Epoxidation of Olefins
J . Org. Chem., Vol. 61, No. 25, 1996 8809
mixture was stirred and then allowed to warm to room
temperature. The aqueous layer was extracted with CH2Cl2,
and combined organics were evaporated. The residue was
distilled to give the corresponding epoxide 3a (106 mg, 88%
yield), which was identified through comparison of its spectral
and physical data with those reported in the literature.43
1,2-Cycloh exa n ed iol. To a solution of cyclohexene (100
mg, 1.2 mmol) in trifluoroacetic acid (2 mL) was added
dropwise at -40 °C a solution of 1a (647 mg, 1.4 mmol) in the
same solvent. After 30 min of stirring at the same tempera-
ture, the reaction mixture was evaporated, the residue was
dissolved in methanol (2 mL), and sodium methylate (45 mg)
was added. The reaction mixture was stirred for 3 h at room
temperature, one drop of trifluoroacetic acid was then added,
and the mixture was evaporated under reduced pressure.
Flash chromatography of the residue afforded 114 mg of 1,2-
cyclohexane diol (82% yield).
served diastereoselection is the subtle balance of several
factors.41 A distinctive feature of the behavior of oxaziri-
dines 1 is the unique difference of diastereoface selectivity
changing from 3-hydroxysteroids 2n ,o, affording prefer-
entially the R-epoxide, to their analogues 2p -r , which
bear an ester or chloride residue in the same position
and give mainly the â epimer.
A pronounced influence of solvent on diastereoselec-
tivity of epoxide formation by dimethyldioxirane has been
described,41 and we have therefore studied this influence
on some of our substrates. No change of diastereoselec-
tivity is observed with carvone 2j. The â-epoxide 3q is
obtained in 86 and 74% excess when benzoyl cholesterol
2q is reacted in chloroform and methylene chloride,
respectively. The â-epoxide 3r is formed in 36 and 14%
excess when methylene chloride and trichlorotrifluoro-
ethane are used with cholesteryl chloride 2r . Other
solvents and solvent mixtures have been tested, and
results are reported in the Experimental Section.
1-Octen e oxid e (3b):44
reaction conditions, CHCl3/HCFC-
225ca,cb ) 1:1, -40 °C, 40 min; 86% yield.
exo-Nor bor n ylen e oxide (3c):33 reaction conditions, CHCl3/
HCFC-225ca,cb ) 1:1, -40 °C, 40 min; 80% yield.
cis-3,4-Ep oxyh exa n -1-ol a ceta te (3d ): reaction conditions,
1
CHCl3/HCFC-225ca,cb ) 1:1, -60 °C, 20 min; 85% yield; H
Con clu sion s
NMR (CDCl3) δ 1.06 (t, 3H, J ) 7.4), 1.40-2.00 (m, 4H), 2.07
(s, 3H), 2.92 and 3.03 (dt, 2H, J ) 4.2, 6.1), 4.10-4.40 (m, 2H);
IR (KBr) 1041, 1241, 1744, 2973; MS (EI) m/ z 158 (M).
tr a n s-Meth yl cin n a m a te oxid e (3e):45 reaction conditions,
CFC-11, rt, 16 h; 82% yield.
Perfluoro-cis-2,3-dialkyloxaziridines 1 are shown to
epoxidize effectively several and structurally different
olefins. Alkyl-substituted double bonds react under
particularly smooth conditions (-40 °C, 30 min). Mildly
and strongly electron deficient substrates can also be
oxidized, and the more electron poor the double bond is,
the more severe the reaction conditions become. The
reaction occurs stereoselectively as cis- and trans-olefins
afford corresponding cis- and trans-epoxides, respectively.
Both aprotic (halogenated hydrocarbons) and protic
solvents (trifluoroethanol and tert-butyl alcohol and their
mixtures) can be used, and this allows a wide range of
substrates to be oxidized in homogeneous reaction condi-
tions. The presence of some functional groups which are
known to be oxidized by oxaziridines 1, notably secondary
alcohols and their ethers, does not interfere with epoxide
formation. The selective transformation of a single
double bond in a di-unsaturated substrate is also possible.
On some substrates the diastereoselectivity obtained with
oxaziridines 1 was higher than that obtained by using
hydrogen peroxide,36 MCPBA,20,28 or dioxiranes,39 and
this is probably related to the higher steric requirements
of these reagents.
Tr iflu or o(t r im et h ylsilyl)et h ylen e oxid e (3f): reaction
conditions, neat, rt, 20 min; 82% yield; 19F NMR (CDCl3) δ
-147.8 (dd, 1F, J ) 26, 9), -114.8 (dd, 1F, J ) 50, 26), -104.9
(dd, 1F, J ) 50, 9); IR (gas) 756, 853, 911, 1030, 1110, 1262,
1499, 2974; MS (EI) m/ z 170 (M).
Ch lor otr iflu or oeth ylen e oxid e (3g): reaction conditions,
30% molar excess of 1a , neat, 100 °C, 16 h; 60% yield; 19F NMR
(CDCl3) δ -114.2 (dd, 1F, J ) 32, 15), -109.6 (dd, 1F, J ) 32,
19), -94.3 (dd, 1F, J ) 19, 15); MS (EI) m/ z 132.5 (M).
tr a n s-Va ccen ic a cid m eth yl ester 11,12-oxid e (3h ):
reaction conditions CHCl3/HCFC-225ca,cb ) 1:1, -50 °C, 5
min; 70% yield; 1H NMR (CDCl3) δ 0.88 (t, 3H, J ) 6.7), 1.25-
1.65 (m, 26H), 2.30 (t, 2H, J ) 7.5), 2.66 (m, 2H, J 11,12 ) 2.3,
H-11 and -12), 3.67 (s, 3H); IR (KBr) 1741, 2854, 2930; MS
(CI, CH4) m/ z 313 (M + 1).
(R)-Citr on ellol a ceta te oxid es (3i):18 reaction conditions,
HCFC-225ca,cb, -40 °C, 20 min; 88% yield; diastereoisomer
ratio 1:1 by GC (SPB-1 fused silica capillary column, 30 m ×
0.25 mm (id), df 1 µm, 20 min, 140 °C).
Car von e 8,9-oxides (3j): reaction conditions, HCFC-225ca,-
cb, -40 °C, 30 min; 75% yield; diastereoisomer ratio 1:1 by
GC (OV-1 fused silica capillary column, 25 m × 0.25 mm (id),
1
df 0.25 µm, 110 °C); H NMR (CDCl3) δ 1.31 and 1.33 (broad
s, 2 × 3H), 1.78 (broad s, 2 × 3H), 2.58 and 2.60 (d, 2 × 1H, J
) 4.5), 2.67 and 2.71 (broad d, 2 × 1H, J ) 4.5), 6.73 (m, 1H);
IR (film) 1674, 2927, 3461; MS (EI), m/ z 166 (M). Other
solvents (CFCl3, CH2Cl2, CCl4, CHCl3, CHCl3:t-BuOH ) 1:1,
CF2ClCFCl2) required similar reaction conditions and gave
similar yields.
Exp er im en ta l Section
Oxaziridines 1a ,b have been prepared in two steps from
perfluorotri-n-butyl- and -tri-n-hexylamine.42 Dichloropen-
tafluoropropane was a 43:56 mixture of HCFC-225ca and
HCFC-225cb (CF3CF2CHCl2 and CClF2CF2CHClF, respec-
tively), purchased from PCR Incorporated. Analytical instru-
ments employed and spectral data format are described in ref
9a. New compounds gave correct analytical data (C ( 0.3; H
( 0.4).
Gen er a l P r oced u r e for th e P r ep a r a tion of Cycloh ex-
en e Oxid e (3a ) w ith P er flu or o-cis-2-n -bu tyl-3-n -p r op y-
loxa zir id in e (1a ). To a solution of cyclohexene (100 mg, 1.2
mmol) in CHCl3 was added, under nitrogen, a solution of the
oxaziridine 1a (647 mg, 1.4 mmol) in HCFC-225ca,cb at -40
°C. After the mixture was stirred for 40 min at the same
temperature, the reaction was quenched by the addition of
saturated aqueous solution of ammonium chloride. The
P icr ot oxin in oxid e (3k ): reaction conditions, CHCl3/
HCFC-225ca,cb ) 1:1, rt, 1 h; 87% yield; de > 98%; mp 189-
1
191 °C (CHCl3); H NMR (CDCl3) δ 1.37 (s, 3H, H3-10), 1.55
(s, 3H, H3-14), 2.11 (broad d, 1H, J ) 15.3, H-7R), 2.61 (d, 1H,
J ) 4.2, H-5), 2.84 (d, 1H, J ) 3.8, H-13R), 2.86 (dd, 1H, J )
15.3, 3.5, H-7â), 2.99 (broad d, 1H, J ) 3.8, H-13â), 3.39 (dd,
1H, J ) 5.3, 4.2, H-4), 3.71 (d, 1H, J ) 3.5, H-8), 4.59 (d, 1H,
J ) 3.2, H-2), 4.75 (broad s, 1H, OH-6), 5.02 (dd, 1H, J ) 5.3,
3.2, H-3); NOEs irradiation of H-2 enhanced H-3 (4%), H3-10
(1.5%), and H3-14 (1.5%); {H-3} enhanced H-2 (5%), H-4 (3.5%),
and H3-14 (1.5%); {H-4} enhanced H-3 (5%), H-5 (4.5%), H-13â
(1%), and H3-14 (1%); {H-5} enhanced H-4 (4%), H-7â (3%),
H-13â (3%), and OH-6 (2%); {H-13â} enhanced H-4 (1%), H-5
(4.5%), H-13R (20.5%), and OH-6 (7.5%); {OH-6} enhanced H-5
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