Asymmetric epoxidation of 1,1-disubstituted terminal olefins by chiral dioxirane via a planar-like transition state

Article abstract of DOI:10.1021/jo801576k

(Chemical Equation Presented) Various 1,1-disubstituted terminal olefins have been investigated for asymmetric epoxidation using chiral ketone catalysts. Up to 88% ee has been achieved with a lactam ketone, and a planar transition state is likely to be a

Full text of DOI:10.1021/jo801576k

Asymmetric Epoxidation of 1,1-Disubstituted Terminal Olefins by
Chiral Dioxirane via a Planar-like Transition State
Bin Wang, O. Andrea Wong, Mei-Xin Zhao, and Yian Shi*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
yian@lamar.colostate.edu
ReceiVed July 16, 2008
Various 1,1-disubstituted terminal olefins have been investigated for asymmetric epoxidation using chiral
ketone catalysts. Up to 88% ee has been achieved with a lactam ketone, and a planar transition state is
likely to be a major reaction pathway.
Introduction
Chiral dioxiranes have recently been shown to be effective
for asymmetric epoxidation of olefins, and a number of
laboratories have extensively investigated chiral ketones of
various structures.1 In our own studies, we found that fructose-
derived ketone 1 is a very effective catalyst for the epoxidation
of trans- and trisubstituted olefins,2 and oxazolidinone-bearing
ketones 2 can give high ee’s for olefins such as conjugated
aromatic cis-olefins,3a,c-e,g conjugated cis-dienes3k and enynes,3a,c,l
styrenes,3b-d,f and certain trisubstituted3h,j and tetrasubstituted
olefins3i,j which had not been effective with ketone 1 (Figure
1). Studies have shown that the enantioselectivity afforded by
ketone 2 results from an apparent attractive interaction between
the Rπ group of the olefin and the spiro-oxazolidinone of the
ketone catalyst.3
FIGURE 1
FIGURE 2
Among six classes of olefins (Figure 2), 1,1-disubstituted
terminal olefins (VI) have generally been challenging for
asymmetric epoxidation.4-8 Epoxidation of R-methylstyrene and
R-isopropylstyrene with ketone 2a gave (S)-R-methylstyrene
oxide in 30% ee and R-isopropylstyrene oxide in 58% ee.3c
Several possible spiro and planar transition states for epoxidation
with ketone 2 are shown in Figure 3.2b,3c Spiro transition states
(A-D) are generally favored stereoelectronically as a result of
the stabilizing interaction of an oxygen lone pair with the π*
orbital of the alkene.1,9,10 However, planar transition states E
and G appear to be sterically more favored as compared to spiro
transition states. Planar transition states F and H are disfavored
* To whom correspondence should be addressed. Phone: 970-491-7424. Fax:
970-491-1801.
(1) For leading reviews, see: (a) Denmark, S. E.; Wu, Z. Synlett 1999, 847.
(b) Frohn, M.; Shi, Y. Synthesis 2000, 1979. (c) Shi, Y. Acc. Chem. Res. 2004,
37, 488. (d) Yang, D. Acc. Chem. Res. 2004, 37, 497. (e) Wong, O. A.; Shi, Y.
Chem. ReV. 2008, 108, 3958.
(2) (a) Tu, Y.; Wang, Z.-X.; Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806. (b)
Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am. Chem. Soc. 1997,
119, 11224. (c) Shu, L.; Shi, Y. Tetrahedron 2001, 57, 5213.
(3) (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. (c)
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Shu, L.; Wang, P.; Gan, Y.; Shi, Y. Org. Lett. 2003, 5, 293. (e) Shu, L.; Shi, Y.
Tetrahedron Lett. 2004, 45, 8115. (f) Goeddel, D.; Shu, L.; Yuan, Y.; Wong,
O. A.; Wang, B.; Shi, Y. J. Org. Chem. 2006, 71, 1715. (g) Wong, O. A.; Shi,
Y. J. Org. Chem. 2006, 71, 3973. (h) Shen, Y.-M.; Wang, B.; Shi, Y. Angew.
Chem., Int. Ed. 2006, 45, 1429. (i) Shen, Y.-M.; Wang, B.; Shi, Y. Tetrahedron
Lett. 2006, 47, 5455. (j) Wang, B.; Shen, Y.-M.; Shi, Y. J. Org. Chem. 2006,
71, 9519. (k) Burke, C. P.; Shi, Y. Angew. Chem., Int. Ed. 2006, 45, 4475. (l)
Burke, C. P.; Shi, Y. J. Org. Chem. 2007, 72, 4093. (m) Burke, C. P.; Shi, Y.
J. Org. Chem. 2007, 72, 6320.
(4) For a leading review on asymmetric epoxidation, see: Xia, Q.-H.; Ge,
H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X. Chem. ReV. 2005, 105, 1603.
(5) For leading references on asymmetric epoxidation of 1,1-disubtituted
terminal olefins directed by hydroxyl groups, see: (a) Johnson, 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. (c) Barlan,
A. U.; Zhang, W.; Yamamoto, H. Tetrahedron 2007, 63, 6075.
10.1021/jo801576k CCC: $40.75
Published on Web 10/14/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 9539–9543 9539

Wang et al.
SCHEME 1
both electronically and sterically, thus they are unlikely to be
significant contributors. Between the two planar transition states
E and G, E is likely to be favored over G due to the associative
interaction between the phenyl group of the olefin and the
oxazolidinone of the ketone catalyst. We hypothesized that
planar E might be the major transition state for the epoxidation
of R-methylstyrene based on the S configuration of the resulting
epoxide obtained with ketone 2a. A higher ee obtained with
R-isopropylstyrene could be due to disfavoring competing spiro
D by a larger isopropyl group.3c On the basis of these
observations, we decided to search for ketone catalysts that can
further favor planar E-like transition state to enhance the
enantionselectivity for the epoxidation of 1,1-disubstituted
terminal olefins. We have found that lactam ketones 3 provide
very promising results (Figure 1). Herein we wish to report our
studies on this subject.
Results and Discussion
The synthesis of lactam ketone 3 is outlined in Schemes 1
and 2. Diol 4, prepared from D-glucose as previously reported,11
was treated with BrCH2COBr to form compound 5, which was
then converted to ketone 3a after cyclization and oxidation.
Upon introduction of a Boc or Ac group, ketone 3a was
converted to ketones 3b and 3c (Scheme 1). Ketones 3d-h were
prepared from D-glucose in four steps by Amadori rearrange-
ment,12 ketalization,3d formation of the six-membered lactam,
(6) For examples of asymmetric epoxidation of 1,1-disubstituted terminal
olefins with chiral metal catalysts, see: (a) Zhang, W.; Loebach, J. L.; Wilson,
S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801. (b) Halterman, R. L.;
Jan, S.-T.; Nimmons, H. L.; Standlee, D. J.; Khan, M. A. Tetrahedron 1997,
53, 11257. (c) Kim, G.-J.; Shin, J.-H. Catal. Lett. 1999, 63, 83. (d) Tanaka, H.;
Kuroboshi, M.; Takeda, H.; Kanda, H.; Torii, S. J. Electroanal. Chem. 2001,
507, 75. (e) Zhang, R.; Yu, W.-Y.; Sun, H.-Z.; Liu, W.-S.; Che, C.-M.
Chem.sEur. J. 2002, 8, 2495. (f) Zhang, H.; Xiang, S.; Li, C. Chem. Commun.
2005, 1209. (g) Fristrup, P.; Dideriksen, B. B.; Tanner, D.; Norrby, P. O. J. Am.
Chem. Soc. 2005, 127, 13672. (h) Zhang, H.; Zhang, Y.; Li, C. Tetrahedron:
Asymmetry 2005, 16, 2417. (i) Yu, K.; Lou, L.-L.; Ding, F.; Wang, S.; Wang,
Z.; Liu, S. Catal. Commun. 2006, 7, 170. (j) Sun, Y.; Tang, N. J. Mol. Catal. A:
Chem. 2006, 255, 171. (k) Lou, L.-L.; Yu, K.; Ding, F.; Zhou, W.; Peng, X.;
Liu, S. Tetrahedron Lett. 2006, 47, 6513.
(7) For examples of asymmetric epoxidation of 1,1-disubstituted terminal
olefins with chiral dioxiranes, see: (a) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong,
M.-K.; Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1996, 118, 491. (b) Ref
2b. (c) Wang, Z.-X.; Shi, Y. J. Org. Chem. 1997, 62, 8622. (d) 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. (e) Wang, Z. X.; Miller, S. M.; Anderson,
O. P.; Shi, Y. J. Org. Chem. 1999, 64, 6443. (f) Ref 3c. (g) Armstrong, A.;
Moss, W. O.; Reeves, J. R. Tetrahedron: Asymmetry 2001, 12, 2779. (h)
Armstrong, A.; Ahmed, G.; Dominguez-Fernandez, B.; Hayter, B. R.; Wailes,
J. S. J. Org. Chem. 2002, 67, 8610. (i) Chan, W.-K.; Yu, W.-Y.; Che, C.-M.;
Wong, M.-K. J. Org. Chem. 2003, 68, 6576. (j) Bez, G.; Zhao, C.-G. Tetrahedron
Lett. 2003, 44, 7403. (k) Bortolini, O.; Fantin, G.; Fogagnolo, M.; Mari, L.
Tetrahedron: Asymmetry 2004, 15, 3831. (l) Armstrong, A.; Tsuchiya, T.
Tetrahedron 2006, 62, 257. (m) Armstrong, A.; Dominguez-Fernandez, B.;
Tsuchiya, T. Tetrahedron 2006, 62, 6614.
(8) For examples of asymmetric epoxidation of 1,1-disubstituted terminal
olefins with oxaziridinium salts, see: (a) Page, P. C. B.; Rassias, G. A.; Barros,
D.; Bethell, D.; Schilling, M. B. J. Chem. Soc., Perkin Trans. 1 2000, 3325. (b)
Page, P. C. B.; Rassias, G. A.; Barros, D.; Ardakani, A.; Buckley, B.; Bethell,
D.; Smith, T. A. D.; Slawin, A. M. Z. J. Org. Chem. 2001, 66, 6926. (c) Page,
P. C. B.; Rassias, G. A.; Barros, D.; Ardakani, A.; Bethell, D.; Merifield, E.
Synlett 2002, 580. (d) Page, P. C. B.; Barros, D.; Buckley, B. R.; Ardakani, A.;
Marples, B. A. J. Org. Chem. 2004, 69, 3595. (e) Page, P. C. B.; Buckley, B. R.;
Rassias, G. A.; Blacker, A. J. Eur. J. Org. Chem. 2006, 803.
(9) (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.
(10) (a) Bach, R. D.; Andre´s, J. L.; Owensby, A. L.; Schlegel, H. B.;
McDouall, J. J. W. J. Am. Chem. Soc. 1992, 114, 7207. (b) Houk, K. N.; Liu,
J.; DeMello, N. C.; Condroski, K. R. J. Am. Chem. Soc. 1997, 119, 10147. (c)
Jenson, C.; Liu, J.; Houk, K. N.; Jorgensen, W. L. J. Am. Chem. Soc. 1997,
119, 12982. (d) Deubel, D. V. J. Org. Chem. 2001, 66, 3790. (e) Singleton,
D. A.; Wang, Z. J. Am. Chem. Soc. 2005, 127, 6679.
FIGURE 3. Proposed spiro and planar transition states for the
epoxidation of 1,1-disubstituted terminal olefins.
(11) Shu, L.; Shen, Y.-M.; Burke, C.; Goeddel, D.; Shi, Y. J. Org. Chem.
2003, 68, 4963.
9540 J. Org. Chem. Vol. 73, No. 24, 2008

1,1-Disubstituted Terminal Olefins
TABLE 1. Asymmetric Epoxidation of r-Isopropylstyrene with
SCHEME 2
Ketones 3a
entry
ketone
solvent
conv (%)b
ee (%)b
1
2
3
4
5
6
7
8
3d
CH3CN/DMM (1/2)
DME
DME/n-BuOH
97
94
99
94
99
100
91
69
10
100
98
71
81
76
84
80
78
82
71
nd
83
83
52
84
1,4-dioxane
1,4-dioxane/DME (2/1)
1,4-dioxane/n-BuOH (1/1)
1.4-dioxane
3a
3b
3c
3e
3f
3g
3h
9
10
11
12
13
80
99
and subsequent oxidation (Scheme 2). The X-ray structure of
ketone 3d is shown in Figure 4. An overlay of ketones 2b and
3d is shown in Figure 5. In contrast to ketone 2b,3d the N-phenyl
group and the lactam carbonyl group in 3d are not coplanar.
a All epoxidations were carried out with the olefin (0.2 mmol), ketone
3 (0.06 mmol), Oxone (0.32 mmol), and K2CO3 (1.344 mmol) in
organic solvent (3 mL) and buffer (0.1 M K2CO3/AcOH, pH 9.3; 2 mL)
at -10 °C for 2 h. b The conversion and ee were determined by chiral
GC (B-DM column).
Allylic, homoallylic, and bishomoallylic alcohols are also effective
substrates (Table 2, entries 16-21). Up to 88% ee was obtained
for 1,1-dialkyl-2-aryl allylic alcohols (Table 2, entries 19-21). A
reasonable enantioselectivity (60% ee) was also obtained for a
nonaromatic allylic alcohol (Table 2, entry 22).
Ketone 3d gave a similar level of enantioselectivity to ketone
2 for epoxidation of cis-olefins (Table 3, entries 1 and 2),
indicating that there still exists an electronic attraction between
the amide moiety and the phenyl group of the olefin in spiro
transition state I (Figure 6). When 1-phenylcyclohexene was
epoxidized with ketone 3d, the (S,S)-epoxide derived from
planar L (Figure 7) was obtained with 80% ee while the
epoxidation with ketones 2a and 2b gave 43% ee of the (S,S)-
epoxide3c and 25% ee of the (R,R)-epoxide,3d respectively,
suggesting that the six-membered lactam moiety provides a more
favorable environment for the attraction between the lactam
moiety of the ketone and the phenyl group of the olefin in the
planar transition state as compared to ketones 2a and 2b. In
the case of 1-phenyl-3,4-dihydronaphthalene, the epoxide result-
ing from the planar transition state was obtained in as high as
90% ee (Table 3, entry 4), further illustrating the aforementioned
attraction in the planar transition state.
FIGURE 4. X-ray structure of ketone 3d (stereoview).
FIGURE 5. Crystal structure overlay of ketones 2b and 3d (stereo-
view).
Initial studies on the epoxidation of R-isopropylstyrene with
ketone 3d showed that 1,4-dioxane was among the best solvents,
giving 94% conversion and 84% ee (Table 1, entry 4). The
enantioselectivity was also affected by the N-substituents of
ketone catalysts with ketones 3a, 3d, 3e, 3f, and 3h giving the
highest enantioselectivity (82-84% ee) (Table 1, entries 7, 4,
10, 11, and 13). Ketone 3d, readily synthesized from inexpensive
starting materials, was subsequently investigated for the epoxi-
dation of 1,1-disubstituted terminal olefins. As shown in Table
2, a variety of aryl-substituted 1,1-disubstituted olefins can be
effectively epoxidized in good enantioselectivities (62-88% ee).
Generally speaking, substrates with bulky alkyl groups at R
positions of olefins produce epoxides with higher enantioselec-
tivity than those with small groups. The substituents on the
phenyl groups of olefins also have some effects on the
enantioselectivities (74-88% ee) (Table 2, entries 7-14).
FIGURE 6. Proposed competing spiro transition states for the epoxi-
dation of cis-olefins with ketone 3.
(12) Hodge, J. E.; Fisher, B. E. Methods Carbohydr. Chem. 1963, 2, 99.
(13) (a) Capriati, V.; Florio, S.; Luisi, R.; Salomone, A. Org. Lett. 2002, 4,
2445. (b) Tanaka, K.; Yoshida, K.; Sasaki, C.; Osano, Y. T. J. Org. Chem. 2002,
67, 3131. (c) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-Mo¨ller, C. R.;
Seebach, D.; Zhang, R. Org. Lett. 2003, 5, 725.
FIGURE 7. Proposed competing spiro and planar transition states for
the epoxidation of 1-phenylcyclohexene with ketone 3.
J. Org. Chem. Vol. 73, No. 24, 2008 9541

Wang et al.
TABLE 2. Asymmetric Epoxidation of 1,1-Disubstituted Terminal Olefins with Ketone 3da
a All epoxidations were carried out with the olefin (0.2 mmol), ketone 3d (0.06 mmol), Oxone (0.32 mmol), and K2CO3 (1.344 mmol) in 1,4-dioxane
(3 mL), and buffer (0.1 M K2CO3/AcOH, pH 9.3; 2 mL) at -10 °C for 2 h (4 h for entries 6, 11, 13, and 14). b Isolated yield except entry 7 which is
crude yield. c The ee was determined by chiral HPLC (Chiracel OD column). d The ee was determined by chiral GC (B-DM column). e The absolute
configurations were determined by comparing the measured optical rotations and HPLC trace with reported ones.
The known absolute configurations of selected epoxides
(Table 2, entries 1, 2, 15, 16, 19, and 21) are consistent with
the notion that the epoxidation proceeds mainly via planar
transition state P (Figure 8). A bulky R substituent on the olefin
disfavors spiro O, thus resulting in higher ee’s as observed.
Further improvement of the enantioselectivity will require
further disfavoring spiro N and/or planar Q transition states.
improvement of the enantioselectivity for this challenging
class of olefins.
Experimental Section
Representive Ketone Synthesis. To a solution of amino alcohol
7d (prepared from D-glucose in two steps)3d (3.09 g, 10.0 mmol)
and Et3N (1.11 g, 1.54 mL, 11.0 mmol) in dry THF (50 mL)
was added a solution of 2-bromoacetyl bromide (2.22 g, 0.95
mL, 11.0 mmol) in dry THF (10 mL) dropwise at rt over 2 h.
After the resulting mixture was stirred at rt for 3 h, NaH (95%,
0.6 g, 23.7 mmol) was added into the reaction mixture carefully.
Upon stirring at rt for 0.5 h, the reaction mixture was quenched
with MeOH (0.25 mL) and filtered. The filtrate was concentrated
and purified by flash chromatography (silica gel, hexane/EtOAc
In summary, a variety of 1,1-disubstituted terminal olefins
can be enantioselectively epoxidized using lactam ketone 3d
as catalyst and Oxone as oxidant, giving up to 88% ee.
Studies indicate that the epoxidation of 1,1-disubstituted
terminal olefins with ketone 3 proceeds mainly via a planar
transition state. Ketone 3 provides a promising lead for further
9542 J. Org. Chem. Vol. 73, No. 24, 2008

1,1-Disubstituted Terminal Olefins
3410, 1661 cm-1 1H NMR (400 MHz, CDCl3) δ 7.21-7.14
;
TABLE 3. Asymmetric Epoxidation of cis- and Trisubstituted
Olefins by Ketone 3da
(m, 4H), 4.40-4.36 (m, 1H), 4.30-4.21 (m, 4H), 4.12 (d, J )
13.2 Hz, 1H), 3.96 (dd, J ) 13.2, 2.8 Hz, 1H), 3.62-3.59 (m,
1H), 3.53-3.48 (m, 1H), 3.10-2.88 (m, 1H), 2.33 (s, 3H), 1.51
(s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.6,
138.4, 137.4, 130.1, 125.8, 109.7, 96.2, 76.5, 73.4, 71.7, 62.7,
60.5, 54.2, 28.2, 26.2, 21.2; HRMS calcd for C18H24O6N (M +
H) 350.1604, found 350.1607.
AcOH (0.15 mL) was added to a slurry of lactam 8d (4.8 g,
13.76 mmol), PDC (10.3 g, 27.5 mmol), and 3 Å MS (6.5 g) in
CH2Cl2 (300 mL). Upon stirring at rt for 3 days (no SM left as
judged by TLC), the reaction mixture was filtered through a pad
of silica gel, and the filter cake was washed with EtOAc. The filtrate
was concentrated and purified by flash chromatography (silica gel,
hexane/EtOAc ) 3/1) to give ketone 3d as a white solid (4.5 g,
95% yield): mp 184-185 °C; [R]25 ) -86.5 (c 1.0, CHCl3); IR
D
(film) 1753, 1674 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.24-7.18
(m, 4H), 4.86 (d, J ) 5.7 Hz, 1H), 4.66-4.64 (m, 1H), 4.49-4.23
(m, 5H), 3.64 (d, J ) 13.8 Hz, 1H), 2.36 (s, 3H), 1.47 (s, 3H),
1.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 197.7, 165.2, 138.2,
137.7, 130.2, 125.8, 111.0, 96.1, 78.4, 75.7, 63.2, 59.9, 51.9, 27.3.
26.2, 21.3; HRMS calcd for C18H22NO6 (M + H) 348.1447, found:
348.1447. Anal. Calcd for C18H21NO6: C, 62.24; H, 6.09. Found:
C, 62.02; H, 6.01.
Representative Epoxidation Procedure (Table 2, Entry
19). To a solution of the olefin (0.032 g, 0.20 mmol), tetrabutyl-
ammonium hydrogen sulfate (0.0038 g, 0.010 mmol), and ketone
3d (0.0208 g, 0.06 mmol) in dioxane (3 mL) was added buffer
(0.1 M K2CO3-AcOH in 4 × 10-4 M aqueous EDTA, pH ) 9.3;
2 mL) with stirring. After the mixture was cooled to -10 °C (bath
temperature), a solution of Oxone (0.20 M in 4 × 10-4 M aqueous
EDTA, 1.6 mL) (0.197 g, 0.32 mmol) and a solution of K2CO3
(0.84 M in 4 × 10-4 M aqueous EDTA, 1.6 mL) (0.185 g, 1.344
mmol) were added separately and simultaneously via a syringe
pump over a period of 2 h. The reaction mixture was quenched
with hexane, extracted with EtOAc, dried over Na2SO4, filtered,
concentrated, and purified by flash chromatography (silica gel was
buffered with 1% Et3N in organic solvent; hexane/Et2O ) 5/1 as
eluent) to give the epoxide as white solid (0.027 g, 76% yield,
87% ee).
a All reactions were carried out with substrate (0.2 mmol), ketone 3d
(0.06 mmol for entry 1, 0.04 mmol for entries 2, 3, and 4), Oxone (0.32
mmol), and K2CO3 (1.344 mmol) in DME/DMM (3:1, v/v; 3.0 mL) and
buffer (0.1 M K2CO3-AcOH in 4 × 10-4 M aqueous EDTA, pH 9.3; 2
mL); For entries 1, 3, and 4, the reaction was carried out at -10 °C for 4 h;
For entry 2, the reaction was carried out at 0 °C for 12 h. b Isolated yield.
c The conversion was determined by GC (B-DM column). d The conversion
was determined by 1H NMR. e The ee was determined by chiral GC
(B-DM column). f The ee was determined by chiral HPLC (Chiracel OD
column). g The absolute configurations were determined by comparing the
measured optical rotations and GC trace with reported ones.
Acknowledgment. We are grateful to the generous financial
support from the General Medical Sciences of the National
Institutes of Health (GM59705-08). We thank Dr. Pingzhen
Wang for obtaining the crystal structure of ketone 2b.
Supporting Information Available: The synthesis and
characterization of ketones 3a-h, the epoxidation procedure
and characterization of epoxides, and the X-ray structures of
ketones 3c, 3d, and 3g along with the data for the determination
of the enantiomeric excess of the epoxides obtained with ketone
3d. This material is available free of charge via the Internet at
http://pubs.acs.org.
FIGURE 8. Proposed competing transition states for the epoxidation
of 1,1-disubstituted terminal olefins with ketone 3.
) 1/6) to give lactam 8d as a white solid (1.42 g, 41% yield):
mp 198-199 °C; [R]25 ) -144.6 (c 1.0, CHCl3); IR (film)
JO801576K
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