Diastereoselectivity in the epoxidation of substituted cyclohexenes by dimethyldioxirane

Article abstract of DOI:10.1021/jo951864j

Three series of compounds based on the cyclohexene framework have been epoxidized by dimetbyldioxirane. A pronounced dependence of epoxide diastereoselectivity on substituent has been observed. In addition there is a solvent influence on this stereoselectivity. The results have been explained by invoking steric, H-bonding, and dipole - dipole influences on the epoxide stereochemistry.

Full text of DOI:10.1021/jo951864j

1830
J . Org. Chem. 1996, 61, 1830-1841
Dia ster eoselectivity in th e Ep oxid a tion of Su bstitu ted
Cycloh exen es by Dim eth yld ioxir a n e1,2
Robert W. Murray,* Megh Singh, Brian L. Williams, and Hazel M. Moncrieff
Department of Chemistry, University of MissourisSt. Louis, St. Louis, Missouri 63121
Received October 17, 1995X
Three series of compounds based on the cyclohexene framework have been epoxidized by
dimethyldioxirane. A pronounced dependence of epoxide diastereoselectivity on substituent has
been observed. In addition there is a solvent influence on this stereoselectivity. The results have
been explained by invoking steric, H-bonding, and dipole-dipole influences on the epoxide
stereochemistry.
In tr od u ction
derivative 4a of 2a with dimethyldioxirane 1 to give the
corresponding epoxides 5, 6, and 7, respectively (eq 1).
In some cases the epoxides were accompanied by the
enone insertion products 8 or 9. All substrates were
The control of chemo-, regio-, and stereoselective
outcomes of chemical reactions has been an ongoing goal
of organic chemists.3 This goal is currently being applied,
by ourselves and others, to the reactions of dioxiranes,4
a class of relatively new and powerful oxidants. This
work gains an additional impetus when the reactions of
dioxiranes and peracids are compared with respect to
these various selectivities. In the work described here
we have examined diastereoselectivity and, to a lesser
extent, chemoselectivity in the reactions of dimethyldiox-
irane (1) with some cyclohexene derivatives. The ob-
served diastereoselectivities are influenced by a mix of
several factors including substituent size, H-bonding
effects, dipole-dipole interactions, and solvent effects. A
number of reports have appeared on diastereoselectivity
in dioxirane reactions5 and particularly with cyclohexene
derivatives6 and glycals.7
Resu lts
We have reacted derivatives of cyclohex-2-en-1-ol (2a ),
3-methylcyclohex-2-en-1-ol (3a ), and the homoallylic
oxidized first in acetone solvent. In most cases a number
of mixed solvents containing acetone were also used. The
results obtained in these reactions for derivatives of 2
are shown in Table 1. The products are the diastereo-
meric epoxides, with the enone product of a C-H inser-
tion reaction of 1 obtained in some cases. The conver-
sions are generally quite high. With only one exception
(2a in acetone), when both products of epoxidation and
insertion are obtained, the epoxidation product is the
major product. The results indicate that epoxide dia-
stereomer ratios are dependent both on the substituent
in 2 and the solvent used. The stereochemical assign-
ments were based on NMR chemical shifts and coupling
constants and comparison with literature examples. The
reaction of one substrate in this series requires an
additional comment. Compound 2g with a benzamido
substituent follows the usual course and gives epoxide
diastereomers, as disclosed by NMR. In this case,
however, the trans epoxide isomer is unstable and
rearranges when chromatographed to the benzoxazole
derivative 10. The trans arrangement of the epoxide and
X Abstract published in Advance ACS Abstracts, March 1, 1996.
(1) Chemistry of Dioxiranes. Part 29. Part 28 is Murray, R. W.; Gu,
H. J . Org. Chem. 1995, 60, 5673.
(2) Portions of this work have been published in preliminary form:
Murray, R. W.; Singh, M.; Williams, B. L.; Moncrieff, H. M. Tetrahe-
dron Lett. 1995, 36, 2437.
(3) (a) For a review of particular relevance to the subject of this
paper see: Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993,
93, 1307. See also: (b) Nogradi, M. Stereoselective Synthesis; VCH Pub-
lishers: New York, 1995; Chapter 4. (c) Berti, G. In Topics in
Stereochemistry; Allinger, N. L., Eliel, E. L., Eds.; Wiley: New York,
1973; Vol. 7, pp 93-251.
(4) For reviews see: (a) Murray, R. W. In Molecular Structure and
Energetics. Unconventional Chemical Bonding; Liebman, J . F., Green-
berg, A., Eds.; VCH Publishers: New York, 1988; Vol. 6, pp 311-351.
(b) Murray, R. W. Chem. Rev. 1989, 89, 1187. (c) Curci, R. In Advances
in Oxygenated Processes; Baumstark, A. L., Ed.; J AI Publishers:
Greenwich, CT, 1990; Vol. 2, Chapter 1, pp 1-59. (d) Adam, W.;
Hadjiarapoglou, L. P.; Curci, R.; Mello, R. In Organic Peroxides; Ando,
W., Ed.; Wiley: New York, 1992; Chapter 4, pp 195-219. (e) Adam,
W.; Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205. (f) Curci,
R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811.
(5) (a) Marples, B. A.; Muxworthy, J . P.; Baggaley, K. H. Tetrahedron
Lett. 1991, 32, 533. (b) Cicala, G.; Curci, R.; Fiorentino, M.; Laricchiuta,
O. J . Org. Chem. 1982, 47, 2670. (c) Schultz, A. G.; Harrington, R. E.;
Tham, F. S. Tetrahedron Lett. 1992, 33, 6097. (d) Curci, R.; Dinoi, A.;
Rubino, M. F. Pure Appl. Chem. 1995, 67, 811.
(6) (a) Adam, W.; Prechtl, F.;Richter, M. J .;Smerz, A. K. Tetrahedron
Lett. 1993, 34, 8427. (b) Kurihara, M.; Ito, S.; Tsutsumi, N.; Miyata,
N. Tetrahedron Lett. 1994, 35, 1577. (c) Armstrong, A.; Barsanti, P.
A.; Clarke, P. A.; Wood, A. Tetrahedron Lett. 1994, 35, 6155. (d)
Asensio, G.; Mello, R.; Boix-Bernardini, C.; Gonzalez-Nunez, M. E.;
Castellano, G. J . Org. Chem. 1995, 60, 3692.
(7) (a) Chow, K.; Danishefsky, S. J . J . Org. Chem. 1990, 55, 4211.
(b) Berkowitz, D. B.; Danishefsky, S. J .; Schulte, G. K. J . Am. Chem.
Soc. 1992, 114, 4518. (c) Dushin, R. G.; Danishefsky, S. J . J . Am. Chem.
Soc. 1992, 114, 3471. (d) Halcomb, R. L.; Danishefsky, S. J . J . Am.
Chem. Soc. 1989, 111, 6661. (e) Danishefsky, S. J .; McClure, K. F.;
Randolph, J . T.; Ruggeri, R. B. Science 1993, 260, 1307.
0022-3263/96/1961-1830$12.00/0 © 1996 American Chemical Society

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1831
Ta ble 1. Dia ster eoselectivity in Dim eth yld ioxir a n e Ep oxid a tion of Cycloh ex-2-en -1-ol Der iva tives 2a
epoxides (%)b
R in 2
solvent system
(%)
trans
cis
epoxides/enone (%)
conversion(%)
OH
(2a )
acetone
(100)
54
30
22
18
66
17
15
6
85
92
87
99
66
65
66
62
62
84
80
87
84
19
4
46
70
78
82
34
83
85
94
15
8
46/54
74/25
84/16
89/11
75/25
88/12
52/48
59/41
78/22
61/39
95/5
94
100
89
CH2Cl2/acetone
CH2Cl2/acetone
CH2Cl2/acetone
MeOH/acetone
CHCl3/acetone
CCl4/acetone
CCl4/acetone
acetone
CCl4/acetone
acetone
CCl4/acetone
acetone
CCl4/acetone
acetone
CH2Cl2/acetone
CCl4/acetone
acetone
CH2Cl2/acetone
CHCl3/acetone
CCl4/acetone
acetone
CH2Cl2/acetone
CCl4/acetone
MeOH/acetone
acetone
(75:25)
(90:10)
(97:3)
(90:10)
(90:10)
(90:10)
(95:5)
(100)
(90:10)
(100)
(90:10)
(100)
(90:10)
(100)
(90:10)
(90:10)
(100)
(90:10)
(90:10)
(90:10)
(100)
(90:10)
(90:10)
(90:10)
(100)
77
100
100
87
86
100
57
100
60
86
25
82
41
22
82
100
54
OCH3
(2b)
(2c)
(2d )
(2e)
OSi(CH3)3
OCdOCH3
OCdOCH2CH3
13
1
90/10
34
35
34
38
38
16
20
13
16
81
96
97
74
45
32
16
18
52
47
53
45
45
40
46
5
COOH
(2f)
73
NHCOPh
(2g)
100
100
100
64
97
56
3
26
55
68
84
82
48
53
47
55
55
60
54
95
96
90
94
82
85
83
51
57
90
93
92
CdOOCH3
OOH
(2h )
(2i)
(2j)
CCl4/acetone
acetone
CH2Cl2/acetone
acetone
CH2Cl2/acetone
CCl4/acetone
acetone
(90:10)
(100)
(50:50)
(100)
(90:10)
(90:10)
(100)
100c
100c
100
100
100
100
100
100
100d
94
96
70
73
100
70
CH3
CH2CH3
i-Bu
(2k )
(2l)
acetone
(100)
CH2Cl2/acetone
CCl4/acetone
acetone
CH2Cl2/acetone
acetone
CH2Cl2/acetone
acetone
CCl4/acetone
MeOH/acetone
acetone
(90:10)
(90:10)
(100)
(50:50)
(100)
(50:50)
(100)
(90:10)
(50:50)
(100)
t-Bu
CF3
Ph
(2m )
(2n )
(2o)
4
10
6
18
15
17
49
43
10
7
90
78
74
76
74
58
CN
Cl
(2p )
(2q)
(2r )
CH2Cl2/acetone
acetone
CH2Cl2/acetone
acetone
(50:50)
(100)
(50:50)
(100)
Br
8
a
b
Reactions performed at rt; substrate/DMD ratio (1:1); conversion was determined by GLC analysis at 60 min. The ratio of epoxide
diastereoisomers was determined by GLC analysis. c Conversion and the ratio of the epoxides was determined by 1H NMR after 20 h.
d
After 120 min.
benzamido groups permits a facile opening8 of the epoxide
as shown in structure 11.
of the trans epoxide when comparisons are made between
substrates bearing the same substituents as in 2. Fi-
nally, Table 3 summarizes the results obtained when
derivatives of 4 are oxidized by 1. No C-H insertion
reactions are observed in this series. Again the conver-
sions are uniformly very high. The variation in epoxide
diastereomer ratio with substituent is also less pro-
nounced in this series although there is clearly a sub-
stituent influence. Here again the substrate with the
benzamido substituent 4f gives an unstable trans epoxide
which rearranges to the benzoxazine 12.
Table 2 gives the results obtained when derivatives of
3 are oxidized by 1. While a smaller number of substit-
uents were used in this series the results are similar to
those given by 2. In this case, however, the epoxide is
the dominant product in all cases where both epoxidation
and insertion reactions are observed. Also, the presence
of the 3-methyl group tends to accentuate the favoring
Discu ssion
Su bstitu en t Effect on Ep oxid e Ster eoselectivity.
An examination of Tables 1-3 reveals that there is a
strong effect of substituent on epoxide stereoisomer ratio,
with the effect being greatest in compounds 3. This is
presumably due to the added steric requirements of the
3-methyl substituent. With compounds in series 2 and
(8) Roush, W. R.; Straub, J . A.; Brown, R. J . J . Org. Chem. 1987,
52, 5127.

1832 J . Org. Chem., Vol. 61, No. 5, 1996
Murray et al.
Ta ble 2. Dia ster eoselectivity in Dim eth yld ioxir a n e Ep oxid a tion of 3-Meth yl-2-cycloh ex-2-en -1-ol Der iva tives 3a
epoxides (%)b
R in 3
OH
solvent system
(%)
trans
cis
epoxides/enone (%)
conversion (%)
(3a )
acetone
(100)
65
39
35
13
82
73
74
17
21
95
95
95
5
95
99
87
88
73
77
31
61
65
87
18
27
26
83
79
5
5
5
95
5
1
65/35
85/15
89/11
94/6
86/14
88/12
89/11
93/7
76/24
87/13
92/8
91/9
80/20
97/3
95
93
96
81
69
85
100
91
89
100
75
92
86
100
86
94
CH2Cl2/acetone
CH2Cl2/acetone
CH2Cl2/acetone
MeOH/acetone
ButOH/acetone
AcOH/acetone
CHCl3/acetone
CCl4/acetone
acetone
CH2Cl2/acetone
CH2Cl2/acetone
CCl4/acetone
acetone
(80:20)
(90:10)
(95:5)
(90:10)
(90:10)
(90:10)
(90:10)
(90:10)
(100)
(80:20)
(95:5)
(95:5)
(100)
OCH3
(3b)
OSi(CH3)3
OCdOCH3
CH3
(3c)
(3d )
(3e)
CCl4/acetone
acetone
CCl4/acetone
acetone
(90:10)
(100)
(90:10)
(100)
96/4
13
12
27
23
63
100c
100c
CH2Cl2/acetone
(70:30)
a
b
Reactions performed at rt; substrate/DMD ratio (1:1); conversion was determined by GLC analysis at 60 min. The ratio of epoxide
diastereoisomers was determined by GLC analysis.
Ta ble 3. Dia ster eoselectivity in Dim eth yld ioxir a n e Ep oxid a tion of Hom oa llylic Cycloh exen es 4a
epoxides (%)b
R in 4
solvent system
(%)
trans
cis
conversion (%)
OH
Br
(4a )
(4b)
acetone
(100)
44
30
28
37
33
26
55
38
40
45
27
40
40
37
39
29
35
38
27
26
41
36
18
13
56
70
72
63
67
74
45
62
60
55
73
60f
60f
63
61
71
65
62
73
74
59
64
82
87
100
100
68
100
92
CH2Cl2/acetone
CH2Cl2/acetone
CHCl3/acetone
CCl4/acetone
CCl4/acetone
MeOH/acetone
acetone
CH2Cl2/acetone
MeOH/acetone
CCl4/acetone
acetone
CH2Cl2/acetone
acetone
CH2Cl2/acetone
CCl4/acetone
acetone
(90:10)
(95:5)
(90:10)
(90:10)
(95:5)
(90:10)
(100)
(50:50)
(50:50)
(90:10)
(100)
(90:10)
(100)
(90:10)
(90:10)
(100)
84
72c
100
100
100d
100e
100
100
100g
96
OCdOCH3
CdOOCH3
(4c)
(4d )
91
CdOOCH2CH3
NHCdOPh
(4e)
(4f)
100g
87
CH2Cl2/acetone
CCl4/acetone
CCl4/acetone
MeOH/acetone
acetone
(90:10)
(90:10)
(95:5)
(90:10)
(100)
89
80
84
100g
100
100
CCl4/acetone
CCl4/acetone
(90:10)
(95:5)
a
b
Reactions performed at rt; substrate/DMD ratio (1:1); conversion was determined by GLC analysis at 60 min. The ratio of epoxide
diastereoisomers was determined by GLC analysis. c After 120 min. After 90 min. e After 300 min. f By 1H NMR. After 15 min.
d
g
3 most of the epoxide ratios appear to be determined
primarily by the steric influence of the substituents. For
substituents where Taft9 steric substituent constants (Es)
are available, a plot of these constants versus log epoxide
trans/cis ratios gives an excellent linear correlation. The
plot in which four of these substituents are included is
shown in Figure 1. This plot has an excellent correlation
coefficient (R ) 0.9954). The slope (δ ) -0.867) of the
correlation line indicates that the steric influence is
similar to that in the model system used to derive the Es
values. When an additional substituent (CH2Br) is
included, a linear plot is again obtained, but with a
slightly lower correlation coefficient (R ) 0.9582). The
larger the substituent the more trans isomer is formed.
With compounds 4 no substituent gave a predominance
of trans isomer. Thus the homoallylic framework allows
for a different interaction between substituent and at-
tacking dioxirane. In these compounds we believe dipole-
dipole interactions are important (vide infra).
Hyd r ogen Bon d in g Effects. There are two substit-
uents which do not appear to follow the steric effect
analysis alone. These are the hydroxyl group in com-
pounds 2a , 3a and 4a and the amide group in 2g and 4f.
The separate influence of these substituents is particu-
larly noticeable when the effect of solvent is examined.
In all of these cases changing the solvent by increasing
the amount of a second solvent leads to an increase in
the amount of the cis epoxide. The diastereomeric
epoxide distribution is, in essence, tunable depending on
choice of solvent. Thus 2a gives an epoxide trans/cis
distribution in 100% acetone of 54/46, while in CCl4/
acetone (95:5) the distribution becomes 6/94 in favor of
(9) Taft, R. W. J . Am. Chem. Soc. 1952, 74, 3120.

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1833
On the other hand, when the diluting solvent is itself able
to H-bond with the substrate, then the effect of the second
solvent is diminished, or, as in the case of 2a in MeOH:
acetone (90:10), actually gives more of the trans isomer
since such solvent H-bonding will block the cis approach
of the dioxirane. Examination of Tables 1-3 reveals that
substrates with substituents which are not capable of
H-bonding give epoxide ratios which are relatively in-
sensitive to change of solvent.
Dip ole-Dip ole Dir ectin g Effects. The stereoselec-
tivity seen in the epoxides produced from substrates
4b-e in the homoallylic series (Table 3) requires another
explanation. In all cases the cis isomer is dominant.
These results clearly run counter to the general steric
effect argument which appears to be controlling for those
compounds in series 2 and 3 not affected by H-bonding
effects. One possible explanation is related to discussions
given earlier by Curci et al.5d and Bovicelli and co-
workers.10 Thus formation of the anti-1,2;3,4-dioxide in
the oxidation of naphthalene by methyl(trifluoromethyl)-
dioxirane was explained5d by postulating an interaction
between the first epoxide formed and the dipolar diox-
irane, leading to an anti attack. On the other hand
oxidation of prednisone acetate by 1 to give 80% of the
1R,2R-oxirane derivative was interpreted10 as indicating
an attractive dipole-dipole interaction between the at-
tacking dioxirane and the carbonyl group at C11. Such a
stereoorienting effect leads to R attack at the neighboring
1,2 double bond. In the absence of the orienting effect
of the C11 carbonyl group, such as in androsta-1,4-diene-
3,7-dione, the major epoxidation product is the 4â,5â-
epoxide.
We believe that the epoxide distributions obtained from
compounds 4b-e can be rationalized on the basis of
similar dipole-dipole interaction arguments. In each of
these compounds there is a strong dipole, a C-Br bond
in 4b and a carbonyl group in compounds 4c-4e. This
dipole could lead to an attractive dipole-dipole interac-
tion with the strong dipole11 of 1 and a resultant favoring
of cis attack by the incoming dioxirane. The intervening
methylene group in the homoallylic compounds must
permit a greater influence of this type of interaction than
in the compounds in series 2 where steric effects domi-
nate in most cases. Some support for this argument
comes from an examination of the epoxide ratio formed
from compound 2k with an ethyl group as substituent.
This compound could be regarded as a member of the
homoallylic series with methyl as substituent. The
epoxide ratio obtained from 2k is 55:45 (trans/cis). Thus
when no dipole is present the steric effect is the dominant
effect. The differences in the amount of the cis epoxide
isomer obtained in compounds 4c-e may reflect a
difference in the proximity of the directing carbonyl group
to the double bond. In compounds 4d and 4e the
carbonyl group is closer to the double bond than it is in
4c leading to a higher % cis isomer in 4d and 4e. The
solvent effect on epoxide diastereoselectivity seen in
compounds 4b-e can be rationalized in a manner which
parallels the explanation given for a similar effect of
solvent on those compounds in series 2 and 3 that are
capable of intramolecular H-bonding. In compound 4e,
for example, diluting the acetone solvent with CCl4 leads
F igu r e 1. Plot of log epoxide trans/ cis ratios versus Taft9
steric substituent constants Es.
the cis isomer. The effect is even more pronounced in
the case of 3a . Here the epoxide ratio in 100% acetone
is 65/31 (trans/cis), but a solvent consisting of CCl4/
acetone (95:5) gives a ratio of 5/95 (trans/cis). A similar
but diminished change is observed for 4a . Here 100%
acetone gives an epoxide ratio of 44/56 (trans/cis) as
compared to a ratio of 26/74 (trans/cis) in a solvent
composition of CCl4/acetone of 95:5. Substrate 2g, con-
taining the NH group of an amide is also susceptible to
this solvent effect. This compound gives a trans/cis
epoxide ratio of 19/81 in 100% acetone, but a ratio of 3/97
in a solvent composition of 90:10, CCl4:acetone. The
corresponding compound 4f in the homoallylic series
gives a trans/cis epoxide ratio of 36/64 in acetone and a
ratio of 18/82 in 90:10, CCl4:acetone. We attribute this
effect of solvent on epoxide isomer distribution, in
substrates containing an OH or NH group, to the relative
ease of attaining a transition state, such as 13 for 2a , in
which H-bonding can occur with the developing negative
charge on one oxygen of the dioxirane in the activated
complex. It should be noted that when the various
epoxide isomer ratios are compared in acetone solvent,
then the amido groups in compounds 2g and 4f give the
highest amount of the cis isomer. This is presumably
due to the increased acidity of the hydrogen in the amido
function. This H-bonding effect should be seen as ac-
companying the apparent greater influence of a dipole-
dipole interaction (vide infra). A similar transition state
involving H-bonding from -NH3+ has been proposed6d for
the epoxidation of some amino-substituted cyclohexenes.
The solvent effect is traceable largely to the ability of
a second solvent to dissociate the dioxirane from its
strong association with acetone. In the current work the
change from 100% acetone to a solvent composition rich
in CCl4, for example, apparently leads to a dioxirane that
is less solvated by acetone and consequently is more able
to take advantage of intermolecular H-bonding as in 13.
(10) Bovicelli, P.; Lupatelli, P.; Mincione, E. J . Org. Chem. 1994,
59, 4304.
(11) The parent dioxirane has been found to have a very strong
dipole (µ ) 2.5 D). Herron, J . T.; Huie, R. E. J . Am. Chem. Soc. 1977,
100, 5582.

1834 J . Org. Chem., Vol. 61, No. 5, 1996
Murray et al.
to more cis epoxide, presumably because the dipole-
dipole interaction is greater in this solvent combination.
The effect of an H-bonding solvent in these compounds
is similar to that seen in series 2 and 3 also. Thus in
compounds 4b and 4e when the second solvent is
methanol less cis epoxide is formed as H-bonding of the
substrates with methanol reduces the opportunity for the
cis-favoring dipole-dipole interaction.
tions. Instead the involvement of dipole-dipole interac-
tions of the type we have described for some of the
compounds in series 4 apparently may provide a similar
stereocontrol.
Su m m a r y. Our results indicate that epoxide diaste-
reoselectivity in the epoxidation of cyclohexene deriva-
tives by dimethyldioxirane is subject to a number of
substrate and solvent influences. Included in the sub-
strate influences are steric effects, H-bonding, and dipole-
dipole interactions. The results suggest that these
various factors could be manipulated to give desired
stereocontrol in these and related epoxidations. Thus if,
for example, the cis epoxide isomer were a synthetic
target in one of the molecular frameworks used here, or
in related frameworks, then the various factors affecting
stereoselectivity could be chosen to maximize cis stereo-
selectivity.
Ch em oselectivity. As shown in Tables 1 and 2
several of the compounds (2a , 2b, 2c, 3a , 3b, and 3c) in
series 2 and 3 give enone 8 or 9, respectively, as well as
epoxide products. None of the compounds in the homoal-
lylic series (Table 3) gave enone products. The enones
are the result of a dioxirane C-H bond insertion reac-
tion.12 A competition between epoxidation and insertion
has been studied by several other groups. Adam and co-
workers6a have found that increasing substitution at the
double bond in cyclohexenols leads to a decreasing
amount of the insertion reaction. Also Marples et al.5a
found, in the oxidation of some steroidal alcohols, that
steric factors can completely block the epoxidation reac-
tion and permit the insertion reaction to be the sole
reaction. In the OH-substituted compounds 2a and 3a
the insertion reaction is rapid as described earlier.4 As
seen in Tables 2 and 3 there is a solvent effect on the
competition between epoxidation and insertion reactions.
This effect is most pronounced for 2a where the % epoxide
formed varies from 89% in 97:3 (CH2Cl2/acetone) to 46%
in 100% acetone. The solvent effect on this reaction
competition is diminished in 3a and the ethers 2b, 2c,
and 3b and 3c.
Com p a r ison to P er a cid Oxid a tion s. The epoxida-
tion of cyclohexene derivatives described here follows the
original13 observation of Henbest and Wilson that the OH
group provides stereocontrol favoring the cis isomer in
peracid epoxidations. Subsequently this same directing
effect has been observed3a in a variety of cyclic allylic
alcohols. An amide group was also found14,15 to give this
same cis stereoselectivity in peracid epoxidations in cyclic
olefins. This observation prompted us to study the effect
of an amide substituent (compounds 2g and 4f) in our
dioxirane epoxidations. Here too we found a parallel with
the peracid epoxidations with this group providing ste-
reocontrol favoring the cis isomer. The stereocontrol
provided by H-bonding substituents in the peracid reac-
tions was explained by invoking the Bartlett16 mechanism
involving H-bonding between the substituent and one of
the oxygens of the peracid. The functionally analagous
process for the dioxirane epoxidations described here is
illustrated in structure 12. In the peracid epoxidations
substituents which do not have OH or NH groups, but
which contain a carbonyl group, are believed3a,6c to give
cis stereoselectivity by H-bonding involving the peracid
proton and the substituent carbonyl group. Obviously a
similar process is not possible for the dioxirane epoxida-
Exp er im en ta l Section
In str u m en ta tion a n d Gen er a l Meth od s. 1H NMR spec-
tra were recorded on a 300 MHz NMR spectrometer with
tetramethylsilane (0.00 ppm) as an internal reference in CDCl3
as the solvent. All NMR data are reported in ppm or δ values
downfield from TMS and coupling constants, J , are reported
in Hz. 13C NMR spectra were recorded at 75 MHz in CDCl3.
The center peak of the solvent CDCl3 at 77.00 ppm was used
as an internal reference. The multiplicities of the 13C NMR
signals were determined by the attached proton test (APT)
pulse sequence. Where necessary, COSY and HETCOR ex-
periments were performed on a 500 MHz spectrometer (1H,
500.13 MHz, and 13C, 125.75 MHz). 19F NMR spectra were
recorded on a 500 spectrometer at 470.55 MHz and are
referenced against internal CFCl3 (δ 0.00 ppm). Electron
impact and chemical ionization mass spectra were recorded,
at 70 eV ionizing voltage, on a twin EI and CI quadrupole mass
spectrometer connected to a gas chromatograph fitted with a
12 m × 0.2 mm × 0.33 µm Ultra-1 (cross-linked methyl
silicone) column. UV-vis spectra were obtained on a UV-vis
spectrophotometer. Infrared spectra were recorded as thin
films between KBr disks or in KBr pellets on an FT-IR
spectrometer. Melting points were determined on a hot-stage
apparatus and are uncorrected. Gas chromatography was
performed on a capillary gas chromatograph using a flame
ionization detector, a fused silica DB-210 capillary column (30
m × 0.318 mm; film thickness 0.5 µm) or a fused silica DB-5
capillary column (30 m × 0.25 mm; film thickness 0.5 µm),
and He as the carrier gas. The chromatograph was interfaced
with an integrator. Preparative GC was performed on a
preparative gas chromatograph employing a dual rhenium-
tungsten filament thermal conductivity detector and using He
3
as carrier. The columns used were a 12 ft × /8 in. aluminum
column packed with 8% SF-96 methyl silicone on chromosorb
3
G 60/80 mesh or a 20 ft ×
/ in. aluminum column packed
8
with a 15% SE-30 on chromosorb W 30/60 mesh or a 10 ft ×
3/8 in. aluminum column packed with 10% UCON-50-HB-280X
on DMCS chromosorb W 45/60 mesh. Chromatographic
separations on the Chromatotron were accomplished using
Kieselgel 60 PF254 gypsum coated plates. Elemental analyses
were performed by Atlantic MicroLab, Inc. (Norcross, GA) and
Quantitative Technologies Inc. (Whitehouse, NJ ).
Ma ter ia ls a n d Rea gen ts. Acetone (Fisher reagent grade)
was fractionally distilled over anhydrous potassium carbonate.
Oxone (Du Pont), 2 KHSO5‚KHSO4‚K2SO4, was obtained from
Aldrich and used as such. Cyclohexene (Fisher), 2-cyclohexen-
1-ol, 2-cyclohexen-2-one, 3-methyl-2-cyclohexen-1-ol, phenyl-
magnesium bromide, ethylmagnesium bromide (all from Al-
drich), 3-methylcyclohexene (J anssen Chimica), 1,3-dimethyl-
cyclohexene, 3-methyl-2-cyclohexen-1-one (both from Wiley
Organics) were of the highest purity and were used as such
after verifying their purity by GLC. In a few cases, neat olefins
were passed through a small column of neutral alumina
(Brockman activity 1) to remove traces of oxygenated impuri-
(12) (a) Murray, R. W.; J eyaraman, R. J .; Mohan, L. J . Am. Chem.
Soc. 1986, 108, 2470. (b) Mello, R.; Fiorentino, M.; Sciacovelli, O.; Curci,
R. J . Org. Chem. 1988, 53, 3890. (c) Mello, R.; Fiorentino, M.; Fusco,
C.; Curci, R. J . Am. Chem. Soc. 1989, 111, 6749. (d) Murray, R. W.;
Gu, D. J . Chem. Soc. Perkin Trans. 2 1994, 451. (e) Curci, R.; D’Accolti,
L.; Fiorentino, M.; Fusco, C.; Adam, W.; Gonzalez-Nunez, M. E.; Mello,
R. Tetrahedron Lett. 1992, 33, 4255. (f) Kuck, D.; Schuster, A.; Fusco,
C.; Fiorentino, M.; Curci, R. J . Am. Chem. Soc. 1994, 116, 2375. (g)
Murray, R. W.; Gu, H. J . Org. Chem. 1995, 60, 5673.
(13) Henbest, H. B.; Wilson, R. A. J . Chem. Soc. 1957, 1958.
(14) Hasegawa, A.; Sable, H. Z. J . Org. Chem. 1966, 31, 4154.
(15) Goodman, L.;Winstein, S.; Boschan, R. J . Am. Chem. Soc. 1958,
80, 4312.
(16) Bartlett, P. D. Rec. Chem. Prog. 1950, 11, 47.

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1835
ties and were analyzed by GLC to verify their purity. 3-Bro-
mocyclohexene (90% from Aldrich and Lancaster), 3-chloro-
cyclohexene (95% from Wiley Organics), and 3-methoxy-
cyclohexene (90% from Alfa Morton Thiokol) were purified by
fractional distillation or by bulb to bulb kugelrohr distillation.
The dimethyldioxirane solution in acetone was prepared
according to the literature procedure17 and was assayed for
dioxirane content using phenyl methyl sulfide, and the GLC
method or concentration was determined using a calibration
curve of concentration of the DMD versus UV absorbance at
335 nm.
P r ep a r a tion , P u r ifica tion a n d Ch a r a cter iza tion of th e
Ep oxid a tion Su bstr a tes. The substrates were prepared
according to the literautre procedures. Analytically pure
samples of liquid substrates were collected by preparative
GLC. The collected samples were characterized by 1H and 13C
NMR and mass spectroscopy.
3-Ch lor ocycloh exen e (2q) was obtained by purification
(GLC) of a technical grade sample and was collected as a
colorless liquid.30
3-Br om ocycloh exen e (2r ) was obtained by purification
(GLC) of a technical grade sample and was collected as a
colorless liquid.31
3-Meth yl-2-cycloh exen -1-ol (3a ) was prepared by LiAlH4
reduction of 3-methyl-2-cyclohexen-1-one in ether.32
3-Meth oxy-1-m eth ylcycloh exen e (3b) was synthesized
by the method of Zon and Paquette.33
3-(Tr im eth ylsilyloxy)-1-m eth ylcycloh exen e (3c) was
prepared by following the literature procedure.19
3-(Acetyloxy)-1-m eth ylcycloh exen e (3d ) was prepared
by the standard acetylation method.34
2-Cycloh exen e-1-m eth a n ol (4a ) was prepared by the
literature procedure.35,36
3-(Br om om eth yl)cycloh exen e (4b) was prepared by the
literature procedure.36
3-Meth oxycycloh exen e (2b). A technical grade sample
was purified by fractional distillation.18
3-[(Acetyloxy)m eth yl]cycloh exen e (4c) was prepared by
the standard procedure.37
(2-Cycloh exen -1-yloxy)tr im eth ylsila n e (2c) was pre-
pared by the literature procedure.19
2-Cycloh exen e-1-a cetic a cid m eth yl ester (4d ) was
prepared by treating 2-cyclohexene-1-acetic acid with an excess
of diazomethane38 as a colorless liquid.20
3-(Acetyloxy)cycloh exen e (2d ) was synthesized by the
standard acetylation method.20,21
2-Cycloh exen e-1-a cetic a cid eth yl ester (4e) was pre-
3-(P r op ion yloxy)cycloh exen e (2e) was prepared by reac-
tion of 2-cyclohexen-1-ol and propionic anhydride.22
Cycloh ex-2-en e-1-ca r boxylic a cid (2f) was prepared by
the literature procedure.23
3-Ben za m id ocycloh exen e (2g) was synthesized by the
literature method.24 An analytically pure sample was isolated
by recrystallization from CH2Cl2-hexane as a colorless crys-
talline solid: mp 101-103 °C; lit.24 mp 100-101.2 °C.
2-Cycloh exen e-1-ca r boxylic a cid m eth yl ester (2h ) was
prepared by the literature procedure.23
3-Eth ylcycloh exen e (2k ) was synthesized by reaction of
3-bromocyclohexene and ethylmagnesium bromide according
to the literature method.20
3-Isobu tylcycloh exen e (2l) was synthesized by reaction
of 3-bromocyclohexene and isobutylmagnesium bromide ac-
cording to the literature method.26
pared by the literature procedure.39
N-(2-Cycloh exen -1-ylm eth yl)ben za m id e (4f). To a solu-
tion of 2-cyclohexene-1-methanol mesylate36 (0.6925 g, 3.64
mmol) in DMF (25 mL) was added sodium azide (0.5755 g,
8.85 mmol) with stirring. The reaction mixture was heated
at 80 °C for 8 h. Water (100 mL) was added, and the solution
was extracted with CH2Cl2 (50 mL). The CH2Cl2 layer was
washed several times with water and dried with anhydrous
Na2SO4. Evaporation of CH2Cl2 in vacuo gave an orange-
yellow liquid. Bulb-to-bulb distillation (oven temp 60 °C/0.1
mmHg) of the crude sample afforded an analytically pure
sample of 3-(azidomethyl)cyclohexene (0.5 g, 100%) as a
colorless liquid: 1H NMR (CDCl3) δ 1.25-1.90 (m, 4H), 1.95-
2.10 (m, 2H), 2.35 (m, 1H), 3.10-3.40 (m, 2H), 5.50-5.60 (m,
1H), 5.75-5.85 (m, 1H); 13C NMR (CDCl3) δ 20.80, 25.19, 26.66,
35.75, 56.50, 127.46, 129.63; MS (EI, 70 eV) m/ z 108 (M+
-
3-ter t-Bu tylcycloh exen e (2m ) was synthesized by reac-
tion of 2-tert-butylcyclohexanone tosylhydrazone and n-butyl-
lithium according to the literature method.27
29,1), 81(100), 79(38), 67(3), 53(13); calcd for C7H11N3: 137.18.
To a solution of 3-(azidomethyl)cyclohexene (0.5 g, 3.64
mmol) in THF (25 mL) was added triphenylphosphine (0.96
g, 3.66 mmol), and the reaction mixture was stirred at 60 °C
for 2 h, a solution of NaOH (2 g in 20 mL water) was added,
and the reaction mixture was stirred at 60 °C for 2 h. Ether
(25 mL) was added to the mixture, and it was extracted with
a 20% HCl solution (50 mL). The aqueous layer was separated
and extracted with ether (25 mL) and made strongly alkaline
with NaOH. The solution was extracted with CH2Cl2 (25 mL)
and anhydrous HCl gas was bubbled through the solution to
afford a shiny white flaky solid which was filtered, washed
with acetone, and dried in vacuo to give 2-cyclohexene-1-
methanamine hydrochloride (0.2868 g, 54%). A part of the
hydrochloride salt was neutralized with NaOH and extracted
with a mixture of ether/hexane. The organic extracts were
dried with anhydrous Na2SO4 and evaporated in vacuo to give
a pale yellow liquid which was purified by preparative GLC
to afford free 2-cyclohexene-1-methanamine as a colorless
liquid: 1H NMR (CDCl3) δ 1.20-1.65 (m, 2H), 1.43 (br s, 2H),
3-(Tr iflu or om eth yl)cycloh exen e (2n ) was prepared by
the literature procedure.28
3-P h en ylcycloh exen e (2o) was prepared by reaction of
3-bromocyclohexene and phenylmagnesium bromide in ether
according to the literature procedure.29
2-Cycloh exen e-1-ca r bon itr ile (2p ) was prepared by the
reaction of 3-bromocyclohexene with NaCN according to the
literature procedure.23
(17) (a) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847.
(b) Singh, M.; Murray, R. W. J . Org. Chem. 1992, 57, 4263.
(18) (a) Lessard, J .; Tan, P. V. M.; Martino, R.; Saunders, J . K. Can.
J . Chem. 1977, 55, 1015. (b) Vishwakarma, L. C.; Walia, J . S. J . Ind.
Chem. Soc. 1976, 53, 156.
(19) Chavdarian, C. G.; Heathcock, C. H. Synth. Commun. 1976, 6,
277.
(20) Pearson, A. J ., Hsu, S.-Y. J . Org. Chem. 1986, 51, 2505.
(21) Chow, Y. L.; Buono-Core, G. E. J . Am. Chem. Soc. 1986, 108,
1234.
(22) (a) Okano, M. J . Sci. Hiroshima Univ., Ser. A: Phys. Chem.
1976, 40, 169; Chem. Abstr. 1977, 86, 43234X. (b) Damin, B.; Garapan,
J .; Sillion, B. Tetrahedron Lett. 1980, 21, 1709.
(23) Davies, S. G. and Whitham, G. H. J . Chem. Soc. Perkin Trans.
1 1976, 2279.
(24) Goodman, L.; Winstein, R.; Boschan, R. J . Am. Chem. Soc. 1958,
80, 4312.
(25) Meyer, C.; Burger, J .; Clement, G.; Balaceanu, J . C. Fr. Patent
1,292,244 (1962); Chem. Abstr. 1962, 57, 14966h. (b) Frimer, A. A. J .
Org. Chem. 1977, 42, 3194. (c) Bloodworth, A. J .; Eggelte, H. J . J .
Chem. Soc. Perkin Trans 1 1981, 1375.
(26) Mark, V.; Pines, H. J . Am. Chem. Soc. 1956, 78, 5946.
(27) Richer, J .-C.; Freppel, C. Can. J . Chem. 1968, 46, 3709.
(28) Bouillon, J .-P.; Maliverney, C.; Mere´nyi, R.; Viehe, H. G. J .
Chem. Soc. Perkin Trans. 1 1991, 2147.
(30) Goering, H. L.; Nevitt, T. D.; Silversmith, E. F. J . Am. Chem.
Soc. 1955, 77, 5026.
(31) Selle´n, M.; Ba¨ckvall, J .-E.; Helquist, P. J . Org. Chem. 1991,
56, 835.
(32) Elphimoff-Felkin, I., Sarda, P. Org. Synth. 1977, 56, 101.
(33) (a) Zon, G.; Paquette, L. A. J . Am. Chem. Soc. 1974, 96, 215.
(b) Chow, H.-F.; Fleming, I. J . Chem. Soc. Perkin Trans. 1 1984, 1815.
(34) Spahic, B.; Thu, T. T. M.; Schlosser, M. Helv. Chim. Acta 1980,
63, 1236.
(35) Chini, M.; Crotti, P.; Flippin, L. A.; Gardelli, C.; Macchia, F. J .
Org. Chem. 1992, 57, 1713.
(36) Walton, J . C. J . Chem. Soc. Perkin Trans. 2 1986, 1641.
(37) (a) Nazarov, I. N.; Kuznetsov, N. V. Doklady Acad. Nauk. SSSR.
1956, 111, 358; Chem. Abstr. 1957, 51, 9504d. (b) Ferrand, G.; Huet,
J . Bull. Soc. Chim. Fr. 1975, 356.
(38) Youssef, A. A.; Sharaf, S. M. J . Org. Chem. 1968, 33, 2581.
(39) J ones, G. B.; Huber, R. S.; Chau, S. Tetrahedron 1993, 49, 369.
(29) (a) Berlande, A. Bull. Soc. Chim. Fr. 1942, 9, 642. (b) Kamigata,
N; Satoh, A.; Kondoh, T.; Kameyama, M. Bull. Chem. Soc. J pn. 1988,
61, 3575.

1836 J . Org. Chem., Vol. 61, No. 5, 1996
Murray et al.
1.65-1.90 (m, 2H), 1.95-2.08 (m, 2H), 2.12 (m, 1H), 2.55-
2.72 (m, 2H), 5.53-5.63 (m, 1H), 5.71-5.84 (m, 1H); 13C NMR
(CDCl3): δ 21.30, 25.44, 26.58, 38.92, 47.58, 128.48, 129.29;
MS (EI, 70 eV): m/ z 112(M + 1,1), 111(M+,9), 94(22), 81(29),
79(100), 67(21), 53(34), 41(26); Calcd for C7H13N: 111.17.
To an ice-cooled solution of 2-cyclohexene-1-methanamine
hydrochloride (0.2 g, 1.3546 mmol) and sodium hydroxide (0.3
g, 0.75 mmol) in water (4 mL) was added benzoyl chloride (0.2
g, 1.4727 mmol) with stirring. The reaction mixture was
stirred for 2 h. A white precipitate was formed immediately.
The precipitate was filtered and washed with a dilute solution
of NaOH and then with water. The residue was dried in vacuo
for 2 h. The residue was purified by radial chromatography
(silica gel plate, acetone/CH2Cl2 (5:95) as the eluent) to afford
pure 4f as a colorless crystalline solid (0.2602 g, 90%): mp
82-84 °C; IR (KBr) 3314 (NH), 2931, 1636 (CdO), 1540, 1489,
0.3), 96(6), 95(4), 83(2), 71(13), 70(100), 58(39), 57(83), 55(13),
43(12), 41(16); calcd for C6H10O2: 114.14.
The third product was identified as 2-cycloh exen -1-on e
(8) by comparing its mass spectral data43 with those in the
literature and on the basis of the following data: a colorless
liquid; 1H NMR (CDCl3): δ 1.95-2.10 (m, 2H), 2.30-2.40 (m,
2H), 2.40-2.50 (m, 2H), 6.03 (dt, J ) 10.0, 2.0 Hz, 1H), 7.01
(dt, J ) 10.0, 4.0 Hz, 1H); MS (EI, 70 eV): m/ z 97(M + 1, 2),
96(M+, 34), 68(100), 55(5), 53(3), 42(4); Calcd for C6H8O: 96.13.
A minor product was also isolated from the reaction mixture
and was identified as 2,3-ep oxycycloh exa n e-1-on e by com-
paring its NMR41 and mass spectral data43 with the literature
values and on the basis of the following data: a colorless liquid;
1H NMR (CDCl3): δ 1.60-1.75 (m, 1H), 1.85-2.15 (m, 3H),
2.20-2.35 (m, 1H), 2.50-2.65 (m, 1H), 3.22 (d, J ) 3.91 Hz,
1H), 3.59 (m, 1H); 13C NMR (CDCl3): δ 16.97, 22.82, 36.34,
55.02, 55.85, 205.64; MS (EI, 70 eV) m/ z 113(M + 1, 2), 112
(M+, 32), 83(17), 68(7), 57(20), 56(15), 55(100), 41(10); calcd
for C6H8O2: 112.13.
1
1433, 1312, 693 cm-1; H NMR (CDCl3) δ 1.25-1.90 (m, 4H),
1.90-2.10 (m, 2H), 2.45 (m, 1H), 3.28-3.40 (m, 1H), 3.42-
3.55 (m, 1H), 5.57-5.68 (m, 1H), 5.75-5.90 (m, 1H), 6.43 (br
s, 1H), 7.30-7.60 (m, 3H), 7.65-7.90 (m, 2H); 13C NMR (CDCl3)
δ 20.98, 25.20, 26.74, 35.53, 44.72, 126.73, 128.11, 128.33,
129.36, 131.12, 134.67, 167.53; MS (EI, 70 eV) m/ z 216(M +
1, 0.3), 215(M+,2), 134(19), 122(19), 105(100), 94(10), 77(30);
calcd for C14H17NO: 215.28. Anal. Calcd for C14H17NO: C,
78.09; H, 7.96; N, 6.51. Found: C, 78.00; H, 7.74; N, 6.53.
Gen er a l P r oced u r e for th e Ep oxid a tion of Cycloh ex-
en e Der iva tives w ith Dim eth yld ioxir a n e. The reactions
were carried out by addition of a solution of dimethyldioxirane
in acetone to a magnetically stirred solution of the substrate
in acetone (or other solvent, see Tables 1-3) at room temper-
ature (20-22 °C). An equimolar solution of dimethyldioxirane
and the substrate was used. The progress of the reaction was
monitored periodically by GLC and GC-MS. The ratio of
epoxide diastereoisomers, as well as the product distribution,
was determined by GLC analysis of the reaction mixture at
60 min unless stated otherwise. Stirring was continued until
consumption of the substrate, or the reaction mixture was
stirred for a longer time to attain a suitable conversion.
Solvent was removed on a rotary evaporator at low tempera-
ture or where necessary, by fractional distillation. GLC
analysis of the distillation fractions indicated that only minor
amounts of products were contained in these fractions. The
relative ratio of epoxide isomers and product distribution was
determined by 1H NMR analysis on the crude reaction mixture
residue obtained after removal of the solvent. The ratios
Ep oxid a tion of 2b by 1. The general procedure was
followed to give a residue which was found to contain three
major products and a minor product. The products were
separated by preparative GLC. One of the major products was
identified as 3-m eth oxy-tr a n s-1,2-epoxycycloh exan e (tr a n s-
5b) by comparing its properties with those in the literature44-46
1
and on the basis of the following data: a colorless liquid; H
NMR (CDCl3) δ 1.10-1.30 (m, 2H), 1.35-1.55 (m, 1H), 1.65-
1.90 (m, 2H), 1.95-2.10 (m, 1H), 3.11 (dd, J ) 3.77, 0.71 Hz,
1H), 3.21 (m, 1H), 3.45 (s, 3H), 3.50 (dd, J ) 7.94, 5.74 Hz,
1H); 13C NMR (CDCl3) δ 14.57, 24.24, 26.31, 52.92, 54.02,
56.93, 75.00; MS (EI, 70 eV) m/ z 128 (M+, 1), 127(1), 97(6),
84(9), 71(100), 67(12), 57(10), 53(8), 41(27); calcd for C7H12O2:
128.17.
The second product was identified as 3-m eth oxy-cis-1,2-
ep oxycycloh exa n e (cis-5b) by comparing its properties with
those in the literature44-46 and on the basis of the following
data: a colorless liquid: 1H NMR (CDCl3) δ 1.15-1.35 (m, 1H),
1.35-1.55 (m, 1H), 1.55-1.75 (m, 2H), 1.75-1.95 (m, 2H), 3.27
(m, 1H), 3.32 (dd, J ) 4.00, 2.05 Hz, 1H), 3.46 (s, 3H), 3.628
(ddd, J ) 8.90, 5.02, 2.14 Hz, 1H); 13C NMR (CDCl3) δ 19.50,
23.05, 24.49, 52.94, 53.94, 56.10, 76.60; MS (EI, 70 eV) m/ z
128 (M+, 0.1), 127(0.3), 97(12), 83(18), 71(100), 67(12), 57(10),
53(4), 41(24); calcd for C7H12O2: 128.17.
The third major product was identified as 2-cycloh exen -
1-on e (8) as described above. A minor product (ca. 1%) was
identified as 2,3-ep oxycycloh exa n -1-on e as described above.
Ep oxid a tion of 2c by 1. The general procedure was
followed to give a residue which was found to contain three
products. The products were separated by preparative GLC.
One of the major products was identified as [(tr a n s-2,3-
ep oxycycloh exa n -1-yl)oxy]tr im eth ylsila n e (tr a n s-5c) by
comparing its 1H NMR spectrum19 and properties with those
in the literature47 and on the basis of the following data: a
colorless liquid: 1H NMR (CDCl3) δ 0.15 (s, 9H), 1.10-2.10
(m, 6H), 3.00 (d, J ) 3.75 Hz, 1H), 3.20 (m, 1H), 3.95 (m, 1H);
13C NMR (CDCl3) δ 0.10, 14.61, 24.19, 30.16, 53.20, 56.61,
66.47; MS (EI, 70 eV) m/ z 186(M+, 0.07), 171(15), 129(38),
115(7), 105(12), 89(7), 75(100), 73(66), 59(7), 45(9); calcd for
C9H18O2Si: 186.32.
1
determined by H NMR analysis were comparable with those
determined by GLC analysis. Products in the residue were
separated by preparative GLC. The collected products were
reanalyzed to insure purity. The products were characterized
1
using H and 13C NMR, infrared, and mass spectroscopy and
by comparison of their spectral and chromatographic proper-
ties with those of authentic samples or with literature values.
Ep oxid a tion of 2a by 1. The general procedure was
followed to give a residue which was found to contain three
major products. The products were separated by preparative
GLC. One of these products was identified as tr a n s-2,3-
ep oxycycloh exa n -1-ol (tr a n s-5a ) by comparing its NMR and
mass spectral data with those in the literature19,40-42 and on
the basis of the following data: a colorless liquid; 1H NMR
(CDCl3) δ 1.10-2.00 (m, 6H), 1.90 (br s, 1H), 3.09 (d, J ) 3.72
Hz, 1H), 3.24 (m, 1H), 4.04 (m, 1H); 13C NMR (CDCl3): δ 14.48,
24.07, 29.49, 53.11, 56.08, 65.80; MS (EI, 70 eV) m/ z
114(M+,0.2), 96(5), 95(4), 83(3), 71(16), 70(100), 58(40), 57(76),
41(15); calcd for C6H10O2; 114.14.
The second product was identified as [(cis-2,3-ep oxycy-
cloh exa n -1-yl)oxy]tr im eth ylsila n e (cis-5c) on the basis of
a comparison of NMR data with the known trans isomer and
the following data: a colorless liquid; 1H NMR (CDCl3) δ 0.16
(s, 9H), 1.10-1.95 (m, 6H), 3.14 (dd, J ) 3.94, 1.93 Hz, 1H),
3.24 (m, 1H), 4.01 (ddd, J ) 9.14, 5.90, 2.00 Hz, 1H); 13C NMR
The second product was identified as cis-2,3-ep oxycyclo-
h exa n -1-ol (cis-5a ) by comparing its NMR spectrum with that
in the literature40-42 and on the basis of the following data: a
(43) Heller, S. R.; Milne, G. W. A. EPA/ NIH Mass Spectral Data
Base; U.S. Government Printing Office: Washington, D.C., 1978; Vol.
1.
(44) Lemiueux, R. U.; Kullnig, R. K.; Moir, R. Y. J . Am. Chem. Soc.
1958, 80, 2237.
1
colorless liquid; H NMR (CDCl3) δ 1.15-2.00 (m, 6H), 2.07
(br s, 1H), 3.35 (m, 2H), 4.01 (m, 1H); 13C NMR (CDCl3) δ 18.13,
23.20, 29.06, 55.31, 55.47, 67.01; MS (EI, 70 eV) m/ z 114(M+,
(45) Bannard, R. A. B.; Casselman, A. A.; Langstaff, E. J .; Moir, R.
Y. Can. J . Chem. 1968, 46, 35.
(46) Bellucci, G; Berti, G.; Bianchini, R., Ingrosso, G.; Mastrorilli,
E. Gazz. Chim. Ital. 1976, 106, 955.
(47) Gassman, P. G.; Gremban, R. S. Tetrahedron Lett. 1984, 25,
3259.
(40) Chamberlain, P.; Roberts, M. L.; Whitham, G. H. J . Chem. Soc.
(B) 1970, 1374.
(41) Magnusson, G.; Thore´n, S. J . Org. Chem. 1973, 38, 1380.
(42) Itoh, T.; J itsukawa, K.; Kaneda, K.; Teranishi, S. J . Am. Chem.
Soc. 1979, 101, 159.

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1837
(CDCl3) δ 0.45, 20.53, 22.71, 28.17, 54.74, 56.14, 69.56; MS
(EI, 70 eV) m/ z 186(M+, 0.08), 171(10), 129(65), 115(6),
105(24), 101(12), 89(7), 79(19), 73(55), 59(11), 45(11); calcd for
C9H18O2Si: 186.32.
epoxy carboxylic acids were converted to their esters by
treating with an excess of diazomethane in ether. Separation
of the esters by preparative GLC afforded trans and cis epoxy
esters which had the same spectral and chromatographic
properties as those of the known tr a n s-5h and cis-5h epoxy
esters isolated during the epoxidation of methyl cyclohex-2-
ene carboxylate with DMD.
A minor product was identified as 8 as described above.
Ep oxid a tion of 2d by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-(a cetyloxy)-tr a n s-
Ep oxid a tion of 2g by 1. The general procedure was
followed to give a colorless solid. 1H NMR analysis of the
reaction mixture indicated the presence of cis epoxide as the
major product and trans epoxide as the minor product.
Separation of the products was accomplished by radial chro-
matography of the residue on a Chromatotron (silica gel plate),
using acetone/CH2Cl2 (5:95) as the eluent. The major product
was identified as 3-ben za m id o-cis-1,2-ep oxycycloh exa n e
(cis-5g) by comparing its properties with those in the litera-
ture24 and on the basis of the following data: colorless needles
1
1,2-ep oxycycloh exa n e (tr a n s-5d ) by comparing its H NMR
spectrum20,48 and properties with those in the literature40,49
1
and on the basis of the following data: a colorless liquid; H
NMR (CDCl3) δ 1.20-2.15 (m, 6H), 2.09 (s, 3H), 3.07 (d, J )
3.66 Hz, 1H), 3.23 (m, 1H), 5.04 (dd, J ) 7.08, 5.92 Hz, 1H),
13C NMR (CDCl3) δ 14.57, 21.17, 23.75, 25.84, 52.58, 53.36,
68.07, 169.94; MS (EI, 70 eV) m/ z 114 (M + 1 - CH3CdO, 7),
113(M+-CH3CdO, 13), 112(17), 96(13), 86(10), 71(11), 70(69),
68(17), 67(16), 57(10), 55(22), 43(100), 41(10); calcd for
C8H12O3: 156.18.
1
(CH2Cl2-hexane), mp 119-121 °C, lit.51 mp 116-117 °C; H
NMR (CDCl3) δ 1.20-1.75 (m, 4H), 1.80-2.00 (m, 2H), 3.34
(s, 2H), 4.55-4.65 (m, 1H), 6.54 (br d, J ) 7.82 Hz, 1H), 7.35-
7.60 (m, 3H), 7.75-7.85 (m, 2H); 13C NMR (CDCl3) δ 18.47,
23.21, 26.37, 45.67, 54.14, 54.52, 126.86, 128.35, 131.33,
134.28, 166.70; MS (EI, 70 eV): m/ z 217(M+, 1), 198(1),
146(15), 122(16), 105(100), 77(43), 67(2), 51(8); calcd for
C13H15NO2: 217.27.
The second product was identified as 3-(a cetyloxy)-cis-1,2-
1
ep oxycycloh exa n e (cis-5d ) by comparing its H NMR spec-
trum20,48 and properties with those in the literature40,49 and
on the basis of the following data: a colorless liquid; 1H NMR
(CDCl3) δ 1.20-2.00 (m, 6H), 2.11 (s, 3H), 3.30 (m, 2H), 5.13
(ddd, J ) 8.93, 5.34, 1.77 Hz, 1H), 13C NMR (CDCl3) δ 19.45,
21.24, 22.60, 24.49, 52.84, 54.25, 70.87, 170.66; MS (EI, 70 eV)
m/ z 114 (M + 1 - CH3CdO, 11), 113(M+-CH3CdO, 16),
112(27), 96(22), 86(15), 71(10), 70(97), 68(18), 67(18), 57(12),
55(16), 43(100), 41(12); calcd for C8H12O3: 156.18.
The minor product formed during the reaction was 3-ben -
za m id o-tr a n s-1,2-ep oxycycloh exa n e (tr a n s-5g) which was
identified on the basis of the following data: (from cis:trans
1
mixture) H NMR (CDCl3) δ 2.00-2.15 (m, 1H), 3.16 (d, J )
3.66 Hz, 1H), 3.21 (m, 1H), 4.37 (m, 1H), 6.39 (br d, 1H); 13C
NMR (CDCl3) δ 15.75, 24.05, 26.84, 45.50, 52.44, 55.00, 126.88,
128.43, 131.40, 134.31, 166.73; MS (EI, 70 eV) m/ z 218(M +
1, 3), 217(M+, 21), 200(12), 188(10), 174(100), 160(7), 146(85),
130(10), 117(17), 104(73), 90(14), 77(46), 57(18), 51(10); calcd
for C13H15NO2: 217.27. This mass spectrum is actually that
of 7-h yd r oxy-2-p h en yl-3a ,4,5,6,7,7a -h exa h yd r ob en zox-
a zole, the thermal rearrangement product of the 3-ben za -
m id o-tr a n s-1,2-ep oxycycloh exa n e.
Ep oxid a tion of 2e by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-(p r op ion yloxy)-
tr a n s-1,2-ep oxycycloh exa n e (tr a n s-5e) on the basis of the
1
following data: a colorless liquid, H NMR (CDCl3) δ 1.19 (t,
J ) 7.55 Hz, 3H), 1.25-2.15 (m, 6H), 2.39 (q, J ) 7.55 Hz,
2H), 3.08 (d, J ) 3.66 Hz, 1H), 3.25 (m, 1H), 5.08 (dd, J )
7.05, 6.90 Hz, 1H); 13C NMR (CDCl3) δ 9.17, 14.57, 23.74,
25.85, 27.73, 52.58, 53.41, 67.79, 173.36; MS (EI, 70 eV) m/ z
126(4), 114(M + 1 - CH3CH2CdO, 4), 113(M+-CH3CH2CdO,
7), 96(8), 70(7), 68(10), 67(9), 57(100), 55(13), 41(7); calcd for
C9H14O3: 170.21. Anal. Calcd for C9H14O3: C, 63.51; H, 8.29.
Found: C, 63.56; H, 8.21.
The rearrangement product was also formed during chro-
matography and was isolated as a colorless viscous liquid and
identified as 7-h yd r oxy-2-p h en yl-3a ,4,5,6,7,7a -h exa h y-
d r oben zoxa zole on the basis of the following data: a colorless
liquid, solidifies very slowly on standing; IR (neat film) 3356
(OH), 2930, 2865, 1635 (CdN), 1450, 1349, 1273, 1064, 967,
911, 782, 734, 700 cm-1; 1H NMR (CDCl3) δ 1.10-2.20 (m, 6H),
2.45 (br s, 1H, OH, exchangeable with D2O), 3.74 (ddd, J )
11.45, 7.03, 4.98 Hz, 1H), 4.26-4.38 (m, 1H), 4.495 (dd, J )
The second product was identified as 3-(p r op ion yloxy)-
cis-1,2-ep oxycycloh exa n e (cis-5e) on the basis of a compa-
rision of NMR data with the trans isomer and the following
1
data: a colorless liquid; H NMR (CDCl3) δ 1.16 (t, J ) 7.57
8.54, 7.08 Hz, 1H), 7.35-7.55 (m, 3H), 7.85-8.10 (m, 2H); 13
C
Hz, 3H), 1.20-2.00 (m, 6H), 2.39 (q, J ) 7.68 Hz, 2H), 3.30
(m, 2H), 5.14 (ddd, J ) 8.74, 5.31 and 1.77 Hz, 1H); 13C NMR
(CDCl3) δ 9.19, 19.47, 22.64, 24.52, 27.73, 52.92, 54.25, 70.65,
174.13; MS (EI, 70 eV): m/ z 126(5), 114(M + 1 - CH3-
CH2CdO, 3), 113(M+-CH3CH2CdO, 6), 96(8), 70(7), 68(7),
67(8), 57(100), 55(9), 41(8); calcd for C9H14O3: 170.21.
NMR (CDCl3) δ 18.50, 26.90, 29.23, 65.03, 71.43, 84.91, 127.72,
128.05, 128.20, 131.36, 131.36, 163.94; MS (EI, 70 eV) m/ z
218(M + 1, 3), 217(M+,21), 200(12), 188(10), 174(100), 160(7),
146(85), 130(10), 117(17), 105(70), 104(73), 90(14), 77(46),
57(18), 51(10); calcd for C13H15NO2: 217.27. Anal. Calcd for
C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.75; H,
6.83, N, 6.40.
Ep oxid a tion of 2f by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products could not be separated by preparative
GLC. A mixture of the products was analyzed by NMR. One
of these products was identified as tr a n s-2,3-ep oxycyclo-
h exa n e-1-ca r boxylic a cid (tr a n s-5f)50 on the basis of the
following data (from trans:cis mixture): 1H NMR (CDCl3) δ
1.00-2.05 (m, 6H), 2.95 (dd, J ) 8.45, 6.01 Hz, 1H), 3.24 (m,
1H), 3.46 (d, J ) 3.77 Hz, 1H), 9.95 (br s, 1H); 13C NMR (CDCl3)
δ 16.75, 23.50, 23.75, 40.38, 52.01, 52.33, 179.02; MS (EI, 70
eV): m/ z 142 (M+, 0.5); calcd for C7H10O3: 142.15.
The second product was identified as cis-2,3-ep oxycyclo-
h exa n e-1-ca r boxylic a cid (cis-5f)50 on the basis of the
following data (from trans:cis mixture): 1H NMR (CDCl3) δ
1.00-2.05 (m, 6H), 2.90 (m, 1H), 3.24 (m, 1H), 3.49 (dd, J )
3.66, 3.17 Hz, 1H), 9.95 (br s, 1H); 13C NMR (CDCl3) δ 18.82,
21.09, 23.11, 40.70, 51.93, 52.41, 178.52; MS (EI, 70 eV): m/ z
142 (M+, 0.2); calcd for C7H10O3: 142.15. The trans and cis
Ep oxid a tion of 2h by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as m eth yl tr a n s-2,3-
ep oxycycloh exa n eca r boxyla te (tr a n s-5h ) by comparing its
NMR50 data with those in the literature and on the basis of
the following data: a colorless liquid: 1H NMR (CDCl3) δ 1.25-
2.15 (m, 6H), 2.90 (dd, J ) 8.98, 5.86 Hz, 1H), 3.21 (m, 1H),
3.41(d, J ) 3.90 Hz, 1H), 3.73 (s, 3H); 13C NMR (CDCl3) δ
16.81, 23.69, 23.89, 40.61, 51.86, 51.90, 52.17, 173.73; MS (EI,
70 eV) m/ z 156(M+, 0.5), 141(3), 125(28), 124(16), 113(26),
100(42), 97(53), 96(83), 95(19), 87(35), 79(58), 71(100), 70(25),
69(47), 68(73), 67(49), 59(27), 58(30), 57(10), 55(57), 41(49);
calcd for C8H12O3: 156.18.
The second product was also isolated as a colorless liquid
and was identified as m eth yl cis-2,3-ep oxycycloh exa n eca r -
boxyla te (cis-5h ) by comparing its NMR50 data with those
in the literature and on the basis of the following data: 1H
(48) J ankowski, K.; Daigle, J .-Y. Can. J . Chem. 1971, 49, 2594.
(49) Heggs, R. P.; Ganem, B. J . Am. Chem. Soc. 1979, 101, 2484.
(50) Davies, S. G.; Whitham, G. H. J . Chem. Soc. Perkin Trans. 1
1977, 572.
(51) Vince, R.; Daluge, S. J . Med. Chem. 1977, 20, 930.

1838 J . Org. Chem., Vol. 61, No. 5, 1996
Murray et al.
NMR (CDCl3) δ 1.15-2.00 (m, 6H), 2.84 (m, 1H), 3.21 (m, 1H),
3.44 (t, J ) 3.5 Hz, 1H), 3.75 (s, 3H); 13C NMR (CDCl3) δ 18.97,
21.36, 23.21, 40.94, 51.93, 52.05, 52.26, 173.10; MS (EI, 70 eV)
m/ z 156(M+, 0.2), 141(1), 125(7), 124(10), 113(24), 100(43),
97(38), 96(71), 95(18), 87(34), 79(57), 71(100), 70(22), 69(52),
68(67), 67(53), 59(30), 58(29), 57(12), 55(61), 41(57); calcd for
C8H12O3: 156.18.
Ep oxid a tion of 2i by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products could not be separated by preparative
GLC. A mixture of the products was analyzed by NMR. One
of these products was identified as tr a n s-2,3-ep oxycyclo-
h exa n -1-yl h yd r op er oxid e (tr a n s-5i) on the basis of the
following data (from trans:cis mixture): 1H NMR (CDCl3) δ
1.10-2.50 (m, 6H), 3.28 (br s, 1H), 3.44 (d, J ) 3.90 Hz, 1H),
4.24 (dd, J ) 9.30, 5.90 Hz, 1H), 9.44 (br s, 1H); 13C NMR
(CDCl3) δ 14.55, 24.13, 24.53, 53.24, 53.31, 78.97; MS (EI, 70
eV) m/z 130(M+, 0.7), 112(M+-18, 13), 97(65), 83(14), 79(86),
71(16), 70(52), 67(85), 57(100), 55(95), 53(19), 41(91); calcd for
C6H10O3: 130.15.
The minor product was identified as cis-2,3-ep oxycyclo-
h exa n -1-yl h yd r op er oxid e (cis-5i) on the basis of the
following data (from trans:cis mixture): 1H NMR (CDCl3): δ
1.10-2.10 (m, 6H, overlapped with trans), 3.37 (m, 1H), 3.54
(dd, J ) 4.15, 2.25 Hz, 1H), 4.39 (ddd, J ) 10.56, 5.18, 2.25
Hz, 1H), 9.44 (br s, 1H); 13C NMR (CDCl3) δ 18.77, 22.89, 23.00,
52.15, 54.28, 80.11; MS (EI, 70 eV) m/ z 130(M+, 0.2), 112(M+-
18, 14), 97(80), 83(20), 79(100), 70(78), 69(59), 68(45), 67(98),
57(96), 56(13), 55(97), 53(22), 41(91); calcd for C6H10O3: 130.15.
The mixture of tr a n s-5i/cis-5i was silylated with N,O-bis-
(trimethylsilyl)acetamide to afford a mixture of [(trans/ cis-
2,3-epoxycyclohexan-1-yl)dioxy]trimethylsilane which was used
for the C,H analysis. Anal. Calcd for C9H18O3Si: C, 53.43;
H, 8.97. Found C, 54.09; H, 8.84.
111(55), 97(69), 93(12), 83(22), 82(34), 79(22), 70(23), 69(21),
67(100), 57(17), 55(66), 43(12), 41(44); calcd for C8H14O:
126.20.
The second product was identified as 3-et h yl-cis-1,2-
1
ep oxycycloh exa n e (cis-5k ) by comparing its H NMR spec-
tral data20 with those in the literature and on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 0.999 (t,
J ) 7.39 Hz, 3H), 1.05-2.00 (m, 7H), 2.10 (m, 1H), 3.104 (dd,
J ) 4.04, 2.22 Hz, 1H), 3.16 (dd, J ) 4.055, 8.31 Hz, 1H); 13C
NMR (CDCl3) δ 11.73, 20.14, 24.02, 24.93, 26.26, 36.82, 52.81,
55.54; MS (EI, 70 eV) m/ z 126 (M+, 2), 111(58), 97(70), 93(13),
83(22), 82(38), 79(24), 70(27), 69(23), 67(100), 57(19), 55(68),
43(14), 41(45); calcd for C8H14O: 126.20.
Ep oxid a tion of 2l by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-isobu tyl-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5l) on the basis of the following
data: a colorless liquid; 1H NMR (CDCl3) δ 0.70-0.85 (m, 1H),
0.90 (d, J ) 6.59 Hz, 3H), 0.93 (d, J ) 6.59 Hz, 3H), 1.15-
1.50 (m, 4H), 1.50-2.00 (m, 4H), 2.00-2.15 (m, 1H), 2.84 (d,
J ) 3.96 Hz, 1H), 3.13 (m or ddd, 1H); 13C NMR (CDCl3) δ
17.33, 22.25, 23.16, 24.98, 25.13, 27.48, 31.99, 43.45, 52.80,
56.74; MS (EI, 70 eV) m/ z 154(M+, 0.06), 139(1), 111(100),
95(28), 93(23), 79(27), 68(29), 67(52), 55(47), 41(69); calcd for
C10H18O: 154.25. Anal. Calcd for C10H18O: C, 77.87; H, 11.76.
Found: C, 77.82; H, 11.71.
The second product was identified a 3-isobu tyl-cis-1,2-
ep oxycycloh exa n e (cis-5l) on the basis of a comparision of
NMR data with the trans isomer and the following data: a
colorless liquid; 1H NMR (CDCl3) δ 0.91 (d, J ) 6.24 Hz, 3H),
0.93 (d, J ) 6.24 Hz, 3H), 1.00-1.30 (m, 3H), 1.30-1.60 (m,
3H), 1.60-2.00 (m, 4H), 3.05 (dd, J ) 3.91, 2.69 Hz, 1H), 3.17
(dd or apt t, J ) 4.15 Hz, 1H); 13C NMR (CDCl3): δ 20.15,
22.82, 22.94, 24.08, 24.91, 25.43, 32.59, 42.60, 53.09, 56.00;
MS (EI, 70 eV) m/ z 154(M+, 0.08), 139(1), 111(100), 95(29),
93(23), 79(28), 68(29), 67(50), 55(48), 41(62); calcd for
C10H18O: 154.25.
Ep oxid a tion of 2j by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-m eth yl-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5j) by comparing its NMR proper-
ties with those in the literature52,53 and on the basis of the
Ep oxid a tion of 2m by 1. The general procedure was
followed to give a residue which was found to contain a major
and a minor product. The products were separated by
preparative GLC. The major product was identified as 3-ter t-
bu tyl-tr a n s-1,2-ep oxycycloh exa n e (tr a n s-5m )52 by com-
1
following data: a colorless liquid; H NMR (CDCl3) δ 0.75-
0.95 (m, 1H), 1.067 (d, J ) 7.32 Hz, 3H), 1.25-1.50 (m, 2H),
1.50-1.80 (m, 2H), 1.90-2.10 (m, 2H), 2.83 (d, J ) 3.91 Hz,
1H), 3.14 (dd, J ) 3.985, 1.845 Hz, 1H); 13C NMR (CDCl3) δ
17.14, 19.21, 24.75, 29.05, 29.21, 52.74, 57.22; MS (EI, 70 eV)
m/ z 112 (M+, 2), 111(3), 97(79), 83(31), 79(20), 71(29), 69(35),
68(100), 67(74), 57(27), 56(49), 55(67), 53(16), 43(17), 41(50);
calcd for C7H12O: 112.17.
1
paring its H NMR spectral data and properties with those in
the literature27 and on the basis of the following data:
a
colorless liquid: 1H NMR (CDCl3) δ 0.75-1.00 (m, 1H), 0.96
(s, 9H), 1.20-1.70 (m, 5H), 2.00-2.15 (m, 1H), 3.03 (d, J )
3.90 Hz, 1H), 3.14 (dd, J ) 3.90, 2.00 Hz, 1H); 13C NMR
(CDCl3) δ 17.80, 22.74, 25.08, 27.37, 32.58, 44.69, 53.13, 54.08;
MS (EI, 70 eV) m/ z 154(M+, 0.5), 139(35), 121(7), 98(18),
97(100), 95(23), 83(20), 79(34), 70(21), 69(25), 57(59), 55(30),
43(17), 41(49); calcd for C10H18O:154.24.
The second product was identified as 3-m eth yl-cis-1,2-
ep oxycycloh exa n e (cis-5j) by comparing its NMR properties
with those in the literature52,53 and on the basis of the following
1
data: a colorless liquid; H NMR (CDCl3) δ 1.09 (d, J ) 6.89
The minor product was identified as 3-ter t-bu tyl-cis-1,2-
ep oxycycloh exa n e (cis-5m ) on the basis of the following
data: MS (EI, 70 eV) m/ z 154(M+, 0.5), 139(35), 121(7), 98(18),
97(100), 95(23), 83(20), 79(34), 70(21), 69(25), 57(59), 55(30),
43(17), 41(49); calcd for C10H18O:154.24. Insufficient sample
was available for NMR spectral determination.
Hz, 3H), 1.10-2.15 (m, 7H), 3.018 (dd, J ) 3.535, 2.565 Hz,
1H), 3.16 (dd, J ) 4.15 and 4.15 Hz, (or t, J ) 4.15 Hz), 1H);
13C NMR (CDCl3) δ 18.52, 20.26, 23.65, 27.02, 30.09, 53.07,
57.03; MS (EI, 70 eV) m/ z 112 (M+, 2), 111(2), 97(97), 83(36),
79(25), 71(27), 69(31), 68(100), 67(73), 57(25), 56(48), 55(64),
53(18), 43(17), 41(54); calcd for C7H12O: 112.17.
Ep oxid a tion of 2n by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-(tr iflu or om eth yl)-
tr a n s-1,2-ep oxycycloh exa n e (tr a n s-5n ) on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 1.15-
1.60 (m, 3H), 1.65-1.90 (m, 2H), 2.05-2.25 (m, 1H), 2.59 (m,
1H), 3.20 (dd, J ) 3.90, 0.49 Hz, 1H), 3.23 (dd, J ) 3.90, 1.87
Hz, 1H); 13C NMR (CDCl3) δ 15.85, 20.41 (q, 4J C-F ) 2.60 Hz),
Ep oxid a tion of 2k by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-eth yl-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5k ) by comparing its 1H NMR
spectral data with those in the literature20 and on the basis of
the following data: a colorless liquid; 1H NMR (CDCl3) δ 0.75-
0.95 (m, 1H), 0.984 (t, J ) 7.40 Hz, 3H), 1.05-2.00 (m, 7H),
2.05 (m, 1H), 2.87 (d, J ) 3.90 Hz, 1H), 3.14 (dd, J ) 4.04,
2.10 Hz, 1H); 13C NMR (CDCl3) δ 11.73, 17.31, 25.02, 26.92,
26.96, 36.00, 52.82, 56.32; MS (EI, 70 eV) m/ z 126 (M+, 2),
2
3
23.99, 39.93 (q, J C-F ) 25.90 Hz), 49.82 (q, J C-F ) 4.23 Hz),
51.93, 126.76 (q, J C-F ) 278.66 Hz); 19F NMR (CDCl3) δ -
1
71.90 (d, J ) 10.0 Hz, 3F); MS (EI, 70eV) m/ z 167(M + 1,
0.5), 166(M+, 7), 165(18), 151(93), 136(10), 125(8), 103(25),
97(100), 83(10), 77(55), 69(42), 54(55), 41(34); calcd for
C7H9F3O: 166.15. Anal. Calcd for C7H9F3O: C, 50.61; H, 5.46.
Found: C, 51.13; H, 5.59.
(52) (a) Bellucci, G; Berti, G.; Ferretti, M., Ingrosso, G.; Mastrorilli,
E. J . Org. Chem. 1978, 43, 422. (b) Fringuelli, F.; Germani, R.; Pizzo,
F.; Savelli, G. Tetrahedron Lett. 1989, 30, 1427.
(53) Claus, P. K.; Vierhapper, F. W.; Miller, R. L. J . Org. Chem.
1977, 42, 4016.
The second product was identified as 3-(tr iflu or om eth yl)-
cis-1,2-ep oxycycloh exa n e (cis-5n ) on the basis of a compa-

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1839
rision of NMR data with the trans isomer and the following
data: a colorless liquid; 1H NMR (CDCl3) δ 1.15-1.40 (m, 1H),
1.45-1.75 (m, 3H), 1.75-2.05 (m, 2H), 2.54 (m, 1H), 3.19 (dd,
J ) 4.15, 4.15 Hz, 1H), 3.30 (dd, J ) 4.05, 1.87 Hz, 1H); 13C
NMR (CDCl3) δ 18.14 (q, 4J C-F ) 2.10 Hz), 19.34, 22.61, 40.83
(q, 2J C-F ) 26.37 Hz), 49.29 (q, 3J C-F ) 3.30 Hz), 50.55, 126.95
(q, 1J C-F ) 279.70 Hz); 19F NMR (CDCl3) δ - 71.11 (d, J ) 9.0
Hz, 3F); MS (EI, 70eV) m/ z 167(M + 1, 0.3), 166(M+, 5),
165(17), 151(88), 136(9), 125(9), 103(20), 97(100), 83(11),
77(50), 69(54), 54(47), 41(34); calcd for C7H9F3O: 166.15.
Ep oxid a tion of 2o by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-p h en yl-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5o)54 on the basis of the following
data: a colorless liquid; 1H NMR (CDCl3) δ 1.18-1.70 (m, 3H),
2.05-2.25 (m, 1H), 3.14 (dd, J ) 9.86, 6.00 Hz, 1H), 3.20 (d, J
) 3.85 Hz, 1H), 3.31 (dd, J ) 3.87, 1.72 Hz, 1H), 7.10-7.50
(m, 5H); 13C NMR (CDCl3) δ 16.88, 24.54, 29.82, 41.22, 52.72,
56.11, 126.24, 127.63, 128.39, 144.04; MS (EI, 70 eV) m/ z
175(M + 1, 3), 174(M+, 26), 146(16), 145(23), 131(25), 130(73),
129(50), 128(16), 117(100), 115(70), 104(37), 103(30), 91(84),
78(24), 77(35), 65(18), 51(20), 41(7); calcd for C12H14O: 174.23.
Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.51;
H, 7.94.
The minor product was identified as 3-p h en yl-cis-1,2-
ep oxycycloh exa n e (cis-5o) on the basis of a comparision of
NMR data with the trans isomer and the following data (from
trans:cis mixture): a colorless liquid; 1H NMR (CDCl3) δ 1.18-
2.10 (m, 6H), 2.97 (m, 1H), 3.20 (m, 1H), 3.26 (m, 1H), 7.10-
7.50 (m, 5H); 13C NMR (CDCl3) δ 21.57, 23.05, 27.39, 42.89,
51.99, 56.01, 124.94, 126.31, 128.27, 144.12; MS (EI, 70 eV)
m/ z 175(M + 1, 3), 174(M+, 26), 146(16), 145(23), 131(25),
130(73), 129(50), 128(16), 117(100), 115(70), 104(37), 103(30),
91(84), 78(24), 77(35), 65(18), 51(20), 41(7); calcd for C12H14O:
174.23.
69(35), 68(28), 67(68), 57(100), 53(19), 41(55); calcd for C6H9-
ClO: 132.59.
The second product was identified as 3-ch lor o-cis-1,2-
ep oxycycloh exa n e (cis-5q) by comparing its NMR spectral
data57 with those in the literature and on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 1.20-
2.10 (m, 6H), 3.35 (m, 2H), 4.29 (ddd, J ) 9.53, 5.86, 1.92 Hz,
1H); 13C NMR (CDCl3) δ 20.91, 22.47, 29.62, 55.41, 56.58,
57.44; MS (EI, 70 eV) m/ z 98(4), 97(M+-Cl, 74), 88(22), 79(43),
69(24), 68(21), 67(49), 57(100), 53(17), 41(54); calcd for C6H9-
ClO: 132.59.
Ep oxid a tion of 2r by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-br om o-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5r ) by comparing its 1H NMR
spectral data58,59 with those in the literature and on the basis
1
of the following data: a colorless liquid; H NMR (CDCl3) δ
1.25.1.95 (m, 1H), 1.80-2.20 (m, 3H), 2.50-2.80 (m, 2H), 3.27
(dd, J ) 5.89, 2.93 Hz, 1H), 3.42 (dd, J ) 3.74, 1.64 Hz, 1H),
4.48 (t, J ) 4.77 Hz, 1H); 13C NMR (CDCl3) δ 15.77, 22.88,
28.59, 47.55, 52.92, 55.33; MS (EI, 70 eV): m/ z 134(3), 132(3),
98(6), 97(M+-Br, 100), 79(56), 77(10), 69(20), 67(36), 55(16),
53(12), 43(12), 41(40); calcd for C6H9BrO: 177.05.
The second product was identified as 3-br om o-cis-1,2-
1
ep oxycycloh exa n e (cis-5r ) by comparing its H NMR spec-
tral data58,59 with those in the literature and on the basis of
the following data: a colorless liquid, 1H NMR (CDCl3) δ 1.15-
2.05 (m, 6H), 3.40-3.50 (m, 2H), 4.37 (m, 1H); 13C NMR
(CDCl3) δ 15.77, 22.80, 28.59, 55.71, 52.92, 55.33; MS (EI, 70
eV) m/ z 134(2), 132(2), 98(6), 97(M+-Br, 100), 79(36), 77(8),
69(12), 67(23), 55(10), 53(9), 43(9), 41(33); calcd for C6H9BrO:
177.05.
Ep oxid a tion of 3a by 1. The general procedure was
followed to give a residue which was found to contain three
major products. The products were separated by preparative
GLC. One of these products was identified as 3-m eth yl-
tr a n s-2,3-ep oxycycloh exa n -1-ol (tr a n s-6a ) by comparing
its NMR spectral data60 spectral data with those in the
literature and on the basis of the following data: a colorless
liquid; 1H NMR (CDCl3) δ 1.10-2.00 (m, 6H), 1.34 (s, 3H), 2.35
(br s, 1H) 2.92 (s, 1H), 3.90-4.10 (m, 1H); 13C NMR (CDCl3) δ
15.78, 23.31, 29.56, 30.00, 58.90, 63.40, 66.66; MS (EI, 70 eV)
m/ z 128(M+, 0.3), 110(2), 95(4), 84(17), 71(82), 70(100), 67(11),
60(20), 59(18), 58(16), 57(25), 55(24), 43(50); calcd for
C7H12O2: 128.17.
The second product was identified as 3-m eth yl-cis-2,3-
ep oxycycloh exa n -1-ol (cis-6a ) by comparing its NMR spec-
tral data40 with those in the literature and on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 1.20-
2.10 (m, 6H), 1.35 (s, 3H), 1.50 (br s, 1H), 3.15 (d, J ) 3.42
Hz, 1H), 4.01 (m, 1H); 13C NMR (CDCl3) δ 18.01, 23.70, 28.52,
28.63, 61.40, 62.32, 66.59; MS (EI, 70 eV) m/ z 128(M+,1),
110(10), 95(4), 84(24), 71(80), 70(100), 67(14), 60(18), 59(17),
57(29), 55(23), 43(52); calcd for C7H12O2: 128.17.
Ep oxid a tion of 2p by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as tr a n s-2,3-ep oxycy-
cloh exa n e-1-ca r bon itr ile (tr a n s-5p )55 on the basis of the
1
following data: a colorless liquid; H NMR (CDCl3): δ 1.30-
1.70 (m, 3H), 1.70-2.10 (m, 3H), 3.14 (dd, J ) 6.65, 6.00 Hz,
1H), 3.24 (m, 1H), 3.34 (d, J ) 3.70 Hz, 1H); 13C NMR (CDCl3)
δ 16.50, 22.89, 23.26, 27.01, 51.46, 51.67, 119.69; MS (EI, 70
eV) m/ z 123(M+, 3), 122(6), 108(20), 94(37), 80(25), 70(30),
69(29), 68(38), 67(55), 57(7), 55(28), 54(100), 42(24), 41(26);
calcd for C7H9NO: 123.16.
The second product was also isolated as a colorless liquid
and was identified as cis-2,3-ep oxycycloh exa n e-1-ca r bo-
n itr ile (cis-5p ) on the basis the following data: 1H NMR
(CDCl3) δ 1.15-1.40 (m, 1H), 1.50-2.10 (m, 5H), 3.08 (m, 1H),
3.25 (ddd, J ) 6.24, 3.71, 1.19 Hz, 1H), 3.31 (dd, J ) 3.47,
3.36 Hz, 1H); 13C NMR (CDCl3) δ 17.84, 22.80, 23.49, 27.76,
50.50, 52.42, 119.64; MS (EI, 70 eV) m/ z 123(M+, 2), 122(4),
108(14), 94(28), 80(24), 70(34), 69(26), 68(35), 67(55), 57(11),
55(28), 54(100), 42(23), 41(29); calcd for C7H9NO: 123.16. Anal.
Calcd for C7H9NO: C, 68.27; H, 7.37; N, 11.37. Found: C,
68.17; H, 7.41, N, 11.48.
Ep oxid a tion of 2q by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-ch lor o-tr a n s-1,2-
ep oxycycloh exa n e (tr a n s-5q) by comparing its NMR spec-
tral data56,57 with those in the literature and on the basis of
the following data: a colorless liquid; 1H NMR (CDCl3) δ 1.20-
2.15 (m, 6H), 3.15-3.40 (m, 2H), 4.37 (t, J ) 5.1 Hz); 13C NMR
(CDCl3) δ 14.96, 23.07, 28.78, 52.75, 54.55, 55.12; MS (EI, 70
eV) m/ z 132(M+, 0.2), 98(6), 97(M+-Cl, 94), 88(43), 79(71),
The third product was identified as 3-m eth yl-2-cyclo-
h exen -1-on e (9) by comparing its NMR40 and mass spectral
data42 with those in the literature and on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 1.90-
2.10 (m, 2H), 1.96 (s, 3H), 2.20-2.45 (m, 4H), 5.88 (m, 1H);
13C NMR (CDCl3) δ 22.57, 24.46, 30.95, 36.98, 126.54, 162.51,
199.43; MS (EI, 70 eV) m/ z 111(M + 1, 3), 110(M+,41), 83(5),
82(100), 67(7), 54(19), 41(3); calcd for C7H10O: 110.15.
Ep oxid a tion of 3b by 1. The general procedure was
followed to give a residue which was found to contain two
major and two minor products. The products were separated
by preparative GLC. One of the major products was identified
as 3-m eth oxy-tr a n s-1,2-epoxy-1-m eth ylcycloh exan e (tr a n s-
1
6b) on the basis of the following data: a colorless liquid; H
(54) Kabuto, K; Shindo, H; Ziffer, H. J . Org. Chem. 1977, 42, 1742.
(55) Mousseron, M.; Winternitz, F. Bull. Soc. Chim. Fr. 1948, 79.
(56) Zhao, S.; Freeman, J . P.; Chidester, C. G.; VonVoigtlander, P.
F.; Mizsak, S. A.; Szmuszkovicz, J . J . Org. Chem. 1993, 58, 4043.
(57) Krosley, K. W.; Gleicher, G. J .; Clapp, G. E. J . Org. Chem. 1992,
57, 840.
(58) Barili, P. L.; Bellucci, G.; Marioni, F., Scartoni, V. J . Org. Chem.
1975, 40, 3331.
(59) Wolinsky, J .; Thorstenson, J . H.; Killinger, T. A. J . Org. Chem.
1978, 43, 875.
(60) Ru¨cker, G.; Ho¨rster, H.; Gajewski, W. Synth. Commun. 1980,
10, 623.

1840 J . Org. Chem., Vol. 61, No. 5, 1996
Murray et al.
NMR (CDCl3) δ 1.10-2.00 (m, 6H), 1.33 (s, 3H), 2.94 (s, 1H),
3.44 (s, 3H), 3.47 (dd, J ) 8.70, 5.76 Hz, 1H); 13C NMR (CDCl3)
δ 15.78, 23.31, 26.83, 29.63, 56.87, 58.57, 61.18, 75.70; MS (EI,
70 eV) m/ z 142(M+, 0.25), 95(3), 86(6), 85(100), 84(7), 74(10),
72(12), 71(49), 55(17), 43(21), 41(16); calcd for C8H14O2: 142.19.
Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.65;
H, 9.59.
One of the minor products was identified as 3-m eth oxy-
cis-1,2-ep oxy-1-m eth ylcycloh exa n e (cis-6b) on the basis of
the following data: MS (EI, 70 eV) m/z 142(M+, 4), 110(4),
95(3), 85(5), 84(100), 83(26), 59(45), 55(19), 41(9); calcd for
C8H14O2: 142.19. No NMR data were obtained for the cis
epoxide due to the very small quantity of sample.
products. The products were separated by preparative GLC.
One of these products was identified as 1,3-d im eth yl-tr a n s-
1,2-ep oxycycloh exa n e (tr a n s-6e)61 on the basis of the
1
following data: a colorless liquid; H NMR (CDCl3) δ 0.70-
0.90 (m, 1H), 1.05 (d, J ) 7.27 Hz, 3H), 1.20-1.45 (m, 2H),
1.30 (s, 3H), 1.45-1.70 (m, 2H), 1.90 (m, 1H), 1.94 (m, 1H),
2.66 (s, 1H); 13C NMR (CDCl3) δ 18.50, 19.66, 23.83, 29.75,
29.78, 30.18, 58.10, 64.76; MS (EI, 70 eV) m/ z 126(M+, 4),
111(57), 108(9), 97(35), 93(22), 83(54), 71(100), 69(35), 68(38),
67(38), 58(43), 56(30), 55(59), 43(95), 41(45); calcd for
C8H14O: 126.19.
The second product was identified as 1,3-d im eth yl-cis-1,2-
ep oxycycloh exa n e (cis-6e)61 on the basis of the following
data: a colorless liquid; 1H NMR (CDCl3) δ 1.00-1.25 (m, 2H),
1.06 (d, J ) 6.9 Hz, 3H), 1.25-1.85 (m, 4H), 1.30 (s, 3H), 1.92
(m, 1H), 2.86 (d, J ) 2.5 Hz, 1H); 13C NMR (CDCl3) δ 18.09,
20.28, 24.41, 26.84, 29.07, 30.02, 58.63, 64.42; MS (EI, 70 eV)
m/ z 126(M+, 5), 111(54), 108(8), 97(35), 93(20), 83(54), 71(100),
69(37), 68(39), 67(36), 58(39), 56(34), 55(64), 43(96), 41(43);
calcd for C8H14O: 126.19.
The second major product was identified as 3-m et h yl-2-
cycloh exen -1-on e (9) as described above.
The second minor product was also isolated and identified
as 3-m eth yl-2,3-ep oxycycloh exa n -1-on e by comparing its
NMR40 and mass42 spectral data with those in the literature
1
and on the basis of the following data: a colorless liquid; H
NMR (CDCl3) δ 1.45 (s, 3H), 1.55-1.75 (m, 1H), 1.75-2.25 (m,
4H), 2.40-2.60 (m, 1H), 3.07 (s, 1H); 13C NMR (CDCl3) δ 17.26,
22.27, 28.44, 35.71, 61.97, 62.41, 206.46; MS (EI, 70 eV) m/ z
127(M + 1, 6), 126(M+, 80), 110(24), 98(21), 97(60), 83(43),
82(60), 81(26), 71(89), 69(51), 55(100), 43(62), 42(22), 41(79);
calcd for C7H10O2: 126.15.
Ep oxid a tion of 3c by 1. The general procedure was
followed to give a residue which was found to contain three
products. The products were separated by preparative GLC.
One of these products was identified as [(3-m eth yl-tr a n s-2,3-
ep oxycycloh exa n -1-yl)oxy]tr im eth ylsila n e (tr a n s-6c) on
the basis of the following data: a colorless liquid; 1H NMR
(CDCl3) δ 0.15 (s, 9H), 1.00-2.00 (m, 6H), 1.31 (s, 3H), 2.84
(s, 1H), 3.89 (dd, J ) 8.67, 5.98 Hz, 1H); 13C NMR (CDCl3) δ
0.11, 15.96, 23.32, 29.67, 30.78, 58.83, 64.05, 67.31; MS (EI,
70 eV) m/ z 186(M + 1 - CH3, 0.09), 185(M+-CH3, 0.05),
171(16), 129(41), 115(6), 105(13), 101(7), 89(7), 79(11), 75(100),
73(64), 59(7), 45(10); calcd for C10H20O2Si: 200.35. Anal.
Calcd for C10H20O2Si: C, 59.95; H, 10.06. Found: C, 59.62;
H, 10.00.
The second product, a minor product, was identified as [(3-
m et h yl-cis-2,3-ep oxycycloh exa n -1-yl)oxy]t r im et h ylsi-
la n e (cis-6c) on the basis of a comparision of NMR data with
the trans isomer and the following data: 1H NMR (CDCl3) δ
0.16 (s, 9H), 1.10-1.85 (m, 6H), 1.31 (s, 3H), 2.96 (d, J ) 1.90
Hz, 1H), 4.00 (m, 1H); 13C NMR (CDCl3) δ 0.45, 20.19, 24.28,
27.76, 28.04, 60.62, 63.15, 69.44; MS (EI, 70 eV) m/ z 185(M+-
CH3, 0.05), 171(9), 129(66), 115(6), 105(21), 101(12), 89(7),
79(18), 75(100), 73(55), 59(13), 45(13); calcd for C10H20O2Si:
200.35.
Ep oxid a tion of 4a by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as tr a n s-2,3-ep oxycy-
cloh exa n e-1-m eth a n ol (tr a n s-7a )62 on the basis of the
1
following data: a colorless liquid; H NMR (CDCl3) δ 0.80-
1.10 (m, 1H), 1.20-1.80 (m, 4H), 1.88 (br s, 1H), 1.95-2.08
(m, 1H), 2.12 (m, 1H), 3.11 (d, J ) 3.91 Hz, 1H), 3.19 (dd, J )
3.91, 1.95 Hz, 1H), 3.63 (dd, J ) 10.70, 7.08 Hz, 1H), 3.72 (dd,
J ) 10.70, 5.65 Hz, 1H); 13C NMR (CDCl3) δ 17.11, 23.85,
24.81, 37.48, 52.76, 54.08, 65.13; MS (EI, 70 eV) m/ z 128(M+,
1), 127(11), 110(20), 98(9), 97(100), 95(25), 85(10), 84(10),
83(21), 82(22), 81(30), 80(9), 79(70), 77(20), 73(8), 71(20),
70(26), 69(35), 68(14), 67(69), 66(10), 57(50), 56(13), 55(47),
54(18), 53(19), 43(23); calcd for C7H12O2: 128.17.
The second product was identified as cis-2,3-ep oxycyclo-
h exa n e-1-m eth a n ol (cis-7a ) on the basis of a comparision
of NMR data with the trans isomer and the following data: a
colorless liquid; 1H NMR (CDCl3) δ 1.10-1.65 (m, 4H), 1.75-
1.85 (m, 2H), 2.06 (m, 1H), 2.22 (br s, 1H), 3.21 (ddd, J ) 5.54,
3.74, 1.71 Hz, 1H), 3.25 (dd, J ) 4.16, 2.49 Hz, 1H), 3.68 (dd,
J ) 10.35, 6.01 Hz, 1H), 3.74 (dd, J ) 10.26, 7.81 Hz, 1H); 13
C
NMR (CDCl3) δ 19.28, 21.73, 23.85, 37.04, 52.26, 53.70, 65.23;
MS (EI, 70 eV) m/ z 128(M+, 0.5), 127(9), 110(15), 98(21),
97(100), 95(21), 85(9), 84(19), 83(44), 82(20), 81(38), 80(12),
79(80), 77(22), 73(7), 71(16), 70(64), 69(39), 68(18), 67(74),
66(11), 57(45), 56(13), 55(55), 54(19), 53(20), 43(25), 42(10),
41(78); Calcd for C7H12O2: 128.17.
Ep oxid a tion of 4b by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-(br om om eth yl)-
tr a n s-1,2-ep oxycycloh exa n e (tr a n s-7b) by comparing its
NMR spectral63 data with those in the literature and on the
basis of the following data: a colorless liquid; 1H NMR (CDCl3)
δ 1.05-1.20 (m, 1H), 1.30-1.50 (m, 2H), 1.60-1.80 (m, 2H),
2.03-2.15 (m, 1H), 2.28 (m, 1H), 3.08 (d, J ) 3.72 Hz, 1H),
The second minor product was identified as 3-m eth yl-2-
cycloh exen -1-on e (9) as described previously.
Ep oxid a tion of 3d by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as 3-(a cetyloxy)-tr a n s-
1,2-ep oxy-1-m eth ylcycloh exa n e (tr a n s-6d ) on the basis of
the following data: a colorless liquid; 1H NMR (CDCl3) δ 1.10-
2.00 (m, 6H), 1.34 (s, 3H), 2.09 (s, 3H), 2.89 (s, 1H), 5.00 (dd,
J ) 7.95, 5.98 Hz, 1H); 13C NMR (CDCl3) δ 15.68, 21.17, 23.14,
26.20, 29.19, 58.36, 60.49, 68.78, 169.92; MS (EI, 70 eV) m/ z
170(M+, 0.1), 128(5), 127(3), 113(7), 112(52), 95(7), 84(16),
81(10), 71(19), 70(72), 67(13), 55(14), 43(100); calcd for
C9H14O3: 170.20. Anal. Calcd for C9H14O3: C, 63.51; H, 8.29.
Found: C, 63.51; H, 8.29.
3.20 (dd, J 1,2 ) 3.66 and J 2,3 ) 2.00 Hz, 1H, 3.40 (dd, J a,b
10.15 and J a,3 ) 6.41 Hz, 1H), 3.54 (dd, J a,b ) 10.16 and J b,3
)
)
5.19 Hz, 1H); 13C NMR (CDCl3) δ 16.88, 24.56, 26.29, 36.53,
36.85, 52.71, 55.02; MS (EI, 70 eV) m/ z 191 (M+, 0.2), 149(2),
148(3), 146(3), 112(5), 111(65), 97(23), 93(54), 91(14), 83(13),
81(16), 79(20), 77(14), 69(17), 68(8), 67(100), 57(20), 55(75),
54(10), 53(18), 43(19), 41(41); calcd for C7H11BrO: 191.07.
The major product was identified as 3-(br om om eth yl)-cis-
1,2-ep oxycycloh exa n e (cis-7b) on the basis of a comparison
of NMR data with the known trans isomer and the following
data: a colorless liquid; 1H NMR (CDCl3) δ 1.10-1.35 (m, 2H),
1.40-1.60 (m, 2H), 1.75-1.95 (m, 2H), 2.23 (m, 1H), 3.24 (ddd,
The second product was identified as 3-(a cetyloxy)-cis-1,2-
ep oxy-1-m eth ylcycloh exa n e (cis-6d ) on the basis of a
comparison of NMR data with the trans isomer and the
1
following data: a colorless liquid; H NMR (CDCl3) δ 1.10-
2.00 (m, 6H), 1.33 (s, 3H), 2.10 (s, 3H), 3.15 (d, J ) 2.44 Hz,
1H), 5.11 (ddd, J ) 8.36, 5.67, 2.47 Hz, 1H); 13C NMR (CDCl3)
δ 19.22, 21.28, 23.94, 24.35, 28.07, 59.61, 60.37, 70.77, 170.70;
MS (EI, 70 eV) m/ z 170(M+, 0.1), 128(4), 127(2), 113(4),
112(42), 95(5), 84(13), 81(8), 71(18), 70(75), 67(11), 55(12),
43(100); calcd for C9H14O3: 170.20.
J ) 7.63, 5.34, 1.54 Hz, 1H), 3.295 (dd, J 1,2 ) 4.10 and J 2,3
)
(61) Kurihara, M.; Ito, S.; Tsutsumi, N.; Miyata, N. Tetrahedron Lett.
1994, 35, 1577.
(62) Mori, M. J pn. Kokai Tokkyo Koho J P 04,208,272 (1992); Chem.
Abstr. 1993, 118, 101785v.
Ep oxid a tion of 3e by 1. The general procedure was
followed to give a residue which was found to contain two
(63) Haufe, G. J . Prakt. Chem. 1982, 324, 896.

Diastereoselective Epoxidation of Cyclohexenes
J . Org. Chem., Vol. 61, No. 5, 1996 1841
2.50 Hz, 1H), 3.346 (dd, J a,b ) 9.84 and J a,3 ) 6.67 Hz, 1H),
3.54 (dd, J a,b ) 9.84 and J b,3 ) 8.18 Hz, 1H); 13C NMR (CDCl3)
δ 19.51, 23.63, 24.46, 35.35, 38.09, 53.08, 53.85; MS (EI, 70
eV) m/ z 191(M+, 0.07), 149(1), 148(2), 146(2), 112(4), 111(63),
97(19), 93(47), 91(10), 81(14), 79(18), 77(11), 69(15), 68(8),
67(100), 57(18), 55(72), 54(9), 53(17), 43(20), 41(48); calcd for
C7H11BrO: 191.07.
Ep oxid a tion of 4c by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products could not be separated by preparative
GLC. A mixture of the products was obtained by preparative
GLC. One of these products was identified as 3-[(a cetyloxy)-
m eth yl]-tr a n s-1,2-ep oxycycloh exa n e (tr a n s-7c) on the
basis of the following data: (from cis:trans mixture) 1H NMR
(CDCl3) δ 0.85-1.05 (m, 1H), 2.08 (s, 3H), 3.01 (d, J ) 3.91
Hz, 1H), 3.21 (dd, J ) 3.91, 1.60 Hz, 1H) 3.95-4.20 (m, 2H);
13C NMR (CDCl3) δ 16.80, 20.74, 21.60, 23.77, 34.12, 52.10,
53.35, 65.95, 170.71. The mass spectrum of the trans-product
was identical with that of the cis-product.
The second product was identified as 3-[(a cet yloxy)-
m eth yl]-cis-1,2-ep oxycycloh exa n e (cis-7c) on the basis of
the following data: (from cis:trans mixture) 1H NMR (CDCl3)
δ 1.10-1.95 (m, 6H), 2.07 (s, 3H), 2.15-2.25 (m, 1H), 3.18 (m,
2H), 3.95-4.20 (m, 2H); 13C NMR (CDCl3) δ 18.95, 20.79, 23.53,
24.49, 34.31, 52.31, 52.70, 65.95, 170.63; MS (EI, 70 eV) m/ z
127(M+-CH3CdOsO, 5), 110(100), 95(90), 83(12), 82(67),
81(76), 67(48), 57(8), 55(21), 43(62); calcd for C9H14O3: 170.21.
Anal. Calcd for C9H14O3: C, 63.51; H, 8.29. Found: C, 63.51;
H, 8.29.
ing data: a colorless liquid; 1H NMR (CDCl3) δ 1.05-1.60 (m,
4H), 1.26 (t, J ) 7.14 Hz, 3H), 1.75-1.95 (m, 2H), 2.33 (dd, J
) 18.04, 6.86 Hz, 1H), 2.35 (m, 1H), 2.57 (dd, J ) 18.01, 9.70
Hz, 1H), 3.16 (dd, J ) 4.02, 1.98 Hz, 1H), 3.20 (dd, J ) 3.94,
3.47 Hz, 1H), 4.15 (q, J ) 7.14 Hz, 2H); 13C NMR (CDCl3) δ
14.33, 19.63, 23.61, 25.07, 31.98, 37.89, 53.25, 55.06, 60.39,
172.51; MS (EI, 70 eV) m/ z 184(M+, 1), 155(18), 138(24), 121-
(16), 113(93), 110(56), 97(68), 93(43), 79(74), 67(100), 55(89),
41(56); calcd for C10H16O3: 184.24.
Ep oxid a tion of 4f by 1. The general procedure was
followed to give a colorless solid. 1H NMR analysis of the
reaction mixture indicated the presence of cis epoxide as the
major product and trans epoxide as the minor product.
Separation of the products was accomplished by radial chro-
matography of the residue on a Chromatotron (silica gel plate),
using acetone/CH2Cl2 (20:80) as the eluent. The major product
was identified as 3-(ben za m id om eth yl)-cis-1,2-ep oxycy-
cloh exa n e (cis-7f) on the basis of the following data: colorless
needles (CH2Cl2-hexane), mp 109-111 °C; IR (KBr) 3310,
2932, 1630 (CdN), 1578, 1536, 1311, 924, 888, 848, 697 cm-1
;
1H NMR (CDCl3) δ 1.15-1.65 (m, 4H), 1.75-2.00 (m, 2H), 2.29
(m, 1H), 3.22 (m, 2H), 3.61 (m, 2H), 6.76 (br s, 1H), 7.35-7.55
(m, 3H), 7.70-7.90 (m, 2H); 13C NMR (CDCl3) δ 19.55, 22.86,
23.65, 33.98, 43.51, 52.56, 54.51, 126.78, 128.43, 131.25,
134.45, 167.50; MS (EI, 70 eV) m/ z 232 (M + 1, 0.1), 231(M+,
1), 134(20), 105(100), 77(21); calcd for C14H17NO2: 231.28.
Anal. Calcd for C14H17NO2: C, 72.69; H, 7.41; N, 6.05.
Found: C, 72.59; H, 7.40; N, 6.03.
The minor product formed during the reaction was 3-(ben z-
a m id om et h yl)-tr a n s-1,2-ep oxycycloh exa n e (tr a n s-7f)
which was identified on the basis of the following data: (from
cis:trans mixture, peaks reported here are not overlapping with
the major isomer) 1H NMR (CDCl3) δ 0.80-1.05 (m, 1H), 2.00-
2.15 (m, 1H), 3.016 (d, J ) 3.91 Hz, 1H), 3.16 (m, 1H), 3.35-
3.47 (m, 1H), 3.55-3.67 (m, 1H), 6.79 (br s, 1H); 13C NMR
(CDCl3) δ 17.00, 24.68, 25.34, 35.47, 42.75, 52.69, 53.93, 126.80,
128.33, 131.26, 134.32, 167.72; MS (EI, 70 eV) m/ z 231(M+,
1), 134(40), 105(100), 77(27); calcd for C14H17NO2: 231.28. This
mass spectrum is actually that of 8-h yd r oxy-2-p h en yl-
4a ,5,6,7,8,8a -h exa h yd r o-4H-1,3-ben zoxa zin e, the thermal
rearrangement product of the 3-(ben za m id om eth yl)-tr a n s-
1,2-ep oxycycloh exa n e.
Ep oxid a tion of 4d by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as (tr a n s-1,2-ep oxycy-
cloh exa n -3-yl)m eth yl a ceta te (tr a n s-7d ) by comparing its
NMR spectral data20,64 spectral data with those in the litera-
ture and on the basis of the following data: a colorless liquid;
1H NMR (CDCl3) δ 0.85-1.05 (m, 1H), 1.30-1.45 (m, 2H),
1.55-1.80 (m, 3H), 2.00-2.15 (m, 1H), 2.36 (m, 1H), 2.46 (AB
m, 2H), 2.94 (d, J ) 3.91 Hz, 1H), 3.17 (dd, J ) 3.91, 2.00 Hz,
1H), 3.70 (s, 3H); 13C NMR (CDCl3): δ 17.02, 24.53, 26.82,
31.43, 38.29, 51.72, 52.65, 55.48, 172.42; MS (EI, 70 eV) m/ z
170(M+, 1), 155(2), 139(29), 111(30), 110(28), 99(100), 97(65),
84(27), 79(23), 74(37), 67(56), 55(58), 41(37); calcd for
C9H14O3: 170.21.
The rearrangement product was also formed during chro-
matography and was isolated as a colorless viscous liquid and
identified as 8-h yd r oxy-2-p h en yl-4a ,5,6,7,8,8a -h exa h yd r o-
4H-1,3-ben zoxa zin e on the basis of the following data: a
colorless viscous liquid, solidifies very slowly on standing; IR
(neat film) 3354(OH), 2934, 2860, 1650(CdN), 1448, 1336,
1279, 1159, 1125, 1070, 1028, 1006, 991, 974, 898, 864, 839,
782, 733, 696 cm-1; 1H NMR (CDCl3) δ 1.40-2.00 (m, 6H), 2.29
(m, 1H), 3.11 (br s, 1H, OH, exchangeable with D2O), 3.42 (dd,
J ) 16.87, 6.57 Hz, 1H), 3.55 (dd, J ) 16.85, 5.62 Hz, 1H),
3.97 (m, 1H), 4.21 (dd, J ) 6.29, 4.15 Hz, 1H), 7.30-7.55 (m,
3H), 7.80-8.00 (m, 2H); 13C NMR (CDCl3) δ 19.95, 25.59, 28.90,
30.00, 46.40, 68.32, 77.51, 126.84, 127.93, 130.35, 133.45,
154.19; MS (EI, 70 eV) m/ z 232(M + 1, 0.3), 231(M+, 2),
134(46), 105(100), 77(20); calcd for C14H17NO2: 231.28. Anal.
Calcd for C14H17NO2: C, 72.69; H, 7.41; N, 6.05. Found: C,
72.53; H, 7.38; N, 6.01.
The major product was identified as (cis-1,2-ep oxycyclo-
h exa n -3-yl)m eth yl a ceta te (cis-7d ) by comparing its NMR
spectral data20,64 with those in the literature and on the basis
1
of the following data: a colorless liquid; H NMR (CDCl3) δ
1.05-1.35 (m, 2H), 1.35-1.60 (m, 2H), 1.70-1.95 (m, 2H), 2.35
(m, 1H), 2.352 (dd, J ) 17.79, 6.85 Hz, 1H), 2.58 (dd, J ) 17.82,
9.58 Hz, 1H), 3.16 (dd, J ) 3.95, 2.15 Hz, 1H), 3.20 (dd, J )
3.94, 3.47 Hz, 1H), 3.69 (s, 3H); 13C NMR (CDCl3) δ 19.59,
23.60, 25.08, 31.95, 37.61, 51.62, 53.28, 55.02, 172.98; MS (EI,
70 eV) m/ z 170(M+, 1), 155(3), 138(16), 121(7), 111(31),
110(34), 99(100), 97(64), 84(29), 79(37), 67(59), 55(54), 41(35);
calcd for C9H14O3: 170.21.
Ep oxid a tion of 4e by 1. The general procedure was
followed to give a residue which was found to contain two
products. The products were separated by preparative GLC.
One of these products was identified as (tr a n s-1,2-ep oxycy-
cloh exa n -3-yl)eth yl a ceta te (tr a n s-7e) on the basis of the
following data: a colorless liquid; 1H NMR (CDCl3) δ 0.85-
1.05 (m, 1H), 1.10-1.50 (m, 2H), 1.27 (t, J ) 7.13 Hz, 3H),
1.60-2.00 (m, 2H), 2.00-2.15 (m, 1H), 2.36 (m, 1H), 2.42 (AB
m, 2H), 2.95 (d, J ) 3.91 Hz, 1H), 3.166 (dd, J ) 3.91, 2.00
Hz, 1H), 4.16 (q, J ) 7.13 Hz, 2H); 13C NMR (CDCl3) δ 14.33,
17.03, 24.55, 26.78, 31.46, 38.57, 52.64, 55.52, 60.50, 171.95;
MS (EI, 70 eV) m/ z 184(M+, 21), 139(45), 113(100), 110(53),
97(68), 95(36), 81(56), 67(81), 55(77), 41(45); calcd for
C10H16O3: 184.24. Anal. Calcd for C10H16O3: C, 65.19; H, 8.75.
Found: C, 65.04; H, 8.80.
Ack n ow led gm en t. We gratefully acknowledge sup-
port of this work by the National Institutes of Health
through Grant No. ES01984. The XL-300 NMR spec-
trometer was purchased with support from the National
Science Foundation. The Bruker ARX-500 NMR spec-
trometer was purchased with support from the U.S.
Department of Energy, Grant No. DE-FG02-
92CH10499. The opinions, findings, conclusions, and
recommendations expressed herein are those of the
authors and do not necessarily reflect the views of the
DOE.
The major product was identified as (cis-1,2-ep oxycyclo-
h exa n -3-yl)eth yl a ceta te (cis-7e) on the basis of the follow-
(64) Kocovsky, P.; Stary, I. J . Org. Chem. 1990, 55, 3236.
J O951864J