Lipase-catalyzed highly enantioselective kinetic resolution of boron-containing chiral alcohols

Article abstract of DOI:10.1021/ol901091f

The first application of enzymes as catalysts to obtain optically pure boron compounds is described. The kinetic resolution of boron-containing chiral alcohols via enantioselective transesterification catalyzed by lipases was studied. Aromatic, allylic, and aliphatic secondary alcohols containing a boronate ester or boronic acid group were resolved by lipase from Candida antartica (CALB), and excellent E values (E > 200) and high enantiomeric excesses (up to >99%) of both remaining substrates and acetylated product were obtained.

Full text of DOI:10.1021/ol901091f

Supporting Information
Lipase-catalyzed kinetic resolution of boron-containing
chiral alcohols
Leandro H. Andrade* and Thiago Barcellos
Institute of Chemistry, University of São Paulo
Av. Prof. Lineu Prestes, 748, CEP 05508-900, São Paulo, SP, Brasil.
*
leandroh@iq.usp.br
Table of Contents
General Techniques
S2
Synthetic Procedures
S4
Enzymatic Procedures and Chromatograms
S16
1
13
11
H, C and B NMR Spectra of new compounds S35
S1

1
General Techniques
Unless otherwise noted, commercially available materials were used without further
purification. Lipase from Candida antarctica (lipase B, CAL-B) immobilized and
commercially available as Novozym® 435 was kindly donated by Novozymes Latin America
Ltda. Others enzymes was purchased from the Sigma-Aldrich Chemical Company and stored
at 4 °C. All solvents were HPLC or ACS grade. Solvents used for moisture sensitive
operations were distilled from drying reagents under a nitrogen atmosphere: THF was
2 2 2
distilled from Na/benzophenone. CH Cl was distilled from CaH .
Analytical thin-layer chromatography (TLC) was performed by using aluminum-backed
silica plates coated with a 0.25 mm thickness of silica gel 60 F254 (Merck), visualized with an
ultraviolet light (λ = 254 nm), followed by exposure to p-anisaldehyde solution, potassium
permanganate solution, or vanillin solution and heating.
Standard chromatographic purification procedures were followed using 35-70 μm (240-
®
4
00 mesh) silica gel purchased from Acros Organics .
Nuclear magnetic resonance (NMR) spectra were recorded on a Varian Gemini 200 or
1
Bruker DRX 500 spectrometer at operating frequencies of 200 and 500 MHz ( H NMR) or 50
1
3
1
and 125 MHz ( C NMR). The H NMR chemical shifts are reported in ppm relative to TMS
peak. Data are reported as follows: chemical shift (δ), multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, sext = sextuplet, m = multiplet, br = broadened signal), and coupling
1
3
constant (J) in Hertz and integrated intensity. The C NMR chemical shifts are reported in
1
1
ppm relative to CDCl
Inova 300 spectrometer equipped with the appropriate decoupling accessories. All
chemical shifts were referenced to external BF .OEt (0.00 ppm).
A note about C NMR spectra: Due to the boron quadrupole, carbons directly attached to
3
or DMSO-d
6
signal. The B NMR spectra were obtained on a Varian
1
1
B
3
2
1
3
1
3
1
this element are often not detected in C spectra.
Melting points were determined on a Buchi melting point apparatus, model B-545 and are
uncorrected.
Infrared spectra were recorded from KBr discs or from a thin film between NaCl plates
on a Bomem Michelson model 101 FTIR spectrometer with internal referencing. Absorption
-
1
maxima (νmax) are reported in wavenumbers (cm ).
Low-resolution mass spectra were obtained on a GC/MS Shimadzu spectrometer,
operating at 70 eV. High-resolution mass spectra (HRMS) were acquired using a Bruker
Daltonics MicroTOF instrument, operating electrospray ionization (ESI) mode.
Optical rotations were measured on a Perkin Elmer-343 digital polarimeter in a 1 mL
cuvette with a 1 dm pathlength. All values are reported in the following format:
D
[α] (temperature of measurement) = specific rotation (concentration of the solution reported
in units of 10 mg sample per 1 mL solvent used).
Gas chromatography (GC) analyses for measurement of enantiomeric excesses were
obtained using a Shimadzu 17-A Gas Chromatograph, equipped with autosampler, Flame
1
Wrackmeyer, B. Prog. In NMR espectroscopy 1979, 12, 227.
S2

Ionization Detector (FID), and a chiral column Varian CP-Chirasil-DEX CB β-ciclodextrin
25 m x 0.32 mm x 0.25μm). Temperature of the detector and injector was 220 º C; flow =
00 kPa, H
High performance liquid chromatograph (HPLC) analyses for measurement of
(
1
2
.
enantiomeric excesses were performed on a Shimadzu, LC-10AD liquid chromatograph
equipped with autosampler and a variable wavelength UV detector (deuterium lamp 190-600
®
®
nm). Chiral columns: Chiralcel OJ-H (0.46 cmφ x 25 cm) or Chiralcel OD (0.46 cmφ x 25
cm) from Daicel Chemical Ind. i-PrOH and hexane (60% n-hexane) HPLC grade purchased
from J. T. Baker were used as the eluting solvents.
The enantioselectivity of the lipase-catalyzed reaction can be described by
enantiomeric ratio (E, E-value). The E-value is defined as the ratio of specificity constant for
2
the two enantiomers and can be expressed in terms of ee and ee (Equation 1).
S
R
⎛
⎜
⎞
⎟
1
− eeS
⎜
⎜
⎟
ln
ln
ee ⎟
S
1
+
⎜
⎟
⎝
eeR
⎠
Equation 1
E =
⎛
⎜
⎞
⎟
1
1
+ eeS
⎜
⎜
⎟
ee ⎟
S
+
⎜
⎝
⎟
eeR
⎠
Reference 4b: Dorsey, B. D.; Iqbal, M.; Chatterjee, S.; Menta, E.; Bernardini, R.; Bernareggi,
A.; Cassara, P. G.; D’Arasmo, G.; Ferretti, E.; De Munari, S.; Oliva, A.; Pezzoni, G.; Allievi,
C.; Strepponi, I.; Ruggeri, B.; Ator, M. A.; Williams, M.; Mallamo, J. P. J. Med. Chem. 2008,
5
1, 1068.
2
(
a) Chen, C-S., Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc. 1982, 104, 7294. (b) Straathof, A. J.
J.; Jongejan, J. A. Enzyme Microb. Technol. 1997, 21, 559.
S3

Synthetic Procedures
1
.1 General procedure for esterification reaction of acetylphenyl boronic acids.
To a 50 mL, two-necked, round-bottomed flask containing anhydrous THF (30 mL) were
added the appropriate acetylphenyl boronic acid (6 mmol, 983 mg) and the appropriate diol (6
mmol). The resultant solution was evaporated under reduced pressure at 40 ºC. This
procedure was repeated (3 times) until TLC analysis indicated a complete conversion. The
crude product was purified by column chromatography using hexanes/EtOAc (8:2) as eluent.
3
1
.1.1 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanone (4a).
Yield: 1.447 g (98%), white solid (mp = 66.3 - 67.7 °C).
1
H NMR (200 MHz, CDCl
3
) δ = 1.36 (s, 12H), 2.61 (s, 3H), 7.92 (s, 4H).
) δ = 24.81, 26.69, 84.16, 127.22, 134.87, 138.95, 198.37.
) δ = 30.59.
1
1
3
C NMR (50 MHz, CDCl
3
1
B NMR (96 MHz, CDCl
3
-1
FT-IR (KBr) νmax = 2986, 1661, 1509, 1398, 1358, 1267, 1142, 1092,959, 857, 830, 654 cm .
+
LRMS (EI) m/z (%) = 246(2, M ), 231(15), 160(16), 147(48), 131(17), 85(16), 77(15),
4
1
2(100).
4
.1.2 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanone (4b).
Yield: 1.461 g (99%), white solid (mp = 50.7 - 52.5 °C).
1
H NMR (200 MHz, CHCl ) δ = 1.36 (s, 12H), 2.63 (s, 3H), 7.47 (t, J=7.4Hz, 1H), 7.97-8.09
3
(
1
m, 2H), 8.36 (s, 1H).
3
C NMR (50 MHz, CDCl
3
) δ = 25.07, 26.92, 84.34, 130.94, 134.99, 136.72, 139.58, 142.62,
1
98.56.
1
1
B NMR (96 MHz, CDCl
3
) δ = 30.69.
-1
FT-IR (KBr) νmax = 2967, 1685, 1596, 1357, 1322, 1250, 1149, 959, 862, 702, 593 cm .
+
LRMS (EI) m/z (%) = 246 (15) [M ], 231(100), 203(42), 185(14), 160(4), 147(55), 131(12),
85(7), 77(4).
3
4
(
a) Claudel, S.; Gosmini, C.; Paris, J. M.; Périchon, J. Chem. Commun 2007, 3667. (b) Ma, Y.; Song, C.; Jiang,
W.; Xue, G.; Cannon, J. F.; Wang, X.; Andrus, M. B. Org. Lett. 2003, 5, 4635. (c) Murata, M.; Oyama, T.;
Watanabe, S., Masuda, Y. J. Org. Chem. 2000, 65, 164. (d) Ishiyama, I. Murata, M., Miyaura, N. J. Org.
Chem. 1995, 60, 7508.
Murata, M.; Oyama, T.; Watanabe, S., Masuda, Y. J. Org. Chem. 2000, 65, 164.
S4

5
1
.1.3 1-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanone (4c).
Yield: 1.351 g (97%), white solid (mp = 89.2 – 90.7 °C).
1
H NMR (200 MHz, CHCl
3
) δ = 1.03 (s, 6H), 2.61 (s, 3H), 3.78 (s, 4H), 7.90 (s, 4H).
1
1
3
C NMR (50 MHz, CDCl
3
) δ = 23.63, 26.86, 33.06, 72.55, 127.60, 134.40, 138.77, 198.77.
) δ = 26.54.
1
B NMR (96 MHz, CDCl
3
-1
FT-IR (KBr) νmax = 2962, 1678, 1477, 1250, 1133, 835, 694, 644 cm .
LRMS (EI) m/z (%) = 232(20, M ), 217(100), 189(6), 147(10), 121(15), 103(12), 77(11),
+
6
1
9(27).
6
.1.4 1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanone (4d).
Yield: 1.337 g (96%), white solid (mp = 56.7 – 57.5 °C).
1
H NMR (200 MHz, CHCl
3
) δ = 1.03 (s, 6H), 2.63 (s, 3H), 3.78 (s, 4H), 7.44 (t, J = 7.2 Hz,
1
H), 8.01 (t, J = 7.2 Hz, 2H), 8.37 (s, 1H).
1
3
C NMR (50 MHz, CDCl
3
) δ = 22.17, 26.97, 32.08, 72.52, 128.03, 130.58, 134.42, 136.56,
1
38.91, 198.81.
1
1
B NMR (96 MHz, CDCl
3
) δ = 26.63.
-1
FT-IR (KBr) νmax = 2971, 1677, 1484, 1426, 1255, 1136, 811, 700, 595 cm .
+
LRMS (EI) m/z (%) = 232(10, M ), 217(100), 189(2), 147(7), 121(13), 102(7), 77(8), 69(30).
1
.2 General procedure to reduction of pinacolyl and neopentyl acetylphenyl boronate
esters.
To a 100 mL round-bottomed flask containing anhydrous methanol (1.5 mL) cooled at 0
°
C with an ice bath, was added NaBH (4 mmol, 160 mg) followed by slow addition of a
4
solution of the boronate ester (2 mmol in methanol, 1.5 mL). The mixture was stirred for 0.5 h
at 0 °C, and additional 4 h at room temperature. The mixture was cooled to 0 °C and treated
with 1N HCl until pH = 7. The mixture was then extracted with EtOAc (3 x 5 mL), dried with
4
anhydrous MgSO , and the solvent was evaporated under reduced pressure. The crude product
was purified by column chromatography using hexanes/EtOAc (8:2) as eluent.
5
(
a) Shi, B.; Boyle, R. W. J. Chem. Soc., Perkin Trans. 1 2002, 1397. (b) Kabalka, G. W.; Akula, M. R.; Zhang,
J. Nucl. Med. Biol. 2002, 29, 841.
Kitamura, Y.; Sakurai, A.; Udzu, T.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Tetrahedron 2007, 63, 10596.
6
S5

1
.2.1 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol (1a).
Yield: 486 mg (98%), white solid (mp = 79.6 – 81.2 °C).
1
H NMR (200 MHz, CDCl ) δ = 1.33 (s, 12H), 1.47 (d, J = 6.4 Hz, 3H), 1.99 (s, 1H), 4.90 (q,
3
J = 6.4 Hz, 1H), 7.37 (d, J = 8 Hz, 2H), 7.79 (d, J = 8 Hz, 2H).
1
3
C NMR (50 MHz, CDCl
B NMR (96 MHz, CDCl
3
): δ = 25.0, 25.33, 70.53, 83.95, 124.83, 135.20, 149.16.
) δ = 30.87.
1
1
3
-1
FT-IR (KBr) νmax = 3330, 2978, 1516, 1362, 1323, 1144, 1093, 859, 661 cm .
LRMS (EI) m/z (%) = 248(7) [M ], 233(100), 165(35), 149(67), 133(28), 101(24), 84(28).
+
+
HRMS (ESI): Calculated for C14
H21BO
3
Na [M + Na] = 271.1481; found: 271.1474.
1
.2.2 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol (1b).
Yield: 486 mg (98%), colourless oil.
1
H NMR (200 MHz, CHCl
3
) δ = 1.34 (s, 12H); 1.49 (d, J = 6.4 Hz, 3H), 2.00 (br, 1H), 4.91
(
q, J = 6.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H)
7
.92 (s, 1H).
1
3
C NMR (50 MHz, CDCl
45.30.
3
): δ = 25.00, 25.30, 70.47, 83.98, 128.10, 128.48, 131.93, 134.07,
1
1
1
B NMR (96 MHz, CDCl
3
) δ = 30.91.
-1
FT-IR (KBr) νmax = 3232, 2978, 1358, 1200, 1144, 864, 710 cm .
LRMS (EI) m/z (%) = 248(6) [M ], 233(100), 165(31), 149(39), 133(27), 101(27), 84(24).
+
+
HRMS (ESI): Calculated for C H BO Na [M + Na] = 271.1481; found: 271.1472.
1
4
21
3
1
.2.3 1-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanol (1c)
Yield: 224 mg (48%), white solid (mp = 61.2 – 63.5 °C).
1
H NMR (200 MHz, CDCl
3
) δ = 1.01 (s, 6H), 1.47 (d, J = 6.4 Hz, 3H), 2.01 (br, 1H), 3.75 (s,
4
H), 4.88 (q, J = 6.4 Hz, 1H), 7.34 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 22.07, 25.27, 32.05, 70.61, 72.48, 124.75, 134.31, 148.50.
) δ = 26.79.
1
1
B NMR (96 MHz, CDCl
3
-1
FT-IR (KBr) νmax = 3289, 2974, 1609, 1479, 1425, 1316, 1249, 1133, 1091, 834, 647 cm .
LRMS (EI) m/z (%) = 234(10) [M ], 219(100), 133(15), 104(52), 91(29), 77(13), 69(56).
+
+
HRMS (ESI): Calculated for C13
H19BO
3
Na [M + Na] = 257.1325; found: 257.1319
1
.2.4 1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanol (1d)
Yield: 253 (54%), white solid (mp = 88 - 89 °C).
1
H NMR (200 MHz, CHCl
3
) δ = 1.01 (s, 6H), 1.49 (d, J = 6.4 Hz, 3H), 2.02 (s, 1H), 3.76 (s,
4
H), 4.88 (q, J = 6.4 Hz, 1H), 7.29 – 7.49 (m, 2H), 7.68 – 7.78 (m, 2H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 22.07, 25.26, 32.04, 70.72, 72.48, 127.94, 128.00, 131.02,
1
33.23, 145.05.
1
1
B NMR (96 MHz, CDCl
3
) δ = 26.78
FT-IR (KBr) νmax = 3409, 2971, 1601, 1485, 1428, 1310, 1251, 1195, 1129, 1086, 1007, 813,
-1
7
11 cm .
S6

+
LRMS (EI) m/z (%) = 234(3) [M ], 219(38), 133(23), 104(65), 91(37), 77(20), 69(70).
+
HRMS (ESI): Calculated for C13
H19BO
3
Na [M + Na] = 257.1325; found: 257.1319.
7
1
.3 General procedure to acetylation of boronate esters (RS)-3a-d.
A 25 mL, two-necked, round-bottomed flask was charged with boronate ester 1 (0.5
mmol, 124 mg for 1a,b or 117 mg for 1c,d), N-bromosuccinamide (10 mol%; 50 μmol, 8.8
mg) and anhydrous dichloromethane (3 mL) under dry nitrogen atmosphere. Acetic anhydride
(
1 mmol, 100 μL) was then added and the mixture was stirred for 12 h. Dichloromethane (10
mL) was added and the resulting solution was washed with 5% NaHCO (2 x 2 mL). The
3
organic layer was dried over anhydrous MgSO , filtrated and the solvent was evaporated
4
under reduced pressure. The crude product was purified by column chromatography using
hexanes/EtOAc (9:1) as eluent.
1
.3.1 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl acetate (2a).
Yield: 139 mg (96%), white solid (mp = 82.7 - 83.7 °C).
1
H NMR (200 MHz, CDCl ) δ = 1.33 (s, 12H), 1.52 (d, J = 6.6 Hz, 3H), 2.07 (s, 3H), 5.88 (q,
3
J = 6,6 Hz,1H), 7.35 (d, J = 7.8 Hz, 2H), 7.80 (d, J = 7.8 Hz, 2H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 21.46, 22.36, 25.00, 72.43, 83.96, 125.48, 135.19, 144.93,
1
70.42.
1
1
B NMR (96 MHz, CDCl
3
) δ = 30.81.
-1
FT-IR (KBr) νmax = 2984, 1750, 1359, 1233, 1140, 1090, 1019, 855, 654 cm .
+
LRMS (EI) m/z (%) = 290(2) [M ], 275(2), 248(17), 231(5), 215(7), 165(15), 144(46),
1
31(56), 105(18), 83(42), 58(37), 42(100).
+
HRMS (ESI): Calculated for C16 Na [M + Na] = 313.1587; found: 313.1578.
H23BO
4
1
.3.2 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl acetate (2b).
Yield: 130 mg (90%), colourless oil.
1
H NMR (200 MHz, CDCl ) δ = 1.34 (s, 12H), 1.53 (d, J = 6.6 Hz, 3H), 2.06 (s, 3H), 5.89 (q,
3
J = 6.6 Hz, 1H), 7.31-7.48 (m, 2H), 7.71-7.80 (m, 2H).
7
Babak, K.; Hassan, S. Synlett 2001, 519.
S7

1
3
C NMR (50 MHz, CDCl
3
): δ = 21.54, 22.37, 25.06, 72.60, 84.04, 128.07, 129.23, 132.58,
1
34.57, 141.11, 170.50.
1
1
B NMR (96 MHz, CDCl
3
) δ = 30.81.
-1
FT-IR (KBr): νmax = 2980, 1742, 1371, 1241, 1145, 709 cm .
+
LRMS (EI) m/z (%) = 290(24) [M ], 275(16), 248(96), 231(41), 215(39), 204(20), 190(19),
1
65(37), 144(82), 131(100), 105(36), 84(40).
+
HRMS (ESI): Calculated for C16 Na [M + Na] = 313.1587; found: 313,1579.
H23BO
4
1
.3.3 1-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethyl acetate (2c).
Yield: 126 mg (92%), colourless oil.
1
H NMR (200 MHz, CDCl
3
) δ = 1.00 (s, 6H), 1.52 (d, J = 6.8 Hz, 3H), 2.06 (s, 3H), 3.75 (s,
4
H), 5.88 (q, J = 6.8 Hz, 1H), 7.33 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 21.17, 21.71, 22.02, 31.71, 72.14, 125.05, 133.94, 143.91,
1
70.13.
1
1
B NMR (96 MHz, CDCl
3
) δ = 26.66.
FT-IR (KBr) νmax = 2958, 1735, 1613, 1478, 1422, 1247, 1135, 1068, 1021, 948, 831, 706,
-1
6
43 cm .
LRMS (EI) m/z (%) = 276(12) [M ], 261(2), 234(57); 216(74), 173(15), 146(17), 130(86),
17(15), 104(64), 77(16), 56(84).
HRMS (ESI): Calculated for C15
+
1
+
H
4
21BO Na [M + Na] = 299.1430; found: 299.1428.
1
.3.4 1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethyl acetate (2d).
Yield: 123 mg (89%), colourless oil.
1
H NMR (200 MHz, CDCl
3
) δ = 1.02 (s, 6H), 1.54 (d, J = 6.6 Hz, 3H), 2.06 (s, 3H), 3.76 (s,
4
H), 5.89 (q, J = 6.6 Hz, 1H), 7.29-7.45 (m, 2H), 7.70-7.82 (m, 2H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 21.58. 22.10, 22.36, 32.05, 72.49, 72.72, 127.94, 128.71,
1
31.75, 133.67, 140.86, 170.53.
1
1
B NMR (96 MHz, CDCl
FT-IR (KBr) ν = 2963, 1732, 1605, 1478, 1432, 1376, 1318, 1242, 1200, 1133, 1066, 944,
8
3
) δ = 26.83.
max
-1
04, 710 cm .
+
LRMS (EI) m/z (%) = 274(2) [M] , 261(2), 233(87), 216(100), 173(18), 146(19), 130(72),
1
17(13), 104(42), 91(6), 77(9), 56(21).
+
HRMS (ESI): Calculated for C15
H21BO
4
Na [M + Na] = 299.1430; found: 299.1429.
S8

1
.4 Reduction of acetylphenylboronic acids 3a,b
8
The title compounds were prepared by adapting previously described procedure
A 25 mL, two-necked, round-bottomed flask was charged with acetylphenylboronic acid
(
(
1.00 g, 6.10 mmol), anhydrous EtOH (5.0 mL), and cooled at 0 °C with an ice bath, NaBH
4
579 mg, 15.2 mmol) was added portionwise. After stirring for 16 h, additional EtOH (5.0
mL) was added and the mixture was stirred for 4 h. The solution was cooled to 0 °C and
treated with 1N HCl (30 mL, 30 mmol). The mixture was then extracted with EtOAc (3 X 15
mL), dried over anhydrous MgSO
4
, filtrated and concentrated under reduced pressure. The
dried solids were triturated with THF (20 mL) and filtered to remove insoluble salts.
1
.4.1 4-(1-hydroxyethyl)phenylboronic acid (1g)
Yield: 942 mg (93 %), white waxy solid.
1
H NMR (200 MHz, DMSO-d ) δ = 1.33 (d, J = 6.4 Hz, 3H), 4.73 (q, J = 6.4 Hz, 1H), 7.33
6
(
d, J = 8 Hz, 2H), 7.75 (d, J = 8 Hz, 2H).
1
3
C NMR (50 MHz, DMSO-d
6
): δ = 26.02, 68.46, 124.77, 134.28, 149.45.
1
1
B NMR (96 MHz, DMSO-d
6
) δ = 19.83.
1
.4.2 3-(1-hydroxyethyl)phenylboronic acid (1h)
Yield: 952 mg (94 %), white solid (mp = 98.2ºC)
1
H NMR (200 MHz, DMSO-d
6
) δ = 1.30 (d, J = 6.4 Hz, 3H), 4.68 (q, J = 6.4 Hz, 1H), 7.22-
7
.38 (m, 2H), 7.61 (d, J = 7 Hz, 1H), 7.72 (s, 1H).
1
3
C NMR (50 MHz, DMSO-d
6
): δ = 26.11, 68.71, 127.62, 127.66, 131.59, 132.84, 146.28.
1
1
B NMR (96 MHz, DMSO-d
6
) δ = 19.84.
9
1
.5 Synthesis of 3-tert-butyldimethylsiloxy-1-butyne (5).
A 25 mL, two-necked, round-bottomed flask was charged with anhydrous
dichloromethane (20 mL) and propargylic alcohol 5 (10 mmol, 700 mg, 0.78 mL) under dry
nitrogen atmosphere. Imidazole (11 mmol, 749 mg) was added at 0 ºC followed by addition of
tert-butyldimethylchloride (11 mmol, 1,65 g). The mixture was stirred for 5 h. Water (5 mL)
was added followed by extraction with hexanes (4 x 15 mL). The combined organic layers
4
were dried over anhydrous MgSO , filtrated and concentrated under reduced pressure. The
8
Molander, G. A.; Petrillo, D. E. J. Am. Chem Soc. 2006, 128, 9634.
Schone, N.; Pietrszka, J. Eur. J. Org. Chem. 2004, 5011.
9
S9

crude product was purified by column chromatography using hexanes as eluent. The
compound 5 was obtained as colourless oil. Yield: 1.509 mg (82%).
1
H NMR (200 MHz, CHCl
3
) δ = 0.08 (s, 3H), 0.12 (s, 3H), 0.9 (s, 9H); 1.44 (d, J = 6.6 Hz,
3
H), 2.38 (d, J = 2 Hz , 1H), 4.52 (qd, J = 6.6 and 2 Hz, 1H).
1
3
C NMR (50 MHz, CDCl
3
): δ = -4.3, -3,2, 18.3, 25.6, 58.8, 70.9, 86.3.
+
LRMS (EI) m/z (%) = 184(0.3) [M] , 169(3), 125(87), 113(5), 101(27), 83(100).
S10

1
.6 Synthesis of (E)-tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
1
0
yl)but-3-en-2-yloxy)silane3-tert-butyldimethylsiloxy-1-butyne (6).
A 25 mL, two-necked, round-bottomed flask was charged with pinacol (6.25 mmol,
99 mg) and anhydrous dichloromethane (2 mL) under dry nitrogen atmosphere. The solution
7
was cooled at 0 °C with an ice bath, and BH
added dropwise. The resultant solution was stirred for 3 h at 0 ºC.
propargylic alcohol 5 (5 mmol, 920 mg) was added slowly at 0 ºC. The reaction mixture was
allowed to warm to room temperature, and stirred for an additional 12 h. Et O (20 mL) was
added followed by saturated aqueous NH Cl solution (4 mL). The aqueous phase was
extracted with Et O (2 x 10 mL). The combined organic phases were washed with saturated
aqueous NH Cl solution (2 x 4 mL), brine (4 mL) and dried over anhydrous MgSO , filtrated
3 2 2
.SMe (5M in Et O, 6.25 mmol, 1.25 mL) was
1
0a
The protected
2
4
2
4
4
and concentrated under reduced pressure. The crude product was purified by column
chromatography using hexanes/EtOAc (8:2) as eluent. The resulting product 6 was obtained
1
0b,c
as colourless oil. Yield: 1.263 g (81%).
1
H NMR (200 MHz, CDCl
3
) δ = 0.05 (s, 9H), 0,90 (s, 9H), 1,21 (d, J = 6.6 Hz, 3H), 1.27 (s,
1
2H), 4.27 (m, 1H), 5.57 (dd, J = 18, 1.8 Hz, 1H), 6.55 (dd, J = 18, 3.8 Hz, 1H).
1
3
C NMR (50 MHz, CDCl ): δ = -4.63, -4.48, 18.49, 23.09, 24.95, 25,01, 26.12, 70.06, 83.31,
3
1
57.22.
-
1
FT-IR (KBr) νmax = 2930, 28,57, 1642, 1369, 1337, 1254, 1146, 835, 775 cm .
LRMS (EI) m/z (%) = 297(2) [M - CH3], 255(30), 197(2), 155(100); 113(64), 75(92).
+
+
HRMS (ESI): Calculated for C16
H
33BO
3
Si Na [M + Na] = 335.2189; found: 335.2193.
10
(
a) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem, 1992, 57, 3482. (b) Movassaghi, M.; Hunt, D. K.;
Tjandra, M. J. Am. Chem. Soc. 2006, 128, 8126 (c) Fortineau, A.; Robert, M.; Guégan, J.; Carrié, D.; Mortier,
J.; Vaultier, M. C. R. Acad. Sci. Paris, t.I 1998, 253.
S11

1
.7 Synthesis
of
(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol
1
0b
(
1e).
OTBS
OH
citric acid
MeOH
O
O
B
B
3
h, rt
O
O
7
8%
(
RS)-6
(RS)-
1e
A 25 mL, two-necked, round-bottomed flask was charged with boronate ester 6 (2 mmol;
6
22 mg) and anhydrous MeOH (2 mL) under dry nitrogen atmosphere. To this solution was
added anhydrous citric acid (2 mmol; 420 mg), and stirred for 3 h. To the reaction mixture
was added EtOAc (5 mL). The organic layer was washed with water (2 x 1 mL) and dried
4
over anhydrous MgSO , filtrated and concentrated under reduced pressure. The crude product
was purified by column chromatography using hexanes/EtOAc (4:1) as eluent. The resulting
product 1e was obtained as colourless oil. Yield: 309 mg (78%).
1
H NMR (200 MHz, CDCl ) δ = 1.24 (d, J = 5.6 Hz, 3H); 1.28 (s, 12H), 2.29 (br, 1H), 4.33
3
(
m, 1H), 6.61 (dd, J = 18, 1.8 Hz, 1H), 6.65 (dd, J = 18, 3.8 Hz, 1H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 22.77, 24.89, 69.68, 83.48, 156.46.
) δ = 29.97.
1
1
B NMR (96 MHz, CDCl
3
-1
FT-IR (KBr) νmax = 3438, 2978, 1644, 1361, 1326, 970, 849 cm .
LRMS (EI) m/z (%) = 183(22) [M - CH3], 155(4), 141(10), 98(100), 83(41), 55(80).
+
+
HRMS (ESI): Calculated for C10
H19BO
3
Na [M + Na] = 221.1325; found: 221.1315.
1
.8 Synthesis
acetate (2e).
of
(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-yl
O
OH
Ac O
NBS (10 mol%)
O
2
O
B
O
B
O
CH Cl 12h, rt
2
2,
92%
O
(
RS)-1e
(
RS)-2e
The title compound was prepared according to the general procedure described in item 1.3,
from boronate ester (RS)-1e (0.5 mmol, 99 mg). The crude product was purified by column
chromatography using hexanes/EtOAc (9:1) as eluent. The resulting product (RS)-2e was
obtained as colourless oil. Yield: 109 mg (92%).
S12

1
H NMR (200 MHz, CDCl ) δ = 1.27 (s, 12H), 1.32 (d, J = 6.6 Hz, 3H), 2.06 (s, 3H), 5.39
3
(
m, 1H), 5.58 (dd, J = 18, 1.8Hz, 1H), 6.55 (dd, J = 18, 4.8Hz, 1H).
1
3
C NMR (50 MHz, CDCl
3
): δ = 19.75, 21.34, 24.92, 71.43, 83.57, 151.38, 170.38.
) δ = 29.84.
1
1
B NMR (96 MHz, CDCl
3
-1
FT-IR (KBr) νmax = 2980, 1741, 1645, 1371, 1333, 1238, 1146, 850 cm .
LRMS (EI) m/z (%) = 225(2) [M - CH3], 197(8), 140(27), 97(19), 83(20).
+
+
HRMS (ESI): Calculated for C12
H21BO
4
Na [M + Na] = 263.1430; found: 263.1420.
1
.9 Synthesis of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-ol (1f).
A 25 mL, two-necked, round-bottomed flask was charged with pinacol (15 mmol, 1.772
g) and anhydrous dichloromethane (10 mL) under dry nitrogen atmosphere. The solution was
cooled with an ice bath, and BH .SMe (5 M in Et O, 15 mmol, 3 mL) was added dropwise.
3
2
2
1
0a
The resulting solution was stirred for 3 h at 0 ºC. 5-hexen-2-one (7) (5 mmol, 294 mg, 345
μl) was dropwise added and stirred for 1 h at 0 ºC. The reaction mixture was allowed to warm
to room temperature, and stirred for an additional 24 h. Et
NH Cl solution (4 mL) was added. The aqueous phase was extracted with Et
The combined organic phases were washed with saturated aqueous NH Cl solution (2 x 4
mL), brine (4 mL) and dried over anhydrous MgSO , filtrated and concentrated under reduced
pressure. The crude product was purified by column chromatography using hexanes/EtOAc
2
O (20 ml) and saturated aqueous
4
2
O (2 x 10 mL).
4
4
(
(
4:1) as eluent. The resulting product (RS)-1f was obtained as colourless oil. Yield: 947 mg
83%).
1
H NMR (500 MHz, CDCl
3
) δ = 0.79 (t, J = 7.6 Hz, 2H), 1.17 (d, J = 6.2 Hz, 3H ), 1.24 (s,
1
2H), 1.34-1.48 (m, 6H), 1.86 (br, 1H), 3.79 (sext, J = 6.2 Hz, 1H).
1
3
C NMR (125 MHz, CDCl
3
): δ = 23.49, 23.94, 24.71, 28.50, 39.17, 67.97, 83.07.
1
1
B NMR (96 MHz, CDCl
3
) δ = 35.15.
-1
FT-IR (KBr) νmax = 3442, 2977, 2931, 1463, 1373, 1320, 1146, 967, 847 cm .
LRMS (EI) m/z (%) = 213(0,2) [M - CH3], 195(0,9), 169(14), 154(10), 127(44), 101(27),
+
8
3(36), 58(100).
+
HRMS (ESI): Calculated for C12
H25BO
3
Na [M + Na] = 251.1794; found: 251.1792.
S13

1
.10 Synthesis of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-yl acetate (2f).
A 25 mL, two-necked, round-bottomed flask was charged with boronate ester (RS)-1f
(
0.5 mmol, 124 mg), Et
mg) and anhydrous dichloromethane (3 mL) under dry nitrogen atmosphere. Acetic anhydride
1 mmol, 100 μL) was then added and the mixture was stirred for 12 h. Dichloromethane (10
mL) was added and the organic phase was washed with 5% NaHCO (2 x 2 mL). The organic
layer was dried over anhydrous MgSO , filtrated and concentrated under reduced pressure.
3
N (1.5 equiv.; 1.5 mmol, 210 μL), DMAP (10 mol%; 50 μmol, 8.8
(
3
4
The crude product was purified by column chromatography using hexanes/EtOAc (9:1) as
eluent. The resulting product (RS)-2f was obtained as colourless oil. Yield: 120 mg (89%).
1
H NMR (500 MHz, CDCl
3
) δ = 0.77 (t, J = 7.6 Hz, 2H), 1.19 (d, J = 6.2 Hz, 3H ), 1.24 (s,
1
2H), 1.28-1.61 (m, 6H), 2.01 (s, 3H), 4.88 (sext, J = 6.2 Hz, 1H).
1
3
C NMR (125 MHz, CDCl ): δ = 20.10, 21.54, 24.03, 24.98, 28.20, 35.87, 71.21, 83.06,
3
1
70.91.
1
1
B NMR (96 MHz, CDCl ) δ = 34.07.
3
-1
FT-IR (KBr) νmax = 2978, 2934, 1737, 1373, 1320, 1244, 1146, 968, 847 cm .
+
LRMS (EI) m/z (%) = 255(2) [M - CH3], 212(17), 169(52), 153(21), 129(42), 101(28),
8
7(46), 83(42), 69(28).
+
HRMS (ESI): Calculated for C14
H
4
27BO Na [M + Na] = 293.1900; found: 293.1902.
1
.11 Suzuki-Miyaura cross-coupling reactions: Preparation of 1-(biphenyl-yl)ethanols
a,b.
8
1
1
The title compounds were prepared by adapting a previously described procedure.
A 10 mL round-bottomed flask equipped with reflux condenser was charged with
appropriate boronate ester (RS)-1a,b (1 mmol, 248 mg), bromobenzene (1 mmol, 157 mg, 104
μL) and degassed i-PrOH (4 mL) under dry nitrogen atmosphere. After 15 min, palladium(II)
acetate (10 μmol, 2.2 mg), Ph
3
2 3
P (20 μmol, 5.2 mg), degassed 2 M aqueous Na CO (0,64 mL)
11
(
a) Callam, C. S.; Lowary, T. L. J. Chem. Ed. 2001, 78, 947. (b) Kourist, R.; Gonzáles-Sabín, J.; Liz, R.;
Rebolledo, F. Adv. Synth. Catal. 2005, 347, 695.
S14

and degassed water (0.4 mL) were added, and the mixture was refluxed for 2.5 h. After
cooling to room temperature, the mixture was stirred under air for 10 min. EtOAc (10 mL)
was added and transferred to a separatory funnel. The aqueous layer was extract with EtOAc
(
(
4 x 2 mL). The combined organic layer was, successively, washed with 5% aqueous Na
2 3
CO
3 x 4 mL) and brine (2 x 4 mL), and dried over anhydrous MgSO . The organic layer was
4
stirred for 20 min in the presence of activated carbon (100 mg). The resulting suspension was
filtrated and concentrated under reduced pressure. The crude product was purified by column
chromatography using chloroform/MeOH (98:2) as eluent.
1
1
1
.11.1 1-(biphenyl-4-yl)ethanol (8a).
Yield: 164 mg (83%), white solid (mp = 96.5-97.5 °C).
1
H NMR (200 MHz, CDCl
H), 7.33-7.62 (m, 9H).
3
) δ = 1.52 (d, J = 6.6 Hz, 3H), 1.97 (br, 1H), 4.93 (q, J = 6.4 Hz,
1
1
3
C NMR (50 MHz, CDCl
3
): δ = 25.35, 70.35, 126.05, 127.28, 127.47, 128.97, 137.71,
1
40.65, 141.06, 145.02.
+
LRMS (EI) m/z (%) = 198(47) [M ], 183(79), 180(48), 155(100), 152(36), 91(18), 77(40).
11
1
.11.2 1-(biphenyl-3-yl)ethanol (8b).
Yield: 156 mg (79%), colourless oil.
1
H NMR (200 MHz, CDCl
H), 7.27-7.60 (m, 9H).
3
) δ = 1.49 (d, J = 6.4 Hz, 3H), 2.29 (br, 1H), 4.89 (q, J = 6.4 Hz,
1
1
3
C NMR (50 MHz, CDCl
3
): δ = 25.38, 70.55, 112.17, 124.42, 126.40, 127.33, 127.50,
1
28.92, 129.07, 141.26, 141.59, 146.52.
+
LRMS (EI) m/z (%) = 198(50) [M ], 183(42), 155(100), 152(23), 91(16), 77(22).
S15

2
Enzymatic Procedures
2
.1 General procedure for small scale enzymatic reactions
A 50 mL flask was charged with the appropriate boronate ester (1a-f, 0.2 mmol), 10 mL of n-
hexane (HPLC grade) and CAL-B (enzyme amount as indicate in the tables 1 to 5) and vinyl
acetate (3 equiv., 0.6 mmol, 55 μL). The reaction mixture was sealed with a rubber stopper
and stirred on a rotary shaker (30 ºC, 150 rpm) until the appropriate time. After that, the
mixture was filtered and the solvent evaporated under reduced pressure.
2
.2 General procedure for preparative-scale enzymatic reactions
A 250 mL Erlenmeyer flask was charged with appropriate boronate ester (1a-f, 1.5
mmol), 75 mL of n-hexane (HPLC grade), CAL-B (150 mg), and vinyl acetate (3 equiv., 4.5
mmol, 412 μL). The reaction mixture was sealed with a rubber stopper and stirred on a rotary
shaker (30 ºC, 150 rpm) until the appropriate time (Table 1-5). After that, the mixture was
filtered and the solvent evaporated under reduced pressure. The ester (2) was separated from
the remaining alcohol (1) by column chromatography using hexanes/EtOAc as eluent.
S16

2
.2.1 Enzymatic kinetic resolution of (RS)-1a.
The enantioenriched compounds (S)-1a and (R)-2a were prepared according to the method
described in item 2.2.
(
S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol, [(S)-1a]
2
4
Yield: 161 mg (43%), >99% ee, [α]
HPLC condition: Chiralcel OJ-H column, n-hexane/i-PrOH (95:5), 1.0 mL/min, 227 nm UV
D
3
= -31.4 (c 1.0, CHCl ).
®
detector, t
R
= 10.6 min for (R) and t
R
= 12.6 min for (S).
OH
O
B
O
(
RS)-1a
OH
O
B
O
(S)-
1a
S17

(
R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl acetate, [(R)-2a]
24
Yield: 186 mg (42.6%), >99% ee, [α]
D
3
= +81.8 (c 1.0, CHCl ).
GC condition: oven 150-180 ºC, rate 1 ºC/min, t = 18.1 min for (S) and t = 18.7 min for (R).
R
R
O
O
O
B
O
(RS)-2a
O
O
O
B
O
(R)-2a
S18

2
.2.2 Enzymatic kinetic resolution of (RS)-1b.
The enantioenriched compounds (S)-1b and (R)-2b were prepared according to the method
described in item 2.2.
(
S)-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol, [(S)-1b]
2
4
Yield: 159 mg (42.6%), >99% ee, [α]
HPLC condition: Chiralcel OJ-H column, n-hexane/i-PrOH (95:5), 1.0 mL/min, 227 nm UV
D
3
= -27.2 (c 1.14, CHCl )
®
detector, t
R
= 8,6 min for (S) and t
R
= 22.5 min for (R).
OH
(
O
RS)-1b
B
O
OH
(
S)-1b
B
O
O
S19

(
R)-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl acetate [(R)-2b]
24
Yield: 186 mg (42.6%), >99% ee, [α]
D
3
= +66.8 (c 1.0, CHCl ).
GC condition: oven 150-180 ºC, rate 1 ºC/min, t = 14.2 min for (S) and t = 14.8 min for (R).
R
R
O
O
(
RS)-1b
B
O
O
O
O
(
R)-1b
B
O
O
S20

2
.2.3 Enzymatic kinetic resolution of (RS)-1c.
The enantioenriched compounds (S)-1c and (R)-2c were prepared according to the method
described in item 2.2
(
S)-1-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanol, [(S)-1c]
2
3
Yield: 137 mg (39%), >99% ee, [α]
HPLC condition: Chiralcel OJ-H column, n-hexane/i-PrOH (95:5), 1.0 mL/min, 227 nm UV
D
3
= -27.9 (c 1.0, CHCl ).
®
detector, t
R
= 23.3 min for (S) and t
R
= 25.4 min for (R).
OH
O
B
O
(RS)-1c
OH
O
B
(
S)-1c
O
S21

(
R)-1-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethyl acetate, [(R)-2c]
2
3
Yield: 174 mg (42%), >99% ee, [α]
D
3
= +95.8 (c 1.0, CHCl ).
GC condition: isotherm 170 ºC, t = 17.2 min for (S) and t = 17.9 min for (R).
R
R
O
O
O
B
(RS)-2c
O
O
O
O
B
(
R)-2c
O
S22

2
.2.4 Enzymatic kinetic resolution of (RS)-1d.
The enantioenriched compounds (S)-1d and (R)-2d were prepared according to the method
described in item 2.2
(
S)-1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanol, [(S)-1d]
2
3
Yield: 123 mg (35%), >99% ee, [α]
HPLC condition: Chiralcel OJ-H column, n-hexane/i-PrOH (95:5), 1.0 mL/min, 227 nm UV
D
3
= -22.1 (c 1.0, CHCl ).
®
detector, t
R
= 14.9 min for (S) and t
R
= 24.3 min for (R).
OH
(
RS)-1d
B
O
O
OH
(S)-1d
B
O
O
S23

(
R)-1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethyl acetate, [(R)-2d]
2
3
Yield: 170 mg (41%), >99% ee, [α]
D
3
= +67.4 (c 1.0, CHCl ).
GC condition: isotherm 160 ºC, t = 22.5 min for (S) and t = 23.4 min for (R).
R
R
O
O
(
RS)-2d
B
O
O
O
O
(
R)-2b
B
O
O
S24

2
.2.5 Enzymatic kinetic resolution of (RS)-1e.
The enantioenriched compounds (S)-1e and (R)-2e were prepared according to the method
described in item 2.2.
(
S)-(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol, [(S)-1e]
2
D
4
10c
25
Yield: 136 mg (45%) >99% ee, [α]
= +11.8 (c 1.0, MeOH). Lit. [α]
D
= +5.4 (c 1.0,
MeOH).
®
HPLC condition: Chiralcel OJ-H column, n-hexane/i-PrOH (99.5:0.5), 0.5 mL/min, 220 nm
UV detector, t
R
= 13.3 min for (R) and t
R
= 15.8 min for (S).
OH
O
B
O
(RS)-1e
OH
O
B
O
(
S)-1e
S25

(
R)-(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol, [(R)-2e]
2
4
Yield: 155 mg (43%) >98% ee, [α]
D
= +42.5 (c 1.0, MeOH).
GC condition: oven 100-150 ºC, rate 2 ºC/min,, t = 19.4 min for (S) and t = 19.8 min for
R
R
(
R).
O
O
O
B
O
(RS)-2e
O
O
O
B
O
(RS)-2e
S26

2
.2.6 Enzymatic kinetic resolution of (RS)-1f
The enantioenriched compounds (S)-1f and (R)-2f were prepared according to the method
described in item 2.2.
(
S)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-ol, [(S)-1f]
2
2
Yield: 156 mg (45%) >99% ee, [α]
D
3
= +3.1 (c 1.08, CHCl ).
GC condition: oven 100-180 ºC, rate 3 ºC/min, t
R
R
= 14.9 min for (S) and t = 15.4 min for (R).
O
O
O
B
O
(RS)-2f
O
O
OH
acetylation
O
O
B
B
O
O
(
S)-1f
(S)-2f
S27

(
R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-yl acetate, [(R)-2f]
2
2
Yield: 192 mg (47%) >99% ee, [α]
D
3
= -0.5 (c 1.0, CHCl ).
GC condition: oven 100-180 ºC, rate 3 ºC/min, t = 14.9 min for (S) and t = 15.4 min for (R).
R
R
O
O
O
B
O
(RS)-2f
O
O
O
B
O
(R)-2f
S28

2
.3 Determination of absolute configuration of 1a and 1b
The enantioenriched compounds (S)-8a and (S)-8b were prepared according to the method
described in item 1.11.
(
S)-1-(biphenyl-4-yl)ethanol, [(S)-8a]
24
D
12
28
D
Yield: 78 mg (79%), 96% ee, [α]
HPLC condition: Chiralcel OD column, n-hexane/i-PrOH (95:5), 0.8 mL/min, 254 nm UV
= -46.6 (c 1.0, CH
3
Cl). Lit, [α]
3
= -43.7 (c 0.75, CHCl ).
®
detector, t
R
= 15,6 min for (S) and t
R
= 18.0 min for (R).
OH
(
RS)-8a
OH
(S)-8a
12
Salvi, N. A.; Chattopadhyay, S. Tetrahedron 2001, 57, 2833.
S29

(
S)-1-(biphenyl-3-yl)ethanol, [(S)-8b]
24
D
11b
20
D
Yield: 79 mg (80%) >99% ee, [α]
HPLC condition: Chiralcel OD column, n-hexane/i-PrOH (95:5), 0.8 mL/min, 254 nm UV
= -37.8 (c 1.0, CH
3
Cl). Lit, [α]
3
= -38.0 (c 1.09, CHCl ).
®
detector, t
R
R
= 14.9 min for (S) and t = 29.5 min for (R).
OH
(RS)-8b
OH
(
S)-8b
S30