Designing new chiral ketone catalysts. Asymmetric epoxidation of cis-olefins and terminal olefins

Article abstract of DOI:10.1021/jo010838k

This paper describes a new class of chiral oxazolidinone ketone catalyst for asymmetric epoxidation. High ee values have been obtained for a number of cyclic and acyclic cis-olefins. The epoxidation was stereospecific with no isomerization observed in the epoxidation of acyclic systems. Encouragingly high ee values have also been obtained for a number of terminal olefins. Mechanistic studies show that electronic interactions play an important role in stereodifferentiation.

Full text of DOI:10.1021/jo010838k

J . Org. Chem. 2002, 67, 2435-2446
2435
Design in g New Ch ir a l Keton e Ca ta lysts. Asym m etr ic Ep oxid a tion
of cis-Olefin s a n d Ter m in a l Olefin s
Hongqi Tian, Xuegong She, Hongwu Yu, Lianhe Shu, and Yian Shi*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
yian@lamar.colostate.edu
Received August 17, 2001
This paper describes a new class of chiral oxazolidinone ketone catalyst for asymmetric epoxidation.
High ee values have been obtained for a number of cyclic and acyclic cis-olefins. The epoxidation
was stereospecific with no isomerization observed in the epoxidation of acyclic systems. Encourag-
ingly high ee values have also been obtained for a number of terminal olefins. Mechanistic studies
show that electronic interactions play an important role in stereodifferentiation.
Asymmetric epoxidation of olefins presents a powerful
strategy for the synthesis of enantiomerically enriched
epoxides.1-3 Great success has been achieved in the
epoxidation of allylic alcohols.1 For asymmetric epoxida-
tion of unfunctionalized olefins, metal catalysts such as
chiral salen and porphyrin complexes provide very high
enantioselectivities, particularly for cis-olefins, conju-
gated trisubstituted olefins, and certain terminal ole-
fins.2,4 Dioxiranes generated in situ from chiral ketones
have been shown to be highly enantioselective for the
asymmetric epoxidation of trans-olefins and trisubsti-
tuted olefins.5-7 However, it has been extremely chal-
lenging for chiral dioxiranes to epoxidize cis-olefins and
terminal olefins with high enantioselectivity. Recently,
we reported a class of promising chiral oxazolidinone
ketones that provided high ee values for the epoxidation
of cis-olefins and terminal olefins.8 Herein we wish to
report our detailed studies on this subject.
For example, epoxidation of cis-â-methylstyrene and
styrene using ketone 1 gave only 39% and 24% ee,
(6) For leading references on asymmetric epoxidation mediated by
chiral ketones, see: (a) Curci, R.; Fiorentino, M.; Serio, M. R. J . Chem.
Soc., Chem. Commun. 1984, 155. (b) Curci, R.; D’Accolti, L.; Fiorentino,
M.; Rosa, A. Tetrahedron Lett. 1995, 36, 5831. (c) Denmark, S. E.;
Forbes, D. C.; Hays, D. S.; DePue, J . S.; Wilde, R. G. J . Org. Chem.
1995, 60, 1391. (d) Brown, D. S.; Marples, B. A.; Smith, P.; Walton, L
Tetrahedron 1995, 51, 3587. (e) Yang, D.; Yip, Y. C.; Tang, M. W.;
Wong, M. K.; Zheng, J . H.; Cheung, K. K. J . Am. Chem. Soc. 1996,
118, 491. (f) Yang, D.; Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.; Tang, M.-
W. J . Am. Chem. Soc. 1996, 118, 11311. (g) Song, C. E.; Kim, Y. H.;
Lee, K. C.; Lee, S. G.; J in, B. W. Tetrahedron: Asymmetry 1997, 8,
2921. (h) Adam, W.; Zhao, C.-G. Tetrahedron: Asymmetry 1997, 8,
3995. (i) Denmark, S. E.; Wu, Z.; Crudden, C. M.; Matsuhashi, H. J .
Org. Chem. 1997, 62, 8288. (j) Wang, Z.-X.; Shi, Y. J . Org. Chem. 1997,
62, 8622. (k) Adam, W.; Fell, R. T.; Saha-Moller, C. R.; Zhao, C.-G.
Tetrahedron: Asymmetry 1998, 9, 397. (l) Armstrong, A.; Hayter, B.
R. Chem. Commun. 1998, 621. (m) Yang, D.; Wong, M.-K.; Yip, Y.-C.;
Wang, X.-C.; Tang, M.-W.; Zheng, J .-H.; Cheung, K.-K. J . Am. Chem.
Soc. 1998, 120, 5943. (n) Yang, D.; Yip, Y.-C.; Chen, J .; Cheung, K.-K.
J . Am. Chem. Soc. 1998, 120, 7659. (o) Adam, W.; Saha-Moller, C. R.;
Zhao, C.-G. Tetrahedron: Asymmetry 1999, 10, 2749. (p) Wang, Z.-X.;
Miller, S. M.; Anderson, O. P.; Shi, Y. J . Org. Chem. 1999, 64, 6443.
(q) Carnell, A. J .; J ohnstone, R. A. W.; Parsy, C. C.; Sanderson, W. R.
Tetrahedron Lett. 1999, 40, 8029. (r) Armstrong, A.; Hayter, B. R.
Tetrahedron 1999, 55, 11119. (s) Armstrong, A.; Hayter, B. R.; Moss,
W. O.; Reeves, J . R.; Wailes, J . S. Tetrahedron: Asymmetry 2000, 11,
2057. (t) Solladie-Cavallo, A.; Bouerat, L. Org. Lett. 2000, 2, 3531. (u)
Yang, D.; J iao, G.-S.; Yip, Y.-C.; Lai, T.-H.; Wong, M.-K. J . Org. Chem.
2001, 66, 4619.
(7) For examples of asymmetric epoxidation mediated by fructose-
derived ketones, see: (a) Tu, Y.; Wang, Z.-X.; Shi, Y. J . Am. Chem.
Soc. 1996, 118, 9806. (b) Wang, Z.-X.; Tu, Y.; Frohn, M.; Shi, Y. J .
Org. Chem. 1997, 62, 2328. (c) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang,
J .-R.; Shi, Y. J . Am. Chem. Soc. 1997, 119, 11224. (d) Frohn, M.;
Dalkiewicz, M.; Tu, Y.; Wang, Z.-X.; Shi, Y. J . Org. Chem. 1998, 63,
2948. (e) Wang, Z.-X.; Shi, Y. J . Org. Chem. 1998, 63, 3099. (f) Zhu,
Y.; Tu, Y.; Yu, H.; Shi, Y. Tetrahedron Lett. 1998, 39, 7819. (g) Tu, Y.;
Wang, Z.-X.; Frohn, M.; He, M.; Yu, H.; Tang, Y.; Shi, Y. J . Org. Chem.
1998, 63, 8475. (h) Wang, Z.-X.; Cao, G.-A.; Shi, Y. J . Org. Chem. 1999,
64, 7646. (i) Warren, J . D.; Shi, Y. J . Org. Chem. 1999, 64, 7675. (j)
Frohn, M.; Zhou, X.; Zhang, J .-R.; Tang, Y.; Shi, Y. J . Am. Chem. Soc.
1999, 121, 7718. (k) Shu, L.; Shi. Y. Tetrahedron Lett. 1999, 40, 8721.
(l) Wang, Z.-X.; Miller, S. M.; Anderson, O. P.; Shi, Y. J . Org. Chem.
2001, 66, 521. (m) Zhu, Y.; Shu, L.; Tu, Y.; Shi, Y. J . Org. Chem. 2001,
66, 1818. (n) Tian, H.; She, X.; Shi, Y. Org. Lett. 2001, 3, 715. (o) Shu,
L.; Shi, Y. Tetrahedron 2001, 57, 5213.
Ca ta lyst Design a n d Syn th esis
Earlier, we reported that the fructose-derived ketone
1 is an effective epoxidation catalyst and gives high ee
values for a variety of trans- and trisubstituted olefins
(eq 1).7 However, epoxidation of cis- and terminal olefins
using this ketone led to rather poor enantioselectivity.7c
* Corresponding author. Phone: 970-491-7424. Fax: 970-491-1801
(1) For recent reviews on highly enantioselective epoxidation of
allylic alcohols, see: (a) J ohnson, R. A.; Sharpless, K. B. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993; Chapter
4.1. (b) Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1.
(2) For recent reviews on metal-catalyzed highly enantioselective
epoxidation of unfunctionalized olefins, see: (a) J acobsen, E. N. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993;
Chapter 4.2. (b) Collman, J . P.; Zhang, X.; Lee, V. J .; Uffelman, E. S.;
Brauman, J . I. Science 1993, 261, 1404. (c) Katsuki, T. Coord. Chem.
Rev. 1995, 140, 189. (d) Mukaiyama T. Aldrichimica Acta 1996, 29,
59.
(3) For a recent review on asymmetric epoxidation of electron-
deficient olefins, see: Porter, M. J .; Skidmore, J . Chem. Commun. 2000,
1215.
(4) For leading references on asymmetric epoxidation of terminal
olefins, see: Collman, J . P.; Wang, Z.; Straumanis, A.; Quelquejeu,
M.; Rose, E. J . Am. Chem. Soc. 1999, 121, 460.
(5) For general leading references on dioxiranes, see: (a) Adam, W.;
Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205. (b) Murray,
R. W. Chem. Rev. 1989, 89, 1187. (c) Curci, R.; Dinoi, A.; Rubino, M.
F. Pure Appl. Chem. 1995, 67, 811. (d) Clennan, E. L. Trends Org.
Chem. 1995, 5, 231. (e) Adam, W.; Smerz, A. K. Bull. Soc. Chim. Belg.
1996, 105, 581. (f) Denmark, S. E.; Wu, Z. Synlett 1999, 847. (g) Frohn,
M.; Shi, Y. Synthesis 2000, 1979.
(8) For a preliminary report of a portion of this work, see: (a) Tian,
H.; She, X.; Shu, L.; Yu, H.; Shi, Y. J . Am. Chem. Soc. 2000, 122, 11551.
(b) Tian, H.; She, X.; Xu, J .; Shi, Y. Org. Lett. 2001, 3, 1929.
10.1021/jo010838k CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/20/2002

2436 J . Org. Chem., Vol. 67, No. 8, 2002
Tian et al.
Sch em e 1
Sch em e 4
Sch em e 2
ketalization and hydrogenation. Compound 3 was then
converted to ketone 2a by a two-step formation of the
oxazolidinone, followed by PCC oxidation, as shown. The
N-substituted ketones 2b-d were prepared as shown in
Scheme 4. Alcohol 4 was protected as TBS ether 5, and
the substituents were then introduced onto the nitrogen
by alkylation or acylation. The resulting TBS ether 6 was
then converted into ketones 2b-d by desilylation and
oxidation.
Sch em e 3
Asym m etr ic Ep oxid a tion Stu d ies
The catalytic properties of ketones 2a -d were then
investigated. Although our initial studies showed that
these ketones did not give an enantioselectivity as high
as 1 for trans-olefins, the ee’s for cis-olefins were higher.
When the epoxidation of cis-â-methylstyrene was carried
out in DMM (dimethoxymethane)-CH3CN (2/1), ketones
2a -d gave the epoxide in 47%, 75%, 59%, and 84% ee,
respectively. The ee could be further enhanced by using
different solvents and running the epoxidation at lower
temperature. For example, when the epoxidation was
carried out with 15 mol % ketone 2d in DME-DMM (3/
1), at -10 °C, (1R,2S)-cis-â-methylstyrene oxide was
obtained in 87% yield with 91% ee (Table 1, entry 1).
Furthermore, like other dioxirane-mediated epoxidations,
the epoxidation of cis-â-methylstyrene was found to be
stereospecific, with no trans-â-methylstyrene oxide formed
during the reaction, as judged by 1H NMR and GC assays
of the crude reaction mixture.
Encouraged by this result, we investigated the epoxi-
dation for a variety of cis-olefins to explore the generality
of ketone 2d . The enantiomeric excesses were generally
high for a variety of acyclic and cyclic cis-olefins conju-
gated with aromatics (Table 1, entries 1-11). Further
studies showed that the enantioselectivity of the epoxi-
dation did not significantly vary with substitution on the
phenyl group of the olefin (Table 1, entries 2-6). The
epoxidation of cis-1-cyclohexyl-1-propene with ketone 2d
resulted in the formation of the (2R,3S)-2-cyclohexyl-3-
methyloxirane in 67% ee, indicating that a conjugated
aromatic group is beneficial for enantioselectivity. The
epoxidation of acyclic cis-enynes was also found to be both
highly enantioselective and stereospecific, providing cis-
epoxides with high ee values (Table 1, entries 12-13).10
respectively. On the basis of our earlier transition state
analysis,7c spiro A and B are likely to be the two major
competing transition states (Scheme 1). The low ee
obtained indicates that the ketone catalyst does not
provide the necessary structural environment to dif-
ferentiate between the phenyl and methyl (or hydrogen)
groups of the olefin (Scheme 1). Since the spiro ketal of
ketone 1 is in the proximity of one of the substituents on
reacting olefins in the transition state, it was envisioned
that replacement of the spiro ketal by other moieties
would enhance selectivity by creating an environment in
which the substituents on the olefin could be sufficiently
differentiated sterically and/or electronically (Scheme 2).
In line with this notion, ketone 2, a nitrogen analogue of
1, was among the ketones investigated for epoxidation.
Ketone 2 replaces the spiro ketal of 1 with an oxazo-
lidinone. Ketones 2a -d were prepared for our initial
studies, and their syntheses are outlined in Schemes 3
and 4. Briefly, the Amadori rearrangement was carried
out by refluxing D-glucose in ethanol with dibenzylamine
in the presence of acetic acid (Scheme 3).9 The resulting
rearranged product was converted into aminodiol 3 by
(10) For leading references on asymmetric epoxidations of enynes
using (salen)Mn(III), see: (a) Lee, N. H.; J acobsen, E. N. Tetrahedron
Lett. 1991, 32, 6533. (b) Brandes, B. D.; J acobsen, E. N. J . Org. Chem.
1994, 59, 4378. (c) Hamada, T.; Irie, R.; Katsuki, T. Synlett, 1994, 479.
(d) Sasaki, H.; Irie, R.; Hamada, T.; Suzuki, K.; Katsuki, T. Tetrahedron
1994, 50, 11827. (e) Hamada, T.; Daikai, K.; Irie, R.; Katsuki, T. Synlett
1995, 407.
(9) Hodge, J . E.; Fisher, B. E. Methods Carbohydr. Chem. 1963, 2,
99.

Designing New Chiral Ketone Catalysts
J . Org. Chem., Vol. 67, No. 8, 2002 2437
Ta ble 1. Asym m etr ic Ep oxid a tion of cis-Olefin s by
Ta ble 2. Asym m etr ic Ep oxid a tion of Ter m in a l Olefin s,
Keton e 2d a
tr a n s-Olefin s, a n d Tr isu bstitu ted Olefin s by Keton e 2d a
a
All reactions were carried out with olefin (0.5 mmol), ketone
(0.075-0.15 mmol), Oxone (0.89 mmol), and K2CO3 (2.01 mmol)
in DME/DMM (3:1, v/v) (7.5 mL) and buffer (0.2 M K2CO3-AcOH,
pH 8.0) (5 mL) at -10 or 0 °C. The reactions were stopped after
b
3.5 h. The epoxides were purified by flash chromatography and
gave satisfactory spectroscopic characterization. c With 0.075 mmol
d
ketone at -10 °C. With 0.15 mmol ketone at -10 °C. e With 0.15
mmol ketone at 0 °C. f Enantioselectivity was determined by chiral
a
g
All reactions were carried out with olefin (0.5 mmol), ketone
GC (Chiraldex G-TA). Enantioselectivity was determined by
h
(0.075-0.15 mmol), Oxone (0.89 mmol), and K2CO3 (2.01 mmol)
in DME/DMM (3:1, v/v) (7.5 mL) and buffer (0.2 M K2CO3-AcOH,
pH 8.0) (5 mL) at -10 or 0 °C. The reactions were stopped after
chiral HPLC (Chiralcel OD). The absolute configurations were
determined by comparing the measured optical rotations with the
reported ones.
b
3.5 h. The epoxides were purified by flash chromatography and
gave satisfactory spectroscopic characterization. c With 0.075 mmol
Further studies showed that encouragingly high ee’s
could also be obtained for styrenes. When the reaction
was carried out with 15 mol % ketone 2d at -10 °C, (R)-
styrene oxide was obtained in 92% yield with 81% ee
(Table 2, entry 1). The ee values are somewhat dependent
on substitution of the phenyl groups of the olefins (Table
2, entries 2-4), with 85% ee obtained for 4-chlorostyrene
(Table 2, entry 4). Aliphatic terminal olefins gave lower
enantioselectivity, as 71% ee was obtained when a phenyl
group of styrene was replaced with a cyclohexyl group
(Table 2, entry 5). The ee’s for 1,1-disubstituted olefins
were rather poor (Table 2, entries 6 and 7).
ketone at -10 °C. With 0.15 mmol ketone at 0 °C. e With 0.10
d
mmol ketone at -10 °C. f With 0.075 mmol ketone at 0 °C. With
g
h
0.15 mmol ketone at -10 °C. The olefin substrate contains a
mixture of cis- and trans-isomers. The yield is for the mixture of
i
cis- and trans-epoxides. Enantioselectivity was determined by
chiral GC (Chiraldex G-TA). Enantioselectivity was determined
by chiral HPLC (Chiralcel OJ ). Enantioselectivity was deter-
mined by chiral HPLC (Chiralcel OB). Enantioselectivity was
determined by chiral HPLC (Chiralpak AD). Enantioselectivity
was determined by chiral HPLC (Chiralcel OD). The absolute
configurations were determined by comparing the measured
optical rotations with the reported ones. o The epoxide was reduced
to the benzylic alcohol with LiAlH4, and the absolute configuration
was determined by comparing the measured optical rotation of
j
k
l
m
n
p
the alcohol with the reported one (ref 16). The epoxide was
Studies with trans- and trisubstituted olefins showed
that the enantioselectivity was substrate dependent
(Table 2). In general, ketone 2d is a less effective catalyst
than ketone 1 for these classes of olefins. However, in
certain cases, 2d gives a higher ee than 1. For example,
95% ee is obtained for 2,2-dimethylstyrene with 2d
(Table 2, entry 10), while only 76% ee was obtained
with 1.7c The epoxidation of 1-phenylcyclohexene and
1-phenyl-3,4-dihydronaphthalene was rather interesting.
For these two olefins, 42% and 80% ee were obtained
respectively with 2d in contrast to 98% and 95% ee with
1. Strikingly, the configuration of the epoxide obtained
with 2d was opposite to the one obtained with 1 (vide
infra).
reduced to 1-(2-naphthyl)propanol with LiAlH4, and the absolute
configuration was determined by comparing the measured optical
rotation of the alcohol with the reported one (ref 16). The epoxide
was reduced with LiAlH4 to the corresponding homopropargyl
alcohol, and the absolute configuration was determined by a
correlation of the resulting alcohol with a prepared authentic
sample by a different route (ref 10a).
q
High ee’s were obtained for 3,3-ethylenedioxycycloalkenes
as well (Table 1, entries 14-16).11
(11) Up to 40% ketone could be recovered after extracting the
aqueous layer of the reaction mixture with CH2Cl2-EtOAc and
purification by flash chromatography. The recovered ketone gave a
similar conversion and ee for the epoxidation.

2438 J . Org. Chem., Vol. 67, No. 8, 2002
Ta ble 3. Asym m etr ic Ep oxid a tion of Olefin s by Keton es 2, 16, a n d 17a
Tian et al.
a
All reactions were carried out with olefin (1 equiv), ketone (0.15 equiv), Bu4NHSO4 (0.05 equiv), Oxone (1.6 equiv), and K2CO3 (4.2
equiv) in DME/DMM (3:1, v/v) and buffer (0.2 M K2CO3-AcOH, pH 8.0) at 0 °C. The reactions were stopped after 3.5 h. Enantioselectivity
b
was determined by chiral GC (Chiraldex G-TA). The epoxide has the (R) configuration. c The epoxide has the (1R,2S) configuration
d
unless otherwise noted. The epoxide has the (R,R) configuration. e The epoxide has the (R) configuration. f 0.3 equiv of ketone used.
g
h
1.0 equiv of ketone used. The epoxide has the (1S,2R) configuration.
Sch em e 5
F igu r e 1. X-ray structure of ketones 2a (left) and 2b (right)
(ORTEP view).
The substituents on the nitrogen of the ketone dis-
played some effect on enantioselectivity of the epoxida-
tion. To further study such an effect, ketones with a
variety of substituents on nitrogen were synthesized and
investigated for the epoxidation (Scheme 5). Ketones
2e-m were prepared as described in Scheme 4. Their
catalytic properties were tested with five substrates
representing terminal, cis-, trans-, and trisubstituted
olefins. As shown in Table 3, the substituents on the
nitrogen had a significant effect on the enantioselectivity
of the epoxidation. Overall, ketones 2d , 2e, 2g, 2i, and
2j were found to be the most effective catalysts. One
noticeable feature of these ketones is that in the case of
1-phenylcyclohexene not only the ee but also the config-
uration of the epoxide significantly varied with the
N-substituents.
F igu r e 2. X-ray structure of ketones 2d (left) and 2e (right)
(ORTEP view).
substituents on the nitrogen are away from the reacting
center (dioxirane) (at least in the solid state). Their
influence on the enantioselectivity of the epoxidation
could be through a conformational or electronic effect
rather than a steric effect. The structures of 2d and 2e
Among these ketones, we were able to obtain the
crystal structures for ketones 2a , 2b, 2d , and 2e (Figures
1 and 2). From these structures, it appears that the

Designing New Chiral Ketone Catalysts
J . Org. Chem., Vol. 67, No. 8, 2002 2439
Sch em e 6
Sch em e 9
The high ee values obtained with ketone 2 for cis-
olefins is rather intriguing. Spiro G and H are the two
plausible competing transition states (Scheme 9). The
determination of the absolute configurations of some
selected epoxides (Table 1) revealed that R groups with
π system (Rπ), regardless of its size, preferred to be
proximal of the spiro oxazolidinone of the ketone. Thus,
spiro G is favored over H. This observation is clearly
difficult to explain solely based on steric interaction. It
seems that there exists some electronic interaction
between Rπ and the ketone catalyst in the transition
state. As a result, groups with π systems (Rπ) could be
significantly differentiated from those without π electrons
(R), leading to high enantioselectivity for the reaction.14
The interaction could involve attractive interaction be-
tween Rπ and the oxazolidinone moiety of the ketone
(interaction a ) and/or some repulsive interaction between
Rπ and the fused ketal moiety of the ketone (interaction
b).
Sch em e 7
Sch em e 8
Although repulsive interaction b is difficult to assess
at the moment, the epoxidation data provides a clear
indication of the involvement of attractive interaction a .
For example, when the epoxidation of 1-phenylcyclohex-
ene was carried out with ketone 1, the epoxide was
obtained in 98% ee in (R,R) configuration, showing that
spiro I is greatly favored over planar J (Scheme 10).7c
However, as shown in Table 3, when the epoxidation was
carried out with ketone 2, the reaction outcome varies
dramatically with the substituents on the nitrogen of the
ketone. In some cases, the (S,S) isomer is obtained,
suggesting that planar L eventually becomes a major
transition state. The flip between spiro K and planar L
is consistent with the attractive interaction between the
Ph group and the oxazolidinone (interaction a ). Such
interaction can be significantly affected by the N-sub-
stituent on the ketone. The X-ray structures of ketones
2d and 2e show that the N-R groups are distant from
the reacting center (dioxirane); thus, they have little
steric effect on the epoxidation. The epoxidation data
also showed that the carbonyl groups of N-Boc and
N-COOPh are coplanar with the oxazolidinone, which
could be important for enantioselectivity. To test the
effect of the fused ketal of the ketone on epoxidation,
ketones 2n and 2o were prepared as described in
Schemes 6 and 7. The comparison studies between 2d ,
2n , and 2o showed that the dimethyl ketal was better
than the diethyl and methylene ketals (Table 3, entries
4, 14, and 15).
Discu ssion
(12) For leading references on the transition states of the dioxirane-
mediated epoxidation, see: (a) Baumstark, A. L.; McCloskey, C. J .
Tetrahedron Lett. 1987, 28, 3311. (b) Baumstark, A. L.; Vasquez, P.
C. J . Org. Chem. 1988, 53, 3437. (c) Bach, R. D.; Andres, J . L.;
Owensby, A. L.; Schlegel, H. B.; McDouall, J . J . W. J . Am. Chem. Soc.
1992, 114, 7207. (d) refs 6f and 6m. (e) Houk, K. N.; Liu, J .; DeMello,
N. C.; Condroski, K. R. J . Am. Chem. Soc. 1997, 119, 10147. (f) J enson,
C.; Liu, J .; Houk, K. N.; J orgensen, W. L. J . Am. Chem. Soc. 1997,
119, 12982. (g) Armstrong, A.; Washington, I.; Houk, K. N. J . Am.
Chem. Soc. 2000, 122, 6297.
(13) Planar transition state F could become the major reaction mode
if a large R1 group is chosen to strongly discourage spiro E and a small
R3 group is chosen to strongly encourage planar F . One such an
example has been observed. The epoxidation of (Z)-3,3-dimethyl-1-
phenyl-2-trimethylsiloxy-1-butene with 1 led to the formation of (S)-
3,3-dimethyl-1-hydroxy-1-phenyl-2-butanone in 43% ee (see ref 6k). The
S configuration of the product suggested that a planar transition state
is favored.
Understanding the reaction mode of the dioxirane-
mediated epoxidation is critical for developing a useful
model to predict the stereochemical outcome of the
reaction and for designing effective ketone catalysts. The
epoxidation of trans- and trisubstituted olefins with
catalyst 1 has been shown to proceed mainly via spiro
transition state E (Scheme 8).7a,7c,12 The main competing
transition state is believed to be planar transition state
F (Scheme 8).7c The nature of the substituents on the
olefins have noticeable effects on the competition between
the two transition states, consequently affecting the
enantioselectivities of the epoxidation.7c In general, higher
ee can be obtained by decreasing the size of R1 (favoring
spiro E) and increasing the size of R3 (disfavoring planar
F ).13
(14) For an observation of electronic interaction in ketone-catalyzed
asymmetric epoxidation, see ref 6n.

2440 J . Org. Chem., Vol. 67, No. 8, 2002
Tian et al.
Sch em e 10
Sch em e 13
Sch em e 11
Sch em e 14
Sch em e 15
Sch em e 12
R group of the olefin and the oxazolidinone in spiro U
(Scheme 15). The S configuration of the resultant epoxide
suggests that spiro U is no longer the major transition
state. Spiro V and planar W are among the possible
competing modes, giving the S isomer. Planar W might
become a major transition state since in this transition
state the Ph group could still have the attractive interac-
tion with the spiro oxazolidinone of the ketone. If this is
true, one would expect that a larger R group on the olefin
would further destabilize spiro U, leading to a higher ee
(Scheme 15). A 58% ee obtained with R-isopropylstyrene
provides support to this hypothesis (Table 2, entry 7). A
better understanding of the transition states for this type
of olefins awaits further study.
obtained with 2g, which contains a small CH3 group
(Table 3, entry 7), further supports the hypothesis.
To further study the interaction between Rπ and the
oxazolidinone, ketone 16, lacking the fused ketal moiety,
was investigated and its synthesis is outlined in Scheme
11. As a comparison, ketone 177g was also tested for the
epoxidation (Scheme 12) (Table 3, entries 16 and 17). The
epoxidation results further support that there is a strong
interaction between Rπ and the oxazolidinone. For ex-
ample, in the case of 2,2-dimethylstyrene, 78% ee was
obtained with ketone 16 in stark contrast to 3% ee with
17. This result suggests that transition state M is greatly
favorable compared to O due to the attractive interaction
between the Ph group with the oxazolidinone (Scheme
13). At this moment, the exact nature of the interaction
between Rπ and the oxazolidinone is not clear and awaits
further study.
On the basis of the above transition state model, a
similar analysis could also be applied to terminal olefins.
Transition state spiro Q appears to be major transition
state, but planar transition state S could also be operat-
ing (Scheme 14). On the other hand, the corresponding
planar T would be less feasible for cis-olefins due to the
steric effect, which could explain why higher ee’s were
obtained for cis-olefins than terminal olefins with ketone
2.
In summary, we report a new class of chiral oxazoli-
dinone ketone catalysts for asymmetric epoxidation. High
ee values have been obtained for a number of cyclic and
acyclic cis-olefins. The epoxidation was stereospecific with
no isomerization observed in the epoxidation of acyclic
systems. Encouragingly high ee’s have also been obtained
for a number of terminal olefins. Although the exact
factors for stereodifferentiation need further investiga-
tion, mechanistic studies suggest that electronic interac-
tions play an important role in the transition state. The
results described show that chiral dioxiranes can also
epoxidize cis-olefins and terminal olefins in addition to
trans-olefins and trisubstituted olefins with a high degree
of enantioselectivity. The transition state information
gained from the current study provides us useful insight
to design new ketone catalysts. Future efforts will be
devoted to the optimization of the ketone structure to
enhance both enantioselectivity and reactivity.
The epoxidation of 1,1-disubstituted olefins with ketone
2 was rather low. For example, only 30% ee was obtained
for R-methylstyrene (Table 2, entry 6). The low ee could
be attributed to the destabilizing interaction between the

Designing New Chiral Ketone Catalysts
J . Org. Chem., Vol. 67, No. 8, 2002 2441
filtered through Celite and washed with Et2O. The filtrate was
concentrated and purified by flash chromatography to give the
ketone 2a as a white solid (0.997 g, 94%): mp 144.5-145.5
°C; [R]20D ) -118.0 (c 0.27, CHCl3); IR (KBr) 3378, 3319, 1759,
Exp er im en ta l Section
Gen er a l Meth od s. Oxone was purchased from Aldrich (it
has been found that the oxidation activity of the purchased
Oxone occasionally varies with different batches). All glass-
ware used for the epoxidation was carefully washed to be free
of any trace metals that catalyze the decomposition of Oxone.
Elemental analyses were performed by M-H-W Laboratories,
Phoenix, AZ. X-ray crystallographic analyses of ketones 2a ,
2b, 2d , and 2e were performed at the X-ray Crystallographic
Laboratory of Colorado State University.
P r ep a r a tion of Am in od iol 3. To a suspension of D-glucose
(36.0 g, 200.0 mmol) and Bn2NH (39.5 g, 200.0 mmol) in
absolute EtOH (200 mL) was added AcOH (12.0 g, 200.0
mmol). Upon refluxing for 3 h, the reaction mixture was cooled
and filtered with suction. The resulting filter cake was washed
with EtOH to colorless and dried in a desiccator over calcium
chloride to give 1-dibenzylamino-1-deoxy-D-fructose as a white
solid (57.0 g, 79%).9
1
1731 cm-1; H NMR (CDCl3) δ 6.51 (s, 1H), 4.84 (d, J ) 5.4
Hz, 1H), 4.66-4.52 (m, 2H), 4.32 (d, J ) 10.7 Hz, 1H), 4.23 (d,
J ) 13.5 Hz, 1H), 3.38 (d, J ) 10.7 Hz, 1H), 1.46 (s, 3H), 1.42
(s, 3H); 13C NMR (CDCl3) δ 195.2, 156.0, 111.0, 102.7, 77.5,
75.5, 61.0, 45.3, 27.2, 26.1; HRMS calcd for C10H14NO6 (M+
+
1) 244.0821, found 244.0824. Anal. Calcd for C10H13NO6‚
0.7H2O: C, 46.95; H, 5.67; N, 5.48. Found: C, 47.16; H, 5.86;
N, 5.43.
P r ep a r a tion of TBS Eth er 5. To a solution of alcohol 4
(10.4 g, 42.45 mmol) in CH3CN (300 mL) were added imidazole
(4.33 g, 63.67 mmol) and TBSCl (6.72 g, 44.57 mmol). Upon
stirring at room temperature for 24 h, the reaction mixture
was quenched with water, extracted with EtOAc, dried (Na2-
SO4), filtered, concentrated, and purified by flash chromatog-
raphy to give TBS ether 5 as a white solid (10.66 g, 70%): mp
153-155 °C; [R]20 ) -92.92 (c 0.12, CHCl3); IR (KBr) 3286,
To a suspension of 1-dibenzylamino-1-deoxy-D-fructose (2.5
g, 6.96 mmol) and trimethyl orthoformate (2.0 mL, 18.3 mmol)
in acetone (80 mL) at 0 °C was added concentrated HCl (0.6
mL). Upon stirring at 0 °C for 2 h, the reaction mixture was
neutralized with NH4OH, filtered, concentrated, and purified
by flash chromatography to give the dibenzylaminodiol as a
syrup (2.01 g, 72%): [R]20D ) -87.9 (c 0.655, CHCl3); IR (KBr)
3446 cm-1; 1H NMR δ 7.42-7.24 (m, 10H), 4.22-3.91 (m, 6H),
3.52-3.48 (m, 2H), 3.30 (d, J ) 7.5 Hz, 1H), 3.08 (d, J ) 13.6
Hz, 1H), 2.71 (d, J ) 13.6 Hz, 1H), 1.53 (s, 3H), 1.36 (s, 3H);
13C NMR δ 138.2, 129.2, 128.4, 127.3, 109.0, 96.4, 77.5, 73.7,
72.1, 59.1, 58.8, 56.6, 28.2, 26.3. Anal. Calcd for C23H29NO5:
C, 69.15; H, 7.32; N, 3.51. Found: C, 69.38; H, 7.28; N, 3.49.
A solution of dibenzylaminodiol (15.0 g, 37.41 mmol) in
ethanol (250 mL) was purged with N2, and 10% Pd/C (2.5 g)
was added. Upon stirring under H2 at room temperature
overnight, the reaction mixture was filtered through a short
Celite column and concentrated. The resulting residue was
recrystallized from CH2Cl2-hexane in a freezer to give amino-
D
1770 cm-1; H NMR δ 5.87 (s, 1H), 4.31-4.18 (m, 3H), 4.08
1
(d, J ) 12.9 Hz, 1H), 3.68 (d, J ) 9.3 Hz, 1H), 3.65 (d, J ) 6.6
Hz, 1H), 3.39 (dd, J ) 9.3, 1.0 Hz, 1H), 1.53 (s, 3H), 1.36 (s,
3H), 0.87 (s, 9H), 0.17 (s, 3H), 0.10 (s, 3H); 13C NMR δ 157.8,
109.3, 104.9, 77.0, 73.5, 73.3, 61.9, 48.9, 28.4, 26.4, 25.9, 18.2,
-3.7, -5.2. Anal. Calcd for C16H29NO6Si: C, 53.46; H, 8.13;
N, 3.90. Found: C, 53.58; H, 7.89; N, 4.03.
P r ep a r a tion of Keton e 2b. To a solution of TBS ether 5
(2.0 g, 5.57 mmol) in THF (20 mL) was added NaH (0.267 g,
6.685 mmol) at 0 °C under N2. Upon stirring for 0.5 h, MeI
(1.58 g, 11.14 mmol) was added. After being stirred for 12 h,
the reaction mixture was quenched with water, extracted with
EtOAc, dried (Na2SO4), filtered, concentrated, and purified by
chromatography to give 6b as a white solid (2.04 g, 98%): mp
107-108 °C; [R]20 ) -62.5 (c 0.20, CHCl3); IR (KBr) 1773
D
cm-1; 1H NMR δ 4.37-4.18 (m, 3H), 4.09 (d, J ) 13.2 Hz, 1H),
3.65 (d, J ) 6.3 Hz, 1H), 3.61 (d, J ) 9.3 Hz, 1H), 3.34 (d, J )
9.3 Hz, 1H), 2.87 (s, 3H), 1.54 (s, 3H), 1.37 (s, 3H), 0.86 (s,
9H), 0.18 (s, 3H), 0.10 (s, 3H); 13C NMR δ 156.4, 109.4, 101.5,
77.1, 73.6, 73.4, 61.9, 54.8, 30.6, 28.5, 26.5, 25.8, 18.2, -3.7,
-5.2. Anal. Calcd for C17H31NO6Si: C, 54.66; H, 8.37; N, 3.75.
Found: C, 54.72; H, 8.26; N, 3.70.
diol 3 as a white crystal (7.25 g, 88%): mp 100-103 °C; [R]20
D
) -158.1 (c 0.21, CHCl3); IR (KBr) 3470, 3361, 1216 cm-1; 1H
NMR δ 4.24-4.12 (m, 3H), 3.94 (d, J ) 13.5 Hz, 1H), 3.47 (d,
J ) 6.9 Hz, 1H), 2.95 (d, J ) 11.7 Hz, 1H), 2.89 (d, J ) 11.7
Hz, 1H), 1.55 (s, 3H), 1.38 (s, 3H); 13C NMR δ 109.2, 96.2, 77.7,
73.9, 72.5, 59.4, 46.3, 28.4, 26.4. Anal. Calcd for C9H17NO5:
C, 49.31; H, 7.82; N, 6.39. Found: C, 49.32; H, 7.60; N, 6.20.
P r ep a r a tion of Alcoh ol 4. To a solution of 3 (17.15 g, 78.31
mmol) and pyridine (100 mL) in CH2Cl2 (350 mL) was added
dropwise 4-methoxyphenyl chloroformate (16.07 g, 86.14 mmol)
at 0 °C. Upon stirring at 0 °C for 5 h, the reaction mixture
was quenched with water, extracted with EtOAc, dried (Na2-
SO4), filtered, concentrated, and purified by flash chromatog-
raphy to give the carbamate as a colorless oil (24.71 g, 86%):
To a solution of TBS ether 6b (2.04 g, 5.47 mmol) in THF
(20 mL) was added TBAF (1.0 M in THF) (5.5 mL, 5.5 mmol).
Upon stirring at room temperature to the completion as judged
by TLC, the reaction mixture was quenched with water,
extracted with EtOAc, dried (Na2SO4), filtered, concentrated,
and purified by flash chromatography to give the alcohol as a
white solid (1.42 g, 99%): mp 144-146 °C; [R]20 ) -158.8 (c
D
0.08, CHCl3); IR (KBr) 3422, 1747 cm-1; 1H NMR δ 4.31-4.23
(m, 3H), 4.10 (d, J ) 12.9 Hz, 1H), 3.82 (d, J ) 9.6 Hz, 1H),
3.71-3.65 (m, 1H), 3.36 (d, J ) 9.6 Hz, 1H), 2.99-2.93 (m,
1H), 2.90 (s, 3H), 1.55 (s, 3H), 1.39 (s, 3H); 13C NMR δ 156.3,
110.0, 101.4, 76.7, 73.4, 71.8, 61.8, 54.6, 30.8, 28.3, 26.2. Anal.
Calcd for C11H17NO6: C, 50.96; H, 6.61; N, 5.40. Found: C,
50.77; H, 6.40; N, 5.30.
[R]20 ) -93.71 (c 0.53, CHCl3); IR (KBr) 3356, 1719, 1205
D
cm-1; 1H NMR δ 7.02 (m, 2H), 6.87 (m, 2H), 5.65 (dd, J ) 7.2,
6.0 Hz, 1H,), 4.23-4.16 (m, 3H), 3.99 (d, J ) 12.9 Hz, 1H),
3.79 (s, 3H), 3.62 (d, J ) 6.0 Hz, 1H), 3.56 (dd, J ) 14.7, 7.2
Hz, 1H), 3.40 (dd, J ) 14.7, 6.0 Hz, 1H), 1.55 (s, 3H), 1.38 (s,
3H); 13C NMR δ 157.1, 144.2, 122.4, 114.4, 109.2, 96.7, 76.2,
73.3, 70.9, 60.0, 55.7, 47.3, 28.2, 26.1.
To a solution of the above alcohol (0.145 g, 0.56 mmol) in
CH2Cl2 (5 mL) were added PDC (0.32 g, 0.84 mmol), 3 Å
molecular sieves (0.5 g), and AcOH (1 drop). Upon stirring at
room temperature for 6 h, EtOAc was added. The resulting
mixture was passed through a short silica gel plug, concen-
trated, and purified by flash chromatography to give ketone
To a solution of the carbamate (10.4 g, 28.01 mmol) in CH3-
CN (125 mL) was added (CH3)3COK (0.38 g, 3.39 mmol). Upon
stirring at room temperature for 0.5 h, the reaction mixture
was concentrated and purified by flash chromatography to give
2b (0.144 g, 99%): [R]20 ) -50.7 (c 0.22, CHCl3); IR (KBr)
D
alcohol 4 as a white solid (6.15 g, 90%): mp 171-173 °C; [R]20
3402, 1749 cm-1; H NMR δ 4.79 (d, J ) 5.7 Hz, 1H), 4.60-
1
D
) -146.25 (c 0.12, CHCl3); IR (KBr) 3346, 1760, 1077 cm-1
;
4.50 (m, 2H), 4.23 (d, J ) 10.2 Hz, 1H), 4.18 (d, J ) 13.5 Hz,
1H), 3.27 (d, J ) 10.5 Hz, 1H), 2.91 (s, 3H), 1.42 (s, 3H), 1.38
(s, 3H); 13C NMR δ 195.2, 154.2, 111.0, 96.6, 77.5, 75.5, 60.9,
50.9, 30.8, 27.2, 26.1; HRMS calcd for C11H16NO6 (M+ + 1)
258.0978, found 258.0979.
1H NMR (CD3OD) δ 4.37-4.34 (m, 1H), 4.27-4.21 (m, 2H),
4.10 (d, J ) 13.8 Hz, 1H), 3.83 (d, J ) 9.9 Hz, 1H), 3.64 (d, J
) 7.8 Hz, 1H), 3.36 (d, J ) 9.9 Hz, 1H), 1.53 (s, 3H), 1.40 (s,
3H); 13C NMR (CD3OD) δ 160.7, 111.2, 107.1, 78.6, 75.5, 73.0,
63.3, 50.1, 29.3, 27.3. Anal. Calcd for C10H15NO6: C, 48.98; H,
6.17; N, 5.71. Found: C, 49.12; H, 6.15; N, 5.67.
P r ep a r a tion of Keton e 2c. TBS ether 6c was prepared
from 5 (2.0 g, 5.57 mmol) in a way similar to 6b: white solid
P r ep a r a tion of Keton e 2a . To a mixture of alcohol 4 (1.07
g, 4.37 mmol) and powdered 3 Å MS (4.0 g) in CH2Cl2 (19 mL)
was added PCC (2.16 g, 10.02 mmol) portionwise over 15 min.
Upon stirring under N2 for 3 h, the reaction mixture was
(2.49 g, 99%); mp 101-103 °C; [R]20 ) -64.8 (c 0.16, CHCl3);
D
IR (KBr) 1769 cm-1; H NMR δ 7.46-7.23 (m, 5H), 4.49 (d, J
1
) 15.0 Hz, 1H), 4.35 (d, J ) 15.0 Hz, 1H), 4.31-4.18 (m, 3H),
4.06 (d, J ) 13.5 Hz, 1H), 3.61 (d, J ) 6.6 Hz, 1H), 3.52 (d, J

2442 J . Org. Chem., Vol. 67, No. 8, 2002
Tian et al.
) 9.3 Hz, 1H), 3.20 (d, J ) 9.3 Hz, 1H), 1.50 (s, 3H), 1.35 (s,
3H), 0.79 (s, 9H), 0.14 (s, 3H), -0.00 (s, 3H); 13C NMR δ 156.4,
135.4, 129.1, 128.4, 128.2, 109.4, 102.0, 77.2, 73.4, 73.2, 61.7,
52.1, 48.2, 28.4, 26.4, 25.9, 18.1, -3.7, -5.2. Anal. Calcd for
149.8, 149.0, 129.7, 126.6, 121.4, 109.6, 101.9, 76.8, 73.9, 73.0,
62.6, 52.1, 28.5, 26.5, 25.9, 18.2, -3.9, -5.2.
TBS ether 6e (0.63 g, 1.32 mmol) was desilylated with Et3N‚
3HF (1.06 g, 6.58 mmol) in a way similar to 6d to give the
alcohol as a white solid (0.372 g, 78%) (about 3 days): mp 185-
C
23H35NO6Si: C, 61.44; H, 7.85; N, 3.12. Found: C, 61.30; H,
7.70; N, 3.09.
186 °C; [R]20 ) -101.8 (c 1.02, CHCl3); IR (KBr) 3474, 1829,
D
TBS ether 6c (2.49 g, 5.55 mmol) was desilylated in a way
similar to 6b to give the alcohol as a white solid (1.79 g, 96%):
1744 cm-1; 1H NMR δ 7.39-7.32 (m, 2H), 7.26-7.19 (m, 1H),
7.17-7.12 (m, 2H), 4.32-4.11 (m, 5H), 3.92 (d, J ) 10.8 Hz,
1H), 3.76 (m, 1H), 2.99 (s, 1H), 1.51 (s, 3H), 1.36 (s, 3H); 13C
NMR δ 150.0, 149.0, 129.6, 126.6, 121.4, 110.1, 101.7, 76.3,
73.0, 71.4, 62.4, 51.7, 28.3, 26.3. Anal. Calcd for C17H19NO8:
C, 55.89; H, 5.24; N, 3.83. Found: C, 56.03; H, 5.40; N, 3.95.
The above alcohol (0.255 g, 0.70 mmol) was oxidized with
PDC to give ketone 2e as a white solid (0.25 g, 96%): mp 190-
mp 171-172 °C; [R]20 ) -171.4 (c 0.08, CHCl3); IR (KBr)
D
1
3402, 1751 cm-1; H NMR δ 7.40-7.23 (m, 5H), 4.46 (s, 2H),
4.33-4.21 (m, 3H), 4.10 (d, J ) 12.9 Hz, 1H), 3.67 (d, J ) 9.6
Hz, 1H), 3.68-3.61 (m, 1H), 3.25 (d, J ) 9.6 Hz, 1H), 1.50 (s,
3H), 1.37 (s, 3H). Anal. Calcd for C17H21NO6: C, 60.89; H, 6.31;
N, 4.18. Found: C, 60.90; H, 6.13; N, 4.14.
The above alcohol (0.041 g, 0.122 mmol) was oxidized with
PDC to give ketone 2c as a white solid (0.038 g, 93%): mp
191 °C; [R]20 ) -55.0 (c 0.93, CHCl3); IR (KBr) 1843, 1759,
D
1720 cm-1; 1H NMR δ 7.45-7.38 (m, 2H), 7.32-7.26 (m, 1H),
7.22-7.18 (m, 2H), 4.83 (d, J ) 5.4 Hz, 1H), 4.78 (d, J ) 11.5
Hz, 1H), 4.65 (m, 1H), 4.55 (dd, J ) 13.7, 2.1 Hz, 1H), 4.29 (d,
J ) 13.7 Hz, 1H), 3.95 (d, J ) 11.5 Hz, 1H), 1.48 (s, 3H), 1.44
(s, 3H); 13C NMR δ 194.5, 149.9, 148.4, 129.7, 126.8, 121.3,
111.5, 99.5, 77.3, 75.4, 61.7, 48.8, 27.3, 26.2. Anal. Calcd for
176-178 °C; [R]20 ) -85.7 (c 0.15, CHCl3); IR (KBr) 3394,
D
1756 cm-1; 1H NMR δ 7.36-7.13 (m, 5H), 4.74 (d, J ) 5.7 Hz,
1H), 4.57-4.30 (m, 4H), 4.12 (d, J ) 13.2 Hz, 1H), 4.05 (d, J
) 10.2 Hz, 1H), 3.10 (d, J ) 10.2 Hz, 1H), 1.34 (s, 3H), 1.33 (s,
3H); 13C NMR δ 195.1, 154.2, 134.6, 129.0, 128.3, 128.0, 111.0,
100.0, 77.5, 75.5, 61.0, 48.5, 48.2, 27.2, 26.1. Anal. Calcd for
C
17H17NO8: C, 56.20; H, 4.72; N, 3.86. Found: C, 56.12; H,
C
17H19NO6‚0.4H2O: C, 59.96; H, 5.82; N, 4.12. Found: C,
4.73; N, 3.82.
59.78; H, 5.89; N, 4.16.
P r ep a r a tion of Keton e 2f. To a solution of 5 (0.718 g, 2.0
mmol) in THF (20 mL) was added Et3N (2.02 g, 20.0 mmol),
DMAP (0.024 g, 0.2 mmol), and Me2NCOCl (0.43 g, 4.0 mmol)
at 0 °C under N2. Upon stirring to completion as judged by
TLC (about 12 h), the reaction mixture was quenched with
water, extracted with EtOAc, dried (Na2SO4), filtered, concen-
trated, and purified by flash chromatography to give compound
P r ep a r a tion of Keton e 2d . To a solution of TBS ether 5
(2.0 g, 5.57 mmol) in THF (20 mL) were added Et3N (2.82 g,
27.86 mmol), DMAP (0.136 g, 1.11 mmol), and (Boc)2O (2.43
g, 11.14 mmol). Upon stirring at room temperature for 24 h,
the reaction mixture was quenched with water, extracted with
EtOAc, dried (Na2SO4), filtered, concentrated, and purified by
flash chromatography to give TBS ether 6d as a white solid
(2.53 g, 99%): mp 114-115 °C; [R]20D ) -67.7 (c 0.118, CHCl3);
IR (KBr) 1828, 1808, 1727 cm-1; 1H NMR δ 4.27-4.08 (m, 4H),
3.94 (d, J ) 10.8 Hz, 1H), 3.68 (d, J ) 10.8 Hz, 1H), 3.65 (d,
J ) 6.9 Hz, 1H), 1.52 (s, 3H), 1.50 (s, 9H), 0.84 (s, 9H), 0.17 (s,
3H), 0.11 (s, 3H); 13C NMR δ 150.3, 148.8, 109.4, 101.1, 84.0,
76.8, 73.8, 73.1, 62.3, 51.8, 28.4, 28.1, 26.4, 25.8, 18.1, -3.7,
-5.3. Anal. Calcd for C23H37NO8Si: C, 54.88; H, 8.11; N, 3.05.
Found: C, 54.77; H, 7.98; N, 3.05.
To a solution of TBS ether 6d (6.43 g, 14.0 mmol) in THF
(100 mL) was added Et3N·3HF (22.6 g, 140.0 mmol). Upon
stirring at room temperature to completion as judged by TLC
(about 4 days), the reaction mixture was quenched with water,
extracted with EtOAc, dried (Na2SO4), filtered, concentrated,
and purified by flash chromatography to give the alcohol as a
white solid (4.47 g, 93%): mp 120.0-121.5 °C; [R]20D ) -113.9
(c 0.33, CHCl3); IR (KBr) 3481, 1812, 1733, 1718, 1222, 1162
cm-1; 1H NMR δ 4.26-4.23 (m, 3H), 4.13 (d, J ) 11.2 Hz, 1H),
4.12 (d, J ) 12.8 Hz, 1H), 3.75 (d, J ) 11.2 Hz, 1H), 3.76-
3.70 (m, 1H), 2.74 (d, J ) 6.8 Hz, 1H, OH), 1.53 (s, 3H), 1.52
(s, 9H), 1.37 (s, 3H); 13C NMR δ 150.5, 148.9, 109.9, 101.0,
84.3, 76.4, 73.1, 71.2, 62.0, 51.4, 28.2, 28.1, 26.2.
6f as a white solid (0.83 g, 96%): mp 129-131 °C; [R]20
)
D
-85.0 (c 0.81, CHCl3); IR (KBr) 1782, 1688 cm-1; H NMR δ
4.26-4.05 (m, 5H), 3.71-3.68 (m, 2H), 2.99 (s, 6H), 1.52 (s,
3H), 1.35 (s, 3H), 0.86 (s, 9H), 0.16 (s, 3H), 0.11 (s, 3H); 13C
NMR δ 152.8, 152.1, 109.4, 102.7, 76.8, 73.0, 72.8, 62.0, 51.7,
28.2, 26.3, 25.9, 18.2, -3.8, -5.1.
1
TBS ether 6f (0.617 g, 1.435 mmol) was desilylated with
Et3N·3HF (2.31 g, 14.35 mmol) in a way similar to 6d to give
the alcohol as a white solid (0.346 g, 76%) (about 3 days): mp
167-169 °C; [R]20 ) -102.3 (c 0.87, CHCl3); IR (KBr) 3428,
D
1
1783, 1683 cm-1; H NMR δ 4.31 (d, J ) 10.4 Hz, 1H), 4.28-
4.23 (m, 3H), 4.12 (d, J ) 13.5 Hz, 1H), 3.78 (m, 1H), 3.66 (d,
J ) 10.4 Hz, 1H), 3.20 (bs, 1H), 3.01 (s, 6H), 1.54 (s, 3H), 1.38
(s, 3H); 13C NMR δ 153.0, 152.0, 109.9, 102.6, 76.2, 73.0, 71.2,
62.2, 51.7, 28.2, 26.2.
The above alcohol (0.217 g, 0.687 mmol) was oxidized with
PDC to give ketone 2f as a white solid (0.204 g, 95%): mp
115-117 °C; [R]20 ) -72.3 (c 1.11, CHCl3); IR (KBr) 3409,
D
1789, 1760, 1688 cm-1; H NMR δ 4.80 (d, J ) 5.4 Hz, 1H),
1
4.65-3.94 (m, 4H), 3.70 (d, J ) 11.1 Hz, 1H), 3.03 (s, 6H),
1.47 (s, 3H), 1.41 (s, 3H). Anal. Calcd for C13H18N2O7‚0.4H2O:
C, 48.56; H, 5.85; N, 8.72. Found: C, 48.85; H, 5.97; N, 8.46.
P r ep a r a tion of Keton e 2g. To a solution of 5 (0.718 g, 2.0
mmol) in THF (20 mL) were added Et3N (1.0 g, 10.0 mmol),
DMAP (0.024 g, 0.2 mmol), and CH3COCl (0.236 g, 3.0 mmol)
at 0 °C under N2. Upon stirring to completion as judged by
TLC (about 12 h), the reaction mixture was quenched with
water, extracted with EtOAc, dried (Na2SO4), filtered, concen-
trated, and purified by flash chromatography to give compound
The above alcohol (1.9 g, 5.51 mmol) was oxidized with PDC
to give ketone 2d as a white solid (1.52 g, 80%): mp 139-140
°C; [R]20 ) -47.9 (c 0.83, CHCl3); IR (KBr): 3446 (hydrate),
D
1823, 1756, 1731 cm-1; H NMR δ 4.79 (d, J ) 5.6 Hz, 1H),
1
4.61 (dd, J ) 5.6, 1.8 Hz, 1H), 4.56 (d, J ) 11.6 Hz, 1H), 4.51
(dd, J ) 13.6, 1.8 Hz, 1H), 4.23 (d, J ) 13.6 Hz, 1H), 3.71 (d,
J ) 11.6 Hz, 1H), 1.53 (s, 9H), 1.45 (s, 3H), 1.41 (s, 3H); 13C
NMR δ 194.9, 149.0, 148.6, 111.3, 98.9, 85.0, 77.4, 75.5, 61.3,
48.4, 28.0, 27.2, 26.0. Anal. Calcd for C15H21NO8: C, 52.47; H,
6.17; N, 4.08. Found: C, 52.32; H, 5.94; N, 3.97.
6g as a white solid (0.727 g, 91%): mp 76-78 °C; [R]20
)
D
-64.0 (c 0.97, CHCl3); IR (KBr) 1794, 1709 cm-1; H NMR δ
4.28-4.13 (m, 4H), 3.99 (d, J ) 11.5 Hz, 1H), 3.76 (d, J ) 11.5
Hz, 1H), 3.69 (d, J ) 6.9 Hz, 1H), 2.50 (s, 3H), 1.55 (s, 3H),
1.38 (s, 3H), 0.83 (s, 9H), 0.19 (s, 3H), 0.10 (s, 3H); 13C NMR
δ 169.9, 151.9, 109.6, 102.2, 76.8, 73.9, 73.0, 62.6, 51.2, 28.5,
26.5, 25.8, 23.7, 18.1, -3.6, -5.2. Anal. Calcd for C18H31NO7-
Si: C, 53.84; H, 7.78; N, 3.49. Found: C, 54.03; H, 7.74; N,
3.41.
1
P r ep a r a tion of Keton e 2e. To a solution of TBS ether 5
(0.718 g, 2.0 mmol) in THF (20 mL) were added Et3N (1.0 g,
10.0 mmol), DMAP (0.024 g, 0.2 mmol), and PhOCOCl (0.47
g, 3.0 mmol) at 0 °C under N2. Upon stirring to completion as
judged by TLC (about 2 h), the reaction mixture was quenched
with water, extracted with EtOAc, dried (Na2SO4), filtered,
concentrated, and purified by flash chromatography to give
compound 6e as a white solid (0.95 g, 99%): mp 123-125 °C;
TBS ether 6g (0.65 g, 1.62 mmol) was desilylated with Et3N·
3HF (0.523 g, 3.24 mmol) in a way similar to 6d to give the
[R]20D ) -47.6 (c 1.19, CHCl3); IR (KBr) 1839, 1806, 1743 cm-1
;
alcohol as a colorless oil (0.267 g, 57%) (about 5 days): [R]20
D
1H NMR δ 7.47-7.41 (m, 2H), 7.33-7.29 (m, 1H), 7.20-7.17
(m, 2H), 4.37-4.19 (m, 4H), 4.19 (d, J ) 11.0 Hz, 1H), 3.95 (d,
J ) 11.0 Hz, 1H), 3.77 (d, J ) 6.9 Hz, 1H), 1.59 (s, 3H), 1.43
(s, 3H), 0.94 (s, 9H), 0.25 (s, 3H), 0.19 (s, 3H); 13C NMR δ 150.0,
) -143.2 (c 0.9, CHCl3); IR (KBr) 3447, 1793, 1709 cm-1; H
1
NMR δ 4.28-4.17 (m, 4H), 4.15 (d, J ) 11.7 Hz, 1H), 3.82 (d,
J ) 11.7 Hz, 1H), 3.75 (d, J ) 5.7 Hz, 1H), 3.21 (s, 1H), 2.51
(s, 3H), 1.54 (s, 3H), 1.38 (s, 3H); 13C NMR δ 170.2, 151.9,

Designing New Chiral Ketone Catalysts
J . Org. Chem., Vol. 67, No. 8, 2002 2443
110.1, 101.9, 76.4, 73.1, 71.4, 62.3, 50.6, 28.3, 26.3, 23.8. Anal.
Calcd for C12H17NO7: C, 50.17; H, 5.96; N, 4.88. Found: C,
50.09; H, 5.70; N, 4.77.
The above alcohol (0.326 g, 0.935 mmol) was oxidized with
PDC to give ketone 2i as a white solid (0.307 g, 95%): mp
66-68 °C; [R]20 ) -91.2 (c 1.06, CHCl3); IR (KBr) 3452
D
The above alcohol (0.18 g, 0.627 mmol) was oxidized with
(hydrate), 1799, 1687 cm-1; 1H NMR δ 7.69-7.43 (m, 5H), 4.81
(d, J ) 6.3 Hz, 1H), 4.78 (d, J ) 12.5 Hz, 1H), 4.65 (m, 1H),
4.51 (dd, J ) 13.8, 2.1 Hz, 1H), 4.29 (d, J ) 13.8 Hz, 1H), 3.98
(d, J ) 12.5 Hz, 1H), 1.51 (s, 3H), 1.44 (s, 3H); 13C NMR δ
194.7, 168.8, 150.0, 132.8, 132.2, 129.2, 128.1, 111.6, 99.9, 77.2,
75.4, 61.9, 48.9, 27.3, 26.2. Anal. Calcd for C17H17NO7: C,
58.79; H, 4.93; N, 4.03. Found: C, 58.78; H, 5.12; N, 4.00.
P r ep a r a tion of Keton e 2j. To a solution of 5 (0.718 g, 2.0
mmol) in THF (20 mL) were added Et3N (2.6 mL, 20.0 mmol),
DMAP (0.024 g, 0.2 mmol), and 4-methoxylbenzoyl chloride
(0.41 g, 2.4 mmol) at 0 °C under N2. Upon stirring to
completion as judged by TLC (about 12 h), the reaction mixture
was quenched with water, extracted with EtOAc, dried (Na2-
SO4), filtered, concentrated, and purified by flash chromatog-
raphy to give compound 6j as a white solid (0.98 g, 99%): mp
139.0-140.5 °C; [R]20D ) -75.5 (c 1.78, CHCl3); IR (KBr) 1794,
1680, 1607 cm-1; 1H NMR δ 7.69-7.64 (m, 2H), 6.93-6.89 (m,
2H), 4.32-4.15 (m, 4H), 4.22 (d, J ) 11.4 Hz, 1H), 3.95 (d, J
) 11.4 Hz, 1H), 3.86 (s, 3H), 3.76 (d, J ) 6.6 Hz, 1H), 1.56 (s,
3H), 1.38 (s, 3H), 0.87 (s, 9H), 0.20 (s, 3H), 0.14 (s, 3H); 13C
NMR δ 168.3, 163.1, 151.6, 131.8, 124.6, 113.3, 109.6, 102.1,
76.9, 73.5, 73.1, 62.4, 55.6, 51.9, 28.5, 26.5, 26.0, 18.3, -3.6,
-5.0.
PDC to give ketone 2g as a colorless oil (0.177 g, 99%): [R]20
D
) -56.8 (c 2.77, CH3CN); IR (KBr) 3427 (hydrate), 1798, 1711
1
cm-1; Keton e: H NMR (CD3CN) δ 4.85 (d, J ) 6.0 Hz, 1H),
4.43-4.15 (m, 3H), 3.71 (d, J ) 12.3 Hz, 1H), 3.61 (d, J ) 12.3
Hz, 1H), 2.40 (s, 3H), 1.47 (s, 3H), 1.40 (s, 3H); 13C NMR (CD3-
CN) δ 196.3, 170.5, 152.4, 111.7, 103.1, 78.2, 76.1, 62.8, 48.9,
27.2, 26.0, 23.7. Hyd r a te: 1H NMR (CD3CN) δ 4.67 (d, J )
5.1 Hz, 1H), 4.43-4.15 (m, 4H), 3.81 (d, J ) 12.7 Hz, 1H), 2.40
(s, 3H), 1.36 (s, 3H), 1.33 (s, 3H); 13C NMR (CD3CN) δ 170.5,
151.5, 110.5, 100.4, 92.0, 76.6, 73.8, 64.5, 51.6, 26.5, 24.8, 23.8;
HRMS calcd for C12H18NO8 (M·H2O + 1) 304.1032, found
304.1026.
P r ep a r a tion of Keton e 2h . To a solution of 5 (0.718 g,
2.0 mmol) in CH2Cl2 (20 mL) were added Et3N (1.0 g, 10.0
mmol), DMAP (0.024 g, 0.2 mmol), and Me3CCOCl (0.326 g,
3.0 mmol) at 0 °C under N2. Upon stirring to completion as
judged by TLC (about 12 h), the reaction mixture was
quenched with water, extracted with EtOAc, dried (Na2SO4),
filtered, concentrated, and purified by flash chromatography
to give compound 6h as a white solid (0.884 g, 99%): mp 145-
148 °C; [R]20 ) -59.2 (c 1.35, CHCl3); IR (KBr) 1789, 1687
D
cm-1; 1H NMR (CDCl3) δ 4.30-4.11 (m, 4H), 4.04 (d, J ) 11.9
Hz, 1H), 3.79 (d, J ) 11.9 Hz, 1H), 3.67 (d, J ) 6.9 Hz, 1H),
1.54 (s, 3H), 1.37 (s, 3H), 1.36 (s, 9H), 0.83 (s, 9H), 0.18 (s,
3H), 0.10 (s, 3H); 13C NMR δ 177.9, 150.4, 109.6, 101.6, 76.9,
73.6, 73.1, 62.2, 53.4, 41.6, 28.5, 26.5, 26.4, 25.9, 18.2, -3.6,
-5.2. Anal. Calcd for C21H37NO7Si: C, 56.86; H, 8.41; N, 3.16.
Found: C, 57.00; H, 8.35; N, 3.23.
TBS ether 6j (0.746 g, 1.512 mmol) was desilylated with
Et3N·3HF (1.22 g, 7.56 mmol) in a way similar to 6d to give
the alcohol as a white solid (0.489 g, 85%) (about 3 days): mp
66-68 °C; [R]20 ) -140.3 (c, 0.94, CHCl3); IR (KBr) 3447,
D
1793, 1680, 1606 cm-1; H NMR δ 7.71-7.66 (m, 2H), 6.94-
1
6.89 (m, 2H), 4.41-4.17 (m, 5H), 3.95 (m, 1H), 3.86 (s, 3H),
3.82 (d, J ) 6.0 Hz, 1H), 1.56 (s, 3H), 1.40 (s, 3H); 13C NMR δ
167.5, 156.9, 150.7, 132.6, 128.8, 123.6, 120.6, 111.0, 110.1,
101.8, 76.3, 73.0., 71.6, 62.4, 56.0, 51.2, 28.3, 26.2. Anal. Calcd
for C18H21NO8: C, 56.99; H, 5.58; N, 3.69. Found: C, 56.76; H
5.74; N, 3.65.
TBS ether 6h (0.75 g, 1.69 mmol) was desilylated with Et3N·
3HF (0.546 g, 3.39 mmol) in a way similar to 6d to give the
alcohol as a colorless oil (0.506 g, 91%) (about 5 days): [R]20
D
) -64.2 (c 1.15, CHCl3); IR (KBr) 3458, 1793, 1691 cm-1; H
1
NMR δ 4.28-4.12 (m, 5H), 3.84 (d, J ) 11.7 Hz, 1H), 3.74 (d,
J ) 5.7 Hz, 1H), 3.06 (bs, 1H), 1.54 (s, 3H), 1.38 (s, 3H), 1.37
(s, 9H); 13C NMR δ 178.2, 150.5, 110.1, 101.4, 76.4, 73.1, 71.4,
62.1, 53.1, 41.6, 28.3, 26.4, 26.2. Anal. Calcd for C15H23NO7:
C, 54.70; H, 7.04; N, 4.25. Found: C, 54.70; H, 7.11; N, 4.14.
The above alcohol (0.40 g, 1.22 mmol) was oxidized with
PDC to give ketone 2h as a white solid (0.372 g, 94%): mp
The above alcohol (0.461 g, 1.216 mmol) was oxidized with
PDC to give ketone 2j as a white solid (0.429 g, 94%): mp 63-
65 °C; [R]20 ) -89.1 (c 0.96, CHCl3); IR (KBr) 1799, 1758,
D
1684, 1606 cm-1; 1H NMR δ 7.72-7.69 (m, 2H), 6.96-6.92 (m,
2H), 4.81 (d, J ) 5.4 Hz, 1H), 4.78 (d, J ) 12.3 Hz, 1H), 4.65
(m, 1H), 4.52 (dd, J ) 13.5, 2.1 Hz, 1H), 4.29 (d, J ) 13.5 Hz,
1H), 3.95 (d, J ) 12.3 Hz, 1H), 3.87 (s, 3H), 1.51 (s, 3H), 1.44
(s, 3H); 13C NMR δ 194.7, 168.0, 163.5, 150.4, 132.0, 126.8,
124.0, 118.0, 113.5, 77.3, 75.5, 61.9, 55.7, 49.1, 27.3, 26.2. Anal.
Calcd for C18H19NO8: C, 57.29; H, 5.08; N, 3.71. Found: C,
57.17; H, 5.24; N, 3.61.
156-157 °C; [R]20 ) -40.4 (c 1.95, CHCl3); IR (KBr) 3468
D
(hydrate), 1799, 1758, 1697 cm-1; H NMR δ 4.78 (d, J ) 5.4
1
Hz, 1H), 4.62 (dd, J ) 5.4, 1.8 Hz, 1H), 4.58 (d, J ) 12.6 Hz,
1H), 4.48 (dd, J ) 13.5, 1.8 Hz, 1H), 4.23 (d, J ) 13.5 Hz, 1H),
3.82 (d, J ) 12.6 Hz, 1H), 1.47 (s, 3H), 1.41 (s, 3H), 1.37 (s,
9H); 13C NMR δ 194.8, 177.7, 149.0, 111.5, 99.5, 77.7, 75.4,
61.6, 50.3, 41.7, 27.3, 26.3, 26.2. Anal. Calcd for C15H21NO7:
C, 55.04; H, 6.47; N, 4.28. Found: C, 55.22; H, 6.31; N, 4.32.
P r ep a r a tion of Keton e 2i. To a solution of 5 (0.718 g, 2.0
mmol) in THF (20 mL) were added Et3N (1.0 g, 10.0 mmol),
DMAP (0.024 g, 0.2 mmol), and PhCOCl (0.422 g, 3.0 mmol)
at 0 °C under N2. Upon stirring to completion as judged by
TLC (about 12 h), the reaction mixture was quenched with
water, extracted with EtOAc, dried (Na2SO4), filtered, concen-
trated, and purified by flash chromatography to give compound
6i as a white solid (0.867 g, 94%): mp 93-95 °C; [R]20D ) -84.7
P r ep a r a tion of Keton e 2k . To a solution of 5 (0.718 g,
2.0 mmol) in THF (20 mL) were added Et3N (2.6 mL, 20.0
mmol), DMAP (0.024 g, 0.2 mmol), and 2-methoxylbenzoyl
chloride (0.41 g, 2.4 mmol) at 0 °C under N2. Upon stirring to
completion as judged by TLC (about 12 h), the reaction mixture
was quenched with water, extracted with EtOAc, dried (Na2-
SO4), filtered, concentrated, and purified by flash chromatog-
raphy to give compound 6k as a white solid (0.9 g, 91%): mp
114-116 °C; [R]20 ) -92.0 (c 1.12, CHCl3); IR (KBr) 1802,
D
1
1685, 1603 cm-1; H NMR δ 7.42 (m, 1H), 7.25 (m, 1H), 7.00
(m, 1H), 6.91 (d, J ) 8.4 Hz, 1H), 4.29-4.12 (m, 5H), 3.96 (d,
J ) 11.7 Hz, 1H), 3.81 (s, 3H), 3.75 (d, J ) 6.6 Hz, 1H), 1.56
1
(c 1.22, CHCl3); IR (KBr) 1796, 1685 cm-1; H NMR δ 7.68-
7.44 (m, 5H), 4.35-4.19 (m, 5H), 4.00 (d, J ) 11.4 Hz, 1H),
3.81 (d, J ) 6.6 Hz, 1H), 1.61 (s, 3H), 1.42 (s, 3H), 0.93 (s,
9H), 0.25 (s, 3H), 0.19 (s, 3H); 13C NMR δ 169.0, 151.2, 132.8,
132.3, 130.2, 129.2, 129, 127.9, 109.6, 102.2, 76.8, 73.6, 73.1,
62.5, 51.7, 28.4, 26.4, 26.0, 18.3, -3.6, -5.1.
(s, 3H), 1.38 (s, 3H), 0.89 (s, 9H), 0.19 (s, 3H), 0.15 (s, 3H); 13
C
NMR δ 167.4, 156.9, 150.5, 132.2, 128.4, 124, 120.5, 111, 109.6,
101.9, 76.8, 73.3, 73.1, 62.3, 55.9, 51.1, 28.4, 26.4, 26, 18.3,
-3.6, -5.1.
TBS ether 6k (0.696 g, 1.411 mmol) was desilylated with
Et3N·3HF (1.14 g, 7.05 mmol) in a way similar to 6d to give
the alcohol as a white solid (0.501 g, 94%) (about 3 days): mp
68-71 °C; [R]20D ) -119.7 (c 1.01, CHCl3); IR (KBr) 3453, 1801,
1684, 1603 cm-1; 1H NMR δ 7.48-7.42 (m, 1H), 7.34 (dd, J )
7.8, 1.8 Hz, 1H), 7.01 (t, J ) 7.8 Hz, 1H), 6.92 (d, J ) 7.8 Hz,
1H), 4.33 (d, J ) 11.7 Hz, 1H), 4.29-4.15 (m, 4H), 3.99 (d, J
) 11.7 Hz, 1H), 3.81 (s, 3H), 3.84-3.79 (m, 1H), 1.56 (s, 3H),
1.39 (s, 3H); 13C NMR δ 167.5, 156.9, 150.7, 132.6, 128.8, 123.6,
120.6, 111.0, 110.1, 101.8, 76.3, 73.0, 71.6, 62.4, 56.0, 51.2, 28.3,
26.2.
TBS ether 6i (0.64 g, 1.382 mmol) was desilylated with Et3N·
3HF (0.569 g, 3.529 mmol) in a way similar to 6d to give the
alcohol as a white solid (0.448 g, 93%) (about 3 days): mp 120-
123 °C; [R]20 ) -134.1 (c 1.09, CHCl3); IR (KBr) 3444, 1794,
D
1685 cm-1; 1H NMR δ 7.67-7.41 (m, 5H), 4.43-4.17 (m, 5H),
3.97 (d, J ) 11.7 Hz, 1H), 3.81 (d, J ) 6.6 Hz, 1H), 3.06 (bs,
1H), 1.56 (s, 3H), 1.40 (s, 3H); 13C NMR δ 169.3, 151.4, 132.5,
129.1, 128, 110.1, 102.1, 76.3, 73.0, 71.4, 62.4, 51.5, 28.3, 26.2.
Anal. Calcd for C17H19NO7: C, 58.45; H, 5.48; N, 4.01. Found:
C, 58.38; H, 5.46; N, 3.95.

2444 J . Org. Chem., Vol. 67, No. 8, 2002
Tian et al.
The above alcohol (0.403 g, 1.063 mmol) was oxidized with
The above alcohol (0.308 g, 0.753 mmol) was oxidized with
PDC to give ketone 2m as a white solid (0.268 g, 87%): mp
72-73 °C; [R]20D ) -60.6 (c 1.12, CHCl3); IR (KBr) 3481, 1805,
PDC to give ketone 2k as a white solid (0.391 g, 97%): mp
160-161 °C; [R]20 ) -75.0 (c 1.09, CHCl3); IR (KBr) 3487
D
(hydrate), 1806, 1758, 1689, 1603 cm-1; 1H NMR δ 7.50-7.44
(m, 1H), 7.35 (dd, J ) 7.4, 1.4 Hz, 1H), 7.05-7.00 (m, 1H),
6.93 (d, J ) 8.4 Hz, 1H), 4.80 (d, J ) 5.4 Hz, 1H), 4.74 (d, J )
12.3 Hz, 1H) 4.63 (m, 1H), 4.49 (dd, J ) 13.8, 2.1 Hz, 1H),
4,27 (d, J ) 13.8 Hz, 1H), 3.99 (d, J ) 12.3 Hz, 1H), 3.83 (s,
3H), 1.50 (s, 3H), 1.43 (s, 3H); 13C NMR δ 194.7, 167.1, 156.9,
149.2, 132.7, 128.9, 123.1, 120.6, 111.5, 110.9, 99.7, 77.2, 75.4,
61.8, 55.9, 48.4, 27.2, 26.1. Anal. Calcd for C18H19NO8: C,
57.29; H, 5.08; N, 3.71. Found: C, 57.17; H, 5.18; N, 3.83.
1758, 1698, 1597 cm-1 1H NMR δ 7.34 (t, J ) 8.4 Hz, 1H),
;
6.57 (d, J ) 8.4 Hz, 2H), 4.79 (d, J ) 5.4 Hz,1H), 4.74 (d, J )
12.3 Hz, 1H), 4.62 (m, 1H), 4.48 (dd, J ) 13.5, 2.1 Hz, 1H),
4.26 (d, J ) 13.5 Hz, 1H), 3.99 (d, J ) 12.3 Hz, 1H), 3.80 (s,
6H), 1.50 (s, 3H), 1.43 (s, 3H); 13C NMR δ 194.8, 157.3, 149.0,
143.8, 132.0, 112.5, 111.5, 103.9, 99.6, 77.3, 75.5, 61.8, 56.2,
48.1, 27.3, 26.2. Anal. Calcd for C19H21NO9: C, 56.02; H, 5.20;
N, 3.44. Found: C, 55.96; H, 5.26; N, 3.41.
P r ep a r a tion of Keton e 2n . To a solution of 5 (2.48 g, 6.91
mmol) in CH3CN-H2O (9/1, v/v) (21 mL) was added DDQ
(0.153 g, 0.691 mmol). Upon stirring at room temperature for
6 h, the reaction mixture was concentrated, redissolved in
EtOAc, dried (Na2SO4), filtered, concentrated, and purified by
flash chromatography to give diol 7 as a pink solid (2.053 g,
P r ep a r a tion of Keton e 2l. To a solution of 5 (0.718 g, 2.0
mmol) in THF (10 mL) were added Et3N (1.01 g, 10.0 mmol),
DMAP (0.024 g, 0.2 mmol), and 2,4-dimethoxylbenzoyl chloride
(0.482 g, 2.4 mmol) at 0 °C under N2. Upon stirring to
completion as judged by TLC (about 5 h), the reaction mixture
was quenched with water, extracted with EtOAc, dried (Na2-
SO4), filtered, concentrated, and purified by flash chromatog-
raphy to give compound 6l as a white solid (0.973 g, 93%):
1
93%):7g mp 210-213 °C; IR (KBr) 3340, 1752 cm-1; H NMR
(CD3CN) δ 5.78 (s, 1H), 3.94 (d, J ) 12.9 Hz, 1H), 3.83 (m,
1H), 3.78-3.69 (m, 3H), 3.64 (d, J ) 10.5 Hz, 1H), 3.29-3.23
(m, 3H), 0.87 (s, 9H), 0.15 (s, 3H), 0.13 (s, 3H); 13C NMR (CD3-
CN) δ 157.9, 106.4, 73.1, 71.1, 70.1, 66.4, 49.7, 26.3, 19.0, -3.2,
-5.1. Anal. Calcd for C13H25NO6Si: C, 48.88; H, 7.89; N, 4.38.
Found: C, 48.79; H, 7.65; N, 4.45.
mp 69-70 °C; [R]20 ) -73.8 (c 1.30, CHCl3); IR (KBr) 1799,
D
1680, 1609 cm-1; 1H NMR δ 7.32-7.29 (m, 1H), 6.54 (dd, J )
8.4, 2.1 Hz, 1H), 6.48 (d, J ) 1.8 Hz, 1H), 4.34-4.17 (m, 5H),
3.98 (d, J ) 11.4 Hz, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.78 (d, J
) 6.6 Hz, 1H), 1.60 (s, 3H), 1.42 (s, 3H), 0.92 (s, 9H), 0.23 (s,
3H), 0.19 (s, 3H); 13C NMR δ 167.0, 163.4, 159.0, 130.5, 116.5,
109.6, 104.7, 101.8, 98.5, 76.9, 73.3, 73.2, 62.3, 55.9, 55.7, 51.3,
28.5, 26.5, 26.0, 18.3, -3.6, -5.1.
To a solution of 7 (0.638 g, 2.0 mmol) in CH2Cl2 (5 mL) were
added TsOH (0.038 g, 0.2 mmol) and 3-petanone (0.516 g, 6.0
mmol). Upon stirring at room temperature to completion as
judged by TLC (about 24 h), the reaction mixture was diluted
with EtOAc, washed with water and brine, dried (Na2SO4),
filtered, concentrated, and purified by flash chromatography
to give compound 8 as a white solid (0.51 g, 66%): mp 158.5-
TBS ether 6l (0.93 g, 1.78 mmol) was desilylated with Et3N·
3HF (1.43 g, 8.89 mmol) in a way similar to 6d to give the
alcohol as a white solid (0.67 g, 92%) (about 3 days): mp 70-
72 °C; [R]20 ) -114.0 (c 1.00, CHCl3); IR (KBr) 3447, 1797,
159.5 °C; [R]20 ) -84.1 (c 1.68, CHCl3); IR (KBr) 3333, 1770
D
D
1676, 1609 cm-1; 1H NMR δ 7.36 (d, J ) 8.4 Hz, 1H), 6.52 (dd,
J ) 8.4, 2.4 Hz, 1H), 6.44 (d, J ) 2.4 Hz, 1H), 4.32 (d, J )
11.7 Hz, 1H), 4.28-4.12 (m, 4H), 3.94 (d, J ) 11.7 Hz, 1H),
3.84 (s, 3H), 3.79 (m, 1H), 3.77 (s, 3H), 1.55 (s, 3H), 1.39 (s,
3H); 13C NMR δ 167.2, 163.6, 159.0, 150.9, 131.0, 116.0, 109.9,
104.8, 101.9, 98.4, 76.2, 73.0, 71.3, 62.2, 55.9, 55.6, 51.2, 28.2,
26.2.
cm-1; 1H NMR δ 6.06 (s, 1H), 4.28-4.04 (m, 4H), 3.68 (d, J )
6.0 Hz, 1H), 3.67 (d, J ) 9.0 Hz, 1H), 3.40 (d, J ) 9.0 Hz, 1H),
1.82-1.66 (m, 2H), 1.62 (q, J ) 7.5 Hz, 2H), 0.97 (t, J ) 7.5
Hz, 3H), 0.89 (t, J ) 7.5 Hz, 3H), 0.88 (s, 9H), 0.19 (s, 3H),
0.10 (s, 3H); 13C NMR δ 158.0, 113.6, 104.9, 76.8, 73.8, 72.9,
62.3, 49.1, 30.5, 28.4, 26.0, 18.3, 8.93, 8.87, -3.7, -5.2. Anal.
Calcd for C18H33NO6Si: C, 55.79; H, 8.58; N, 3.61. Found: C,
55.66; H, 8.49; N, 3.79.
The above alcohol (0.518 g, 1.267 mmol) was oxidized with
PDC to give ketone 2l as a white solid (0.44 g, 85%): mp 74-
Compound 9 was prepared in a way similar to 6d : white
76 °C; [R]20 ) -78.0 (c 1.04, CHCl3); IR (KBr) 1805, 1758,
solid (93%); mp 102-104 °C; [R]20 ) -59.1 (c 1.16, CHCl3);
D
D
1681, 1609 cm-1; 1H NMR δ 7.36 (d, J ) 8.4 Hz, 1H), 6.53 (dd,
J ) 8.4, 2.4 Hz, 1H), 6.44 (d, J ) 2.1 Hz, 1H), 4.80 (d, J ) 6.0
Hz, 1H), 4.72 (d, J ) 12.3 Hz, 1H), 4.63 (m, 1H), 4.49 (dd, J )
13.5, 1.8 Hz, 1H), 4.27 (d, J ) 13.5 Hz, 1H), 3.97 (d, J ) 12.6
Hz, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 1.50 (s, 3H), 1.43 (s, 3H);
13C NMR δ 194.8, 166.7, 163.9, 149.5, 131.2, 115.7, 111.6,
105.0, 99.8, 98.5, 77.3, 75.5, 61.9, 56.0, 55.7, 48.7, 27.3, 26.2.
Anal. Calcd for C19H21NO9: C, 56.02; H, 5.20; N, 3.44. Found:
C, 56.20; H, 5.34; N, 3.39.
IR (KBr) 1807, 1724 cm-1; 1H NMR δ 4.30-4.18 (m, 3H), 4.08
(d, J ) 12.9 Hz, 1H), 3.94 (d, J ) 10.5 Hz, 1H), 3.69 (d, J )
10.5 Hz, 1H), 3.68 (d, J ) 6.6 Hz, 1H), 1.82-1.65 (m, 2H), 1.62
(q, J ) 7.5 Hz, 2H), 1.52 (s, 9H), 0.98 (t, J ) 7.5 Hz, 3H), 0.89
(t, J ) 7.5 Hz, 3H), 0.86 (s, 9H), 0.19 (s, 3H), 0.12 (s, 3H); 13
C
NMR δ 150.3, 148.9, 113.7, 101.1, 84.1, 76.7, 74.1, 72.7, 62.7,
52.0, 30.5, 28.4, 28.2, 25.9, 18.2, 8.9, -3.7, -5.3. Anal. Calcd
for C23H41NO8Si: C, 56.65; H, 8.47; N, 2.87. Found: C, 56.62;
H, 8.24; N, 2.87.
P r ep a r a tion of Keton e 2m . To a solution of 5 (0.718 g,
2.0 mmol) in THF (10 mL) were added Et3N (1.01 g, 10.0
mmol), DMAP (0.024 g, 0.2 mmol), and 2,6-dimethoxylbenzoyl
chloride (0.482 g, 2.4 mmol) at 0 °C under N2. Upon stirring
to completion as judged by TLC (about 12 h), the reaction
mixture was quenched with water, extracted with EtOAc, dried
(Na2SO4), filtered, concentrated, and purified by flash chro-
matography to give compound 6m as a white solid (1.02 g,
TBS ether 9 (0.596 g, 1.224 mmol) was desilylated with
Et3N·3HF (0.986 g, 6.12 mmol) in a way similar to 6d to give
the alcohol as a colorless oil (0.451 g, 99%) (about 4 days):
[R]20D ) -92.1 (c 0.70, CHCl3); IR (KBr) 3478, 1817, 1728 cm-1
;
1H NMR δ 4.26-4.11 (m, 3H), 4.06 (d, J ) 10.8 Hz, 1H), 3.99
(d, J ) 13.2 Hz, 1H), 3.84 (s, 1H, OH), 3.68 (d, J ) 6.6 Hz,
1H), 3.63 (d, J ) 10.8 Hz, 1H), 1.64 (q, J ) 7.5 Hz, 2H), 1.54
(q, J ) 7.5 Hz, 2H), 1.42 (s, 9H), 0.86 (t, J ) 7.5 Hz, 3H), 0.80
(t, J ) 7.2 Hz, 3H); 13C NMR δ 150.5, 148.7, 113.6, 101.1, 84.0,
75.8, 72.6, 70.9, 62.2, 51.5, 30.0, 28.5, 27.9, 8.6, 8.5. Anal. Calcd
for C17H27NO8: C, 54.68; H, 7.29; N, 3.75. Found: C, 54.48;
H, 7.18; N, 3.91.
97%): mp 63-67 °C; [R]20 ) -74.9 (c 1.07, CHCl3); IR (KBr)
D
1800, 1698, 1598 cm-1
;
1H NMR δ 7.34 (t, J ) 8.4 Hz, 1H),
6.59 (d, J ) 8.4 Hz, 2H), 4.31-3.78 (m, 7H), 3.82 (s, 6H). 1.60
(s, 3H), 1.41 (s, 3H), 0.94 (s, 9H), 0.23 (s, 3H), 0.19 (s, 3H); 13
C
NMR δ 165.3, 157.1, 150.3, 131.5, 109.5, 103.8, 101.7, 76.9,
The above alcohol (0.39 g, 1.05 mmol) was oxidized with
PDC to give ketone 2n as a colorless oil (0.361 g, 93%): [R]20
)
73.14, 73.1, 62.2, 56.1, 50.9, 28.4, 26.4, 26.0, 18.3, -3.7, -5.1.
D
TBS ether 6m (0.64 g, 1.22 mmol) was desilylated with Et3N·
3HF (0.99 g, 6.12 mmol) in a way similar to 6d to give the
alcohol as a white solid (0.498 g, 99%) (about 3 days): mp 75-
-25.7 (c 2.37, CHCl3); IR (KBr) 3454 (hydrate), 1833, 1754,
1732 cm-1; H NMR δ 4.73 (d, J ) 6.0 Hz, 1H), 4.63 (dd, J )
1
6.0, 1.8 Hz, 1H), 4.51 (d, J ) 11.2 Hz, 1H), 4.46 (dd, J ) 13.8,
1.8 Hz, 1H), 4.23 (d, J ) 13.8 Hz, 1H), 3.70 (d, J ) 11.2 Hz,
1H), 1.70-1.59 (m, 4H), 1.53 (s, 9H), 0.94-0.87 (m, 6H); 13C
NMR δ 194.9, 148.8, 148.4, 115.5, 98.7, 84.9, 76.8, 75.0, 61.7,
48.8, 29.8, 29.1, 28.1, 8.7, 8.4; HRMS calcd for C17H26NO8 (M+
+ 1) 372.1658, found 372.1662. Anal. Calcd for C17H25NO8: C,
54.98; H, 6.79; N, 3.77. Found: C, 55.06; H, 6.91; N, 3.71.
78 °C; [R]20 ) -87.6 (c 1.02, CHCl3); IR (KBr) 3447, 1799,
D
1694, 1597 cm-1; H NMR δ 7.35 (t, J ) 8.4 Hz, 1H), 6.59 (d,
1
J ) 8.4 Hz, 2H), 4.35-4.13 (m, 5H), 4.00 (d, J ) 11.7 Hz, 1H),
3.82 (m, 1H), 3.81 (s, 6H), 1.57 (s, 3H), 1.41 (s, 3H); 13C NMR
δ 165.5, 157.2, 150.5, 131.7, 112.9, 109.9, 103.9, 101.8, 76.2,
73.0, 71.3, 62.3, 56.2, 50.8, 28.2, 26.2.

Designing New Chiral Ketone Catalysts
J . Org. Chem., Vol. 67, No. 8, 2002 2445
P r ep a r a tion of Keton e 2o. A mixture of thiocarbonyldi-
imidazole (1.12 g, 6.3 mmol) and diol 7 (1.826 g, 5.724 mmol)
in toluene (30 mL) was heated at reflux for 1 h. Upon cooling,
the reaction mixture was washed with water and brine, dried
(Na2SO4), filtered, concentrated, and purified by flash chro-
1H NMR δ 5.13 (s, 1H), 4.99 (s, 1H), 4.83 (d, J ) 5.4 Hz, 1H),
4.52-4.42 (m, 3H), 4.26 (d, J ) 13.5 Hz, 1H), 3.67 (d, J ) 11.7
Hz, 1H), 1.49 (s, 9H); 13C NMR δ 193.6, 148.7, 148.3, 98.7, 95.8,
84.9, 78.4, 74.6, 61.1, 48.4, 28.0; HRMS calcd for C13H18NO8
(M+ + 1) 316.1032, found 316.1040. Anal. Calcd for C13H17
-
matography to give 10 as a white solid (1.523 g, 74%): mp
NO8: C, 49.52; H, 5.43; N, 4.44. Found: C, 49.37; H, 5.60; N,
4.31.
1
219-222 °C; [R]20 ) -102.5 (c 0.49, CHCl3); H NMR δ 5.95
D
(s, 1H), 5.02-4.90 (m, 2H), 4.33 (s, 2H), 3.79 (d, J ) 6.0 Hz,
1H), 3.73 (d, J ) 9.6 Hz, 1H), 3.25 (d, J ) 9.6 Hz, 1H), 0.90 (s,
9H), 0.24 (s, 3H), 0.17 (s, 3H); 13C NMR δ 190.1, 156.9, 103.6,
82.2, 79.5, 71.4, 60.2, 48.6, 25.8, 18.3, -3.9, -5.1. Anal. Calcd
for C14H23NO6SSi: C, 46.52; H, 6.41; N, 3.87. Found: C, 46.70;
H, 6.39; N, 4.03.
P r ep a r a tion of Keton e 16. A suspension of thiocarbonate
10 (0.565 g, 1.566 mmol) in 1,3-dimethyl-2-phenyl-1,3,2-
diazaphospholidine (0.911 g, 4.698 mmol) was stirred under
N2 at 40 °C for 20 h. Upon cooling, the mixture was purified
by flash chromatography to give olefin 13 as a colorless oil
(0.287 g, 64%):20 [R]20 ) +9.63 (c 1.6, CHCl3); IR (KBr) 3281,
D
1763 cm-1; H NMR δ 6.53 (s, 1H), 5.77 (d, J ) 10.5 Hz, 1H),
1
Compound 10 (0.5 g, 1.385 mmol), Ph3SnH (0.972 g, 2.77
mmol), and AIBN (0.014 g, 0.085 mmol) were dissolved in
anhydrous toluene (35 mL). Upon stirring at reflux to comple-
tion as judged by TLC, the reaction mixture was concentrated
and purified by flash chromatography to give 11 as a white
5.65 (d, J ) 10.5 Hz, 1H), 4.48 (dd, J ) 16.5, 1.2 Hz, 1H), 4.26
(s, 1H), 4.17 (dd, J ) 16.5, 1.2 Hz, 1H), 3.64 (d, J ) 9.6 Hz,
1H), 3.40 (d, J ) 9.6 Hz, 1H), 0.88 (s, 9H), 0.12 (s, 3H), 0.10
(s, 3H); 13C NMR δ 158.5, 126.1, 125.5, 102.6, 67.5, 63.0, 49.3,
25.8, 18.1, -3.7, -4.6.
solid (0.457 g, 99%):19 mp 179-182 °C; [R]20 ) -95.5 (c 1.17,
D
CHCl3); IR (KBr) 3295, 1767 cm-1
;
1H NMR δ 6.27 (s, 1H),
Compound 14 was prepared in a way similar to 6d : colorless
oil (78%); [R]20D ) +19.0 (c 1.45, CHCl3); IR (KBr) 1827, 1806,
1726 cm-1; 1H NMR δ 5.80-5.74 (m, 1H), 5.66-5.61 (m, 1H),
4.50-4.42 (m, 1H), 4.29-4.26 (m, 1H), 4.25-4.17 (m, 1H), 3.91
(d, J ) 10.5 Hz, 1H), 3.71 (d, J ) 10.5 Hz, 1H), 1.52 (s, 9H),
0.87 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR δ 150.5, 149.1,
125.7, 125.4, 98.8, 83.9, 67.8, 63.6, 52.2, 28.2, 25.8, 18.1, -3.6,
-4.7.
5.18 (s, 1H), 5.00 (s, 1H), 4.31-4.25 (m, 2H), 4.16 (d, J ) 13.8
Hz, 1H), 4.01 (dd, J ) 5.4, 1.8 Hz, 1H), 3.69 (d, J ) 9.3 Hz,
1H), 3.60 (d, J ) 7.2 Hz, 1H), 3.39 (d, J ) 9.3 Hz, 1H), 0.87 (s,
9H), 0.17 (s, 3H), 0.09 (s, 3H); 13C NMR δ 158.0, 104.9, 94.8,
76.3, 74.4, 71.5, 61.6, 48.8, 25.9, 18.3, -3.8, -5.2. Anal. Calcd
for C14H25NO6Si: C, 50.73; H, 7.60; N, 4.23. Found: C, 50.86;
H, 7.56; N, 4.22.
Compound 12 was prepared in a way similar to 6d : white
A mixture of 14 (0.303 g, 0.787 mmol) and 10% Pd-C
(0.0303 g) in MeOH (10 mL) was stirred under H2 for 24 h.
Upon filtration, the mixture was concentrated and purified by
flash chromatography to give 15 as a colorless oil (0.301 g,
solid (0.522 g, 88%); mp 119.0-120.5 °C; [R]20D ) -65.0 (c 1.13,
1
CHCl3); IR (KBr) 1827, 1807, 1726 cm-1; H NMR δ 5.20 (s,
1H), 5.03 (s, 1H), 4.31-4.24 (m, 3H), 4.04 (m, 1H), 3.99 (d, J
) 10.8 Hz, 1H), 3.72 (d, J ) 10.8 Hz, 1H), 3.63 (d, J ) 7.2 Hz,
1H), 1.54 (s, 9H), 0.88 (s, 9H), 0.20 (s, 3H), 0.13 (s, 3H); 13C
NMR δ 150.2, 148.8, 101.1, 94.8, 84.2, 76.0, 74.2, 71.8, 62.0,
51.7, 28.2, 25.9, 18.2, -3.9, -5.4. Anal. Calcd for C19H35NO8-
Si: C, 52.88; H, 7.71; N, 3.25. Found: C, 52.92; H, 7.60; N,
3.40.
99%): [R]20 ) -13.7 (c 1.31, CHCl3); IR (KBr) 1824, 1799,
D
1727 cm-1; 1H NMR δ 3.90 (d, J ) 8.0 Hz, 1H), 3.93-3.86 (m,
1H), 3.72-3.68 (m, 1H), 3.61-3.57 (m, 1H), 3.57 (d, J ) 8.0
Hz, 1H), 1.96-1.66 (m, 4H), 1.50 (s, 9H), 0.83 (s, 9H), 0.065
(s, 6H); 13C NMR δ 150.9, 149.2, 101.4, 83.7, 71.6, 63.3, 52.3,
28.1, 28.0, 25.7, 24.4, 17.9, -3.5, -5.0; HRMS calcd for C18H34
-
TBS ether 12 (0.522 g, 1.21 mmol) was desilylated with
Et3N·3HF (0.975 g, 6.06 mmol) in a way similar to 6d to give
the alcohol as a colorless oil (0.363 g, 94%) (about 4 days):
NO6Si (M+ + 1) 388.2155, found 388.2163.
TBS ether 15 (0.3 g, 0.775 mmol) was desilylated with Et3N·
3HF (0.625 g, 3.876 mmol) in a way similar to 6d to give the
[R]20 ) -115.7 (c 1.28, CHCl3); IR (KBr) 3468, 1812, 1726
D
alcohol as a colorless oil (0.187 g, 88%) (about 4 days): [R]20
D
1
cm-1; H NMR δ 5.21 (s, 1H), 4.99 (s, 1H), 4.32 (dd, J ) 7.5,
) -71.2 (c 1.10, CHCl3); IR (KBr) 3496, 1806, 1725 cm-1; H
1
5.4 Hz, 1H), 4.24 (dd, J ) 13.5, 2.0 Hz, 1H), 4.18 (d, J ) 13.5
Hz, 1H), 4.14 (d, J ) 10.8 Hz, 1H), 4.04 (dd, J ) 5.7, 2.0 Hz,
1H), 3.72 (d, J ) 10.8 Hz, 1H), 3.65 (dd, J ) 7.5, 7.2 Hz, 1H),
3.41 (d, J ) 7.2 Hz, 1H), 1.51 (s, 9H); 13C NMR δ 150.6, 148.9,
101.1, 95.0, 84.5, 75.7, 74.2, 69.5, 61.6, 51.3, 28.1. Anal. Calcd
for C13H19NO8: C, 49.21; H, 6.04; N, 4.41. Found: C, 49.26;
H, 5.96; N, 4.54.
NMR δ 4.11 (d, J ) 8.1 Hz, 1H), 3.85 (td, J ) 8.4, 2.4 Hz, 1H),
3.70 (dd, J ) 8.4, 2.4 Hz, 1H), 3.63 (d, J ) 8.1 Hz, 1H), 3.52
(m, 1H), 2.59 (s, 1H), 2.06 (m, 1H), 1.82-1.71 (m, 3H), 1.50 (s,
9H); 13C NMR δ 151.4, 149.1, 102.0, 84.1, 69.1, 62.9, 51.6,
28.15, 28.1, 24.7; HRMS calcd for
274.1291, found 274.1291.
C
12H20NO6 (M+ + 1)
The above alcohol (0.18 g, 0.659 mmol) was oxidized with
The above alcohol (0.309 g, 0.974 mmol) was oxidized with
PDC to give ketone 16 as a colorless oil (0.16 g, 90%): [R]20
D
PDC to give ketone 2o as a colorless oil (0.30 g, 98%): [R]20
D
) +15.1 (c 1.24, CHCl3); IR (KBr) 3475, 1827, 1736 cm-1; H
1
) -35.6 (c 1.22, CHCl3); IR (KBr) 3453, 1821, 1757, 1729 cm-1
;
NMR δ 4.47 (d, J ) 11.1 Hz, 1H), 4.26 (td, J ) 11.4, 3.6 Hz,
1H), 3.89-3.83 (m, 1H), 3.49 (d, J ) 11.1 Hz, 1H), 2.86-2.75
(m, 1H), 2.61-2.55 (m, 1H), 2.27-2.08 (m, 2H), 1.45 (s, 9H);
13C NMR δ 197.0, 149.1, 148.5, 99.0, 84.3, 62.7, 48.5, 35.8, 27.9,
27.0; HRMS calcd for C12H18NO6 (M+ + 1) 272.1134, found
272.1139.
Rep r esen ta tive Asym m etr ic Ep oxid a tion P r oced u r e.
To a solution of cis-â-methylstyrene (0.059 g, 0.5 mmol) and
ketone 2d (0.026 g, 0.075 mmol) in DME-DMM (3:1, v/v) (7.5
(15) (a) Witkop, B.; Foltz, C. M. J . Am. Chem. Soc. 1957, 79, 197.
(b) Zhang, W.; Loebach, J . L.; Wilson, S. R.; J acobsen, E. N. J . Am.
Chem. Soc. 1990, 112, 2801. (c) Kano, S.; Yokomatsu, T.; Shibuya, S.
J . Chem. Soc., Chem. Commun. 1978, 785. (d) Larrow, J . F.; Roberts,
E.; Verhoeven, T. R.; Ryan, K. M.; Senanayake, C. H.; Reider, P. J .;
J acobsen, E. N. Org. Synth. 1998, 76, 46. (e) Boyd, D. R.; Dorrity, M.
R. J .; Malone, J . F.; McMordie, R. A. S.; Sharma, N. D.; Dalton, H.;
Williams, P. J . Chem. Soc., Perkin Trans. 1 1990, 489. (f) Pietikainen,
P. Tetrahedron 1998, 54, 4319. (g) Lee, N. H.; Muci, A. R.; J acobsen,
E. N. Tetrahedron Lett. 1991, 32, 5055. (h) Hashihayata, T.; Ito, Y.;
Katsuki, T. Tetrahedron 1997, 53, 9541. (i) J acobsen, E. N.; Zhang,
W.; Muci, A. R.; Ecker, J . R.; Deng, L. J . Am. Chem. Soc. 1991, 113,
7063.
(16) (a) Capillon, J .; Guette, J .-P. Tetrahedron 1979, 35, 1817. (b)
Chaloner, P. A.; Perera, S. A. R. Tetrahedron Lett. 1987, 28, 3013. (c)
Chaloner, P. A.; Langadianou, E.; Perera, S. A. R. J . Chem. Soc., Perkin
Trans. 1 1991, 2731. (d) Chelucci, G.; Conti, S.; Falorni, M.; Giacomelli,
G. Tetrahedron 1991, 47, 8251. (e) Kang, J .; Lee, J . W.; Kim, J . I. J .
Chem. Soc., Chem. Commun. 1994, 2009.
mL) were added buffer (0.2 M K2CO3-AcOH in 4 × 10-4
M
aqueous EDTA, buffer pH ) 8.0) (5 mL) and Bu4NHSO4
(0.0075 g, 0.02 mmol) with stirring. After the mixture was
cooled to about -10 °C (bath temperature) via a NaCl-ice
bath, a solution of Oxone (0.212 M in 4 × 10-4 M aqueous
EDTA, 4.2 mL) (0.548 g, 0.89 mmol) and K2CO3 (0.479 M in 4
× 10-4 M aqueous EDTA, 4.2 mL) (0.278 g, 2.01 mmol) were
added dropwise separately over a period of 3.5 h via a syringe
pump. The reaction was then quenched with the addition of
pentane and extracted with pentane. The combined organic
layers were washed with brine, dried (Na2SO4), filtered,
concentrated, and purified by flash chromatography [the silica
(17) (a) Archelas, A.; Furstoss, R. J . Org. Chem. 1999, 64, 6112. (b)
Nugent, W. A.; Harlow, R. L. J . Am. Chem. Soc. 1994, 116, 6142. (c)
Nelson, A.; Warren, S. J . Chem. Soc., Perkin Trans. 1 1999, 1963. (d)
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2446 J . Org. Chem., Vol. 67, No. 8, 2002
Tian et al.
gel was buffered with 1% Et3N in pentane; pentane-ether (1/0
to 50/1) was used as eluent] to give cis-â-methylstyrene oxide
as a colorless oil (0.058 g, 87% yield, 91% ee) (Table 1, entry
1).
1347 cm-1; 1H NMR δ 3.45 (dt, J ) 3.9, 1.8 Hz, 1H), 3.16 (qd,
J ) 5.1, 3.9 Hz, 1H), 2.70 (td, J ) 7.2, 1.8 Hz, 2H), 1.63-1.25
(m, 8H), 1.45 (d, J ) 5.1 Hz, 3H), 0.93 (t, J ) 6.9 Hz, 3H); 13
C
NMR δ 100.1, 86.8, 54.1, 46.1, 31.5, 30.1, 28.6, 22.7, 19.0, 14.9,
14.3. Anal. Calcd for C11H18O: C, 79.46; H, 10.91. Found: C,
79.28; H, 10.95.
(1R,2S)-cis-â-Meth ylstyr en e oxide (Table 1, en tr y 1):15a,b
colorless oil; [R]20 ) -45.5 (c 0.67, CHCl3).
D
(1R,2S)-1-(4-Meth ylp h en yl)-1-p r op en e oxid e (Ta ble 1,
en tr y 2):15c colorless oil; 1H NMR δ 7.16 (m, 4H), 4.04 (d, J )
4.2 Hz, 1H), 3.29-3.26 (m, 1H), 2.40 (s, 3H), 1.14 (d, J ) 5.1
Hz, 3H); 13C NMR δ 128.8, 126.6, 57.7, 55.3, 21.4, 12.7.
(1R,2S)-1-(3-Meth ylp h en yl)-1-p r op en e oxid e (Ta ble 1,
(+)-3,3-E t h ylen ed ioxycyclop en t en e oxid e (Ta b le 1,
en tr y 14): colorless oil; [R]20D) +12.7 (c 0.132, CHCl3); IR
(KBr) 1347, 1130 cm-1 1H NMR δ 4.10-3.85 (m, 4H), 3.51
;
(m, 1H), 3.25 (d, J ) 3 Hz, 1H), 2.10 (m, 1H), 1.85-1.55 (m,
3H); 13C NMR δ 114.8, 65.4, 65.0, 55.9, 55.7, 29.5, 25.2. Anal.
Calcd for C7H10O3: C, 59.14; H, 7.09. Found: C, 59.32; H, 7.18.
(+)-3,3-E t h ylen ed ioxycycloh exen e oxid e (Ta b le 1,
en tr y 15):15i colorless oil; [R]20D) + 9.7 (c 2.3, hexane).
(+)-3,3-E t h ylen ed ioxycycloh ep t en e oxid e (Ta b le 1,
en tr y 16): colorless oil; [R]20D ) +6.5 (c 0.71, CHCl3); IR (KBr)
1147, 1087, 1061 cm-1; 1H NMR δ 4.10-3.86 (m, 4H), 3.09 (td,
J ) 5.3, 1.2 Hz, 1H), 2.95 (dd, J ) 4.5, 1.2 Hz, 1H), 2.28-2.21
(m, 1H), 1.95-1.43 (m, 6H), 1.30-1.21 (m, 1H); 13C NMR δ
110.9, 65.1, 64.9, 59.4, 54.3, 34.9, 28.0, 23.7, 22.9. Anal. Calcd
for C9H14O3: C, 63.51; H, 8.29. Found: C, 63.65; H, 8.50.
(R)-(-)-Styr en e oxid e (Ta ble 2, en tr y 1):17a colorless oil;
1
en tr y 3): colorless oil; H NMR δ 7.26-7.09 (m, 4H), 4.04 (d,
J ) 4.2 Hz, 1H), 3.37-3.30 (m, 1H), 2.37 (s, 3H), 1.10 (d, J )
5.7 Hz, 3H); 13C NMR δ 137.7, 128.3, 128.0, 127.3, 123.7, 57.7,
55.3, 21.6, 12.8; HRMS calcd for C10H12O 148.0888, found
148.0888.
(1R,2S)-1-(3,5-Dim eth ylph en yl)-1-pr open e oxide (Table
1
1, en tr y 4): colorless oil; H NMR δ 6.95-6.85 (m, 3H), 4.00
(d, J ) 4.2 Hz, 1H), 3.32 (qd, J ) 5.7, 4.2, 1H), 2.32 (s, 6H),
1.10 (d, J ) 5.7 Hz, 3H); 13C NMR δ 129.2, 124.4, 57.7, 55.2,
21.5, 12.8; HRMS calcd for C11H14O 162.1045, found 162.1042.
(1R,2S)-1-(4-F lu or op h en yl)-1-p r op en e oxid e (Ta ble 1,
1
en tr y 5): colorless oil; H NMR δ 7.30-7.19 (m, 2H), 7.09-
[R]20 ) -19.2 (c 1.34, CHCl3).
D
(R)-(-)-2-Ch lor ostyr en e oxid e (Ta ble 2, en tr ys 2):17a
colorless oil; [R]20D) -49.7 (c 0.7, CHCl3).
6.98 (m, 2H), 4.03 (d, J ) 4.2 Hz, 1H), 3.33 (qd, J ) 5.1, 4.2
Hz, 1H), 1.07 (d, J ) 5.1 Hz, 3H); 13C NMR δ 128.3, 128.2,
115.2, 115.0, 57.2, 55.3, 12.7. Anal. Calcd C9H9FO: C, 71.04;
H, 5.96. Found: C, 71.21; H, 5.90.
(R)-(-)-3-Ch lor ostyr en e oxid e (Ta ble 2, en tr y 3):17a
colorless oil; [R]20 ) -10.3 (c 1.04, CHCl3).
D
(R)-(-)-4-Ch lor ostyr en e oxid e (Ta ble 2, en tr y 4):17a
(1R,2S)-1-(4-Tr iflu or om eth ylp h en yl)-1-p r op en e oxid e
1
colorless oil; [R]20 ) -21.8 (c 0.83, CHCl3).
(Ta ble 1, en tr y 6): colorless oil; H NMR δ 7.62 (d, J ) 8.1
D
Cycloh exyloxir a n e (Ta ble 2, en tr y 5):17b,c colorless oil.
Hz, 2H), 7.43 (d, J ) 8.1 Hz, 2H), 4.10 (d, J ) 4.2 Hz, 1H),
3.39 (m, 1H), 1.08 (d, J ) 5.4 Hz, 3H); 13C NMR δ 127.0, 125.1,
57.2, 55.4, 12.7. Anal. Calcd C10H9F3: C, 59.41; H, 4.49.
Found: C, 59.19; H, 4.65.
(S)-(+)-r-Meth ylstyr en e oxid e (Ta ble 2, en tr y 6):17a
colorless oil; [R]20 ) +2.78 (c 1.1, CHCl3).
D
(+)-r-Isop r op ylstyr en e oxid e (Ta ble 2, en tr y 7):17d
1
colorless oil; [R]20 ) +23.2 (c 0.6, hexane); H NMR δ 7.44-
(1R,2S)-1-(2-Na p h th yl)-1-p r op en e oxid e (Ta ble 1, en tr y
D
7): white solid; [R]20 ) -13.5 (c 1.31, CHCl3); IR (KBr) 3051,
7.30 (m, 5H), 3.05 (d, J ) 5.1 Hz, 1H), 2.77 (d, J ) 5.1 Hz,
1H), 2.21-2.07 (m, 1H), 1.02 (d, J ) 6.9 Hz, 3H), 1.00 (d, J )
6.9 Hz, 3H); 13C NMR δ 139.4, 128.0, 127.4, 127.3, 64.7, 53.4,
33.4, 18.8, 18.1.
D
1511, 1341 cm-1; 1H NMR δ 7.86-7.77 (m, 4H), 7.50-7.44 (m,
3H), 4.23 (d, J ) 4.5 Hz, 1H), 3.43 (qd, J ) 5.4, 4.5 Hz, 1H),
1.12 (d, J ) 5.4 Hz, 3H); 13C NMR δ 133.1, 132.9, 127.9, 127.8,
126.3, 125.9, 125.6, 124.6, 57.9, 55.6, 12.8. Anal. Calcd for
C
13H12O: C, 84.75; H, 6.57. Found: C, 84.60; H, 6.41.
Ack n ow led gm en t. We are grateful to the generous
financial support from the General Medical Sciences of
the National Institutes of Health (GM59705-03), the
Arnold and Mabel Beckman Foundation, the Camille
and Henry Dreyfus Foundation, Alfred P. Sloan Foun-
dation, DuPont, Eli Lilly, GlaxoWellcome, and Merck.
(1R,2S)-In d en e oxid e (Ta ble 1, en tr y 8):15d colorless oil;
[R]20 ) -38.3 (c 1.2, CHCl3).
D
(1R,2S)-3,4-Dih yd r on a p h th a len e oxid e (Ta ble 1, en tr y
9):15b,10d colorless oil; [R]20 ) +133.2 (c 1.57, CHCl3).
D
(5R,6S)-5,6-E p oxy-6,7,8,9-t et r a h yd r o-5H -b en zocyclo-
h ep ten e (Ta ble 1, en tr y 10):15e,f colorless oil; [R]20 ) -23.4
(c 0.82, CHCl3).
D
(3R ,4R )-6-Cya n o-3,4-e p oxy-2,2-d im e t h ylc h r om e n e
Su p p or tin g In for m a tion Ava ila ble: X-ray structural
data of ketones 2a , 2b, 2d , and 2e containing atomic coordi-
nates and bond lengths and angles. This material is available
free of charge via the Internet at http://pubs.acs.org.
(Ta ble 1, en tr y 11): white solid; [R]20 ) +62.7 (c 0.71,
D
CHCl3).
(2S,3R)-2-Meth yl-3-(p h en yleth yn yl)oxir a n e (Ta ble 1,
en tr y 12):10a,d colorless oil; [R]20 ) -33.0 (c 0.98, CHCl3).
D
(2S,3R)-2-Meth yl-3-(1-octyn yl)oxir a n e (Ta ble 1, en tr y
13): colorless oil; [R]20D ) -31.4 (c 0.29, CHCl3); IR (KBr) 2215,
J O010838K