A novel cyclopropane ring fragmentation of bicyclo[3.1.0]hexene epoxides to 2,5-dienals

Full text of DOI:10.1021/jo951850d

1184
J . Org. Chem. 1996, 61, 1184-1186
A Novel Cyclop r op a n e Rin g F r a gm en ta tion
of Bicyclo[3.1.0]h exen e Ep oxid es to
2,5-Dien a ls
Robert M. Coates,* Zhanqi Ho, and Lijuan Zhu
Roger Adams Laboratory, Department of Chemistry,
University of Illinois, 600 S. Mathews Avenue,
Urbana, Illinois 61801
Received October 13, 1995
Epoxides of strained cyclic alkenes undergo a variety
of ring fragmentation reactions which lead to unsatur-
ated carbonyl compounds.1 Two of the many known
examples are shown in eqs 1 and 2.2 In this note we
report a novel cyclopropane fragmentation of strained
bicyclo[3.1.0]hexene epoxides to 2,5-dienals.
for 4, δH 3.16 and 3.46 (J ) 2.9 Hz), δC 65.9 and 67.6; for
7, δH 3.24 and 3.46 (J ) 2.4 Hz), δC 58.2 and 62.8.
The epoxide of bicyclo[3.1.0]hexene itself is a known
compound,6 and the literature does not indicate any
tendency toward fragmentation. Although the prepara-
tion of thujene epoxide (9) by photosensitized epoxidation
of thujene with biacetyl and oxygen has been recorded
in the patent literature,7 this unstable epoxide was
characterized only by 1H NMR spectral data in CCl4. We
succeeded in preparing thujene epoxide by dimethyldiox-
Angular and linear tetracyclic vinylcyclopropanes 1
and 5 were prepared by intramolecular photoannulation
of 1-(1,5-dimethyl-4-hexenyl)-2-methylbenzene as de-
scribed by Wender and Ternansky.3 The 60:40 mixture
of isomeric olefins was separated by chromatography on
silver nitrate-impregnated silica gel. Attempted epoxi-
dation of 1 with m-chloroperoxybenzoic acid in the
presence or absence of bicarbonate buffer afforded a
mixture of dienal 2 (63%) and its epoxidation product 3
(26%). Similar epoxidation of the linear isomer 5 gave
rise to dienal 6 (78%). No evidence for the suspected
epoxide intermediates could be obtained by TLC and GC
analyses during and after the reactions. The Z stereo-
chemistry of the 2,3-double bond in the two 2,5-dienal
products is assigned on the basis of the coupling interac-
1
irane epoxidation at room temperature (97%). Its H and
13C NMR spectra show absorptions characteristic of the
trisubstituted oxirane: δH 2.93, δC 60.86 and 70.64.
Attempts to effect epoxidation of thujene with m-chlo-
roperoxybenzoic acid gave complex mixtures. Thujene
epoxide underwent thermal fragmentation to the conju-
gated dienal 11 (8%). However, the major product
p-cymene (64%) arose from a competing aromatization
pathway. (E,E)-2,5,6-Trimethyl-2,4-heptadienal (11) is
a known compound resulting from a similar enzyme-
catalyzed tandem rearrangement-fragmentation of R-
pinene epoxide to the 2,5-heptadienal isomers followed
by isomerization to the fully conjugated form.8-10 How-
ever, to our knowledge, complete physical and spectral
data for 11 have not been previously reported.
1
tion between the vicinal vinyl protons in their H NMR
spectra (for 2, J 2,3 ) 11.2 Hz; for 3, J 2,3 ) 11.5 Hz; for 6,
J 2,3 )12.8 Hz). Literature values for (E)-and (Z)-6-
(tetrahydropyranyloxy)-2-hexenals are 15.6 and 11.1 Hz,
respectively.4
The unstable epoxides of 1 and 5 were obtained by
epoxidation with dimethyldioxirane5 in acetone at -20
°C for 10 h. The more sensitive epoxide 4 was invariably
produced as a 1:1 mixture with its dienal fragmentation
product. The epoxides were characterized by IR, MS, 1H
NMR, and 13C NMR spectra. The NMR chemical shifts
for the oxiranyl ring protons and carbons are as follows:
These epoxide to dienal fragmentation reactions occur
by simultaneous or successive cleavages of the epoxide
C-O bond, the adjacent cyclopropane C-C bond, and an
oxygen-bearing C-C bond. The reaction rates were
measured in toluene (with and without added m-chlo-
(1) Ho, T.-L. Heterolytic Fragmentation of Organic Molecules;
Wiley: New York, 1993.
(2) (a) Miller, J . A.; Ullah, G. M. J . Chem. Soc. Perkin. Trans. 1
1989, 633. (b) Meinwald, J .; Labana, S. S.; Chadha, M. S. J . Am. Chem.
Soc. 1963, 85, 582.
(3) Wender, P. A.; Ternansky, R. J . Tetrahedron Lett. 1985, 26,
2625.
(4) Mancini, I.; Guella, G.; Pietra, F. Helv. Chim. Acta 1991. 74,
941.
(5) (a) Murray, R. W. Chem. Rev. 1989, 89, 1187. (b) Adam, W.;
Hadjiarapoglou, L.; Smerz, A. Chem. Ber. 1991, 124, 227.
(6) Corey, E. J .; Dawson, R. L. J . Am. Chem. Soc. 1963, 85, 1782.
(7) Japanese Patent 55051081, 1980 (Chem. Abstr. 1980, 93, 204889b).
(8) Griffiths, E. T.; Harries, P. C.; J effcoat, R.; Trudgill, P. W. J .
Bacteriol. 1987, 169, 4980.
(9) Griffiths, E. T.; Bociek, S. M.; Harries, P. C.; J effcoat, R.; Sissons,
D. J .; Trudgill, P. W. J . Bacteriol. 1987. 169, 4972.
(10) (a) Burfield, A. G.; Best, D. J .; Davis, K. J . UK Patent 2208863,
1989 (Chem. Abstr. 1990, 112, 34430m). (b) Burfield, A. G.; Best, D.
J .; Davis, K. J . EP 88307701, 1988 (Chem. Abstr. 1990, 112, 234029z).
0022-3263/96/1961-1184$12.00/0 © 1996 American Chemical Society

Notes
Ta ble 1. Kin etic Da ta for F r a gm en ta tion Rea ction s of
J . Org. Chem., Vol. 61, No. 3, 1996 1185
chemical shifts for the compound are consistent with
literature data.4
Ep oxid es 4, 7, a n d 9 a t 18.6 °C (see eqs 3-5)
b
epoxide
solventa
k (s-1
)
krel
4
toluenec
acetone
methanol
3.8 ( 0.5 × 10-6
1.5 ( 0.6 × 10-5 107
27
37
5.2 ( 0.7 × 10-6
toluene with m-ClC6H4CO2H 1.9 ( 0.1 × 10-4 1357
7
9
toluene
1.7 ( 0.1 × 10-7
1.2
(1.0)
acetone
methanol
1.4 ( 0.5 × 10-7
1.4 ( 0.4 × 10-5 100
toluene with m-ClC6H4CO2H 1.7 ( 0.3 × 10-5 121
toluene
4.1 ( 0.7 × 10-6
29
29
acetone
methanol
4.1 ( 0.9 × 10-6
3.2 ( 0.2 × 10-5 229
toluene with m-ClC6H4CO2H 3.6 ( 0.3 × 10-5 257
a
In all cases the solvent is deuterated to greater than 99.9%.
The rate is the average of the disappearance of starting material
b
and the formation of the product. c Rate measurements taken over
256 h (first half of one half-life).
Exp er im en ta l Section
Gen er a l Asp ects.11 1H and 13C NMR spectra were recorded
in CDCl3 at 400 and 100 MHz, respectively. GC analyses were
carried out on a 30-m RTX-5 fused silica capillary column using
helium as a carrier gas. Complete experimental procedures for
the preparation of tetracyclic olefins 1 and 5 based on brief ones
given in the literature3 are presented as supporting information.
Dim eth yld ioxir a n e. Solutions of dimethyldioxirane in ac-
etone were generated by a literature procedure.5b The concen-
tration (0.05-0.1 M) of the dimethyldioxirane was determined
by addition of excess thioanisole and quantitative analysis of
1
the resulting sulfoxide by integration of the H NMR spectrum.
[1R -(1r,3a r,5â)]-(()-1,2,3,3a ,4,5-H exa h yd r o-1,4,4,6-t et -
r a m eth yl-5-[(Z)-2-for m yleth en yl]-6,6a -ep oxyp en ta len e (2),
[1R-(1r,3a r,5b)]-(()-1,2,3,3a ,4,5,6,6a -octa h yd r o-1,4,4,6-tet-
r a m eth yl-5-[(Z)-2-for m yleth en yl]-6,6a -ep oxyp en ta len e (3).
A solution of 1 (50 mg, 0.25 mmol) in 10 mL of CH2Cl2 was
stirred at 0 °C as m-CPBA (43.2 mg, 0.25 mmol) was added in
one portion. The solution was allowed to warm to rt and stirred
for another 10 min when the reaction was complete according
to TLC analyses. The reaction mixture was washed with
aqueous saturated sodium metabisulfite (10 mL), saturated
aqueous Na2CO3 (10 mL), and aqueous saturated NaCl (20 mL).
The organic layer was dried (MgSO4) and evaporatated at
reduced pressure. Purification by flash chromatography using
hexane-ether (20:1) provided 34 mg (63%) of dienal 2 and 15
mg (26%) of epoxy aldehyde 3.
robenzoic acid), acetone, and methanol by 1H NMR
spectroscopy to evalute the polarity of the transition state
and to determine a probable mechanism for the process.
The data in Table 1 show similar slow rates in nonpolar
and polar aprotic solvents (toluene and acetone) which
increase by 4-100 times in the hydrogen bonding me-
dium of methanol. The 8.8-121-fold rate increases
observed in the presence of m-chlorobenzoic acid clearly
implicate a stepwise mechanism involving protic acid
catalysis and cyclopropylcarbinyl and homoallyl carboca-
tion intermediates as shown in eq 7, or alternatively by
a concerted fragmentation of a delocalized cyclopropyl-
carbinyl ion directly to the protonated dienal.
For 2. IR (neat): 1680. 1H NMR: δ 0.95 (3 H, s), 1.03 (3 H,
s), 1.04 (3 H, d, J ) 6.8 Hz), 1.27 (1 H, m), 1.48 (2 H, m), 1.55 (3
H, s), 2.20 (1 H, m), 2.51 (1 H, app qd, J ) 6.8, and 0.7 Hz), 2.91
(1 H, m), 3.60 (1 H, d, J ) 6.1 Hz), 5.99 (1 H, ddd, J ) 11.2, 8.3,
and 0.7 Hz), 6.60 (1 H, dd, J ) 11.7 and 11.2 Hz), 10.07 (1 H, d,
J ) 8.3 Hz). 13C NMR: δ 12.78, 19.90, 24.05, 24.80, 25.49, 31.01,
38.83, 44.47, 59.15, 65.19, 125.77, 129.49, 152.04, 154.06, 191.26.
MS (EI, 70 eV) m/z (relative intensity): 218 (M+, 11.4). Anal.
Calcd for C15H22O: C, 82.52; H, 10.16. Found: C, 82.55; H,
10.17.
For 3. Mp: 49.5-51.0 °C; IR (neat): 3032, 2869, 1680 (CdO),
1363. 1H NMR: δ 0.93 (3 H, s), 0.94 (3 H, s), 1.01 (3 H, d, J )
7.1 Hz), 1.18 (3 H, d, J ) 1.8 Hz), 1.71 (1 H, m), 1.90 (1 H, app.
sextet, J ) 7.2 Hz), 2.11 (2 H, m), 3.24 (1 H, d, J ) 11.5 Hz),
6.20 (1 H, dd, J ) 11.5 and 8.0 Hz), 6.73 (1 H, t, J ) 11.5 Hz),
9.96 (1 H, d, J ) 8.0 Hz); 13C NMR: δ 15.72, 18.34, 24.93, 25.71,
27.26, 27.83, 32.65, 42.33, 51.28, 52.17, 70.89, 82.23, 132.45,
150.48, 190.66. MS (EI, 70eV) m/z (relative intensity): 234 (M+,
1.7), 123(40.3), 95(100), 41 (100). Anal. Calcd for C15H22O2: C,
76.88; H, 9.46. Found: C, 77.17; H, 9.46.
[1R-(1r,3a r,5a â,8a R*)]-(()-1,2,3,3a ,4,4a ,4b,6b-Octa h yd r o-
1,4,4,6a -tetr a m eth yl-5,6-ep oxycyclop r op a [cd ]cyclop en ta -
[c]p en ta len e (4). Olefin 1 (202 mg, 1.0 mmol) was stirred at
-20 °C as freshly generated dimethyl dioxirane in acetone (20
mL, 0.072 M, 1.44 mmol)5b was added in one portion. The
solution was stirred at -20 °C for 10 h, and the reaction was
followed by TLC. The reaction mixture was allowed to warm to
0 °C, diluted with pentane (20 mL), and dried (MgSO4). The
A similar mechanism for the conversion of thujene
epoxide to conjugated dienal 11 and p-cymene is proposed
in eq 8. In this case, the homoallyl carbocation presum-
ably undergoes competive eliminations and bond cleavage
to the observed products. The unstable 2,5-dienal formed
undergoes rapid isomerization to the thermodynamically
more stable (E,E)-2,4-dienal. The (E,E) stereochemistry
is assigned to 11 for this reason, and the 1H NMR
(11) Yee, N. K. N.; Coates, R. M. J . Org. Chem. 1992, 57, 4598.

1186 J . Org. Chem., Vol. 61, No. 3, 1996
Notes
solvent was carefully removed by rotary evaporation at 0 °C to
obtain a 1:1 mixture of epoxide 4 and dienal 2 (186 mg, 85%).
The 1H and 13C NMR specra were recorded with the mixture.
When this mixture was stored at rt for 24 h, 2 was the only
product.
( 1 R , 2 S , 3 R , 5 R ) -2 -M e t h y l -5 -( 1 -m e t h y l e t h y l ) -2 , 3 -
ep oxybicyclo[3.1.0]h exa n e (r-th u jen e ep oxid e) (9). Epoxi-
dation of thujene (204 mg, 1.5 mmol) with freshly generated
dimethyldioxirane in acetone (30 mL, 0.0557 M, 1.67 mmol) at
rt for 4 h gave 9 (221 mg, 97%) as a light yellow oil. IR (neat):
3027, 2951, 2868, 1456, 1390, 845. 1H NMR: δ 0.29 (1 H, t, J
) 4.1 Hz), 0.63 (1 H, dd, J ) 8.1, 4.1 Hz), 0.80 (3 H, d, J ) 7.0
Hz), 0.86 (3 H, d, J ) 7.0 Hz), 0.40-1.05 (3 H, m), 1.43 (3 H, s,
CH3), 2.93 (1 H, t, J ) 1.0). 13C NMR: δ 16.56, 18.00, 19.60,
19.61, 30.36, 30.97, 31.69, 32.29, 60.86, 70.64. MS (EI, 70 eV)
m/z (relative intensity): 152 (M+, 11.4). Anal. Calcd for
For 4. 1H NMR: δ 1.04 (3 H, s), 1.07 (3 H, s), 1.13 (3 H, d, J
) 7.0 Hz), 1.15 (3 H, s), 1.27 (1 H, m), 1.48 (2 H, m), 2.20 (1 H,
m), 2.51 (1 H, app qd, J ) 6.8, and 0.7 Hz), 2.91 (1 H, m), 3.16
(1 H, dd, J ) 2.9 and 0.9 Hz), 3.46 (1 H, dd, J ) 2.9 Hz). 13C
NMR: δ 19.07, 19.10, 27.94, 28.72, 30.37, 33.03, 34.02, 36.48,
37.68, 38.45, 47.10, 54.76, 59.45, 65.91, 67.58.
[1R-(1r,3ar,4ab,4bâ,6bS*)]-(()-1,2,3,3a,4,4a,4b,6a-Octah y-
d r o-1,4,4,4b -t et r a m et h yl-5,6-ep oxycyclop r op a [cd ]cyclo-
p en ta [c]p en ta len e (7) a n d [1R-(1R,3a R,6a S*)]-(()-1,2,3,-
3 a ,4 ,6 a -h e x a h y d r o -1 ,4 ,4 ,6 -t e t r a m e t h y l -6 a -[ ( Z ) -2 -
for m yleth en yl]p en ta len e (6). Epoxidation of 5 (202 mg, 1.0
mmol) with freshly generated dimethyldioxirane in acetone (20
mL, 0.0557 M, 1.11 mmol) was carried out at -20 °C for 2 days.
The product epoxide 7 (216 mg, 99%) was isolated as described
above for 4.
C
10H16O: C, 78.90; H, 10.59. Found: C, 78.88; H, 10.58.
Meth yl-4-(1-m eth yleth yl)ben zen e (p-cym en e 10) a n d
(E,E)-2,5,6-tr im eth ylh ep ta -2,4-d ien a l (11)7 fr om th e F r a g-
m en ta tion of r-Th u jen e Ep oxid e (9). R-Thujene epoxide (76
mg, 0.50 mmol) and benzene (1 mL) were placed in a reaction
vial with a resealable cap under N2. The vial was sealed with
a Teflon cap and heated at 135 °C for 8 h. The reaction was
followed by TLC. The solution was cooled to 0 °C, diluted with
pentane (20 mL), washed with brine (10 mL), and dried (MgSO4).
Evaporation of solvents afforded a light yellow oil (75 mg).
Purification by chromatography (pentane) gave 10 (43 mg, 64%)
and 11 (6 mg, 8%).
For 7. IR (neat): 3027, 2951, 2868, 1456, 1390, 845. 1H
NMR: δ 0.87 (3 H, d, J ) 9.3 Hz), 0.93 (3 H, s), 0.96 (3 H, s),
1.17 (3 H, s), 1.48 (2 H, m), 1.73 (4 H, m), 2.01 (1 H, dd, J ) 9.0,
ans 3.2 Hz), 2.11 (1 H, s), 3.24 (1 H, d, J ) 2.7 Hz), 3.46 (1 H, d,
J ) 2.2 Hz). 13C NMR: δ 16.50, 18.86, 23.47, 23.54, 23.79, 33.15,
35.13, 35.70, 37.75, 50.38, 51.48, 53.58, 55.74, 58.24, 62.80. MS
(EI, 70 eV) m/z (relative intensity): 218 (M+, 11.4), 203 (30.0),
161 (48.7), 119 (65.3), 105(70.0), 95 (100.0). Anal. Calcd for
For 10. IR (neat): 1514. 1H NMR: δ 1.22 (6 H, d, J ) 6.8
Hz), 2.29 (3 H, s), 2.85 (1 H, septet, J ) 6.8), 7.08 + 7.10 (4 H,
AA′BB′, J ) 8.3, 8.2, 1.9, 1.8, 0.1 Hz). 13C NMR: δ 20.94, 24.11,
33.70, 126.25, 128.97, 135.09, 145.80. MS (EI, 70 eV) m/z
(relative intensity): 134 (M+, 11.4). Anal. Calcd for C10H14: C,
89.49; H, 10.51. Found: C, 89.51; H, 10.52.
C
15H22O: C, 82.52; H, 10.16. Found: C, 82.58; H, 10.15.
A solution of epoxide 7 (110 mg, 0.50 mmol) in methanol-d4
For 11. IR (neat): 1678. 1H NMR: δ 1.10 (6 H, d, J ) 6.8
Hz), 1.85 (3 H, d, J ) 0.9 Hz), 1.92 (3 H, d, J ) 1.2 Hz), 2.48 (1
H, septet, J ) 6.6 Hz), 6.50 (1 H, d of quintets, J ) 11.5 and 1.0
Hz), 7.14 (1 H, dq, J ) 11.7 and 1.2 Hz), 9.46 (1 H, s). 13C
NMR: δ 9.29, 14.81, 22.66, 34.11, 38.11, 118.50, 135.90, 145.94,
157.09, 195.36. MS (EI, 70 eV) m/z (relative intensity): 152 (M+,
20.87). Anal. Calcd for C10H16O: C, 78.90; H, 10.59. Found:
C, 78.91; H, 10.57.
(1 mL) was placed in a 15-mL reaction vial with a resealable
cap under N2 and was heated at 135 °C for 8 h. The reaction
was followed by TLC. The reaction mixture was diluted with
pentane (10 mL), and the solution was washed with brine (1
mL) and dried (MgSO4). Removal of the solvent and purification
by chromatography (pentane:ether ) 9:1) gave 6 (93 mg, 84%)
as a light yellow oil.
For 6. IR (neat): 2955, 1672, 1456, 1074. 1H NMR: δ 0.99
(3 H, s), 1.03 (3 H, d, J ) 7.1 Hz), 1.05 (3 H, s), 1.72 (3 H, d, J
) 1.1 Hz), 2.35 (1 H, t, J ) 8.6 Hz), 5.13 (1 H, s), 5.84 (1 H, dd,
J ) 12.8, ans 8.2 Hz), 6.55 (1 H, d, J ) 12.8 Hz), 10.18 (1 H, d,
J ) 8.2 Hz). 13C NMR: δ 13.35, 15.81, 24.45, 27.95, 31.16, 35.71,
44.58, 44.98, 64.55, 67.13, 127.89, 137.68, 140.64, 154.91, 193.63.
MS (EI, 70eV) m/z (relative intensity): 218 (M+, 14.6), 161 (49.2),
191 (84.0), 95 (100), 41(67.9). Anal. Calcd for C15H22O: C, 82.52;
H, 10.16. Found: C, 82.16; H, 9.86.
(1R,5S)-2-Met h yl-5-(1-m et h ylet h yl)b icyclo[3.1.0]h ex-2-
en e (r-th u jen e) (8). (+)-Sabinene (1.43 g, 10.5 mmol) was
isomerized to (-)-thujene according to a literature procedure.12
Purification by chromatography on AgNO3-impregnated silica
gel (15% w/w) with pentane as eluant followed by distillation
afforded 1.03 g (83%) of 8 as a colorless liquid (95% purity by
NMR analysis). Bp: 159-162 °C. IR (neat): 3027, 2951, 2868,
1456, 1390, 845. 1H NMR: δ 0.29 (1 H, t, J ) 4.1 Hz), 0.63 (1
H, dd, J ) 8.1, 4.1 Hz), 0.80 (3 H, d, J ) 7.0 Hz), 0.86 (3 H, d,
J ) 7.0 Hz), 0.40-1.05 (3 H, m), 1.43 (3 H, s), 2.93 (1 H, t, J )
1.0). 13C NMR: δ 16.56, 18.00, 19.60, 19.61, 30.36, 30.97, 31.69,
32.29, 60.86, 70.64. MS (EI, 70 eV) m/z (relative intensity): 152
(M+, 11.4). Anal. Calcd for C10H16: C, 78.90; H, 10.59. Found:
C, 78.88; H, 10.58.
Kin etic Mea su r em en ts. Rates in Table 1 were determined
by placing the cyclopropyl epoxide (0.10 mmol) and the deuter-
ated solvent (1.0 mL) in an NMR tube under N2 with tetra-
methylsilane and benzene as internal standards. Toluene-d8,
acetone-d6, or methanol-d4, were employed as solvents. The
solution was then placed in the thermostated probe of the NMR
spectrometer (18.6 ( 0.2 °C), and spectra were recorded at
regular intervals. The disappearance of starting material (cy-
clopropyl-H) was monitored as a function of time. The concen-
tration of the starting epoxide at various time intervals was
calculated from the ratio of intensity of the corresponding NMR
signal of the compound to that of the internal standard.
Ack n ow led gm en t. We are grateful to Dr. Alan
Hochstetler, Givaudan-Roure, Clifton, NJ , for a gift of
sabinene. This work was supported by NIH grant GM
13956.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for tetracyclic olefins 1 and
5 (3 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(12) Acharya, S. P.; Brown, H. C.; Suzuki, A.; Nozawa, S.; Itoh, M.
J . Org. Chem. 1969, 34, 3015.
J O951850D