Control of stereochemistry in an intramolecular Diels-Alder reaction by the phenylsulfonyl group; an improved synthesis of pisiferol

Article abstract of DOI:10.1039/a702761c

Thermolysis of 4a (X = H) gives 6a and 6b (X = H) in a ratio of 1:4 whereas 4b (X = SO₂Ph) gives more of the trans-ring junction product 6a (X = SO₂Ph) suitable for the synthesis of pisiferol [ratio 6a:6b (X = SO₂Ph) = 1.5:1]. Base catalysed elimination of the phenylsulfonyl group from 6a (X = SO₂Ph) gives 18 which is hydrogenated to 6a (X = H), an intermediate in the synthesis of pisiferol. Both 6a and 6b (X = SO₂Ph) have ring B in a half-boat conformation.

Full text of DOI:10.1039/a702761c

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Control of stereochemistry in an intramolecular Diels–Alder reaction
by the phenylsulfonyl group; an improved synthesis of pisiferol
Edward J. Bush† and (the late) David W. Jones
School of Chemistry, University of Leeds, Leeds, UK LS2 9JT
Thermolysis of 4a (X = H) gives 6a and 6b (X = H) in a ratio of 1:4 whereas 4b (X = SO2Ph) gives more
of the trans-ring junction product 6a (X = SO2Ph) suitable for the synthesis of pisiferol [ratio 6a:6b
(X = SO2Ph) = 1.5:1]. Base catalysed elimination of the phenylsulfonyl group from 6a (X = SO2Ph)
gives 18 which is hydrogenated to 6a (X = H), an intermediate in the synthesis of pisiferol. Both 6a
and 6b (X = SO2Ph) have ring B in a half-boat conformation.
Kametani et al.1 have described the synthesis of pisiferol methyl
ether 1 starting with alkylation of the benzocyclobutene 2 with
the iodide 3a. Thermolysis of the product 4a (X = H) is believed
HOH2C
H
MeO
to proceed via the (Z)-o-quinodimethane 5 (X = H) which
undergoes intramolecular Diels–Alder addition (IMDA) to give
the products 6a and 6b (X = H) with the pisiferic acid skeleton,
X
1
7
in 80% yield. Unfortunately 6a (X = H) with the required trans-
R
R
BC ring junction is the minor product and 6b (X = H) the major
product (1:4 ratio). The stereochemical problem was corrected
but at the expense of an additional sequence of seven reactions
proceeding in 21% overall yield. The IMDA reactions of most
o-quinodimethanes with a four carbon chain linking diene and
alkene give trans-adducts via exo-addition of the connecting
chain. Since these o-quinodimethanes lack a (Z)-cyano group,
the observed endo-chain preference for 5 (X = H) can tentatively
be ascribed to repulsion between an exo-orientated chain and
the (Z)-cyano group.
NC
NC
I
3a R = Me
3b R = H
MeO
R
R
MeO
i
X
4a R = Me
4b R = H
2
ii
Craig et al.2 have used the bulky phenylsulfonyl group placed
trans to the connecting chain as in 7 (X = SO2Ph) to obtain
mostly the product of endo-chain (exo-SO2Ph) addition. In con-
trast, related systems with X = H give comparable quantities of
cis- and trans-products. Craig suggests the SO2Ph group prefers
the less sterically demanding exo-position. With this back-
ground we argued that in 5 (X = SO2Ph) steric repulsion
between the (Z)-cyano group and an exo-directed SO2Ph
group might force the SO2Ph endo and the connecting chain
exo so that the desired trans-BC product 6a (X = SO2Ph)
would be favoured. To test this notion 4a (X = H) was cleaved
to the aldehyde 8a which gave 4a (X = SO2Ph) by reaction with
PhSO2CH2Li and elimination of the resulting alcohol (Scheme
1).
v
NC
MeO
iii, iv
CN
X
MeO
R
R
v
R = Me
only
O
5
8a R = Me
8b R = H
NC
C
NC
H
H
Thermolysis of 4a (X = SO2Ph) at 180 ЊC (3 h) gave 6a
(X = SO2Ph) and 6b (X = SO2Ph) in a much improved trans:cis
ratio of 1.5:1 and 67% yield. In addition to the desired adducts
the thermolysis also provided the (E,E)-diene 9 (Y = CN,
X = SO2Ph) (ca. 23%). Although not reported by the earlier
workers,1 a similar quantity of 9 [Y = (E)-CN, X = H] is formed
in the thermolysis of 4a (X = H). These products arise via a 1,5-
sigmatropic hydrogen shift in an (E)-o-quinodimethane inter-
mediate as shown by the arrows in 10. The size and π-electron
accepting ability of the cyano group favour its inward conrota-
tion3 in competition with an alkyl chain. However the benzo-
cyclobutene ring-opening will be reversible unless the 1,5-shift
and IMDA reaction are fast. In the event of such reversibility
the ratio of products will depend less on the torquoselectivity
of ring-opening4 as on the relative rates of the 1,5-shift and
MeO
MeO
B
A
X
X
6b
6a
Scheme 1 Reagents and conditions: i, NaH–DMF, 65 ЊC, 0.5 h; ii,
OsO4–THF–H2O–NaIO4, 20 ЊC, h; iii, PhSO2Me–BuLi–THF,
Ϫ78 ЊC, 1 h; iv, MeSO2Cl–Et3N–THF, Ϫ5 ЊC, 14 h; v, o-dichloro-
benzene, 180 ЊC, 3 h
7
IMDA reaction. The situation is therefore finely balanced and
represents a potentially serious flaw in the use of benzo-
cyclobutenes as sources of o-quinodimethanes for IMDA reac-
tions.5 For example we attempted to increase the trans:cis
adduct ratio by using the larger CO2Me group in place of CN in
4a (X = SO2Ph). The ester 11 was readily obtained by treating
4a (X = SO2Ph) with methanol saturated with hydrogen chlor-
ide. However thermolysis of 11 at 160 ЊC (48 h) gave only prod-
ucts 12 and 13 derived via 1,5-sigmatropic hydrogen shifts in the
† Contact address: Zeneca Pharmaceuticals, Process Development
Department, Hurdsfield Industrial Estate, Macclesfield, Cheshire,
UK SK10 2NA.
J. Chem. Soc., Perkin Trans. 1, 1997
3531

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show vicinal couplings for the ring-B protons suggesting both
compounds prefer to exist with ring B in a half-boat conform-
ation (Experimental section). The boat structure for 6a
(X = SO2Ph) was confirmed by an X-ray structure determin-
ation (Fig. 1).6 Existence of 6a (X = SO2Ph) in the boat-like
conformation shown above is understandable as in the altern-
ative half-chair conformation the SO2Ph and nearby α-Me are
much closer. For the half-chair conformation corresponding to
6b (X = SO2Ph) the SO2Ph and CN groups would be 1,3-
diaxial.
To complete the synthesis of pisiferol the sulfone 6a
(X = SO2Ph) was heated in 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) at 130 ЊC (3 h) to give the alkene 18 (92% yield). Hydro-
NC
MeO
H
O
MeO
O
Fig. 1
PhO2S
18
Y
19
MeO
Y
MeO
genation of 18 over Pd–C gave 6a (X = H) (ca. 98% yield) con-
vertible into pisiferol by reduction, first by diisobutylaluminium
hydride and then with sodium borohydride followed by sodium
ethanethiolate mediated demethylation of the aryl ether.1
The improvement in the trans:cis adduct ratio and the
pisiferol synthesis observed here raise interesting possibilities of
similar control of the Diels–Alder reactions of other dienes
with (Z)-substituents, including 1,4-bridged dienes, e.g. cyclo-
pentadiene, cyclohexadiene, α-pyrone and furan. We have
already shown the effect is important for the 2-benzopyran-3-
one 19.7 The use of more bulky arylsulfonyl groups may be of
value in extending these studies.
R
H
10
9
X
CO2Me
MeO2C
MeO
MeO
Me
PhO2S
PhO2S
11
12 (E)-isomer
13 (Z)-isomer
Experimental
Mps were determined with a Kofler hot-stage apparatus and are
uncorrected. Infrared spectra were recorded on a Philips PU
8706 infrared spectrophotometer, and referenced to the peak at
1601 cmϪ1 of polystyrene. Ultraviolet and visible spectra were
o-quinodimethane intermediate. A similar result attended our
efforts to test the effect of an internal SO2Ph group rather than
a terminal one upon the trans:cis product ratio. For an internal
SO2Ph group the greater proximity of CN and SO2Ph in the
exo-SO2Ph transition state was expected to favour exo dis-
position of the connecting chain. However thermolysis of 14 at
160 ЊC gave only the 1,5-shift product 15 and a dimeric product
of unknown structure. The benzocyclobutene 14 was prepared
as outlined in Scheme 2 starting with the aldehyde 8b prepared
as outlined in Scheme 1.
recorded on
a Pye-Unicam PU 8800 UV–VIS spectro-
photometer; log ε values are in parentheses. Unless otherwise
1
stated H NMR spectra were measured in CDCl3 with tetra-
methylsilane as internal standard; 400 MHz NMR spectra were
measured on a Bruker WH-400 instrument, and 300 MHz
spectra on a General Electric Nicolet QE 300 spectrometer. All
NMR absorbances are expressed in parts per million; coupling
constants J are in Hz. Mass spectra were obtained on an
Autospec mass spectrometer. Chromatography on silica refers
to short-column chromatography over Kieselgel G60
(Merck).8 Thin layer chromatography was carried out on
glass plates (15 × 5 cm), dipped in an ethyl acetate suspension
of Kieselgel G60 and dried in an air oven at 120 ЊC for at
least one hour. Ether refers to diethyl ether and petroleum to
the fraction bp 60–80 ЊC. ‘Base-washed glassware’ was soaked
in 2  aqueous potassium hydroxide (18 h), washed with
water and acetone, and oven dried (120 ЊC, 16 h). All solvents
were distilled and dried before use by standard procedures.9
Unless otherwise stated, all reactions were conducted under
an atmosphere of dry, oxygen-free argon. For procedures
requiring anhydrous conditions all glassware was oven dried
prior to use. Solvents were evaporated under reduced pressure
using a Buchi rotary evaporator at water aspirator pressure
followed by heating on a steam bath at water aspirator
pressure.
NC
MeO
NC
i–iii
iv,v
8b
P(O)(OEt)2
SO2Ph
SO2Ph
17
16
CN
MeO
NC
vi
SO2Ph
Me
PhO2S
14
15
Scheme 2 Reagents and conditions: i, NaBH4; ii, Ph3P–CBr4; iii,
PhSO2Na, HMPA, 20 ЊC; iv, LDA then ClP(O)(OEt)2, Ϫ78 ЊC then
HOAc; v, BuLi then (HCHO)n; vi, 160 ЊC
The allocation of stereochemistry to 6a and 6b (X = SO2Ph)
was initially made on the basis of a very shielded methyl reson-
ance (δH Ϫ0.26) in the NMR spectrum of 6b (X = SO2Ph) which
was absent for 6a (X = SO2Ph). The spectra of both isomers
Oxidative cleavage of 4a (X ؍ H)
To a solution of the alkene1 (2.19 g, 7.04 mmol) and OsO4 (50
mg) in THF (20 ml) and water (7 ml) was added at room temp.
3532
J. Chem. Soc., Perkin Trans. 1, 1997

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sodium metaperiodate (3.21 g, 15.2 mmol) in portions over 8 h.
The mixture was stirred at 20 ЊC (2.5 h), poured into water,
extracted (Et2O), dried (MgSO4) and concentrated. Chrom-
atography on silica (120 g) in benzene–ether (24:1) gave 1-(4,
4-dimethyl-5-oxopentyl)-4-isopropyl-5-methoxy-1,2-dihydro-
benzocyclobutene-1-carbonitrile 8a (1.28 mg, 58%) mp 109.5–
110.0 ЊC (from dichloromethane–ethanol) (Found: C, 76.6; H,
8.4; N, 4.7. C20H27NO2 requires C, 76.7; H, 8.6; N, 4.5%);
νmax(Nujol)/cmϪ1 2220 and 1725; δH(300 MHz) 1.11 (6H, s,
2 × Me), 1.19 (6H, d, J 7.0, CHMe2), 1.57 (4H, m), 1.94 (2H,
m), 3.18 (1H, d, J 13.5, benzylic-H), 3.35 (1H, septet, J 7.0,
CHMe2), 3.64 (1H, d, J 13.5, benzylic-H), 3.83 (3H, s, OMe),
6.71 (1H, s, Ar-H), 7.01 (1H, s, Ar-H), 9.48 (1H, s, CHO);
m/z 313 (Mϩ), 298, 270, 242, 214, 200, 198, 161, 43 and 41 (64.4,
70.5, 88.8, 72.2, 73.2, 100.0, 51.7, 75.6, 66.2 and 56.3%).
1.37 mmol) in o-dichlorobenzene (190 ml) was heated at reflux
(3 h). Chromatography of the concentrated product on neutral
alumina (18 g) (Fluka type 507C), eluting with benzene–ether
(24:1) gave the exo-chain adduct 7-isopropyl-6-methoxy-1,1-
dimethyl-10-phenylsulfonyl-1,2,3,4,4a,9,10,10a-octahydro-
phenanthrene-4a-carbonitrile 6a (X = SO2Ph) (192 mg, 31%),
mp 153–154 ЊC (ethanol) (Found: Mϩ, 451.2195. C27H33NO3S
requires M, 451.2181); νmax(film)/cmϪ1 2970 and 2220; δH(300
MHz) 1.15 (3H, d, J 6.9, CHMe2), 1.23 (3H, s, Me), 1.25 (3H, d,
J 7.0, CHMe2), 1.36 (3H, s, Me), 1.50 (1H, m), 1.70–2.00 (3H,
m), 2.15 (1H, m), 2.22 (1H, d, J 5.0, endo-methine), 2.71 (1H,
m), 2.97 (1H, d, J 16.5), 3.27 (1H, septet, J 7.0, CHMe2), 3.51
(1H, dd, J 6.0 and 16.5), 3.77 (1H, t, J 5.5, CHSO2Ph), 3.81
(3H, s, OMe), 6.63 (1H, s, Ar-H), 6.71 (1H, s, Ar-H), 7.48 (2H,
m, SO2Ph), 7.62 (3H, m, SO2Ph); m/z 451 (Mϩ), 310, 309, 227,
77, 55, 44, 43, 41 and 40 (8.6, 27.9, 100.0, 16.7, 15.3, 15.2, 28.4,
14.8, 18.6 and 94.1%).
Preparation of 1-(4,4-dimethyl-6-phenylsulfonylhex-5-enyl)-4-
isopropyl-5-methoxy-1,2-dihydrobenzocyclobutene-1-carbo-
nitrile 4a (X = SO2Ph)
The column was flushed with ethanol to give an oil. Chroma-
tography of the oil on silica (140 g) in benzene–ether (47:3)
gave in order of elution: 2-(4-isopropyl-5-methoxy-2-methyl-
To a stirred solution of methyl phenyl sulfone (1.55 g, 9.9
mmol) in dry THF (26 ml) under argon at Ϫ78 ЊC was added
dropwise by syringe n-butyllithium (4.0 ml of a 2.5  solution in
hexanes, 9.9 mmol) to give a colourless solution of the anion.
After 10 min a solution of the aldehyde 8a (1.24 g, 3.97 mmol)
in dry THF (25 ml) was added, rinsing with further THF (10
ml) at Ϫ78 ЊC. After 1 h the reaction was quenched by the
addition of a solution of acetic acid in THF (20 ml of a 1.0 
solution, 20 mmol), stirred (10 min) and allowed to warm to
20 ЊC (0.5 h). The solution was poured into saturated aqueous
NaHCO3, extracted (CH2Cl2), washed (3 × H2O), dried
(MgSO4) and concentrated to give a solid. Chromatography on
silica (80 g) eluting initially with dichloromethane then
changing to benzene–ether (4:1) gave the diastereomeric β-
hydroxy sulfones (1.51 g, 81%) (Found: C, 69.0; H, 7.4; N, 2.8;
S, 6.8. C27H35NO4S requires C, 69.1; H, 7.5; N, 3.0; S, 6.8%);
νmax(film)/cmϪ1 3520, 2960 and 2220; δH(300 MHz) 0.85 (6H, s,
2 × Me), 0.88 (3H, s, Me), 0.89 (3H, s, Me), 1.19 (12H, d, J
7.0, CHMe2), 1.42–1.67 (8H, m), 1.87 (4H, m), 3.10–3.37
(10H, m), 3.63 (2H, dd, J 3.0 and 13.5), 3.82 (6H, s, OMe),
3.93 (2H, t, J 10.5), 6.72 (1H, s, Ar-H), 6.74 (1H, s, Ar-H), 7.01
(2H, s, Ar-H), 7.58–7.71 (6H, m, SO2Ph), 7.94–7.96 (4H, m, SO2-
Ph); m/z 469 (Mϩ), 270, 242, 216, 200, 199, 198, 77, 69 and 43
(53.8, 37.7, 100.0, 41.3, 37.6, 31.4, 36.0, 46.3, 36.1 and 37.1%).
To a stirred solution of the foregoing β-hydroxy sulfones
(1.46 g, 3.1 mmol) in dry CH2Cl2 (45 ml) under argon at Ϫ10 ЊC
was added dropwise by pipette triethylamine (3.11 g, 30.6
mmol) in dichloromethane (4 ml) followed by methanesulfonyl
chloride (7 equiv. 2.47 g) in dichloromethane (4 ml). The reac-
tion was stirred at Ϫ10 ЊC (16 h), then allowed to warm to room
temp. and stirred (24 h). The mixture was poured into saturated
aqueous ammonium chloride, extracted (CH2Cl2), washed with
water, dried (MgSO4) and concentrated to give an oil. Chrom-
atography on silica (16 g) eluting with benzene–ether (19:1)
gave the sulfone 4a (X = SO2Ph) (714 mg, 51%), mp 139.5–
140.5 ЊC (from ethanol) (Found: C, 71.8; H, 7.5; N, 3.1; S, 6.9.
C27H33NO3S requires C, 71.8; H, 7.3; N, 3.1; S, 7.1%); νmax(film)/
cmϪ1 2950, 2220 and 1600; δH(300 MHz) 1.09 (3H, s, Me), 1.10
(3H, s, Me), 1.18 (6H, d, J 6.9, CHMe2), 1.50 (4H, m), 1.88 (2H,
m), 3.13 (1H, d, J 13.5, benzylic-H), 3.38 (1H, septet, J 7.0,
CHMe2), 3.61 (1H, d, J 13.5, benzylic-H), 3.82 (3H, s, OMe),
6.23 (1H, d, J 15.5, olefinic-H), 6.69 (1H, s, Ar-H), 6.96 (1H, d,
J 15.5, olefinic-H), 7.01 (1H, s, Ar-H), 7.58 (3H, m, SO2Ph),
7.89 (2H, m, SO2Ph); m/z 452, 451 (Mϩ), 436, 242, 215, 214,
200, 199, 125 and 41 (27.7, 74.0, 52.9, 100.0, 40.3, 43.8, 44.8,
28.1, 26.8 and 28.1%).
phenyl)-6,6-dimethyl-8-phenylsulfonylocta-2,7-dienenitrile
9
(Y = CN, X = SO2Ph) (105 mg, 17%) (Found: C, 71.6; H, 7.1; N,
2.9. C27H33NO3S requires C, 71.8; H, 7.3; N, 3.1%); νmax(film)/
cmϪ1 2220 and 1620; δH(300 MHz) 1.15 (6H, s, 2 × Me), 1.20
(6H, d, J 7.0, CHMe2), 1.63 (2H, m), 2.31 (3H, s, Ar-Me),
2.43 (2H, m), 3.28 (1H, septet, J 7.0, CHMe2), 3.81 (3H, s,
OMe), 6.28 (1H, d, J 15.5, olefinic-H), 6.35 (1H, t, J 7.5,
olefinic-H), 6.63 (1H, s, Ar-H), 6.98 (1H, d, J 15.5, olefinic-
H), 7.01 (1H, s, Ar-H), 7.56 (3H, m, SO2Ph), 7.89 (2H, m,
SO2Ph); m/z 452, 451 (Mϩ), 436, 309, 243, 242, 210, 125, 77
and 41 (37.0, 78.8, 31.4, 27.8, 28.6, 100.0, 25.7, 32.5, 32.1 and
25.3%).
Further elution of the column gave the endo-chain adduct 6b
(X = SO2Ph) (124 mg, 20%) mp 209–210 ЊC (from ethanol)
(Found: Mϩ, 451.2175); νmax(Nujol)/cmϪ1 2980 and 2220; δH
(400 MHz, C6D6) Ϫ0.26 (3H, s, Me), 1.05 (1H, m), 1.10 (2H,
m), 1.12 (3H, s, Me), 1.13 (3H, d, J 7.0, CHMe2), 1.17 (3H, d,
J 7.0, CHMe2), 1.36 (1H, m), 1.77 (1H, td, J 14.0 and 4.0),
2.52 (1H, br d, J 15.0), 2.71 (1H, dd, J 12.0 and 15.0), 3.11
(1H, d, J 3.0, exo-methine), 3.23 (3H, s, OMe), 3.37 (2H, m,
CHMe2 and CHSO2Ph), 3.72 (1H, dd, J 7.0 and 15.0), 6.54
(1H, s, Ar-H), 6.67 (1H, s, Ar-H), 7.00 (3H, m, SO2Ph), 7.97
(2H, m, SO2Ph); m/z 451 (Mϩ), 310, 309, 227, 225, 184, 77, 55,
43 and 41 (6.7, 37.9, 100.0, 57.0, 24.8, 21.3, 20.1, 16.4, 19.6 and
21.7%).
Further elution of the column gave a dimer of the o-quino-
dimethane intermediate (101 mg, 16%) as an oil (Found: C,
71.6; H, 7.5; N, 2.9; S, 7.2. C54H66N2O6S2 requires C, 71.8; H,
7.3; N, 3.1; S, 7.1%); νmax(film)/cmϪ1 2215 and 2205; δH(300
MHz) 1.04 (6H, s), 1.12 (18H, m), 1.44 (7H, m), 2.34 (2H, m,
>6 lines), 2.80 (2H, m, >6 lines), 2.92 (2H, d, J 6.5), 3.24
(2H, m, CHMe2), 3.59 (1H, m, >5 lines), 3.81 (6H, s, OMe),
6.10 (1H, t, J 7.5), 6.19 (1H, d, J 15.5), 6.28 (1H, d, J 15.5),
6.55 (1H, s), 6.76 (1H, s), 6.78 (1H, s), 6.88 (2H, d, J 5.5),
6.97 (2H, d, J 15.5), 7.60 (6H, m, SO2Ph), 7.88 (4H, m,
SO2Ph); m/z 903, 902 (Mϩ), 453, 452, 409, 408, 202, 198, 184
and 125 (31.6, 51.8, 30.6, 88.8, 28.5, 100.0, 25.0, 22.1, 41.5
and 64.6%).
Further elution of the column gave a second dimer of the
o-quinodimethane intermediate as an oil (64 mg, 5%) (Found:
C, 71.7; H, 7.5; N, 2.9; S, 7.0%); νmax(film)/cmϪ1 2215 and 2205;
δH(300 MHz) 0.87 (6H, s), 0.97 (6H, s), 1.03 (6H, t, J 7.0), 1.12
(6H, t, J 7.0), 1.35 (7H, m), 1.65 (1H, m), 1.82 (2H, m), 2.69
(4H, br s), 3.18 (2H, m, CHMe2), 3.69 (1H, m), 3.71 (3H, s,
OMe), 3.74 (3H, s, OMe), 6.05 (1H, d, J 15.5), 6.13 (1H, d, J
15.5), 6.44 (1H, s), 6.55 (1H, t, J 7.5), 6.70 (1H, s), 6.72 (1H, s),
6.72 (1H, d, J 15.5), 6.86 (1H, d, J 15.5), 6.91 (1H, s), 7.48 (6H,
m, SO2Ph), 7.79 (4H, m, SO2Ph); m/z 903, 902 (Mϩ), 453, 452,
409, 408, 202, 198, 184 and 125 (37.5, 52.5, 42.5, 100.0, 24.4,
66.5, 27.4, 21.6, 41.8 and 54.7%).
Further elution of the column gave unreacted starting
material 8a (380 mg, 26%).
IMDA Addition of 4a (X = SO2Ph)
A solution of the benzocyclobutene 4a (X = SO2Ph) (620 mg,
J. Chem. Soc., Perkin Trans. 1, 1997
3533

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By conducting the reaction in dilute solution (0.3 mg mlϪ1
the formation of dimeric products was avoided and a 67% yield
of adducts obtained [40% of 6a (X = SO2Ph)].
)
(1H, t, J 8.0, olefinic-H), 6.62 (1H, s, Ar-H), 7.00 (1H, s, Ar-
H); m/z 311 (Mϩ), 296, 283, 186, 83, 69, 57, 55, 43 and 41
(56.4, 79.0, 100.0, 64.1, 60.7, 67.7, 81.8, 71.4, 76.9 and
75.1%).
Alcoholysis of the nitrile 4a (X ؍ SO2Ph)
Further elution of the column gave the mixture of adducts 6a
and 6b (X = H) (ratio 1:4) (11.8 mg, 66%). The 400 MHz H
NMR spectrum was consistent with the published data.
1
Dry hydrogen chloride was bubbled through a solution of 4a
(X = SO2Ph) (29 mg, 0.064 mmol) in dry methanol (1.5 ml) at
0–5 ЊC (1 h). The reaction was stirred at this temperature (3 h)
and then allowed to warm to 20 ЊC (14 h). The solution was
poured into brine, extracted with ether (×3), washed with water,
dried (MgSO4) and concentrated to give an oil. Chrom-
atography on silica (20 g) in benzene–ether (93:7) gave methyl
1-(4,4-dimethyl-6-phenylsulfonylhex-5-enyl)-4-isopropyl-5-
methoxy-1,2-dihydrobenzocyclobutene-1-carboxylate 11 (26
mg, 84%) (Found: Mϩ, 484.2271. C28H36O5S requires Mϩ,
484.2283); νmax(film)/cmϪ1 1730; δH(300 MHz) 1.05 (6H, s,
CMe2), 1.17 (3H, d, J 7.0, CHMe2), 1.18 (3H, d, J 7.0, CHMe2),
1.34 (4H, m), 1.93 (2H, m), 2.94 (1H, d, J 13.5, benzylic-H),
3.32 (1H, septet, J 7.0, CHMe2), 3.53 (1H, d, J 13.5, benzylic-
H), 3.69 (3H, s, CO2Me), 3.81 (3H, s, OMe), 6.19 (1H, d, J 15.5,
olefinic-H), 6.72 (1H, s, Ar-H), 6.95 (2H, m, Ar-H and olefinic-
H), 7.58 (3H, m, SO2Ph), 7.87 (2H, m, SO2Ph); m/z 485, 484
(Mϩ), 247, 187, 173, 145, 125, 77, 43 and 41 (38.3, 100.0, 36.8,
25.2, 30.4, 30.1, 33.7, 23.9, 18.4 and 20.2%).
Alkylation of 2 with the iodide 3b
A solution of the benzocyclobutene 2 (300 mg, 1.49 mmol) and
sodium hydride (72 mg, 3.0 mmol) in dry distilled DMF (7 ml)
was heated at 65 ЊC (0.5 h). The reaction mixture was cooled to
room temperature and a solution of the iodide 3b (0.44 g, 2.1
mmol) in dry DMF (1.2 ml) was added. The reaction mixture
was then heated at 65 ЊC (1 h), cooled to room temperature,
poured into water, diluted with ether and washed with water
(×3). The ether layer was dried (MgSO4) and concentrated to
give an oil. Chromatography on silica (40 g) eluting with ben-
zene gave the alkene 4b (X = H) as an oil (329 mg, 78%) (Found:
C, 80.5; H, 9.1; N, 4.8. C19H25NO requires C, 80.6; H, 8.8; N,
5.0%); νmax(Nujol)/cmϪ1 2940 and 2230; δH(300 MHz) 1.18 (6H,
d, J 7.0, CHMe2), 1.48 (2H, m), 1.68 (2H, m), 1.95 (2H, m), 2.11
(2H, m), 3.17 (1H, d, J 13.5, benzylic-H), 3.34 (1H, septet, J 7.0,
CHMe2), 3.63 (1H, d, J 13.5, benzylic-H), 3.81 (3H, s, OMe),
4.99 (2H, m, olefinic-H), 5.82 (1H, m, olefinic-H), 6.72 (1H, s,
Ar-H), 7.00 (1H, s, Ar-H); m/z 283 (Mϩ), 268, 200, 71, 69, 57,
55, 43, 41 and 39 (26.9, 100.0, 43.4, 39.0, 42.2, 71.6, 72.6, 87.2,
92.7 and 34.6%).
Attempted IMDA addition of 11
The title compound (22 mg, 0.045 mmol) was dissolved in deu-
terated benzene (0.5 ml) inside an NMR tube and subjected to
five freeze–pump–thaw cycles to remove any dissolved oxygen
in the system before it was sealed under vacuum. The tube was
heated in a thermostatically controlled bath at 160 ЊC (48 h)
and concentrated under reduced pressure to give an oil. Chro-
matography on silica (28 g) in benzene–ether (24:1) gave methyl
2-(4-isopropyl-5-methoxy-2-methylphenyl)-8-phenylsulfonyl-
octa-2,7-dienoate 13 (5.4 mg, 24%) (Found: Mϩ, 484.2286.
C22H36O5S requires Mϩ, 484.2283); νmax(film)/cmϪ1 1715; δH(300
MHz) 1.13 (6H, s, CMe2), 1.20 (6H, d, J 7.0, CHMe2), 1.60 (2H,
m), 2.10 (3H, s, Ar-Me), 2.44 (2H, m), 3.27 (1H, septet, J 7.0,
CHMe2), 3.71 (3H, s, CO2Me), 3.81 (3H, s, OMe), 6.01 (1H, t, J
7.7, olefinic-H), 6.26 (1H, d, J 15.5, olefinic-H), 6.59 (1H, s,
Ar-H), 6.96 (1H, s, Ar-H), 7.01 (1H, d, J 15.5, olefinic-H), 7.57
(3H, m, SO2Ph), 7.90 (2H, m, SO2Ph); m/z 484 (Mϩ), 283, 243,
85, 71, 69, 57, 55, 43 and 41 (31.4, 54.0, 69.9, 44.4, 61.5, 47.1,
100.0, 54.5, 82.2 and 56.6%).
Further elution of the column gave the styrene 12 (13.2 mg,
60%) (Found: Mϩ, 484.2285); νmax(film)/cmϪ1 1710; δH(300
MHz) 0.94 (6H, s, CMe2), 1.20 (6H, d, J 7.0, CHMe2), 1.47 (2H,
m), 1.84 (2H, m), 2.02 (3H, s, Ar-Me), 3.27 (1H, septet, J 7.0,
CHMe2), 3.72 (3H, s, CO2Me), 3.75 (3H, s, OMe), 6.12 (1H, d, J
15.5, olefinic-H), 6.42 (1H, s, Ar-H), 6.84 (1H, d, J 15.5,
olefinic-H), 6.99 (1H, t, J 7.5, olefinic-H), 7.02 (1H, s, Ar-H),
7.56 (3H, m, SO2Ph), 7.80 (2H, m, SO2Ph); m/z 484 (Mϩ), 86,
84, 71, 69, 57, 55, 49, 43 and 41 (100.0, 40.3, 70.0, 60.1, 53.6,
95.2, 56.5, 77.9, 89.8 and 64.1%).
Preparation of the aldehyde 8b
To a solution of the alkene 4b (X = H) (304 mg, 1.07 mmol) and
OsO4 (10 mg) in THF (3.25 ml) and water (1.1 ml) at room
temp. was added sodium metaperiodate (493 mg, 2.31 mmol) in
portions over 2 h. The reaction mixture was stirred (3 h) then
poured into water and extracted with ether (×3), dried (MgSO4)
and concentrated to give the crude aldehyde. Chromatography
on silica (24 g) eluting with benzene–ether (19:1) gave the alde-
hyde 8b (286 mg, 93%) (Found: C, 75.6; H, 8.3; N, 5.2.
C18H23NO2 requires C, 75.8; H, 8.1; N, 4.9%); νmax(Nujol)/cmϪ1
2940, 2230 and 1725; δH(300 MHz) 1.18 (6H, d, J 6.5, CHMe2),
1.71 (4H, m), 1.98 (2H, m), 2.51 (2H, m), 3.18 (1H, d, J 13.5,
benzylic-H), 3.34 (1H, septet, J 6.5, CHMe2), 3.63 (1H, d, J
13.5, benzylic-H), 3.81 (3H, s, OMe), 6.72 (1H, s, Ar-H), 7.01
(1H, s, Ar-H), 9.78 (1H, t, J 1.5, CHO); m/z 285 (Mϩ), 270, 198,
115, 91, 55, 44, 43, 41 and 39 (52.0, 89.7, 50.5, 64.2, 71.1, 50.4,
82.1, 77.5, 100.0 and 86.4%).
Preparation of sulfone 16
To a stirred solution of the foregoing aldehyde (275 mg, 0.96
mmol) in ethanol (15 ml) was added sodium borohydride (55
mg, 1.45 mmol) at 0 ЊC, and the mixture was allowed to reach
room temperature over 1 h. The reaction mixture was poured
into water, extracted with ether (×3) and dried (MgSO4).
Chromatography of the evaporated product on silica (22 g)
eluting with benzene-ether (1:1) gave the alcohol (262 mg,
95%), mp 63–64 ЊC (from dichloromethane–petroleum)
(Found: C, 75.5; H, 8.9; N, 4.7. C18H25NO2 requires C, 75.3; H,
8.7; N, 4.9%); νmax(Nujol)/cmϪ1 3340, 2930 and 2220; δH(300
MHz) 1.18 (6H, d, J 7.0, CHMe2), 1.28 (1H, m), 1.48 (2H, m),
1.64 (3H, m), 1.97 (2H, m), 3.18 (1H, d, J 13.5, benzylic-H),
3.34 (1H, septet, J 7.0, CHMe2), 3.80 (3H, m, benzylic-H and
CH2OH), 3.82 (3H, s, OMe), 6.72 (1H, s, Ar-H), 7.01 (1H, s,
Ar-H); the OH signal was not recorded; m/z 287 (Mϩ), 273, 272,
216, 215, 214, 200, 199, 198 and 78 (38.4, 20.5, 100.0, 20.2,
16.2, 20.2, 25.6, 12.1, 14.1 and 18.7%).
Thermolysis of 4a (X = H)
The benzocyclobutene 4a (18 mg) was dissolved in o-dichloro-
benzene (0.5 ml) in an NMR tube and subjected to five freeze–
pump–thaw cycles to remove any dissolved oxygen in the sys-
tem before it was sealed under vacuum. The tube was heated in
a thermostatically controlled bath at 180 ЊC (3 h) and concen-
trated under reduced pressure to give an oil. Chromatography
on silica (28 g) eluting with benzene–petroleum 40–60 ЊC (3:7)
gave in order of elution: 1-(4-isopropyl-5-methoxy-2-methyl-
phenyl)-5,5-dimethylhepta-1,6-diene 9 (X = Y = H), (3.2 mg,
18%) (Found: Mϩ, 311.2250. C21H29NO requires Mϩ,
311.2249); νmax(film)/cmϪ1 2920 and 2205; δH(400 MHz) 1.20
(12H, m), 1.51 (2H, m), 2.31 (3H, s, Ar-Me), 2.48 (2H, m),
3.27 (1H, septet, J 7.0, CHMe2), 3.81 (3H, s, OMe), 5.00 (2H,
m, olefinic-H), 5.80 (1H, dd, J 11.0 and 17.0, olefinic-H), 6.40
To a stirred solution of the foregoing alcohol (208 mg,
0.72 mmol) and carbon tetrabromide (300 mg, 0.91 mmol) in
dichloromethane (5 ml) was added portionwise triphenylphos-
phine (285 mg, 1.1 mmol) at 0 ЊC. The mixture was stirred at
20 ЊC (1.5 h), poured into water, extracted with CH2Cl2 (×3),
3534
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
dried (MgSO4) and concentrated to give an oil. Chrom-
atography on silica (24 g) eluting with petroleum–benzene (3:7)
gave the bromide (233 mg, 92%) (Found: C, 61.9; H, 6.8; N, 4.4.
C18H24BrNO requires C, 61.7; H, 6.9; N, 4.0%); νmax(film)/cmϪ1
2940 and 2220; δH(300 MHz) 1.18 (6H, d, J 7.0, CHMe2), 1.55
(2H, m), 1.72 (2H, m), 1.96 (4H, m), 3.18 (1H, d, J 13.5,
benzylic-H), 3.34 (1H, septet, J 7.0, CHMe2), 3.43 (2H, t, J 6.5,
CH2Br), 3.64 (1H, d, J 13.5, benzylic-H), 3.82 (3H, s, OMe),
6.72 (1H, s, Ar-H), 7.01 (1H, s, Ar-H); m/z 351, 350 (Mϩ), 349,
336, 335, 334, 215, 214, 200 and 41 (30.3, 6.8, 30.5, 100.0, 21.2,
98.6, 28.5, 33.9, 33.0 and 27.2%).
phenylsulfonyl-1-(4-isopropyl-5-methoxy-2-methylphenyl)octa-
2,7-dienenitrile 15 (5.3 mg, 31%) (Found: Mϩ, 423.1861.
C25H29NO3S requires Mϩ, 423.1868); νmax(film)/cmϪ1 2940 and
2220; δH(300 MHz) 1.20 (6H, d, J 6.5, CHMe2), 1.77 (2H, m),
2.29 (3H, s, Ar-Me), 2.38 (2H, m), 2.52 (2H, m), 3.28 (1H,
septet, J 6.5, CHMe2), 3.81 (3H, s, OMe), 5.81 (1H, s, olefinic-
H), 6.34 (1H, t, J 7.5, olefinic-H), 6.42 (1H, s, olefinic-H), 6.62
(1H, s, Ar-H), 7.01 (1H, s, Ar-H), 7.59 (3H, m, SO2Ph), 7.90
(2H, m, SO2Ph); m/z 423 (Mϩ), 200, 149, 77, 71, 69, 57, 55, 43
and 41 (100.0, 65.1, 69.7, 65.8, 52.1, 44.3, 86.8, 53.3, 91.3 and
59.6%).
To a stirred solution of the foregoing bromide (206 mg, 0.59
mmol) in dry distilled hexamethylphosphoramide (HMPA) (2.5
ml) was added sodium benzenesulfinate (216 mg, 1.31 mmol).
The reaction mixture was stirred for 0.5 h at room temperature
then poured into water, diluted with ether, washed with water
(×3) and dried (MgSO4). Chromatography of the evaporated
product on silica (35 g) eluting with benzene–ether (93:7) gave
4-isopropyl-5-methoxy-1-(5-phenylsulfonylpentyl)-1,2-dihydro-
benzocyclobutene-1-carbonitrile 16 (210 mg, 87%), mp 142–
143 ЊC (from dichloromethane–ethanol) (Found: C, 69.8; H,
7.0; N, 3.4. C24H29NO3S requires C, 70.1; H, 7.1; N, 3.4%);
νmax(Nujol)/cmϪ1 2950 and 2230; δH(300 MHz) 1.18 (6H, d, J
7.0, CHMe2), 1.43 (2H, m), 1.62 (2H, m), 1.81 (2H, m), 1.92
(2H, m), 3.12 (3H, m, CH2SO2Ph and benzylic-H), 3.34 (1H,
septet, J 7.0, CHMe2), 3.62 (1H, d, J 13.5, benzylic-H), 3.82
(3H, s, OMe), 6.69 (1H, s, Ar-H), 7.00 (1H, s, Ar-H), 7.63 (3H,
m, SO2Ph), 7.92 (2H, m, SO2Ph); m/z 412, 411 (Mϩ), 396, 214,
203, 201, 200, 199, 78 and 77 (53.6, 100.0, 66.2, 34.1, 35.0, 47.9,
50.6, 31.5, 83.2 and 64.8%).
Further elution of the column gave a dimer of the o-quino-
dimethane intermediate (8.8 mg, 52%); νmax(film)/Ϫ1 2240 and
2220; δH(400 MHz) 1.20 (12H, m), 1.44 (4H, m), 1.72 (4H, m),
2.20 (2H, m, >5 lines), 2.33 (2H, t, J 8.0), 2.44 (2H, m, >8 lines),
2.75 (2H, m), 2.89 (2H, t, J 7.5), 3.25 (2H, m, CHMe2), 3.60
(1H, dd, J 9.5 and 4.5), 3.80 (6H, s, OMe), 5.69 (1H, s), 5.79
(1H, s), 6.13 (1H, t, J 7.5), 6.34 (1H, s), 6.39 (1H, s), 6.54 (1H,
s), 6.76 (2H, d, J 12.5), 6.88 (1H, s), 7.58 (6H, m, SO2Ph), 7.85
(4H, m, SO2Ph); m/z 846 (Mϩ), 424, 380, 125, 78, 77, 71, 69, 57
and 43 (59.0, 100.0, 80.0, 41.7, 38.8, 46.1, 48.7, 41.8, 64.6 and
59.1%).
Desulfurisation of the adduct 6a (X = SO2Ph)
A solution of the adduct (132 mg, 0.29 mmol) in DBU (20 ml)
was heated at a bath temperature of 130 ЊC (3 h). The solution
was diluted with ether, washed with dilute HCl then water, dried
(MgSO4) and concentrated to give 7-isopropyl-6-methoxy-1,1-
dimethyl-1,2,3,4,4a,10a-hexahydrophenanthrene-4a-carbo-
nitrile 18. Chromatography on silica (20 g) eluting with
benzene–petroleum gave the olefin 18 (83 mg, 92%), mp 157.5–
158.0 ЊC (from dichloromethane–ethanol) (Found: Mϩ,
309.2105. C21H27NO requires M, 309.2093); νmax(Nujol)/cmϪ1
2220 and 1610; δH(400 MHz) 1.03 (3H, s, Me), 1.19 (3H, d, J
7.0, CHMe), 1.21 (3H, d, J 7.0, CHMe), 1.28 (3H, s, Me), 1.58
(1H, m), 1.63 (1H, m), 1.75 (1H, dt, J 13.5 and 3.5), 1.86 (1H,
dq, J 14.0 and 3.5), 2.01 (1H, tt, J 14.0 and 3.5), 2.09 (1H, t, J
3.0, endo-methine), 2.73 (1H, m), 3.28 (1H, septet, J 7.0,
CHMe2), 3.85 (3H, s, OMe), 6.00 (1H, dd, J 2.5 and 10.0,
olefinic-H), 6.66 (1H, dd, J 3.0 and 10.0, olefinic-H), 6.80 (1H,
s, Ar-H), 7.01 (1H, s, Ar-H); m/z 310, 309 (Mϩ), 294, 227, 225,
210, 56, 55, 43 and 41 (24.9, 100.0, 30.3, 45.5, 27.9, 32.7, 18.4,
14.4, 17.5 and 23.4%).
Preparation of the alkene 14
To a stirred solution of LDA (2.6 equiv., 0.766 mmol) in THF
(2.5 ml) at Ϫ78 ЊC under argon was added a solution of the
sulfone 16 (120 mg, 0.29 mmol) in THF (3 ml) rinsing with
further THF (1 ml) at Ϫ78 ЊC. The reaction mixture was stirred
(15 min) then a solution of diethyl chlorophosphate (61 mg, 3.5
mmol) in THF (1 ml) was added at Ϫ78 ЊC and the reaction
mixture was left to reach room temperature over 1 h, when it
was poured into dilute HCl (2 mol dmϪ3), extracted with ether
(×3), washed with water and dried (MgSO4) to give the crude
phosphonate. The crude product (160 mg, 0.29 mmol) was dis-
solved in dry THF (3 ml) and cooled to Ϫ78 ЊC under argon
and n-butyllithium (1.2 equiv. 0.35 mmol) was added. The solu-
tion was taken to 0 ЊC (ice–water bath), paraformaldehyde (56
mg, 0.59 mmol) was added and the mixture was stirred at 0 ЊC
(1 h). The solution was poured into water, extracted with ether
(×3) and dried (MgSO4). Chromatography of the evaporated
product on silica (28 g) eluting with benzene–ether (19:1) gave
4-isopropyl-5-methoxy-1-(5-phenylsulfonylhex-5-enyl)-1,2-
dihydrobenzocyclobutene-1-carbonitrile 14 (91.4 mg, 74%)
(Found: C, 70.7; H, 7.0; N, 3.1; S, 7.5. C25H29NO3S requires C,
70.9; H, 6.9; N, 3.3; S, 7.6%); νmax(film)/cmϪ1 2940 and 2220;
δH(300 MHz) 1.18 (6H, d, J 7.0, CHMe2), 1.60 (4H, m), 1.87
(2H, m), 2.28 (2H, m), 3.12 (1H, d, J 13.5, benzylic-H), 3.33
(1H, septet, J 7.0, CHMe2), 3.60 (1H, d, J 13.5, benzylic-H),
3.81 (3H, s, OMe), 5.75 (1H, s, olefinic-H), 6.39 (1H, s, olefinic-
H), 6.67 (1H, s, Ar-H), 7.00 (1H, s, Ar-H), 7.59 (3H, m, SO2Ph),
7.88 (2H, m, SO2Ph); m/z 424, 423 (Mϩ), 408, 242, 214, 200,
199, 198, 78 and 77 (23.0, 75.4, 50.0, 100.0, 26.6, 66.9, 22.0,
21.2, 57.1 and 38.7%).
Hydrogenation of the olefin 18
A solution of the title compound (72 mg, 0.23 mmol) in dry
distilled ethyl acetate (5.5 ml) was hydrogenated in the presence
of 10% Pd on activated charcoal (15 mg) for 2 h. The solution
was filtered through Celite and concentrated to give the nitrile
6a (X = H) (72 mg, 98%), mp 154.0–154.5 ЊC (from dichloro-
methane–ethanol) (Found: C, 80.8; H, 9.5; N, 4.5. C21H29NO
requires C, 81.0; H, 9.3; N, 4.5%); νmax(film)/cmϪ1 2220; δH(400
MHz) 1.01 (3H, s, Me), 1.16 (3H, s, Me), 1.18 (3H, d, J 7.0,
CHMe2), 1.19 (3H, d, J 7.0 CHMe2), 1.26 (1H, td, J 14.0 and
3.5), 1.37 (1H, dd, J 12.0 and 2.0, endo-methine), 1.52 (1H, td, J
13.5 and 3.5), 1.59 (1H, m), 1.83 (2H, m, CH2CH masked by
ring C CH2), 2.04 (2H, m, CH2CH masked by ring C CH2), 2.80
(2H, m, benzylic-H masked by ring C CH2), 2.94 (1H, ddd, J
16.5, 6.0 and 1.5, benzylic-H), 3.24 (1H, septet, J 7.0, CHMe2),
3.81 (3H, s, OMe), 6.83 (1H, s, Ar-H), 6.92 (1H, s, Ar-H); m/z
312, 311 (Mϩ), 297, 296, 284, 176, 163, 161, 147 and 117 (25.1,
77.9, 34.3, 100.0, 8.2, 5.9, 6.0, 7.1, 6.4 and 5.7%).
Attempted IMDA addition of the sulfone 14
The benzocyclobutene 14 (17 mg, 0.04 mmol) was dissolved in
deuterated benzene (0.5 ml) in an NMR tube and subjected to
five freeze–pump–thaw cycles to remove any dissolved oxygen
in the system before it was sealed under vacuum. The tube was
heated in a thermostatically controlled bath at 160 ЊC (16 h).
Chromatography of the evaporated product on silica (20 g)
eluting with benzene–ether (24:1) gave in order of elution: 7-
Acknowledgements
We thank the EPSRC for a maintenance grant (to E. J. B.),
Dr Mark Thornton-Pett for the X-ray structure determination
of compound 6a (X = SO2Ph), Miss Diane Woodall for prepar-
ation of compound 2, and Fisons PLC (Astra Charnwood) and
AgrEvo (Saffron Walden) for financial assistance.
J. Chem. Soc., Perkin Trans. 1, 1997
3535

View Article Online
5 C. W. G. Fishwick and D. W. Jones, ortho-Quinonoid Compounds
References
in The Chemistry of Quinonoid Compounds, ed. S. Patai and
Z. Rappoport, Wiley, 1988, vol. II, pp. 403–453 and cited references.
6 Preliminary communication of some of these results: E. J. Bush,
D. W. Jones and M. Thornton-Pett, Tetrahedron Lett., 1994, 35, 9755.
7 E. J. Bush, D. W. Jones and F. M. Nongrum, J. Chem. Soc., Chem.
Commun., 1994, 2145.
8 B. J. Hunt and W. Rigby, Chem. Ind. (London), 1967, 1868.
9 D. D. Perrin, W. C. F. Armagego and D. Perrin, The Purification of
Laboratory Chemicals, Pergamon, Oxford, 2nd edn., 1980.
1 T. Kametani, H. Kondoh, M. Tsubuki and T. Honda, J. Chem. Soc.,
Perkin Trans. 1, 1990, 5.
2 D. Craig, D. A. Fischer, O. Kemal, A. Marsh, T. Plessner, A. M. Z.
Slawin and D. J. Williams, Tetrahedron, 1991, 47, 3095.
3 S. Niwayama and K. N. Houk, Tetrahedron Lett., 1993, 34, 1251;
E. Piers and K. A. Ellis, ibid., 1993, 34, 1875 and references cited by
these authors. Unlike the CHO group, CO2Et generally prefers
outward conrotation in competition with hydrogen (but compare
K. Shishido, E. Shitara, K. Fukumoto and T. Kametani, J. Am.
Chem. Soc., 1985, 107, 5810; C. W. Jefford, G. Bernardinelli, Y. Wang,
A. B. Spellmeyer and K. N. Houk, J. Am. Chem. Soc., 1992, 114,
1157).
Paper 7/02761C
Received 22nd April 1997
Accepted 17th June 1997
4 T. Kametani, M. Tsubuki, Y. Shiratori, Y. Kato, H. Nemoto,
M. Ihara, K. Fukumoto and F. Satoh, J. Org. Chem., 1977, 42, 2672.
3536
J. Chem. Soc., Perkin Trans. 1, 1997