mmol) and Na-SG(I) (3.58 g,
27.1 wt% stage I, 42.2 mmol). Alcohol 2e was obtained as an off-white solid (0.385 g, 93%
yield). mp = 83-84 °C. 1H NMR (500 MHz, CDCl3) δ 9.16 (br, 1H), 6.99 (d, J = 8.0 Hz, 2H),
6.67 (d, J = 8.0 Hz, 2H), 4.62 (br-t, J = 4.5 Hz, 1H), 3.53 (td, J = 7.5, 4.0 Hz, 2H), 2.61 (t, J =
7.0 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3) δ 155.5 (C), 129.8 (CH), 129.5 (C), 115.0 (CH),
62.7 (CH2), 38.3 (CH2) ppm. EI-MS m/z: M+ 138 (18.0%), 107 (100%).

OH

MeO
2-(4-Methoxyphenyl)ethanol (2f). Alcohol 2f was prepared according to the general
procedure using methyl 4-methoxyphenylacetate (1f, 0.48 mL, 3.02 mmol) and Na-SG(I) (3.54
g, 27.1 wt% stage I, 41.7 mmol). Alcohol 2f was obtained as a yellow oil (0.430 g, 94% yield).
1
H NMR (500 MHz, CDCl3) δ 7.15 (d, J = 9.0 Hz, 2H), 6.86 (d, J = 9.0 Hz, 2H), 3.82 (t, J = 6.5
Hz, 2H), 3.79 (s, 3H), 2.81 (t, J = 6.5 Hz, 2H), 1.56 (br, 1H) ppm. 13C NMR (125 MHz, CDCl3)
δ 158.2, 130.3, 129.9, 113.9, 63.8, 55.2, 38.2 ppm. EI-MS m/z: M+ 152 (20.2%), 121 (100%), 91
(4.2%).

OH

H2N
2-(4-Aminophenyl)ethanol (2g) from reduction of ethyl 4-aminophenylacetate (1g).
Alcohol 2g was prepared according to the general procedure using ethyl 4-aminophenylacetate
(1g, 0.538 g, 3.00 mmol) and Na-SG(I) (3.57 g, 27.1 wt% stage I, 42.1 mmol). Alcohol 2g was
obtained as a yellow solid (0.321 g, 78% yield). 1H NMR (500 MHz, CDCl3) δ 6.84 (d, J = 8.5
Hz, 2H), 6.47 (d, J = 8.5 Hz, 2H), 4.83 (br, 2H), 4.56 (t, J = 5.5 Hz, 1H), 3.48 (td, J = 7.5, 5.5
Hz, 2H), 2.53 (t, J = 7.5 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3) δ 146.6 (C), 129.2 (CH),
126.1 (C), 113.8 (CH), 62.9 (CH2), 38.4 (CH2) ppm. EI-MS m/z: M+ 137 (13.3%), 106 (100%).

2-(4-Aminophenyl)ethanol (2g) from reduction of ethyl 4-nitrophenylacetate (1h).

Alcohol 2g was prepared according to the general procedure using ethyl 4-nitrophenylacetate
(1h, 0.627 g, 3.00 mmol) and Na-SG(I) (3.59 g, 27.1 wt% stage I, 42.3 mmol). Alcohol 2g was
obtained as an orange solid (0.150 g, 36% yield).

S7
 OH OH

F
2-(4-Fluorophenyl)ethanol (2k) and phenylethanol (2a) from reduction of methyl 4-
fluorophenylacetate (1k). The reduction of methyl 4-fluorophenylacetate (1k, 0.504 g, 3.00
mmol) using Na-SG(I) (3.58 g, 27.1 wt% stage I, 42.2 mmol) was followed according to the
general procedure. A mixture of alcohol 2k and 2a was obtained in a ratio of 2:1 from
integration of 1H NMR multiplets at 7.00 ppm and 7.24 ppm, which corresponded to signals for
2k and 2a, respectively. 2k: EI-MS m/z: M+ 140 (37.7%), 123 (5.7%), 109 (100%).

OH

2-(4-Isobutylphenyl)propan-1-ol (2m). Alcohol 2m was prepared according to the

general procedure using ibuprofen ester 1m (0.663 g, 3.01 mmol) and Na-SG(I) (3.56 g, 27.1
wt% stage I, 42.0 mmol). Alcohol 2m was obtained as a colorless oil (0.555 g, 96% yield). 1H
NMR (500 MHz, CDCl3) δ 7.14 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 3.67 (d, J = 7.0
Hz, 2H), 2.91 (sextet, J = 7.0 Hz, 1H), 2.44 (d, J = 7.5 Hz, 2H), 1.88-1.80 (m, 1H), 1.47 (br, 1H),
1.26 (d, J = 7.0 Hz, 3H), 0.90 (d, J = 7.0 Hz, 6H) ppm. 13C NMR (125 MHz, CDCl3) δ 140.6,
140.0, 129.3, 127.1, 68.7, 45.0, 42.0, 30.2, 22.4, 17.6 ppm. EI-MS m/z: M+ 192 (12.7%), 175
(4.8%), 161 (100%), 119 (25.7%), 105 (14.0%), 91 (10.4%).

OH

(1-Phenylcyclopropyl)methanol (2n). Alcohol 2n was prepared according to the

general procedure using ester 1n (0.531 g, 3.01 mmo) and Na-SG(I) (3.57 g, 27.1 wt% stage I,
42.1 mmol). Alcohol 2n was obtained as yellow oil (0.401 g, 90% yield). 1H NMR (500 MHz,
CDCl3) δ 7.35-7.33 (m, 2H), 7.30 (t, J = 8.0 Hz, 2H), 7.23-7.17 (m, 1H), 3.62 (s, 2H), 1.82 (br,
1H), 0.86 (m, 2H), 0.83 (m, 2H) ppm. 13C NMR (125 MHz, CDCl3) δ 142.6, 128.9, 128.3,
126.5, 70.6, 27.9, 11.3 ppm. EI-MS m/z: M+ 148 (8.1%), 131 (100%), 117 (34.4%), 91 (22.2%).

OH

(1-Phenylcyclopentyl)methanol (2o). Alcohol 2o was prepared according to the general

procedure using ester 1o (0.608 g, 2.98 mmol) and Na-SG(I) (3.58 g, 27.1 wt% stage I, 42.2
mmol). Alcohol 2o was obtained as a yellow oil (0.425 g, 81% yield). 1H NMR (500 MHz,
CDCl3) δ 7.32-7.27 (m, 4H), 7.20-7.16 (m, 1H), 3.46 (s, 2H), 2.02-1.97 (m, 2H), 1.88-1.81 (m,
2H), 1.73-1.69 (m, 4H), 1.43 (br, 1H) ppm. 13C NMR (125 MHz, CDCl3) δ 146.8, 128.2, 127.2,
126.0, 70.1, 53.1, 34.1, 23.7 ppm. CI-MS m/z: [M-OH]+ 159 (100%), 145 (1.7%), 91 (6.1%).

S8
 OH

3-Phenyl-1-propanol (4) from reduction of ethyl hydrocinnamate (3). Alcohol 4 was

prepared according to the general procedure using ethyl hydrocinnamate (3, 0.530 mL, 3.02
mmol) and Na-SG(I) (3.56 g, 27.1 wt% stage I, 42.0 mmol). Alcohol 4 was obtained as a yellow
oil (0.384 g, 93% yield). 1H NMR (500 MHz, CDCl3) δ 7.29 (m, 2H), 7.21 (m, 3H), 7.68 (t, J =
6.5 Hz, 2H), 2.71 (t, J = 7.5 Hz, 2H), 1.89 (m, 2H), 1.52 (br, 1H) ppm. 13C NMR (125 MHz,
CDCl3) δ 141.8, 128.38, 128.35, 125.8, 62.2, 34.2, 32.0 ppm. EI-MS m/z: M+ 136 (3.7%), 118
(57.7%), 117 (100%), 105 (7.7%), 91 (36.0%).

3-Phenyl-1-propanol (4) from reduction of methyl trans-cinnamate (5). Alcohol 4

was prepared according to the general procedure using methyl trans-cinnamate (5, 0.506 g, 3.12
mmol) and Na-SG(I) (3.56 g, 27.1 wt% stage I, 42.0 mmol). Alcohol 4 was obtained as a yellow
oil (0.407 g, 96% yield).

OH

MeO
3-(4-Methoxyphenyl)-1-propanol (7) from reduction of methyl 3-(4-
methoxyphenyl)propionate (6). Alcohol 7 was prepared according to the general procedure
using methyl 3-(4-methoxyphenyl)propionate (6, 0.582 g, 3.00 mmol) and Na-SG(I) (3.56 g,
27.1 wt% stage I, 42.0 mmol). Alcohol 7 was obtained as a yellow oil (0.495 g, 99% yield). 1H
NMR (500 MHz, CDCl3) δ 7.10 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 3.77 (s, 3H), 3.63
(t, J = 6.5 Hz, 2H), 2.63 (t, J = 8.0 Hz, 2H), 2.11 (br, 1H), 1.83 (m, 2H) ppm. EI-MS m/z: M+
166 (24.0%), 147 (7.4%), 121 (100%), 91 (9.8%).

3-(4-Methoxyphenyl)-1-propanol (7) from reduction of methyl 4-methoxycinnamate

(8). Alcohol 7 was prepared according to the general procedure using ester 8 (0.576 g, 3.00
mmol) and Na-SG(I) (3.52 g, 27.1 wt% stage I, 41.5 mmol). Alcohol 7 was obtained as a yellow
oil (0.486 g, 98% yield).

OH

OH
2-(3-Hydroxypropyl)phenol (10) from reduction of dihydrocoumarin (9). Alcohol 10
was prepared according to the general procedure using dihydrocoumarin (9, 0.38 mL, 3.00
mmol) and Na-SG(I) (3.58 g, 27.1 wt% stage I, 42.2 mmol). Alcohol 10 was obtained as a
yellow oil (0.423 g, 93% yield). 1H NMR (500 MHz, CDCl3) δ 7.50 (br, 1H), 7.11-7.08 (m, 2H),
6.88-6.83 (m, 2H), 3.63 (t, J = 6.0 Hz, 2H), 3.06 (br, 1H), 2.78 (t, J = 7.0 Hz, 2H), 1.87 (m, 2H)
ppm. 13C NMR (125 MHz, CDCl3) δ 154.4 (C), 130.6 (CH), 127.5 (CH), 127.2 (C), 120.7 (CH),
115.9 (CH), 60.6 (CH2), 32.2 (CH2), 25.1 (CH2) ppm. EI-MS m/z: M+ 152 (100%), 134 (77.0%),
119 (77.6%), 107 (74.9%), 91 (85.9%).

2-(3-Hydroxypropyl)phenol (10) from reduction of coumarin (11). Alcohol 10 was

prepared according to the general procedure using coumarin (11, 0.438 g, 3.00 mmol) and Na-

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SG(I) (3.57 g, 27.1 wt% stage I, 42.1 mmol). Alcohol 10 was obtained as a yellow oil (0.350 g,
77% yield).

OH

OH
2-(2-Hydroxyethyl)phenol (13). Alcohol 13 was prepared according to the general
procedure using 2-coumaranone (12, 0.401 g, 2.99 mmol) and Na-SG(I) (3.58 g, 27.1 wt% stage
I, 42.2 mmol). Alcohol 13 was obtained as an orange oil (0.396 g, 96% yield). 1H NMR (500
MHz, CDCl3) δ 7.17-7.11 (m, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.89-6.84 (m, 2H), 3.94 (t, J = 5.5
Hz, 2H), 2.88 (t, J = 5.5 Hz, 2H), 2.08 (br, 1H) ppm. 13C NMR (125 MHz, CDCl3) δ 154.9,
131.0, 128.3, 126.5, 120.6, 116.8, 64.5, 34.4 ppm. CI-MS m/z: [M+H]+ 139 (5.1%), 121 (100%).

OH

Lauryl alcohol (15). Lauryl alcohol (15) was prepared according to the general
procedure using ethyl laurate (0.80 mL, 3.02 mmol) and Na-SG(I) (3.56 g, 27.1 wt% stage I,
42.0 mmol). Alcohol 15 was obtained as a colorless oil that became a white solid upon storage
at -20 °C (0.560 g, 99.5% yield). 1H NMR (500 MHz, CDCl3) δ 3.63 (t, J = 6.5 Hz, 2H), 1.82
(br, 1H), 1.56 (m, 2H), 1.35-1.25 (m, 18H), 0.88 (t, J = 7.0 Hz, 3H) ppm. 13C NMR (125 MHz,
CDCl3) δ 62.9 (CH2), 32.7 (CH2), 31.9 (CH2), 29.64 (CH2), 29.61 (CH2), 29.60 (CH2), 29.58
(CH2), 29.4 (CH2), 29.3 (CH2), 25.7 (CH2), 22.7 (CH2), 14.1 (CH3) ppm. CI-MS m/z: [M-H]+
185 (9.1%), 169 (16.2%), 168 (12.7%), 127 (12.9%), 113 (45.9%), 111 (41.6%), 99 (100%), 97
(45.1%).

OH

1-Adamantanemethanol (19). Alcohol 19 was prepared according to the general

procedure using ester 18 (0.582 g, 3.00 mmol) and Na-SG(I) (3.52 g, 27.1 wt% stage I, 41.5
mmol). Alcohol 19 was obtained as a white solid (0.480 g, 96% yield). mp = 108-110 °C. 1H
NMR (500 MHz, CDCl3) δ 3.20 (s, 2H), 2.00 (m, 3H), 1.75 (m, 1H), 1.72 (m, 2H), 1.66 (m, 2H),
1.64 (m, 1H), 1.51 (m, 6H), 1.36 (br, 1H) ppm. EI-MS m/z: M+ 166 (0.6%), 148 (4.5%), 135
(100%), 107 (16.3%), 93 (19.5%).

OH
H2N
Phenylalaninol (21). Alcohol 21 was prepared according to the general procedure using
L-phenylalanine ethyl ester hydrochloride (20, 0.689 g, 3.00 mmol) and Na-SG(I) (4.00 g, 27.1
wt% stage I, 47.2 mmol) and methanol (3.50 mL, 86.5 mmol). A yellow oil (0.410 g, 90% crude
yield) was obtained from the reaction. Pure alcohol 21 was obtained by recrystallization from
toluene as white crystals (0.121 g, 27% yield). mp = 80-83 °C. 1H NMR (500 MHz, DMSO-d6)
δ 7.27-7.22 (m, 2H), 7.19-7.10 (m, 3H), 4.65 (br, 1H), 3.26 (dd, J = 10.5, 5.0 Hz, 1H), 3.16 (dd,
J = 10.5, 6.5 Hz, 1H), 2.86-2.81 (m, 1H), 2.65 (dd, J = 13.5, 6.0 Hz, 1H), 2.39 (dd, J = 13.5, 8.0

S10
Hz, 1H), 1.35 (br, 2H) ppm. 13C NMR (125 MHz, DMSO-d6) δ 139.9, 129.2, 128.1, 125.7, 65.9,
54.5, 40.2 ppm. APCI-MS m/z: [M+H]+ 152.2 (100%), 117.2 (23.8%), 91.2 (23.0%).

Ph Ph
CO2H O
EDC•HCl
OH + OH
H2N CH2Cl2 N
OMe H
21
OMe
% ee Determination of phenylalaninol (21) by N-acylation and chiral HPLC
analysis. Amine 21 (54 mg, 0.36 mmol) and o-anisic acid (61 mg, 0.40 mmol) were dissolved in
6 mL of anhydrous CH2Cl2. EDC•HCl (99 mg, 0.52 mmol) was added in one portion and the
mixture was stirred at RT under Ar for 19 h. The solution was concentrated and the residue was
partitioned between H2O (15 mL) and EtOAc (20 mL). The layers were separated and the
aqueous layer was extracted with EtOAc (2 x 20 mL). The combined organic layers were
washed with 10 wt% aqueouw citric acid (3 x 20 mL), H2O (20 mL), saturated NaHCO3 (3 x 20
mL), H2O (20 mL), and brine (20 mL), dried over MgSO4, filtered, and concentrated to yield a
yellow oil (85 mg, 83% yield).
The sample was analyzed by HPLC through a Astec Chirobiotic T 5 µM 250 x 4.6 mm
column using 1 mL/min of 85% H2O/CH3CN and detection at 220 nm. Two signals
corresponding to the R and S enantiomers were observed at 14.5 min and 13.2 min, respectively.
The absolute configuration of the isomers was determined from N-acylation of commercially
available R and S enantiomers of amine 21. The % ee of the recrystallized sample of amine 21
was 98%. The % ee of the filtrate of the recrystallized amine 21 was 26%. The crude mixture
obtained from reduction of L-phenylalanine ethyl ester hydrochloride was derivatized, analyzed,
and was obtained with 59% ee. In all cases the major enantiomer was S as shown in the
structure.

OH

N
H
2-(1H-Indol-3-yl)ethanol (23). Alcohol 23 was prepared according to the general
procedure using ethyl 3-indoleacetate (22, 0.609 g, 3.00 mmol) and Na-SG(I) (3.57 g, 27.1 wt%
stage I, 42.1 mmol). Alcohol 23 was obtained as a light brown solid (0.458 g, 95% yield). mp =
54-55 °C. 1H NMR (500 MHz, CDCl3) δ 8.11 (br, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0
Hz, 1H), 7.23-7.19 (m, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.03 (d, J = 2Hz, 1H), 3.89 (t, J = 6.5 Hz,
2H), 3.02 (t, J = 6.5 Hz, 2H), 1.69 (br, 1H) ppm. 13C NMR (125 MHz, CDCl3) δ 136.3, 127.3,
122.5, 122.1, 119.4, 118.8, 112.0, 111.2, 62.5, 28.6 ppm. APCI-MS m/z: [M+H]+ 162.2 (100%),
144.2 (79.0%).

Presentation of NMR Spectra

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