Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)CoIII complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols

Article abstract of DOI:10.1021/ja016737l

The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral (salen)Co^III complex 1·OAc affords both recovered unreacted epoxide and 1,2-diol product in highly enantioenriched form. As such, the HKR provides general access to useful, highly enantioenriched chiral building blocks that are otherwise difficult to access, from inexpensive racemic materials. The reaction has several appealing features from a practical standpoint, including the use of H₂O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable, commercially available catalyst. In addition, the HKR displays extraordinary scope, as a wide assortment of sterically and electronically varied epoxides can be resolved to ≥ 99% ee. The corresponding 1,2-diols were produced in good-to-high enantiomeric excess using 0.45 equiv of H₂O. Useful and general protocols are provided for the isolation of highly enantioenriched epoxides and diols, as well as for catalyst recovery and recycling. Selectivity factors (k_rel) were determined for the HKR reactions by measuring the product ee at ca. 20% conversion. In nearly all cases, k_rel values for the HKR exceed 50, and in several cases are well in excess of 200.

Full text of DOI:10.1021/ja016737l

Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides
Catalyzed by Chiral (salen)Cobalt(III)-Complexes.
Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols
SUPPORTING INFORMATION
Scott E. Schaus, Bridget D. Brandes, Jay. F. Larrow, Makoto Tokunaga, Karl B.
Hansen, Alexandra E. Gould, Michael E. Furrow, and Eric N. Jacobsen*
Department of Chemistry and Chemical Biology, Harvard University
Cambridge, Massachusetts 02138
Experimental Section
General. All reactions were conducted in glassware with magnetic stirring. Racemic
epoxides were either purchased or synthesized by known procedures. Both enantiomers
of the (salen)Co(II) complex 1 are commercially available from Aldrich.
Tetrahydrofuran and TBME were distilled from sodium/benzophenone. Yields of the
HKR are reported as a fraction of the theoretical maximum 50%. Optical rotations were
measured on a Jasco DIP 370 digital polarimeter with a sodium (λ= 489 nm) lamp, and
are reported as follows: [α]T
, (c g/100 mL, solvent). Optical rotation measurements
λ
were conducted using a Jasco DIP 370 digital polarimeter. All epoxides were purified
by distillation or chromatography prior to use. Epoxides recovered from the reaction
were purified by filtration through a SiO2 plug to remove residual H2O and concentrated
by rotary evaporation to remove solvent.
Determination of Enantiomeric Purity.
Enantiomeric excesses (ee’s) were
determined by capillary GC analysis using a Hewlett Packard 5890 Series II Gas
Chromatograph with H2 as a carrier gas or by chiral HPLC analysis using a Hewlett
Packard 1050 HPLC. The following GC columns were employed: Cyclodex-B (30m x
0.25mm id x 0.25µm film; J&W Scientific) set at a column head pressure of 13 psi;
Chiraldex G-TA (20m x 0.25mm id x 0.125µm film; Advanced Separation
Technologies, Inc.) set at a column head pressure of 7 psi. The following HPLC
columns were employed: Chiracel® OD (Chiral Technologies Inc., 24 cm x 0.46 cm
i.d.), Chiralpak® AS (Chiral Technologies Inc., 24 cm x 0.46 cm i.d.), Whelk-O 1
(Regis® Technologies Inc., 25 cm x 0.46 cm i.d.), L-Leucine (Regis® Technologies Inc.,
25 cm x 0.46 cm).
S - 1

Representative Procedure for the Hydrolytic Kinetic Resolution of Terminal
Epoxides. Pre-oxidation of Complex 1 to 1•OAc. Method A.
(S)-Propylene Oxide (Table 1, entry1). A 100 mL flask equipped with a stir bar was
charged with (S,S)-1 (242 mg, 400 µmol, 0.002 equiv). The catalyst was dissolved in 5
mL PhMe and treated with AcOH (240 µL, 4.2 mmol). The solution was allowed to stir
at rt open to air for 30 min over which time the color changed from orange-red to a dark
brown. The solution was concentrated in vacuo to leave a crude brown solid. The
resulting catalyst residue was dissolved in propylene oxide (14.0 mL, 11.6 g, 200 mmol)
at rt, the solution was cooled to 0 °C, and H2O (1.98 mL, 110 mmol, 0.55 equiv) was
added dropwise over 5 min. The reaction was allowed to warm to rt and stir 14 h at
which time (S)-propylene oxide (5.35 g, 92.1 mmol, 46%) was isolated by distillation
from the reaction mixture at 36
distillation (65
collection by vacuum filtration. The ee of the propylene oxide was determined to be
99.7% by chiral GC analysis of the 1-azido-2-trimethylsiloxypropane derivative
prepared by ring-opening of the epoxide with TMSN3 (Cyclodex-B, 55
tR(minor) = 12.29 min, tR(major) = 12.57 min). [α]23 –11.6
1 [α]20D –18.7
D
(c 5.83, CCl4).
Representative Procedure for the HKR of Terminal Epoxides. In situ Oxidation of
Complex 1 to 1•OAc. Method B.
(R)-1,2-Epoxy-5-hexene (Table 1, entry 4). A 100 mL flask equipped with a stir bar
was charged with (R,R)-1 (302 mg, 500 µmol, 0.005 equiv). The catalyst was treated
with ( )-1,2-epoxy-5-hexene (11.3 mL, 9.81 g, 100 mmol), AcOH (120 µL, 2.1 mmol,
0.02 equiv) and 1 mL THF. The solution was cooled to 0
2O (1.0 mL, 55
mmol, 0.55 equiv) was added in one portion. The reaction was allowed to warm to rt
and stir 16 h at which time the volatiles were separated by vacuum transfer at 0.25 torr
into a cooled (-78
de was passed through a
silica plug to removed residual water and the THF was removed by rotary evaporation to
yield (R)-1,2-epoxy-5-hexene (4.23 g, 43.1 mmol, 43%). The diol was distilled under
reduced pressure (56
ered by suspension of the
residue in MeOH and vacuum filtration. The ee of the recovered epoxide was
determined to be 99.5% by chiral GC analysis of the 1-azido-2-trimethylsiloxy-5-hexene
derivative (Cyclodex-B, 70
tR(minor) = 38.00 min, tR(major) = 39.06
min). [α]25D +9.36
(R)-1,2-Epoxyhexane (Table 1, entry 2). Method B. The catalyst ((R,R)-1, 242 mg,
400 µmol, 0.005 equiv) was treated with ( )-1,2-epoxyhexane (9.64 mL, 8.01 g, 80
mmol) containing 2-3% AcOH (available from Aldrich). The solution was cooled to 0
2O (0.80 mL, 44 mmol, 0.55 equiv) was added in one portion. After 16 h, (R)-
1,2-epoxyhexane (3.44 g, 34.4 mmol, 43%) was isolated by vacuum transfer at 0.25 torr
into a cooled (-78
ol was distilled under reduced pressure (65
GC analysis of the 1-azido-2-trimethylsiloxyhexane derivative (Cyclodex-B, 80
(1)
Ellis, M. K.; Golding, B. T. Org. Synth., Coll. Vol. VII 1990, 356-359.

2
isothermal, tR(minor) = 20.60 min, tR(major) = 21.02 min). [α]23 +14.3
D
[α]20D +9.6 c 0.76, EtOH).
(R)-1,2-Epoxytetradecane (Table 1, entry 3). Method A. A solution of the catalyst
((R,R)-1, 75 mg, 125 µmol, 0.005 equiv) in 2 mL CH2Cl2 was treated with 75 µL AcOH.
The crude catalyst residue obtained after concentration was treated with ( )-1,2-
epoxytetradecane (6.28 mL, 5.31 g, 25 mmol) and 1 mL i-PrOH. The solution was
cooled to 0
2O (450 µL, 25 mmol). After 24 h at rt, the reaction
was diluted with 50 mL hexanes and filtered to remove the 1,2-diol. The filtrate was
concentrated by rotary evaporation and (R)-1,2-epoxytetradecane (2.25 g,10.6 mmol,
42%) was obtained by vacuum distillation (86
epoxide was determined to be >99% by chiral HPLC analysis of the 2-napthylsulfide
derivative (obtained by ring opening with 2-napthalenethiol in MeOH using 1 equiv
TEA at 0
® OD, 99.5:0.5 hexanes:EtOH, 1.5 mL / min, 220 nm, tR(minor)
= 21.55 min, tR(major) = 26.71 min). [α]23 +7.3 (neat); lit.3 [α]D +4.31 (c 1.42,
D
CHCl3).
(R)-(2,3-Epoxypropyl)benzene (Table 1, entry 5). Method B. The catalyst ((R,R)-1,
151 mg, 250 µmol, 0.005 equiv) was dissolved in ( )-(2,3-epoxypropyl)benzene (6.57
mL, 6.70 g, 50 mmol), AcOH (60 µL, 1.0 mmol, 0.02 equiv) and 0.5 mL THF. The
solution was cooled to 0
2O (495 µL, 27.5 mmol, 0.55 equiv).
After 16 h, (R)-(2,3-epoxypropyl)benzene (3.10 g, 23.1 mmol, 46%) was distilled (72
C) receiving flask. The ee of the recovered epoxide was
determined to be 99% by chiral HPLC analysis ((R,R)-Whelk O-1, 99.5:0.5
hexanes:EtOH, 1 mL / min, 254 nm, tR(minor) = 9.07 min, tR(major) = 9.51 min). [α]23
D
+27.2
4 [α]25D +17.5 c 1.94, EtOH).
(S)-Vinylcyclohexane oxide (Table 1, entry 6). Method B. The catalyst ((S,S)-1, 60
mg, 100 µmol, 0.005 equiv) was dissolved in ( )-vinylcyclohexane oxide5 (2.71 mL,
2.52 g, 20 mmol), AcOH (23 µL, 0.4 mmol, 0.02 equiv) and 0.2 mL THF. The solution
was cooled to 0
2O (200 µL, 11.1 mmol, 0.55 equiv). After 16 h,
(S)-vinylcyclohexane oxide (1.12 g, 8.87 mmol, 44%) was isolated by vacuum transfer
at 0.25 torr into a cooled (-78
was
determined to be 99.9% by chiral GC analysis (G-TA, 60
tR(minor) =
11.19 min, tR(major) = 13.25 min). [α]23 +2.2 c 10.5, CHCl3); lit.6 [α]20 +2.1
D
D
(neat).
(2)
(3)
Goergens, U.; Schneider, M. P. Tetrahedron: Asymmetry. 1992, 3, 1149-1152.
Savle, P. S.; Lamoreaux, M. J.; Berry, J. F.; Gandour, R.D. Tetrahedron: Asymmetry 1998, 9,
1843-1846.
(4)
(5)
Klunder, J. M.; Onami, T.; Sharpless, K. B. J. Am. Chem. Soc. 1989, 54, 1295-1304.
Cohen, T.; Jeong, I.-H.; Mudryk, B.; Bhupathy, M.; Awad, M. M. A. J. Org. Chem. 1990, 55,
1528-1536.
(6)
Nugent, W. A.; Harlow, R. L. J. Am Chem. Soc. 1994, 116, 6142-6148.

(R)-tert-Butyloxirane (Table 1, entry 7). Method A. A solution of the catalyst ((R,R)-
1, 483 mg, 800 µmol, 0.02 equiv) in 3 mL PhMe was treated with 500 µL AcOH. The
crude catalyst residue obtained after concentration was treated with ( )-tert-
butyloxirane7 (4.88 mL, 4.00 g, 40.0 mmol). To the reaction flask was added 1.2 mL
( )-1,2-hexane diol, the mixture was cooled to 0
2O (400 µL, 22 mmol, 0.55
equiv) was added in one portion. After 48 h, (R)-tert-butyloxirane (1.61 g, 16.1 mmol,
41%) was isolated by vacuum transfer at 0.25 torr into a cooled (-78
The recovered epoxide was determined to be 99.4% ee by chiral HPLC analysis of the 2-
benzothiazolesulfide derivative (obtained by ring opening with 2-mercaptobenzothiazole
in MeOH using 1 equiv TEA at 0
Chiralcel® OD, 99.5:0.5 hexanes:EtOH, 1 mL / min, 230 nm, tR(minor) = 22.61 min,
tR(major) = 27.65 min). [α]24D –15.2
8 [α]25D –18.4 c 1.8, PhH, 97% ee).
(R)-Epichlorohydrin (Table 2, entry 1). Method A. A solution of the catalyst ((S,S)-1,
242 mg, 400 µmol, 0.005 equiv) in 5 mL CH2Cl2 was treated with 250 µL AcOH. The
crude catalyst residue obtained after concentration was treated with ( )-epichlorohydrin
(6.26 mL, 7.40 g, 80 mmol) and 0.8 mL THF. The solution was cooled to 0
treated with H2O (800 µL, 44 mmol, 0.55 equiv) and the reaction was maintained at 0 –
4
R)-Epichlorohydrin (2.98 g, 32.2 mmol, 43%) was isolated by vacuum
transfer (25
-78
flask. The recovered epoxide was determined to be >99% ee by chiral GC analysis (G-
26
TA, 50
tR(minor) = 4.15 min, tR(major) = 4.44 min). [α]D –32.8o (c
1.27, MeOH); lit.9 [α]D22 –33.0o (c 4.22, MeOH).
(S)-Epifluorohydrin (Table 2, entry 3). Method A. A solution of the catalyst ((R,R)-1,
80 mg, 131 µmol, 0.005 equiv) in 2 mL PhMe was treated with 80 µL AcOH. The
crude catalyst residue obtained after concentration was dissolved in ( )-epifluorohydrin
(2.00 g, 26.3 mmol). The solution was cooled to 0
2O (260 µL, 14.4 mmol,
0.55 equiv) was added to the solution. After 16 h, (S)-epifluorohydrin (0.810 g, 10.6
mmol, 42%) was isolated by vacuum transfer (0.25 torr) from the reaction mixture into a
cooled (-78
to be >99% ee
by chiral HPLC analysis of the 2-napthylsulfide derivative (obtained by ring opening
with 2-napthalenethiol in MeOH using 1 equiv TEA at 0
product obtained, Chiralcel® OD, 95:5 hexanes:i-PrOH, 1 mL / min, 230 nm, tR(minor)
= 27.00 min, tR(major) = 32.65 min). [α]25D –4.1 (c 3.01, CHCl3); lit.10 [α]16D –6.1 (c
2.12, MeOH).
(S)-1,1,1-Trifluoro-2,3-epoxypropane (Table 2, entry 4). Method A. A solution of the
(7)
(8)
(9)
Mischitz, M.; Kroutil, W.; Wandel, U.; Faber, K. Tetrahedron: Asymmetry 1995, 6, 1261-1272.
Chadha, A.; Georgens, U.; Schneider, M. P. Tetrahedron: Asymmetry 1993, 4, 1449-1450.
Baldwin, J. J.; Raab, A. W.; Mensler, K.; Arison, B. H.; McClure, D. E. J. Org. Chem. 1978, 43,
4876-4878.
(10)
Kawakami, Y.; Asai, T.; Umeyama, K.; Yamashita, Y. J. Org. Chem. 1982, 47, 3581-3585.

catalyst ((R,R)-1, 151 mg, 250 µmol, 0.005 equiv) in 2 mL PhMe was treated with 150
µL AcOH. The crude catalyst residue obtained after concentration was treated with ( )-
1,1,1-trifluoro-2,3-epoxypropane11 (5.60 g, 50 mmol). The solution was cooled to 0
and treated with H2O (500 µL, 27.8 mmol, 0.55 equiv). After 16 h, (S)-1,1,1-trifluoro-
2,3-epoxypropane (2.09 g, 18.7 mmol, 42%) was isolated by vacuum transfer (0.25 torr)
from the reaction mixture into a cooled (-78
was determined to be >99% ee by chiral HPLC analysis of the 2-napthylsulfide
derivative (obtained by ring opening with 2-napthalenethiol in MeOH using 1 equiv
TEA at 0
® OD, 95:5 hexanes:i-
PrOH, 1 mL / min, 230 nm, tR(minor) = 12.85 min, tR(major) = 15.30 min). [α]24
12.3 (c 8.40, CHCl3); lit.12 [α]22D –10.92 (c 5.0, CHCl3, 96% ee).
–
D
(R)-Benzyl glycidyl ether (Table 3, entry 1). Method B. The catalyst ((R,R)-1, 151 mg,
250 µmol, 0.005 equiv) was dissolved in ( )-benzyl glycidyl ether13 (8.20 g, 50.0
mmol), AcOH (57 µL, 1.0 mmol, 0.02 equiv) and 0.5 mL THF. The solution was
cooled to 0
2O (495 µL, 27.5 mmol, 0.55 equiv). After 16 h, (R)-
benzyl glycidyl ether (3.82 g, 23.3 mmol, 48%) was isolated by vacuum distillation (82
determined to be >99% by chiral HPLC analysis (Chiralcel® OD, 95:5 hexanes:i-PrOH,
1 mL / min, 214 nm, tR(minor) = 11.56 min, tR(major) = 9.72 min). [α]26D +10 (c 5.2,
MeOH); lit.14 [α]32D +9.8 (c 5.13, MeOH).
(S)-(tert-Butyldimethylsilyl) glycidyl ether (Table 3, entry 2). Method B. The
catalyst ((R,R)-1, 91 mg, 150 µmol, 0.005 equiv) was dissolved in ( )-(tert-
butyldimethylsilyl) glycidyl ether15 (5.64 g, 30.0 mmol), AcOH (32 µL, 0.6 mmol, 0.02
equiv) and 0.3 mL THF. The solution was cooled to 0
2O (297 µL,
16.5 mmol, 0.55 equiv). After 16 h, (S)-(tert-butyldimethylsilyl) glycidyl ether (2.72 g,
14.5 mmol, 47%) was isolated by vacuum distillation (30
chiral HPLC analysis of the 2-napthylsulfide derivative (obtained by ring opening with
2-napthalenethiol in MeOH using 1 equiv TEA at 0
obtained, Chiralcel® OD, 99.25:0.75 hexanes:EtOH, 1 mL / min, 230 nm, tR(minor) =
20.38 min, tR(major) = 22.47 min). [α]25 +11 c 3.9, C6H6); lit.16 [α]19 +4.95 c
D
D
1.94, C6H6).
(S)-Phenyl glycidyl ether (Table 3, entry 3). Method B. The catalyst ((R,R)-1, 151 mg,
250 µmol, 0.005 equiv) was dissolved in ( )-phenyl glycidyl ether (7.50 g, 50.0 mmol),
(11)
(12)
(13)
(14)
Available from Oakwood Products, Inc.; catalog no. 1533.
Ramachandran, P. V.; Gong, B.; Brown, H. C. J. Org. Chem. 1995, 60, 41-46.
Ichikawa, Y.; Isobe, M.; Bai, D.-L.; Goto, T. Tetrahedron 1987, 43, 4737.
Takano, S.; Sekiguchi, Y.; Setoh, M.; Yoshimitsu, T.; Inomata, K.; Takahashi, M.; Ogasawara,
K. Heterocycles 1990, 31, 1715-1719.
(15)
(16)
Cywin, C. L.; Webster, F. X.; Kallmerten, J. J. Org. Chem. 1991, 56, 2953-2955.
Kotsuki, H.; Ushio, Y.; Kadota, I.; Ochi, M. J. Org. Chem. 1989, 54, 5153-5161.

AcOH (57 µL, 1.0 mmol, 0.02 equiv) and 0.5 mL THF. The solution was cooled to 0
and treated with H2O (495 µL, 27.5 mmol, 0.55 equiv). After 16 h, (R)-phenyl glycidyl
ether (3.52 g, 23.4 mmol, 47%) was isolated by vacuum distillation (80
into a cooled (0
be >99% by chiral HPLC analysis (Chiralcel® OD, 9:1 hexanes:i-PrOH, 1 mL / min, 214
nm, tR(minor) = 8.38 min, tR(major) = 11.40 min). [α]23 +5.2 c 7.5, CHCl3); lit.17
D
[α]D –3.6 c 0.33, CHCl3, (R)-epoxide).
(S)-(1-Napthyl) glycidyl ether (Table 3, entry 4). Method B. The catalyst ((R,R)-1, 30
mg, 50 µmol, 0.005 equiv) was dissolved in ( )-(1-napthyl) glycidyl ether18 (2.00 g,
10.0 mmol), AcOH (80 µL, 1.4 mmol, 0.08 equiv) and 2 mL THF. The solution was
treated with H2O (180 µL, 10.0 mmol, 1.0 equiv). After 60 h, the reaction was
concentrated in vacuo, the solid was suspended in 9:1 hexanes:CH2Cl2 and removed by
filtration. The filtrate was concentrated and (R)-(1-napthyl) glycidyl ether (0.756 g, 3.78
mmol, 38%) was obtained by vacuum distillation (140
recovered epoxide was determined to be >99% by chiral HPLC analysis (Chiralcel® OD,
9:1 hexanes:i-PrOH, 1 mL / min, 260 nm, tR(minor) = 8.47 min, tR(major) = 11.05 min).
[α]26D +28.3 (c 1.73, CHCl3); lit.19 [α]25D +32.9 (c 1, MeOH).
(S)-(2-Phenylmethoxyethyl)oxirane (Table 3, entry 5). Method B. The catalyst ((S,S)-
1, 151 mg, 250 µmol, 0.005 equiv) was dissolved in ( )-(2-phenylmethoxyethyl)
oxirane20 (8.90 g, 50.0 mmol), AcOH (57 µL, 1.0 mmol, 0.02 equiv) and 0.5 mL THF.
The solution was cooled to 0
2O (495 µL, 27.5 mmol, 0.55 equiv).
After 16 h, (S)-(2-phenylmethoxyethyl) oxirane (3.70 g, 20.8 mmol, 42%) was isolated
by vacuum distillation (70
ooled (0
the recovered epoxide was determined to be >99% by chiral HPLC analysis (Chiralcel®
OD, 99.5:0.5 hexanes:i-PrOH, 1 mL / min, 215 nm, tR(minor) = 16.02 min, tR(major) =
17.55 min). [α]24D –15.7
3); lit21 [α]25D –15.1
3).
(R,R)-Butadiene diepoxide (Table 3, entry 6). Method A. The catalyst ((S,S)-1, 604
mg, 1.0 mmol, 0.01 equiv) was dissolved in 10 mL CH2Cl2 and 600 µL AcOH. The
crude catalyst residue obtained after concentration was treated with ( )-butadiene
diepoxide22 (8.61 g, 100 mmol). The solution was treated with 17 mL THF, cooled to 0
2O (1.08 mL, 60 mmol, 0.60 equiv). After 16 h, the reaction was
concentrated by rotary evaporation and (R,R)-butadiene diepoxide (3.07 g, 35.7 mmol,
36%) was isolated by vacuum distillation (0.25 torr, 60
into a cooled (0
(17)
(18)
Collington, E. W.; Finch, H.; Montana, J. G. J. Chem. Soc. Perkin Trans. I 1990, 1839-1845.
Slater, R. A.; Howson, W.; Swayne, G. T. G.; Taylor, E. M.; Reavil, D. R. J. Med. Chem. 1988,
31, 345-351.
(19)
(20)
(21)
(22)
Bevinakatti, H. S.; Banerji, A. A. J. Org. Chem. 1991, 56, 5372-5375.
Muehlbacher, M.; Poulter, C. D. J. Org. Chem. 1988, 53, 1026-1030.
March, P.; Figueredo, M.; Font, J.; Monsalvatje, M. Synth. Commun. 1995, 25, 331-342.
Available from Aldrich as the d,l mixture only.

ee by chiral HPLC analysis of the di-2-napthylsulfide derivative (obtained by ring
opening with 2 equiv 2-napthalenethiol in MeOH using 2 equiv TEA at 0
analysis of the product obtained, Chiralcel® OD, 8:2 hexanes:EtOH, 1 mL / min, 220
nm, tR(minor) = 8.94 min, tR(major) = 10.58 min). [α]26 –29.5 c 2.27, CHCl3); lit23
D
[α]25D –24 c 4, CCl4, >98% ee).
(S)-Glycidyl butyrate (Table 4, entry 1). Method B. The catalyst ((R,R)-1, 91 mg, 150
µmol, 0.005 equiv) was dissolved in ( )-glycidyl butyrate24 (4.32 g, 30.0 mmol), AcOH
(32 µL, 0.6 mmol, 0.02 equiv) and 0.3 mL THF. The solution was cooled to 0
treated with H2O (297 µL, 16.5 mmol, 0.55 equiv). After 16 h, (S)-glycidyl butyrate
(1.90 g, 13.2 mmol, 46%) was isolated by vacuum distillation (30
cooled (0
The ee of the recovered epoxide was determined to be
>99% by chiral HPLC analysis of the 2-napthylsulfide (obtained by ring opening with 2-
napthalenethiol in MeOH using 1 equiv TEA at 0
obtained, Chiralcel® OD, 97:3 hexanes:EtOH, 1 mL / min, 260 nm, tR(minor) = 27.89
min, tR(major) = 32.33 min). [α]23 +29 c 8.2, CHCl3); lit.25 [α]20 –26.3 c 1.0,
D
D
CHCl3, (R)-epoxide).
(R)-Ethyl-3,4-epoxybutyrate (Table 4, entry 2). Method B. The catalyst ((R,R)-1, 60
mg, 100 µmol, 0.005 equiv) was dissolved in ( )-ethyl-3,4-epoxybutyrate26 (2.60 g, 20.0
mmol), AcOH (23 µL, 0.4 mmol, 0.02 equiv) and 0.2 mL THF. The solution was
cooled to 0
(R)-ethyl-3,4-epoxybutyrate (1.19 g, 9.15 mmol, 92%) was isolated by vacuum
distillation (50 -78
2O (200 µL, 11.1 mmol, 0.55 equiv) was added at once. After 16 h,
recovered epoxide was determined to be >99% by chiral HPLC analysis of the 2-
napthylsulfide derivative (obtained by ring opening with 2-napthalenethiol in MeOH
®
using 1 equiv TEA at 0
OD,
9:1 hexanes:i-PrOH, 1 mL / min, 280 nm, tR(minor) = 8.9 min, tR(major) = 11.8 min).
[α]25D +8.4 c 3.55, CHCl3); lit.27 [α]20D +24.7 c 3.93, MeOH).
(S)-{[(tert-Butoxycarbonyl)amino]methyl}oxirane (Table 4, entry 3). Method A. The
catalyst ((S,S)-1, 242 mg, 400 µmol, 0.02 equiv) in 6 mL CH2Cl2 was treated 240 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-{[(tert-butoxycarbonyl)amino]methyl} oxirane28
(3.46 g, 20 mmol). THF (0.6 mL) was added, the solution was cooled to 0
(23)
(24)
(25)
Vanhessche, K. P. M.; Wang, Z.- M.; Sharpless, K. B. Tetrahedron Lett. 1994, 35, 3469-3472.
Ladner, W. E.; Whitesides, G. M. J. Am. Chem. Soc. 1984, 106, 7250-7251.
Sommerdijk, N. A. J. M.; Buynsters, P. J. J. A.; Akdemir, H.; Geurts, D. G.; Nolte, R. J. M.;
Zwanenburg, B. J. Org. Chem. 1997, 62, 4955-4960.
(26)
Available by m-CPBA epoxidation of the corresponding alkene. a) Rambaud, R.; Vessière, M.
Bull. Soc. Chim. Fr. 1960, 1115-1116. b) For an efficient synthesis of ethyl but-3-enoate see:
Ozeki, T.; Kusaka, M. Bull. Chem. Soc. Japan 1966, 39, 1995-1998.
(27)
(28)
Larchevêque, M.; Henrot, S. Tetrahedron 1990, 46, 4277-4282.
Edwards, M. L.; Snyder, R. D.; Stemerick, D. M. J. Med. Chem. 1991, 34, 2414-2420.

H2O was added at once (200 µL, 11 mmol, 0.55 equiv). After stirring 38 h at rt, the
mixture reaction was concentrated by rotary evaporation and the epoxide was recovered
by flash chromatography over silica gel using 7:3 hexanes:EtOAc as the eluent. The
solid obtained was recrystallized from hexanes at –20
1.24 g (7.18 mmol,
36%) of opaque needlelike crystals. The ee of the recovered epoxide before
recrystallization was determined to be 99.3% by chiral GC analysis (Cyclodex-B, 110
tR(minor) = 21.57 min, tR(major) = 21.85 min). [α]25 –14.2 (c 2.26,
D
CHCl3); lit.29 [α]25D +5.1 c 1.4, MeOH, (R)-epoxide).
(R)-Methyl glycidate (Table 4, entry 4). Method A. The catalyst ((S,S)-1, 604 mg, 1.0
mmol, 0.02 equiv) in 10 mL CH2Cl2 was treated 600 µL AcOH and stirred in air for 30
min. The crude catalyst residue obtained after concentration was dissolved in ( )-
methyl glycidate30 (5.10 g, 50 mmol) and THF (2.5 mL). The solution was cooled to 0
2O (500 µL, 27.8 mmol, 0.55 equiv). After 24 h at rt, (R)-methyl
glycidate (2.18 g, 21.4 mmol, 43%) was isolated by vacuum distillation (50
torr) into a cooled (-78
to be >99% by chiral GC analysis (Cyclodex-B, 50
tR(minor) = 8.38 min,
tR(major) = 8.51 min). [α]27D +16.4 31 [α]25D +10.4 c 3.6, MeOH).
(S)-3,4-Epoxy-2-butanone (Table 4, entry 5). Method A. The catalyst ((R,R)-1, 480
mg, 800 µmol, 0.02 equiv) in 10 mL CH2Cl2 was treated 480 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
3,4-epoxy-2-butanone32 (3.44 g, 40 mmol). To the solution was added THF (0.8 mL)
and AcOH (50 µL, 0.8 mmol, 0.02 equiv), the mixture was cooled to 0
2O (500 µL,
27.8 mmol, 0.70 equiv) was added at once, and the reaction mixture was then placed
under an atmosphere of O2 (balloon pressure). After 48 h at rt, (S)-3,4-epoxy-2-
butanone (1.41 g, 16.4 mmol, 40%) was isolated by vacuum distillation (70
into a cooled (-78
be 99.9% by chiral GC analysis (G-TA, 40
tR(major) = 16.33 min). [α]24 –72 (c 8.35, MeOH); lit.33 [α]20 –108.9 c 4.69,
ceiving flask. The ee of recovered epoxide was determined to
tR(minor) = 15.16 min,
D
D
CH2Cl2).
(S)-1,2-Epoxy-3-pentanone (Table 4, entry 6). Method A. The catalyst ((R,R)-1, 363
mg, 600 µmol, 0.02 equiv) in 6 mL CH2Cl2 was treated 360 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
1,2-epoxy-3-pentanone34 (3.00 g, 30 mmol) and THF (0.35 mL), the mixture cooled to 0
(29)
Kitchin, J.; Bethell, R. C.; Cammack, N.; Dolan, S.; Evans, D. N.; Holman, S.; Holmes, D. S.;
McMeekin, P.; Mo, C. L.; Nieland, N.; Orr, D. C.; Saunders, J.; Shenoy, B. E. V.; Starkey, I. D.;
Storer, R. J. Med. Chem. 1994, 37, 3707-3716.
(30)
(31)
(32)
(33)
(34)
Nemes, A.; Czibula, L.; Visky, G.; Farkas, M.; Kreidl, J Heterocycles 1991, 32, 2329-2338.
Larchevêque, M.; Petit, Y. Tetrahedron Lett. 1987, 1993-1996.
Wellman, G. R.; Lam, B.; Anderson, E. L.; White, E. Synthesis 1976, 547-548.
Pégorier, L.; Petit, Y.; Mambu, A.; Larchevêque, M. Synthesis 1994, 1403-1405.
Available by epoxidation of ethyl vinyl ketone. Klein, E.; Ohloff, G. Tetrahedron 1963, 19,
1091-1102.

2O (330 µL, 18 mmol, 0.60 equiv) was added. The reaction was then placed
under an atmosphere of O2 (balloon pressure). After 16 h at rt, (S)-1,2-epoxy-3-
pentanone (1.09 g, 10.9 mmol, 37%) was isolated by vacuum distillation (54
into a cooled (0
99.7% by chiral GC analysis (G-TA, 50
tR(minor) = 17.48 min,
tR(major) = 19.27 min). [α]24 –78 (c 8.6, CHCl3); lit.62 [α]20 –102.6
D
D
MeOH).
(R)-Butadiene monoxide (Table 5, entry 7). Method A. The catalyst ((R,R)-1, 1.81 g,
3.0 mmol, 0.015 equiv) in 15 mL PhMe was treated with 1.8 mL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
butadiene monoxide35 (14.0 g, 200 mmol). The solution was cooled to 0
2O
(2.50 mL, 140 mmol, 0.70 equiv) was added. After 72 h at rt, (R)-butadiene monoxide
(4.96 g, 70.8 mmol, 36%) was isolated by vacuum transfer (0.25 torr) into a cooled (-78
HPLC analysis of the 2-napthylsulfide derivative (obtained by ring opening with 2-
napthalenethiol in MeOH using 1 equiv TEA at 0
obtained, Chiralcel® OD, 95:5 hexanes:i-PrOH, 1 mL / min, 230 nm, tR(minor) = 17.40
min, tR(major) = 20.67 min). [α]24 –10.4 (c 2.97, i-PrOH); lit.36 [α]22 –12 (c 4.9,
D
D
dioxane).
(R)-1-(tert-Butyldimethylsilyl)-3,4-epoxy-1-butyne (Table 5, entry 8). Method A.
The catalyst ((R,R)-1, 48 mg, 80 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated 50 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-1-(tert-butyldimethylsilyl)-3,4-epoxy-1-butyne37
(1.84 g, 10 mmol) and i-PrOH (200 µL). The solution was cooled to 0
with H2O (100 µL, 5.5 mmol, 0.55 equiv). After 20 h at rt, (R)-1-(tert-
butyldimethylsilyl)-3,4-epoxy-1-butyne (758 mg, 4.12 mmol, 41%) was isolated by
vacuum distillation (36
The ee of
recovered epoxide was determined to be >99% by chiral HPLC analysis of the 2-
napthylsulfide (obtained by ring opening with 2-napthalenethiol in MeOH using 1 equiv
TEA at 0
-Leucine, 99.8:0.2 hexanes:i-
PrOH, 1 mL / min, 220 nm, tR(minor) = 46.49 min, tR(major) = 40.10 min). [α]23D –60
(c 5.1, CHCl3); lit.38 [α]20D –72.3 (c 5.63, CH2Cl2).
(R)-Styrene oxide (Table 5, entry 1). Method A. The catalyst ((R,R)-1, 966 mg, 1.60
mmol, 0.008 equiv) in 20 mL CH2Cl2 was treated 1 mL AcOH and stirred in air for 30
min. The crude catalyst residue obtained after concentration was dissolved in ( )-
styrene oxide (22.8 mL, 24.0 g, 200 mmol) and THF (2 mL). The solution was cooled
(35)
(36)
Available in bulk from Eastman Kodak Co..
Chenault, H. K.; Kim, M.; Akiyamam, A.; Miyazawa, T.; Simon, E. S.; Whitesides, G. M. J.
Org. Chem. 1987, 52, 2608-2611.
(37)
(38)
Available by m-CPBA epoxidation of the corresponding alkene.
Lopp, M.; Kanger, T.; Müraus, A.; Pehk, T.; Lille, Ü. Tetrahedron Asymm. 1991, 2, 943-944.

to 0
2O (2.0 mL, 110 mmol, 0.55 equiv). After 72 h at rt, (R)-
styrene oxide (10.5 g, 87.4 mmol, 44%) was isolated by vacuum distillation (27
torr) into a cooled (-78
to be >99% by chiral HPLC analysis ((R,R)-Whelk-O 1, 99:1 hexanes:i-PrOH, 1 mL /
min, 220 nm, tR(minor) = 8.42 min, tR(major) = 10.48 min). [α]23 +28.6 (neat); lit.39
D
[α]20D +34.3
(R)-4-Chlorostyrene oxide (Table 5, entry 2). Method A. The catalyst ((R,R)-1, 193
mg, 320 µmol, 0.008 equiv) in 5 mL CH2Cl2 was treated 200 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
4-chlorostyrene oxide40 (6.20 g, 40 mmol) and THF (400 µL). The solution was cooled
to 0
2O (400 µL, 22.2 mmol, 0.55 equiv). After 40 h at rt, (R)-4-
chlorostyrene oxide (2.41 g, 15.5 mmol, 38%) was isolated by vacuum distillation (40
s
determined to be >99% by chiral HPLC analysis ((R,R)-Whelk-O 1, 99.75:0.25
hexanes:i-PrOH, 1 mL / min, 220 nm, tR(minor) = 12.56 min, tR(major) = 16.76 min).
[α]24D –23.8 (c 3.41, CHCl3); lit.69 [α]20D +19.3 c 1.16, CHCl3, (S)-epoxide).
(R)-3-Chlorostyrene oxide (Table 5, entry 3). Method A. The catalyst ((R,R)-1, 242
mg, 400 µmol, 0.008 equiv) in 5 mL CH2Cl2 was treated 250 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
3-chlorostyrene oxide41 (7.75 g, 50 mmol). The solution was cooled to 0
with H2O (500 µL, 27.5 mmol, 0.55 equiv). After 40 h at rt, (R)-3-chlorostyrene oxide
(3.10 g, 20.0 mmol, 40%) was isolated by vacuum distillation (55
cooled (0
eiving flask. The ee of recovered epoxide was determined to be >99%
by chiral HPLC analysis ((R,R)-Whelk-O 1, 99.75:0.25 hexanes:i-PrOH, 1 mL / min,
220 nm, tR(minor) = 11.11 min, tR(major) = 13.56 min). [α]26D +21 (c 2.9, EtOH); lit.42
[α]D 24.05 c 1.24, EtOH, 95% ee).
(R)-2-Chlorostyrene oxide (Table 5, entry 6). Method A. The catalyst ((R,R)-1, 181
mg, 300 µmol, 0.015 equiv) in 5 mL CH2Cl2 was treated 200 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
2-chlorostyrene oxide43 (3.10 g, 20 mmol) and THF (200 µL). The solution was cooled
to 0
2O (200 µL, 11 mmol, 0.55 equiv). After 40 h at rt, (R)-2-
chlorostyrene oxide (1.16 g, 7.48 mmol, 38%) was isolated by vacuum distillation (32
ide was
determined to be >99% by chiral HPLC analysis ((R,R)-Whelk-O 1, 99.75:0.25
(39)
(40)
Myers, A. G.; McKinstry, L. J. Org. Chem. 1996, 61, 2428-2440.
Moreau, S. P.-; Morisseau, C.; Zylber, J.; Archelas, A.; Baratti, J.; Furstoss, R. J. Org. Chem.
1996, 61, 7402-7407.
(41)
(42)
(43)
Brandes, B. D.; Jacobsen, E. N. Tetrahedron: Asymmetry 1997, 8, 3927-3933.
Hudlicky, T.; Boros, E. E.; Boros, C. H. Tetrahedron: Asymmetry 1993, 4, 1365-1386.
Spelberg, J. H. L.; Rink, R.; Kellogg, R. M.; Janssen, D. B. Tetrahedron: Asymmetry 1998, 9,
459-466.

hexanes:i-PrOH, 1 mL / min, 220 nm, tR(minor) = 8.31 min, tR(major) = 9.39 min).
[α]26D –60.3 (c 3.22, CHCl3); lit.72 [α]25D +32.2 c 1.19, CHCl3, (S)-epoxide).
(S)-3-Methoxystyrene oxide (Table 5, entry 4). Method A. The catalyst ((S,S)-1, 97
mg, 160 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated 100 µL AcOH and stirred in air
for 30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
3-methoxystyrene oxide44 (3.00 g, 20 mmol) and THF (200 µL). The solution was
cooled to 0
2O (200 µL, 11 mmol, 0.55 equiv). After 40 h at rt,
(S)-3-methoxystyrene oxide (1.23 g, 8.21 mmol, 41%) was isolated by vacuum
distillation (28
epoxide was determined to be >99% by chiral HPLC analysis (Chiralpak® AS, 95:5
hexanes:i-PrOH, 1 mL / min, 220 nm, tR(minor) = 5.38 min, tR(major) = 6.04 min).
[α]24D +11.5 (c 2.94, CHCl3).
(R)-3-Nitrostyrene oxide (Table 5, entry 5). Method A. The catalyst ((R,R)-1, 97 mg,
160 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated 100 µL AcOH and stirred in air for
30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-3-
nitrostyrene oxide45 (3.30 g, 20 mmol) and THF (200 µL). The solution was cooled to 0
2O (200 µL, 11 mmol, 0.55 equiv). After 40 h at rt, the reaction
mixture was purified by flash chromatography over silica gel using 4:1 hexanes:EtOAc
as the eluent yielded (R)-3-nitrostyrene oxide (1.26 g, 7.64 mmol, 38%) as an opaque
yellow solid. The ee of recovered epoxide was determined to be >99% by chiral HPLC
analysis (Chiralpak® AS, 99:1 hexanes:i-PrOH, 1 mL / min, 254 nm, tR(minor) = 22.45
min, tR(major) = 24.97 min). [α]24D –2.9 (c 1.72, CHCl3).
(S)-1,2-Hexanediol (Table 6, entry 2). Method B. The catalyst ((R,R)-1, 302 mg, 500
µmol, 0.005 equiv) was dissolved in ( )-1,2-epoxyhexane (12.1 mL, 10.0 g, 100 mmol)
containing 2-3% AcOH (Aldrich). The solution was cooled to 0
2O (0.810 mL,
45 mmol, 0.45 equiv) was added in one portion. After 10 h, the residual epoxide was
isolated by vacuum transfer at 0.25 torr into a cooled (-78
S)-
1,2-hexanediol (5.29 g, 44.8 mmol, 44%) was distilled under reduced pressure (65
0.25 torr). The ee of the product was determined to be 99.2% by chiral GC analysis of
the bistrifluoroacetate (G-TA, 60
tR(minor) = 8.98 min, tR(major)
= 10.27 min). [α]25D –3.9 (neat); lit.46 [α]22D +15.2 (c 13.14, EtOH, R-diol).
(S)-1,2-Propanediol (Table 6, entry 1). Method A. The catalyst ((R,R)-1, 242 mg, 400
µmol, 0.002 equiv) in 5 mL PhMe was treated with 250 µL AcOH and stirred in air for
30 min. The crude catalyst residue obtained after concentration was dissolved in ( )-
propylene oxide (14.0 mL, 11.62 g, 200 mmol). The solution was cooled to 0
treated with H2O (1.62 mL, 90 mmol). After 12 h, the residual propylene oxide was
distilled from the reaction mixture and (S)-1,2-propanediol (6.81 g, 89.6 mmol, 45%)
(44)
(45)
(46)
Alvarez, M.; Granados, R.; Lavilla, R.; Salas, M. J. Heterocyclic Chem. 1985, 22, 745-750.
Penning, T. M.; Thornton, R.; Ricigliano, J. W. Steroids 1991, 56, 420-427.
Lavene, P. A.; Haller, H. L. J. Biol. Chem. 1928, 53, 475-488.

was isolated by vacuum distillation (50
of the product was
determined to be 99.1% by chiral GC analysis of the bistrifluoroacetate (G-TA, 60
min, 1
tR(minor) = 3.25 min, tR(major) = 5.04 min). [α]23D +17.2 (neat); lit.47
[α]25D +17.48 (neat).
(R)-1,2-Tetradecanediol (Table 6, entry 3).48 Method A. The catalyst ((S,S)-1, 242
mg, 400 µmol, 0.005 equiv) in 6 mL CH2Cl2 was treated with 250 µL AcOH and stirred
in air for 30 min. The crude catalyst residue obtained after concentration was dissolved
in ( )-1,2-epoxytetradecane (20.1 mL, 17.0 g, 80.0 mmol) and TBME (16 mL). The
solution was cooled to 0
2O (720 µL, 40.0 mmol). After 16 h at rt,
the resulting heterogeneous mixture was concentrated in vacuo, the solid was collected
by vacuum filtration and rinsed with 100 mL 95:5 hexanes:EtOAc. The powder
obtained (8.28 g, 36.0 mmol, 36%) was determined to be >99% ee by HPLC analysis of
the dibenzoate ester ((S,S)-Whelk-O 1, 1.5 mL / min, 98:2 hexanes:i-PrOH, 240 nm,
tR(minor) = 9.02 min, tR(major) = 7.99 min). [α]28D –0.90 (c 1.13, CHCl3).
(S)-5-Hexene-1,2-diol (Table 6, entry 4). Method B. The catalyst ((R,R)-1, 302 mg,
500 µmol, 0.005 equiv) was dissolved in ( )-1,2-epoxy-5-hexene (11.3 mL, 9.82 g, 100
mmol), AcOH (120 µL, 2.1 mmol, 0.02 equiv) and THF (1 mL). The solution was
cooled to 0
After 10 h, the residual epoxide was was isolated by vacuum transfer at 0.25 torr into a
cooled (-78 S)-5-hexene-1,2-diol (5.20 g, 44.8 mmol, 44%) was
2O (0.810 mL, 45 mmol, 0.45 equiv) was added in one portion.
distilled under reduced pressure (68
determined to be 99.3% by chiral GC analysis of the bistrifluoroacetate (G-TA, 60
min, 1
tR(minor) = 9.32 min, tR(major) = 10.50 min). [α]23D –3.9 (neat); lit.49
[α]D –19.04 (c 10.0, EtOH).
(S)-3-Phenyl-1,2-propanediol (Table 6, entry 5). Method B. The catalyst ((R,R)-1, 30
mg, 50 µmol, 0.005 equiv) was dissolved in ( )-(2,3-epoxypropyl)benzene (1.31 mL,
1.34 g, 10 mmol), AcOH (11 µL, 0.2 mmol, 0.02 equiv) and 0.1 mL THF. The solution
was cooled to 0
2O (81 µL, 4.5 mmol, 0.45 equiv). After 12 h, the
reaction was diluted with 4:1 hexanes:CH2Cl2 and organic layer was extracted 3 X 5 mL
H2O. The aqueous layer was filtered to remove solid catalyst reside and concentrated in
vacuo to yield (S)-3-phenyl-1,2-propanediol (0.611 g, 4.02 mmol, 40%). The ee of the
product was determined to be 95% by chiral GC analysis of the bistrifluoroacetate (G-
TA, 75
tR(minor) = 42.80 min, tR(major) = 45.99 min). [α]27
–
D
29.4 (c 1.10, EtOH); lit.50 [α]18D –35.4 (c 1.00, EtOH).
(47)
(48)
(49)
Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1978, 100, 5491-5494.
Horn, D. H. S.; Hougen, F. W.; Rudloff, E. v.; Sutton, D. A. J. Chem. Soc. 1954, 177-180.
Bradshaw, J. S.; Huszthy, P.; McDaniel, C. W.; Zhu, C. Y.; Dalley, N. K.; Izatt R. M.; Lifson, S.
J. Org. Chem. 1990, 55, 3129-3137.
(50)
Sone, H.; Shibata, T.; Fujita, T.; Ojika, M.; Yamada, K. J. Am. Chem. Soc. 1996, 118, 1874-
1880.

(S)-2-Cyclohexyl-1,2-ethanediol (Table 6, entry 6). Method B. The catalyst ((R,R)-1,
30 mg, 50 µmol, 0.005 equiv) was dissolved in ( )-vinylcyclohexane oxide51 (1.35 mL,
1.26 g, 10 mmol), AcOH (11 µL, 0.2 mmol, 0.02 equiv) and 0.1 mL THF. The solution
was cooled to 0
2O (81 µL, 4.5 mmol, 0.45 equiv). After 12 h, the
residual epoxide was removed in vacuo and (S)-2-cyclohexyl-1,2-ethanediol (0.590 g,
4.09 mmol, 41%) was isolated by vacuum distillation (84
analysis of the bistrifluoroacetate (G-TA, 80
tR(minor) = 12.85 min,
tR(major) = 14.61 min). [α]27 –2.6 (c 1.81, EtOH); lit.52 [α]25 –9.4 (c 2.59, EtOH,
D
D
73% ee).
(S)-2-(tert-Butyl)-1,2-ethanediol (Table 6, entry 7). Method A. The catalyst ((R,R)-1,
120 mg, 200 µmol, 0.02 equiv) in 2 mL PhMe was treated with 120 µL AcOH and
stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-tert-butyloxirane53 (1.20 mL, 1.00 g, 10.0 mmol). The solution was
treated with 0.5 mL i-PrOH, cooled to 0
2O (81 µL, 4.5 mmol, 0.45 equiv).
After 20 h, the residual epoxide was removed in vacuo (S)-2-(tert-butyl)-1,2-enthanediol
(0.471 g, 4.0 mmol, 40%) was isolated by vacuum distillation (50
cooled (0
determined to be 95% ee by chiral GC analysis of the bistrifluoroacetate (G-TA, 50
8 min, 2
tR(minor) = 9.63 min, tR(major) = 12.62 min). [α]24 +28
D
MeOH); lit.54 [α]23D –28.5
3, (R)-diol).
(R)-3-Chloro-1,2-propanediol (Table 6, entry 8). Method A. The catalyst ((R,R)-1,
242 mg, 400 µmol, 0.005 equiv) in 6 mL CH2Cl2 was treated with 250 µL AcOH and
stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-epichlorohydrin (6.25 mL, 7.40 g, 80.0 mmol). The solution was
cooled to 0
12 h at 4
2O (650 µL, 36.0 mmol, 0.45 equiv). After
in vacuo at 20
diluted with 100 mL 5:3 hexanes:EtOAc and 30 mL H2O and the resulting mixture was
filtered to remove solid. The layers were separated and the organic layer was extracted
2 X 30 mL H2O. The combined aqueous layers were concentrated to yield (R)-3-chloro-
1,2-propanediol (3.57 g, 32.3 mmol, 40%). The product was determined to be 95% ee
by chiral GC analysis of the corresponding acetal prepared from 2,2-dimethoxypropane
and catalytic TsOH (Cyclodex-B, 75
tR(minor) = 6.57 min, tR(major) =
6.80 min). [α]23D –1.24 55 [α]20D –6.4 c 5.0, H20).
(51)
Cohen, T.; Jeong, I.-H.; Mudryk, B.; Bhupathy, M.; Awad, M. M. A. J. Org. Chem. 1990, 55,
1528-1536.
(52)
(53)
(54)
(55)
Cho, B. T.; Chun, Y. S. J. Org. Chem. 1998, 63, 5280-5282.
Mischitz, M.; Kroutil, W.; Wandel, U.; Faber, K. Tetrahedron: Asymmetry 1995, 6, 1261-1272.
Deffiuex, A.; Sepulchre, M.; Spassky, N. J. Organometallic Chem. 1974, 80, 311-327.
Crans, D. C.; Whitesides, G. M. J. Am. Chem. Soc. 1985, 107, 7019-7027.

(R)-3-Bromo-1,2-propanediol (Table 6, entry 9). Method A. The catalyst ((R,R)- and
stirred in air for 30 min, 1.21 g, 2.0 mmol, 0.02 equiv) in 20 mL CH2Cl2 was treated
with 1.2 mL AcOH and stirred in air for 30 min. The crude catalyst residue obtained
after concentration was dissolved in ( )-epibromohydrin (8.60 mL, 17.7 g, 100 mmol).
The solution was cooled to 0
1.5 equiv) portionwise over 10 min. After 48 h at 4
2O (2.70 mL, 150 mmol,
ted with 35
mL PhMe and 25 mL H2O. The layers were separated and the organic layer was
extracted 2 X 25 mL H2O. The combined aqueous layers were extracted 2 X 30 mL
hexanes and concentrated to yield (R)-3-bromo-1,2-propanediol (14.0 g, 90.4 mmol,
90%). The product was determined to be 96% ee by chiral GC analysis of the
corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 75
0.69
tR(minor) = 15.47 min, tR(major) = 16.09 min). [α]25
–
D
56 [α]25D –3.94 c 5.07, CHCl3).
(R)-3-Fluoro-1,2-propanediol (Table 6, entry 10). Method A. The catalyst ((R,R)-1,
80 mg, 130 µmol, 0.005 equiv) in 2 mL PhMe was treated with 80 µL AcOH and stirred
in air for 30 min. The crude catalyst residue obtained after concentration was dissolved
in ( )-epifluorohydrin (2.00 g, 26.3 mmol). The solution was cooled to 0
with H2O (210 µL, 11.7 mmol, 0.45 equiv). After 12 h, the residual epoxide was
removed in vacuo and (R)-3-fluoro-1,2-propanediol (0.928 g, 9.87 mmol, 38%) was
isolated by vacuum distillation (55
(0
of the corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 60
tR(minor) = 4.97 min, tR(major) = 5.18 min). [α]24
–
D
7.0 c 10, H2O); lit.85 [α]11D –17.4 c 3.05, EtOH).
(R)-1,1,1-Trifluoro-2,3-propanediol (Table 6, entry 11). Method A. The catalyst
((R,R)-1, 54 mg, 89 µmol, 0.005 equiv) in 2 mL PhMe was treated with 50 µL AcOH
and stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-1,1,1-trifluoro-2,3-epoxypropane57 (2.00 g, 17.8 mmol). The solution
was cooled to 0
the residual epoxide was was isolated by vacuum transfer (0.25 torr) from the reaction
mixture into a cooled (-78 9:1
2O (140 µL, 7.8 mmol, 0.45 equiv). After 16 h,
hexanes:CH2Cl2 and collected by vacuum filtration. The hygroscopic solid obtained
(0.962 g, 7.4 mmol, 42%) was determined to be >99% ee by HPLC analysis of the
dibenzoate ester (Chiralcel® OD, 99.5:0.5 hexanes:i-PrOH, 1.0 mL / min, 230 nm,
tR(minor) = 9.38 min, tR(major) = 11.06 min). [α]24D +12 c 3.3, EtOH); lit.58 [α]22
10.95 c 1.4, MeOH, S-diol, 96% ee).
–
D
(56)
(57)
(58)
Kawakami, Y.; Asai, T.; Umeyama, K.; Yamashita, Y. J. Org. Chem. 1982, 47, 3581-3585.
Available from Oakwood Products, Inc.; catalog no. 1533.
Ramachandran, P. V.; Gong, B.; Brown, H. C. J. Org. Chem. 1995, 60, 41-46.

(R)-3-Benzyloxy-1,2-propanediol (Table 6, entry 12). Method B. The catalyst ((R,R)-
1, 91 mg, 150 µmol, 0.005 equiv) was dissolved in ( )-benzyl glycidyl ether59 (4.92 g,
30.0 mmol), AcOH (34 µL, 0.6 mmol, 0.02 equiv) and 0.3 mL THF. The solution was
cooled to 0
remaining epoxide was isolated by vacuum distillation (110
(0 receiving flask and (R)-3-benzyloxy-1,2-propanediol (2.21 g, 12.2 mmol, 40%)
2O (495 µL, 27.5 mmol, 0.45 equiv). After 12 h, the
was obtained by vacuum distillation (110
product was determined to be 95% by chiral HPLC analysis (Chiralcel® OD, 9:1
hexanes:i-PrOH, 1 mL / min, 214 nm, tR(minor) = 19.69 min, tR(major) = 15.73 min).
[α]23D –1.4 (c 3.31, EtOH); lit.60 [α]D –5.7 (neat).
(R)-3-(tert-Butyldimethylsiloxy)-1,2-propanediol (Table 6, entry 13). Method B. The
catalyst ((R,R)-1, 60 mg, 100 µmol, 0.005 equiv) was dissolved in ( )-(tert-
butyldimethylsilyl) glycidyl ether61 (3.76 g, 20.0 mmol), AcOH (22 µL, 0.4 mmol, 0.02
equiv) and 0.3 mL THF. The solution was cooled to 0
9.0 mmol, 0.45 equiv). After 12 h, the remaining epoxide was isolated by vacuum
distillation (30 R)-3-(tert-
butyldimethylsiloxy)-1,2-propanediol (1.72 g, 8.35 mmol, 42%) was isolated by vacuum
distillation (85 determined to be 98% by chiral
2O (162 µL,
HPLC analysis of the 1-napthylcarboxylate ester (obtained by acylation with 1-napthoyl
chloride in CH2Cl2 using 1 equiv TEA at 0
obtained, Chiralcel® OD, 97:3 hexanes:EtOH, 1 mL / min, 230 nm, tR(minor) = 10.50
min, tR(major) = 13.02 min). [α]26D +9.3 (c 2.92, EtOH).
(R)-3-Phenoxy-1,2-propanediol (Table 6, entry 14). Method B. The catalyst ((R,R)-1,
91 mg, 150 µmol, 0.005 equiv) was dissolved in ( )-phenyl glycidyl ether (4.50 g, 30.0
mmol), AcOH (34 µL, 0.6 mmol, 0.02 equiv) and 0.5 mL THF. The solution was
cooled to 0
2O (240 µL, 13.3 mmol, 0.45 equiv). After 12 h, the
remaining epoxide was isolated by vacuum distillation (70
C) receiving flask. The solid obtained remaining the reaction flask was suspended in
30 mL 4:1 hexanes:CH2Cl2 and filtered to yield to yield (R)-3-phenoxy-1,2-propanediol
(2.07 g, 12.3 mmol, 41%) as an opaque white powder. The ee of the product was
determined to be 95% by chiral HPLC analysis (Chiralcel® OD, 9:1 hexanes:EtOH, 1
mL / min, 260 nm, tR(minor) = 14.21 min, tR(major) = 9.10 min). [α]23D –10.0 (c 1.90,
EtOH); lit.62 [α]20D –10.8 (c 1, EtOH).
(R)-3-(1-Napthyloxy)-1,2-propanediol (Table 6, entry 15). Method B. The catalyst
((R,R)-1, 15 mg, 25 µmol, 0.005 equiv) was dissolved in ( )-(1-napthyl) glycidyl ether63
(59)
(60)
(61)
(62)
(63)
Ichikawa, Y.; Isobe, M.; Bai, D. –L.; Goto, T. Tetrahedron 1987, 43, 4737-4748.
Gigg, J.; Gigg, R. J. Chem. Soc. C 1967, 1865-1866.
Cywin, C. L.; Webster, F. X.; Kallmerten, J. J. Org. Chem. 1991, 56, 2953-2955.
Theil, F.; Weidner, J.; Ballschuh, S.; Kunath, A.; Schick, H. J. Org. Chem. 1994, 54, 388-393.
Slater, R. A.; Howson, W.; Swayne, G. T. G.; Taylor, E. M.; Reavil, D. R. J. Med. Chem. 1988,
31, 345-351.

(1.00 g, 5.0 mmol), AcOH (10 µL, 0.2 mmol, 0.04 equiv) and 0.1 mL THF. The
solution was cooled to 0 2O (40 µL, 2.25 mmol, 0.45 equiv). After
12 h, the reaction was concentrated in vacuo, the solid was suspended in 9:1
hexanes:CH2Cl2 and filtered to yield (R)-3-(1-napthyloxy)-1,2-propanediol (460 mg,
2.11 mmol, 42%) as an opaque white powder. The ee of the product was determined to
be 97% by chiral HPLC analysis (Chiralcel® OD, 9:1 hexanes:i-PrOH, 1 mL / min, 230
nm, tR(minor) = 26.84 min, tR(major) = 22.05 min). [α]25 –7.6 (c 1.2, EtOH); lit.64
D
[α]25D –8.5 (c 4.5, MeOH).
(S)-4-Phenylmethoxy-1,2-butanediol (Table 6, entry 16). Method B. The catalyst
((R,R)-1, 91 mg, 150 µmol, 0.005 equiv) was dissolved in ( )-(2-phenylmethoxyethyl)
oxirane65 (5.34 g, 30.0 mmol), AcOH (35 µL, 0.6 mmol, 0.02 equiv) and 0.3 mL THF.
The solution was cooled to 0
After 12 h, the remaining epoxide was isolated by vacuum distillation (70
into a cooled (0 ing flask and (S)-4-phenylmethoxy-1,2-butanediol (2.50 g,
2O (240 µL, 13.3 mmol, 0.45 equiv).
12.7 mmol, 42%) was isolated by vacuum distillation (70
oil. The ee of the product was determined to be 95% by chiral HPLC analysis of the 1-
tert-butyl diphenylsilyl ether (Chiralcel® OD, 9:1 hexanes:i-PrOH, 1 mL / min, 220 nm,
tR(minor) = 10.00 min, tR(major) = 6.27 min). [α]23D –22.5 (c 1.10, EtOH); lit.66 [α]20
+22.7 (c 5.6, EtOH, R-epoxide).
D
(S,S)-3,4-Epoxy-1,2-butanediol (Table 6, entry 17). Method A. The catalyst ((S,S)-1,
127 mg, 209 µmol, 0.01 equiv) in 3 mL CH2Cl2 was treated with 150 µL AcOH and
stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-butadiene diepoxide67 (1.80 g, 20.9 mmol) and THF (4 mL). The
solution was cooled to 0
2O (150 µL, 8.4 mmol, 0.40 equiv). After
12 h, the reaction was concentrated by rotary evaporation and diluted with 30 mL 2:1
hexanes:CH2Cl2. The organic layer was extracted 3 X 10 mL H2O and the combined
aqueous extracts were filtered and concentrated in vacuo to yield (S,S)-3,4-epoxy-1,2-
butanediol (0.773 g, 7.43 mmol, 36%). The product was determined to be 96% ee by
chiral HPLC analysis of the 1-tert-butyldiphenylsilyl ether (Chiralcel® OD, 95:5
hexanes:i-PrOH, 1 mL / min, 220 nm, tR(minor) = 10.16 min, tR(major) = 8.44 min).
[α]24D +13 (c 8.5, MeOH); lit.68 [α]25D +1.29 (c 1, MeOH).
(R)-Butyryl glycerol (Table 6, entry 18). Method B. The catalyst ((R,R)-1, 60 mg, 100
µmol, 0.005 equiv) was dissolved in ( )-glycidyl butyrate69 (2.88 g, 20.0 mmol), AcOH
(24 µL, 0.4 mmol, 0.02 equiv) and 0.3 mL THF. The solution was cooled to 0
treated with H2O (162 µL, 9.0 mmol, 0.45 equiv). After 12 h at rt, the reaction was
(64)
(65)
(66)
(67)
(68)
(69)
Leftheris, K.; Goodman, M. J. Med. Chem. 1990, 33, 216-223.
Muehlbacher, M.; Poulter, C. D. J. Org. Chem. 1988, 53, 1026-1030.
Jakob, B.; Voss, G.; Gerlach, H. Tetrahedron: Asymmetry 1996, 7, 3255-3262.
Available from Aldrich as the d,l mixture only.
Claffey, D. J.; Ruth, J. A. Tetrahedron Lett. 1996, 37, 7929-7932.
Ladner, W. E.; Whitesides, G. M. J. Am. Chem. Soc. 1984, 106, 7250-7251.

concentrated by rotary evaporation and the diol was recovered by flash chromatography
over silica gel using 1:1 EtOAc:hexanes as the eluent. The clear viscous liquid obtained
(1.46 g, 9.0 mmol, 45%) was determined to be 43% ee by chiral HPLC of the 1-tert-
butyldiphenylsilyl ether (Chiralcel® OD, 98:2 hexanes:EtOH, 1 mL / min, 230 nm,
tR(minor) = 8.40 min, tR(major) = 9.59 min). [α]26D –5.5 c 10, pyridine); lit.70 [α]24
8.3 c 10.0, pyridine).
–
D
(R)-Ethyl-3,4-dihydroxybutanoate (Table 6, entry 19). Method B. The catalyst ((S,S)-
1, 30 mg, 50 µmol, 0.005 equiv) was dissolved in ( )-ethyl-3,4-epoxybutyrate71 (1.30 g,
10.0 mmol), AcOH (12 µL, 0.2 mmol, 0.02 equiv) and 0.1 mL THF. The solution was
cooled to 0
2O (80 µL, 4.5 mmol, 0.45 equiv). After 12 h, the
reaction was concentrated in vacuo and the residue was dissolved in 9:1 hexanes:EtOAc.
The organic layer was extracted 3 X 10 mL H2O and the combined aqueous extracts
were filtered and concentrated in vacuo to yield (R)-ethyl-3,4-dihydroxybutanoate
(0.613 g, 4.1 mmol, 41%). The ee of the recovered epoxide was determined to be 95%
ee by chiral HPLC analysis of the 1-tert-butyldiphenylsilyl ether (Chiralcel® OD,
99.2:0.8 hexanes:EtOH, 1 mL / min, 230 nm, tR(minor) = 12.88 min, tR(major) = 10.75
min). [α]26D –9.3 (c 1.9, EtOH); lit.72 [α]25D 6.22 (c 1.22, CHCl3, S-diol).
(S)-N-tert-Butyloxycarbonyl-3-aminopropane-1,2-diol (Table 6, entry 20). Method
A. The catalyst ((R,R)-1, 121 mg, 200 µmol, 0.02 equiv) in 5 mL CH2Cl2 was treated
with 150 µL AcOH and stirred in air for 30 min. The crude catalyst residue obtained
after concentration was dissolved in ( )-{[(tert-butoxycarbonyl)amino]methyl}
oxirane73 (1.73 g, 10 mmol). The solution was treated with 0.3 mL THF, cooled to 0
and treated with H2O (80 µL, 11 mmol, 0.45 equiv). After 12 h at rt, the reaction was
concentrated by rotary evaporation and the diol was recovered by flash chromatography
over silica gel using 95:5 EtOAc:EtOH as the eluent. The solid obtained (680 mg, 35.6
mmol, 36%) was determined to be 78% ee by chiral HPLC of the 1-tert-
butyldiphenylsilyl ether (Chiralcel® OD, 96:4 hexanes:i-PrOH, 1 mL / min, 220 nm,
tR(minor) = 7.95 min, tR(major) = 9.74 min). [α]25 –6.1 c 1.2, MeOH); lit.74 [α]20
D
D
+13.6 c 0.72, MeOH, R-diol).
(R)-Methyl-2,3-dihydroxypropanoate (Table 6, entry 21). Method A. The catalyst
((R,R)-1, 181 mg, 300 µmol, 0.02 equiv) in 3 mL CH2Cl2 was treated with 200 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
(70)
(71)
Baer, E.; Fischer, H. O. L. J. Am. Chem. Soc. 1945, 67, 2031-2037.
Available by m-CPBA epoxidation of the corresponding alkene. a) Rambaud, R.; Vessière, M.
Bull. Soc. Chim. Fr. 1960, 1115-1116. b) For an efficient synthesis of ethyl but-3-enoate see:
Ozeki, T.; Kusaka, M. Bull. Chem. Soc. Japan 1966, 39, 1995-1998.
(72)
(73)
(74)
Saito, S.; Ishikawa, T.; Kuroda, A.; Koga, K.; Moriwake, T. Tetrahedron 1992, 48, 4067-4086.
Edwards, M. L.; Snyder, R. D.; Stemerick, D. M. J. Med. Chem. 1991, 34, 2414-2420.
Kitchin, J.; Bethell, R. C.; Cammack, N.; Dolan, S.; Evans, D. N.; Holman, S.; Holmes, D. S.;
McMeekin, P.; Mo, C. L.; Nieland, N.; Orr, D. C.; Saunders, J.; Shenoy, B. E. V.; Starkey, I. D.;
Storer, R. J. Med. Chem. 1994, 37, 3707-3716.

concentration was dissolved in ( )-methyl glycidate75 (1.53 g, 15 mmol). The solution
was treated with 0.4 mL THF, cooled to 0 2O (120 µL, 6.7 mmol,
0.45 equiv). After 12 h at rt, the reaction was diluted 30 mL 1:1 hexanes:EtOAc and the
organic layer was extracted 3 X 10 mL H2O. The combined aqueous extracts were
filtered and concentrated in vacuo to yield (R)-methyl-2,3-dihydroxypropanoate (0.670
g, 5.58 mmol, 37%). The product was determined to be 97% ee by chiral GC analysis of
the corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 95
tR(minor) = 6.29 min, tR(major) = 6.71 min). [α]26
D
+6.6 c 4.8, CHCl3); lit.76 [α]31D +4.1 c 1.7, CHCl3).
(R)-3,4-Dihydroxy-2-butanone (Table 6, entry 22). Method A. The catalyst ((R,R)-1,
242 mg, 400 µmol, 0.02 equiv) in 5 mL CH2Cl2 was treated with 250 µL AcOH and
stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-3,4-epoxy-2-butanone77 (1.72 g, 20 mmol). The solution was treated
with 0.5 mL THF, cooled to 0
2O (160 µL, 9.0 mmol, 0.45 equiv).
After 6 h at rt, the reaction was diluted 30 mL 1:1 hexanes:EtOAc and the organic layer
was extracted 3 X 10 mL H2O. The combined aqueous extracts were filtered and
concentrated in vacuo to yield (R)-3,4-dihydroxy-2-butanone (0.840 g, 8.08 mmol,
40%). The product was determined to be 97% ee by chiral GC analysis of the
corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 95
tR(minor) = 4.12 min, tR(major) = 4.37 min). [α]26
–
D
70.1 c 5.80, CHCl3); lit.78 [α]D +0.3 c 4, H2O).
(R)-1,2-Dihydroxy-3-pentanone (Table 6, entry 23). Method A. The catalyst ((R,R)-1,
181 mg,300 µmol, 0.02 equiv) in 5 mL CH2Cl2 was treated with 180 µL AcOH and
stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-1,2-epoxy-3-pentanone79 (1.50 g, 15 mmol). The solution was treated
with 0.2 mL THF, cooled to 0
2O (120 µL, 6.7 mmol, 0.45 equiv).
After 6 h at rt, the reaction was diluted 30 mL 1:1 hexanes:EtOAc and the organic layer
was extracted 3 X 10 mL H2O. The combined aqueous extracts were filtered and
concentrated in vacuo to yield (R)-1,2-dihydroxy-3-pentanone (0.580 g, 4.90 mmol,
33%). The product was determined to be 96% ee by chiral GC analysis of the
corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 95
65.6 c 4.17, CHCl3).
tR(minor) = 6.24 min, tR(major) = 6.93 min). [α]26
–
D
(75)
(76)
(77)
(78)
(79)
Nemes, A.; Czibula, L.; Visky, G.; Farkas, M.; Kreidl, J. Heterocycles 1991, 32, 2329-2338.
Shapira, M.; Gutman, A. L. Tetrahedron: Asymmetry 1994, 5, 1689-1700.
Wellman, G. R.; Lam, B.; Anderson, E. L.; White, E. Synthesis 1976, 547-549.
Yokota, A.; Sasajima, K. Abric. Biol. Chem. 1984, 48, 1643-1646.
Available by epoxidation of ethyl vinyl ketone. Klein, E.; Ohloff, G. Tetrahedron 1963, 19,
1091-1102.

(S)-3-Butene-1,2-diol (Table 6, entry 30). Method B. The catalyst ((R,R)-1, 302 mg,
500 µmol, 0.005 equiv) was dissolved in ( )-butadiene monoxide80 (7.0 g, 100 mmol)
and AcOH (110 µL, 2 mmol, 0.02 equiv). The solution wascooled to 0
with H2O (810 µL, 45 mmol, 0.45 equiv). After 12 h at 4
removed in vacuo and (S)-3-butene-1,2-diol (3.36 g, 38.2 mmol, 38%) was isolated by
vacuum distillation (0.25 torr, 50
by chiral GC analysis of the bistrifluoroacetate (G-TA, 47
tR(minor) = 10.28 min, tR(major) = 11.58 min). [α]25D –44 c 2.5, i-PrOH); lit.81 [α]22
–43.6 c 4.62, i-PrOH).
D
(S)-1-(tert-Butyldimethylsilyl)-3,4-dihydroxy-1-butyne (Table 6, entry 31). Method
A. The catalyst ((R,R)-1, 24 mg, 40 µmol, 0.008 equiv) in 1 mL CH2Cl2 was treated
with 50 µL AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-1-(tert-butyldimethylsilyl)-3,4-epoxy-1-butyne82
(910 mg, 5.0 mmol). The solution was treated with 200 µL i-PrOH, cooled to 0
treated with H2O (40 µL, 2.2 mmol, 0.45 equiv). After 12 h at rt, the remaining epoxide
was isolated by vacuum distillation (36
flask. The residue left was suspended in MeOH and the catalyst was removed by
filtration. The filtrate was concentrated to yield (S)-1-(tert-butyldimethylsilyl)-3,4-
dihydroxy-1-butyne (389 mg, 2.1 mmol, 41%). The product was determined to be 99%
ee by chiral GC analysis of the corresponding acetal prepared from 2,2-
dimethoxypropane and catalytic TsOH (Chiraldex-B, 100
/ min,
tR(minor) = 21.78 min, tR(major) = 22.17 min). [α]27D +9.8 c 1.2, EtOH).
(S)-2-Phenyl-1,2-ethanediol (Table 6, entry 24). Method A. The catalyst ((R,R)-1, 242
mg, 400 µmol, 0.008 equiv) in 6 mL CH2Cl2 was treated with 250 µL AcOH and stirred
in air for 30 min. The crude catalyst residue obtained after concentration was dissolved
in ( )-styrene oxide (5.70 mL, 6.00 g, 50 mmol) and THF (0.5 mL). The solution was
cooled to 0
2O (400 µL, 22.5 mmol, 0.45 equiv). After 12 h at rt,
the residual epoxide was isolated by vacuum distillation (27
(-78
S)-2-phenyl-1,2-ethanediol (2.80 g, 20.3 mmol, 40%) was
isolated by vacuum distillation (100 - 105
pon standing.
The product was determined to be 98% ee by chiral GC analysis of the corresponding
acetal prepared from 2,2-dimethoxypropane and catalytic TsOH (Chiraldex-B, 100
isothermal, tR(minor) = 18.77 min, tR(major) = 20.39 min). [α]23D +38.4 (c 4.38, EtOH);
lit.83 [α]13D +39.3 (c 3.13, EtOH).
(S)-2-(4-Chlorophenyl)-1,2-ethanediol (Table 6, entry 25). Method A. The catalyst
((R,R)-1, 97 mg, 160 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated with 100 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
(80)
(81)
(82)
(83)
Available in bulk from Eastman Kodak Co..
Crawford, R. J.; Lutener, S. B.; Cockcroft, R. D. Can. J. Chem. 1976, 54, 3364-3376.
Available by m-CPBA epoxidation of the corresponding alkene.
King, R. B.; Bakos, J.; Hoff, C. D.; Markó, L. J. Org. Chem. 1979, 44, 1729-1731.

concentration was dissolved in ( )-4-chlorostyrene oxide84 (3.10 g, 20 mmol) and THF
(200 µL). The solution was cooled to 0 2O (160 µL, 9.0 mmol,
0.45 equiv). After 16 h at rt, the reaction was diluted with 20 mL 95:5 hexanes:EtOAc
and filtered to yield (S)-2-(4-chlorophenyl)-1,2-ethanediol (1.27 g, 7.36 mmol, 37%) as
an opaque white solid. The product was determined to be 94% ee by chiral GC analysis
of the corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 120
tR(minor) = 19.53 min, tR(major) = 20.03
min). [α]27D +27.4 (c 1.49, EtOH); lit.85 [α]25D +30.1 c 1.01, EtOH).
(S)-2-(3-Chlorophenyl)-1,2-ethanediol (Table 6, entry 26). Method A. The catalyst
((R,R)-1, 97 mg, 160 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated with 100 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-3-chlorostyrene oxide86 (3.10 g, 20 mmol). The
solution was cooled to 0
2O (160 µL, 9.0 mmol, 0.45 equiv). After
16 h at rt, the residual epoxide was isolated by vacuum distillation (55
a cooled (0
5:5
hexanes:EtOAc and extracted 3 X 20 mL H2O. The combined aqueous extracts were
filtered and concentrated in vacuo to yield (S)-2-(3-chlorophenyl)-1,2-ethanediol (1.50
g, 8.67 mmol, 44%) as an opaque white solid. The product was determined to be 91%
ee by chiral GC analysis of the corresponding acetal prepared from 2,2-
dimethoxypropane and catalytic TsOH (Chiraldex-B, 120
tR(minor) = 19.30 min, tR(major) = 19.89 min). [α]26D +21.1 (c 1.31, EtOH); lit.87 [α]D
+24.05 c 1.24, EtOH).
(S)-2-(2-Chlorophenyl)-1,2-ethanediol (Table 6, entry 29). Method A. The catalyst
((R,R)-1, 181 mg, 300 µmol, 0.015 equiv) in 5 mL CH2Cl2 was treated with 200 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-2-chlorostyrene oxide88 (3.10 g, 20 mmol) and THF
(200 µL). The solution was cooled to 0
0.45 equiv). After 16 h at rt, the remaining epoxide was isolated by vacuum distillation
(32 The residue was dissolved in 70
2O (160 µL, 9.0 mmol,
mL 9:1 hexanes:EtOAc and extracted 3 X 20 mL H2O. The combined aqueous extracts
were filtered and concentrated in vacuo to yield (S)-2-(2-chlorophenyl)-1,2-ethanediol
(1.45 g, 8.36 mmol, 42%). The product was determined to be 94% ee by chiral GC
analysis of the corresponding acetal prepared from 2,2-dimethoxypropane and catalytic
TsOH (Chiraldex-B, 110
tR(minor) = 21.32 min, tR(major) =
(84)
Moreau, S. P.-; Morisseau, C.; Zylber, J.; Archelas, A.; Baratti, J.; Furstoss, R. J. Org. Chem.
1996, 61, 7402-7407.
(85)
(86)
(87)
(88)
Nymann, K.; Jensen, L.; Svendsen, J. S. Acta Chem. Scand. 1996, 50, 832-841.
Brandes, B. D.; Jacobsen, E. N. Tetrahedron: Asymmetry 1997, 8, 3927-3933.
Hudlicky, T.; Boros, E. E.; Boros, C. H. Tetrahedron: Asymmetry 1993, 4, 1365-1386.
Spelberg, J. H. L.; Rink, R.; Kellogg, R. M.; Janssen, D. B. Tetrahedron: Asymmetry 1998, 9,
459-466.

21.49 min). [α]27 +65 (c 1.7, EtOH); lit.89 [α]25D –56.5 (c 1.8, EtOH, 66% ee, R-
D
diol).
(S)-2-(3-Methoxyphenyl)-1,2-ethanediol (Table 6, entry 27). Method A. The catalyst
((R,R)-1, 97 mg, 160 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated with 100 µL
AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-3-methoxystyrene oxide90 (3.00 g, 20 mmol) and
THF (200 µL). The solution was cooled to 0
2O (160 µL, 9.0
mmol, 0.55 equiv). After 16 h at rt, the residual epoxide was isolated by vacuum
distillation (28
dissolved in 50 mL 9:1 hexanes:EtOAc and extracted 3 X 30 mL H2O. The combined
aqueous extracts were filtered and concentrated in vacuo to yield (S)-2-(3-
methoxyphenyl)-1,2-ethanediol91 (1.37 g, 8.18 mmol, 41%) as an opaque white solid.
The product was determined to be 95% ee by chiral GC analysis of the corresponding
acetal prepared from 2,2-dimethoxypropane and catalytic TsOH (Chiraldex-B, 120
15 min, 5
1.12, EtOH).
tR(minor) = 21.73 min, tR(major) = 22.08 min). [α]27 +26.9 (c
D
(S)-2-(3-Nitrophenyl)-1,2-ethanediol (Table 6, entry 28). Method A. The catalyst
((R,R)-1, 58 mg, 97 µmol, 0.008 equiv) in 3 mL CH2Cl2 was treated with 60 µL AcOH
and stirred in air for 30 min. The crude catalyst residue obtained after concentration was
dissolved in ( )-3-nitrostyrene oxide92 (2.00 g, 12.1 mmol) and THF (100 µL). The
solution was cooled to 0
2O (100 µL, 5.5 mmol, 0.45 equiv). After
16 h at rt, the reaction was diluted with 10 mL 9:1 hexanes:EtOAc and filtered to yield
(S)-2-(3-nitrophenyl)-1,2-ethanediol (980 mg, 5.35 mmol, 44%) as an opaque white
solid. The product was determined to be 99% ee by chiral GC analysis of the
corresponding acetal prepared from 2,2-dimethoxypropane and catalytic TsOH
(Chiraldex-B, 155
tR(minor) = 22.08 min, tR(major) = 22.88 min). [α]23
D
+18.0 (c 1.68, EtOH); lit.93 [α]25D -19 c 0.29, EtOH, R-diol).
Catalyst Recycling Experiments (Table 8). Cycle 1. ( )-Epichlorohydrin was resolved
according to the experimental procedure outlined above. The catalyst ((R,R)-1, 242 mg,
400 µmol, 0.005 equiv) in 5 mL CH2Cl2 was treated with 250 µL AcOH and stirred in
air for 30 min. The crude catalyst residue obtained after concentration was dissolved in
( )-epichlorohydrin (6.26 mL, 7.40 g, 80 mmol) and 0.8 mL THF. The solution was
cooled to 0
2O (800 µL, 44 mmol, 0.55 equiv) and the reaction was
maintained at 0 – 4
isolated by vacuum transfer (25
S)-Epichlorohydrin (3.01 g, 32.5 mmol, 41%) was
-
(89)
(90)
(91)
(92)
(93)
Wei, Z.; Li, Z.; Lin, G. Tetrahedron 1998, 54, 13059-13072.
Alvarez, M.; Granados, R.; Lavilla, R.; Salas, M. J. Heterocyclic Chem. 1985, 22, 745-750.
Jones, G. B.; Guzel, M. Tetrahedron: Asymmetry 1998, 9, 2023-2026.
Penning, T. M.; Thornton, R.; Ricigliano, J. W. Steroids 1991, 56, 420-427.
(a) Michael J. Grogan, Ph. D. Thesis, Harvard University; Cambridge, Massachusetts, 1999. (b)
Corey, E. J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1994, 35, 6427-6430.

78
xide was determined to be >99% ee by chiral
GC analysis. The receiving flask was exchanged and the diol was distilled from the
reaction flask (56
dissolved in 100 mL 3:1 hexanes:EtOAc and rinsed 3 X 100 mL H2O. The organic layer
was dried over Na2SO4, filtered and concentrated in vacuo to yield a crude catalyst
residue that was utilized in the next cycle.
Cycle 2. ( )-Propylene oxide was resolved according to the experimental procedure
described above. The catalyst (400 µmol, 0.002 equiv) was dissolved in 5 mL PhMe
and treated with AcOH (240 µL, 4.2 mmol). After stirring at rt open to air for 30 min
the solution was concentrated in vacuo to leave a crude brown solid once all of the
residual AcOH had been removed. The resulting catalyst residue was dissolved in
propylene oxide (14.0 mL, 11.6 g, 200 mmol) at rt, the solution was cooled to 0 °C, and
H2O (1.98 mL, 110 mmol, 0.55 equiv) was added dropwise over 5 min. The reaction
was allowed to warm to rt and stir 14 h at which time (R)-propylene oxide (5.12 g, 88.1
mmol, 44%) was distilled from the reaction mixture at 36
oxide was determined to be >99% by chiral GC analysis of the 1-azido-2-
trimethylsiloxypropane. The propylene diol was removed by vacuum distillation (65
0.25 torr). The catalyst residue was used as is in cycle 3.
Cycle 3. ( )-Styrene oxide was resolved according to the experimental procedure
described above. Method A. The catalyst (400 µmol, 0.008 equiv) in 50 mL CH2Cl2
was treated 0.5 mL AcOH and stirred in air for 30 min. The crude catalyst residue
obtained after concentration was dissolved in ( )-styrene oxide (5.7 mL, 6.0 g, 50 mmol)
and THF (0.5 mL). The solution was cooled to 0
mmol, 0.55 equiv). After 72 h at rt, (R)-styrene oxide (2.47 g, 20.6 mmol, 41%) was
isolated by vacuum distillation (27 -78
2O (0.5 mL, 27.5
The ee of recovered epoxide was determined to be >99% by chiral HPLC analysis. The
catalyst and diol mixture was allowed to solidify. The solid was treated with 100 mL
9:1 hexanes:EtOAc. The catalyst solution was filtered from the diol. The filtrate was
rinsed 3 X 100 mL H2O. The organic layer was dried over Na2SO4, filtered and
concentrated in vacuo to yield a crude catalyst residue that was utilized in the next cycle.
Cycle 4. ( )-Methyl glycidate was resolved according to the experimental procedure
described above. The catalyst (400 µmol, 0.02 equiv) in 10 mL CH2Cl2 was treated 400
µL AcOH and stirred in air for 30 min. The crude catalyst residue obtained after
concentration was dissolved in ( )-methyl glycidate (2.04 g, 20 mmol) and THF (0.2
mL). The solution was cooled to 0
equiv). After 24 h at rt, (R)-methyl glycidate (0.82 g, 8.0 mmol, 40%) was isolated by
vacuum distillation (50 -78
treated with H2O (200 µL, 11 mmol, 0.55
recovered epoxide was determined to be >99% by chiral GC analysis. The diol was
distilled (60 C, 0.25 torr) into a cooled (0
residue was dissolved in 100 mL 4:1 hexanes:EtOAc. The organic layer was rinsed 5 X
15 mL H2O. The organic layer was dried over Na2SO4, filtered and concentrated in
vacuo to yield a crude catalyst residue that was utilized in the next cycle.
Cycle 5. ( )-Phenyl glycidyl ether was resolved according to the experimental
procedure described above. The catalyst (400 µmol, 0.005 equiv) was dissolved in ( )-
phenyl glycidyl ether (12.0 g, 80.0 mmol), AcOH (90 µL, 1.6 mmol, 0.02 equiv) and 0.8
mL THF. The solution was cooled to 0
2O (800 µL, 44.4 mmol,

0.55 equiv). After 16 h, (S)-phenyl glycidyl ether (5.18 g, 34.5 mmol, 43%) was
isolated by vacuum distillation (80
The ee of the recovered epoxide was determined to be >99% by chiral HPLC analysis.
The catalyst and diol mixture was allowed to solidify. The solid was treated with 100
mL 4:1 hexanes:EtOAc. The diol was isolated by filtration and was rinsed 3 X 100 mL
H2O. The organic solution was dried over Na2SO4, filtered and concentrated in vacuo to
yield a crude catalyst residue that was utilized in the next cycle.
Cycle 6. ( )-1,2-Epoxyhexane was resolved according to the experimental procedure
described above. Method B. The catalyst (400 µmol, 0.005 equiv) was dissolved in ( )-
1,2-epoxyhexane (9.6 mL, 8.0 g, 80 mmol) containing 2-3% AcOH (available from
Aldrich). The solution was cooled to 0
2O (0.80 mL, 44 mmol, 0.55 equiv) was
added in one portion. After 16 h, (R)-1,2-epoxyhexane (3.28 g, 32.8 mmol, 41%) was
was isolated by vacuum transfer at 0.25 torr into a cooled (-78
diol was distilled under reduced pressure (65
epoxide was determined to be >99% by chiral GC analysis of the 1-azido-2-
trimethylsiloxyhexane. The catalyst residue was suspended in MeOH and recovered by
filtration (212 mg, 351 µmol, 88% of the amount introduced in cycle 1).