Thermal reaction of diastereomeric benzocyclobutenols. Evidence for reversible opening of 1,2-dihydrobenzocyclobutenols to hydroxy-o-xylylenes

Article abstract of DOI:10.1039/a908326j

Thermolysis of 1,2-dihydrobenzocyclobutenols 2a,b or 3a-c without solvent at 120 °C gave a 1:1 mixture of 2a-c and 3a-c together with 3-hydroxy-2,2-dimethyl-1-(o-methylphenyl)alkan-1-ones 1a-c and o-methylisobutyrophenone 5. Thermolysis of 2a or 3a under

Full text of DOI:10.1039/a908326j

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Thermal reaction of diastereomeric benzocyclobutenols.
Evidence for reversible opening of 1,2-dihydrobenzocyclobutenols
to hydroxy-o-xylylenes
1
Etsuya Kawata, Masaichi Saito and Michikazu Yoshioka*
Department of Chemistry, Faculty of Science, Saitama University, Shimo-okubo, Urawa,
Saitama 338-8570, Japan
Received (in Cambridge, UK) 18th October 1999, Accepted 21st January 2000
Thermolysis of 1,2-dihydrobenzocyclobutenols 2a,b or 3a–c without solvent at 120 ЊC gave a 1:1 mixture of 2a–c and
3a–c together with 3-hydroxy-2,2-dimethyl-1-(o-methylphenyl)alkan-1-ones 1a–c and o-methylisobutyrophenone 5.
Thermolysis of 2a or 3a under the same conditions but at 150 ЊC gave only 5. Thermolysis of 2c or 3c in benzene-d6
at 120 ЊC resulted in clean interconversion between 2c and 3c. Thermolysis of 1,2-dihydrobenzocyclobutenols 2d–f
or 3d–f without solvent at 150 ЊC gave a mixture of 2d–f and 3d–f together with 3-acetoxy-2,2-dimethyl-1-(o-methyl-
phenyl)alkan-1-ones 1d–f and benzyl ketones 9a–c.
It is well known that benzocyclobutenes undergo an electro-
cyclic ring opening of the four-membered ring to generate
o-xylylenes. The o-xylylenes are so reactive that they react with
various dienophiles to give [4 ϩ 2] cycloadducts1 or undergo
dimerization.2 The inter- and intramolecular cycloaddition
reactions of o-xylylenes have been used in the synthesis of poly-
cyclic ring systems.3 Thermolysis of benzocyclobutenols affords
hydroxy-o-xylylenes,4 the geometry of which has been investi-
gated by the analysis of the adduct with maleic anhydride or N-
phenylmaleimide.4a The benzocyclobutenol preferentially opens
to produce the (E)-dienol. Although the reaction of (E)-dienols
in the presence of dienophiles has been widely studied,5 there
are few reports on recyclization of dienols generated from
benzocyclobutenols. Sammes and co-workers reported that
heating optically active 1-methyl-1,2-dihydrobenzocyclobut-
enol at 110 ЊC readily gave 2-methylacetophenone because the
Scheme 1 Condition: i, hν.
intermediary (E)-dienol underwent proton transfer faster than
recyclizationtoproduceracemic1-methyl-1,2-dihydrobenzocyclo-
butenol.4a We report here the thermal interconversion of dia-
stereomeric 1,2-dihydrobenzocyclobutenols 2 and 3, which are
prepared by photocyclization of 3-hydroxy- and 3-acetoxy-2,2-
dimethyl-1-(o-methylphenyl)alkan-1-ones 1.
1
assigned by comparison of their H NMR spectra to those of
2a and 3a. Irradiation of acetoxy ketones 1d–f under the same
conditions also gave two diastereomeric benzocyclobutenols
2d–f and 3d–f in 95% yield. The configurations of these com-
pounds were determined by the X-ray crystallographic analyses
of 3d, 2e7 and 2f. Results of the photochemical reaction of
hydroxy and acetoxy ketones 1a–f are given in Table 1.
Results and discussion
Irradiation of the hydroxy ketone 1a in methanol with Pyrex-
filtered light gave two diastereomeric 1,2-dihydrobenzocyclo-
butenols 2a and 3a together with trans- and cis-cyclopropane-
1,2-diols 4 (Scheme 1).6 The 1,2-dihydrobenzocyclobutenols 2a
and 3a could be isolated by column chromatography on silica.
The configuration of 2a was determined by X-ray crystallo-
graphic analysis to be (3S*,1ЈS*), so that 3a had the (3S*,1ЈR*)
configuration. The 1H NMR spectrum of 2a showed peaks due
to two methylene protons of the four-membered ring as an AB
quartet at δ 2.96 and 3.60 and two methyl singlets on C-2 at
δ 0.78 and 1.13, whereas that of 3a showed two methylene pro-
tons at δ 3.03 and 3.55 and two methyl singlets at δ 0.71 and
1.25. The two methylene signals of 2a were further apart than
those of 3a and the two methyl singlets of 2a were closer than
those of 3a. Irradiation of hydroxy ketones 1b,c under the same
conditions also gave two diastereomeric 1,2-dihydrobenzocyclo-
butenols 2b,c and 3b,c, the configurations of which could be
When the (3S*,1ЈS*)-1,2-dihydrobenzocyclobutenol 2a was
heated at 120 ЊC in a sealed glass tube and the progress of the
reaction was monitored by H NMR, the gradual disappear-
1
ance of 2a was observed together with the gradual formation of
the (3S*,1ЈR*)-1,2-dihydrobenzocyclobutenol 3a as well as
with the formation of small amounts of the hydroxy ketone 1a
and o-methylisobutyrophenone 5 (Scheme 2). After 20 h, a
thermal equilibrium between 2a and 3a was established, where
the 2a:3a ratio was 1:1. The yields of the mixture of 2a and 3a,
the hydroxy ketone 1a and o-methylisobutyrophenone 5
were 93, 2 and 5%, respectively. Heating the (3S*,1ЈR*)-1,2-
dihydrobenzocyclobutenol 3a under the same conditions for
20 h also gave the 1:1 mixture of 2a and 3a together with small
amounts of 1a and 5. However, when 2a or 3a was heated under
the same conditions but at 150 ЊC for 10 h, only 2-methyl-
isobutyrophenone 5 was obtained. At 150 ЊC, the 1,2-dihydro-
benzocyclobutenols 2a and 3a were converted completely into
DOI: 10.1039/a908326j
J. Chem. Soc., Perkin Trans. 1, 2000, 1015–1019
This journal is © The Royal Society of Chemistry 2000
1015

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heating in benzene-d6 at 120 ЊC. The acetoxy-substituted 1,2-
dihydrobenzocyclobutenols 2d–f and 3d–f were also inter-
converted into each other on heating at 150 ЊC without solvent,
together with the formation of 1d–f and benzyl ketones 9a–c.
After 20 h, a thermal equilibrium between 2d–f and 3d–f was
established. Results of the thermal reaction of 2 and 3 are given
in Table 2.
As already mentioned, the 1,2-dihydrobenzocyclobutenol
undergoes selective thermal opening of the cyclobutene ring
to form the (E)-dienol. The thermal interconversion of the
diastereomeric 1,2-dihydrobenzocyclobutenols 2 and 3 prob-
ably proceeds via the (E)-dienol intermediate 6 because the
(E)-dienol species is sufficiently long-lived to be able to cyclize
to give epimers.8 As shown in Table 2, the major reaction of the
diastereomeric 1,2-dihydrobenzocyclobutenols 2 and 3 was the
interconversion of diastereomers. Since the (E)-dienols formed
from 2 and 3 are very congested because of the orientation
of the bulky quarternary alkyl group, the possibility that
β-hydroxy- and β-acetoxy ketones 1a–f are formed from the
(Z)-dienol cannot be ruled out. However, since the thermolysis
of a dilute benzene-d6 solution of 2c or 3c cleanly gave a 1:1
mixture of 2c and 3c, the 1,2-dihydrobenzocyclobutenols 2 and
3 would open selectively to the (E)-dienol because the (Z)-
dienol is very short-lived and undergoes a rapid 1,5-sigmatropic
hydrogen shift to give the ketone 1.9 The resulting (E)-dienol
undergoes recyclization to give 1,2-dihydrobenzocyclobutenols
2 and 3 along with intermolecular hydrogen transfers to give
hydroxy and acetoxy ketones 1.10 The lower yields of hydroxy
ketones 1a,b compared with 1c in the thermolysis of 3a–c with-
out solvent at 120 ЊC may be due to a bulkier substituent in 3a,b
than in 3c. The bulky substituent may prevent the approach of
the initially formed (E)-dienols. The (E)-dienols formed from
1,2-dihydrobenzocyclobutenols having a relatively small sub-
stituent react with various dienophiles to give cycloadducts.5
However, when the 1,2-dihydrobenzocyclobutenol 2a or 3a was
heated at 120 ЊC in the presence of dimethyl acetylenedicarb-
oxylate or maleic anhydride, no adduct of the (E)-dienol 6
(R2 = Pri) with the dienophile could be detected but the inter-
conversion between 2a and 3a was observed, perhaps due to
steric congestion of 6 (R2 = Pri) preventing the access of the
dienophile.
Scheme 2 Conditions: i, 120 ЊC; ii, 150 ЊC.
the hydroxy ketone 1a which further underwent retro-aldol
cleavage to give 5. The 1,2-dihydrobenzocyclobutenols 2b and
3b also underwent thermal interconversion at 120 ЊC. However,
since the 1,2-dihydrobenzocyclobutenol 2c has a melting point
of 136 ЊC, it remained unchanged on heating at 120 ЊC without
solvent. On the other hand, when a dilute benzene-d6 solution
of 2c in an NMR tube was heated at 120 ЊC, the conversion into
the diastereomeric isomer 3c occurred cleanly without form-
ation of either the hydroxy ketone 1c or 2-methylisobutyro-
phenone 5, though a long time was required to reach a thermal
equilibrium between 2c and 3c. The compound 3c, having a
melting point below 120 ЊC, was converted into 2c on heating at
120 ЊC without solvent. In this case, a large amount of the
hydroxy ketone 1c was formed after heating for 20 h. However,
3c was converted cleanly into a 1:1 mixture of 2c and 3c on
Table 1 Photochemical reaction of o-tolyl ketones 1a–f
Yield (%)c
Irradiation Conversion
Ketone 1 time/ha
(%)b
(2 ϩ 3)d
4
2:3 Ratioe
a
b
c
d
e
f
2
4
5
15
15
15
66
74
50
97
100
94
17
47
37
95
95
95
43
—
—
—
—
—
4:1
3:2
4:3
3:2
6:5
1:1
a A solution of the ketone (600 mg) in methanol (160 cm3) was irradi-
ated with a 100 W high-pressure mercury lamp through a Pyrex filter.
Ketones 1a–c were irradiated under ice-cooling. Ketones 1d–f were
irradiated at room temperature. b Based on the amount of consumed
starting material. c Isolated yield based on converted starting material.
d Sum yield of 2 and 3. These compounds could be isolated by repeated
chromatography. e Determined by 1H NMR on the fractions of the
mixture after chromatography.
The 2a–c:3a–c ratios in the photochemical reaction of 1a–c
increased with increasing size of R2, whereas these ratios were
1:1 in the thermal reactions of 2a–c and 3a–c regardless of the
size of R2 (Table 1 and 2). It is well known that benzocyclobut-
enols are prepared from the (E)-dienols generated by the
irradiation of o-tolyl ketones.11 The photochemically generated
(E)-dienols from 1a–c in methanol must be solvated by meth-
Table 2 Thermal reaction of benzocyclobutenols 2a–f and 3a–f
Yield (%)a
Benzocyclo-
butenol
Solvent
Temp/ЊC
Time/h
1
(2 ϩ 3)
5
9
2:3 Ratiob
2a
3a
2a
3a
2b
3b
2c
3c
3c
2d
3d
2e
3e
2f
None
None
None
None
None
None
C6D6
None
C6D6
None
None
None
None
None
None
120
120
150
150
120
120
120
120
120
150
150
150
150
150
150
20
20
10
10
20
20
80
20
80
20
20
20
20
20
20
2
5
—
—
7
93
84
—
—
71
71
100
16
100
72
68
62
60
66
66
5
3
—
—
—
—
—
—
—
—
—
8
11
11
11
2
1:1
1:1
—
88
88
—
—
—
6
—
—
—
—
—
—
—
—
1:1
1:1
1:1
1:1
1:1
7:4
7:4
3:2
3:2
2:3
2:3
6
—
63
—
20
9
7
18
11
20
3f
7
a Isolated yield. b Estimated by 1H NMR on the fractions after chromatography.
1016
J. Chem. Soc., Perkin Trans. 1, 2000, 1015–1019

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anol. The solvated (E)-dienols may cyclize to 2 and 3 in a ratio
that depends on the size of R2.12 The 2d–f:3d–f ratios in the
thermal reaction of 2d–f or 3d–f were also different from those
in the photochemical reaction of 1d–f. In both thermal and
photochemical reactions, the 2d–f:3d–f ratios increased with
increasing size of R2. Finally, the benzyl ketone 9 may be formed
by a process involving homolytic cleavage between the aryl
carbon and C-1 followed by hydrogen transfer (Scheme 3).13
(3 H, s) (1-H3 and 2-Me), 0.99 (3 H, d, J 7) and 1.06 (3 H, d, J 7)
(CHMe2), 2.00 (1 H, m, CHMe2), 3.03 (1 H) and 3.55 (1 H)
(AB-pair, J 15, 2Ј-H2), 3.01 (1 H, br s, OH), 3.78 (1 H, m, 3-H),
4.10 (1 H, br s, OH) and 7.1–7.3 (4 H, m, ArH); δC (50 MHz)
16.4 (q), 17.3 (q), 21.4 (q) and 23.2 (q) (4 × Me), 29.5 (d, C-4),
42.5 (s, C-2), 43.1 (t, C-2Ј), 80.3 (d, C-3), 89.6 (s, C-1Ј), 121.9
(d), 123.5 (d), 127.1 (d), 129.2 (d), 142.5 (s) and 148.3 (s) (ArC).
(3S*,1ЈS*)-2-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-2-methylpentan-3-ol 2b. Mp 96–97 ЊC (from hexane)
(Found: C, 76.4; H, 9.2. C14H20O2 requires C, 76.3; H, 9.2%);
νmax/cmϪ1 3300br (OH); δH (200 MHz) 0.75 (3 H, s) and 0.92
(3 H, s) (1-H3 and 2-Me), 0.99 (3 H, t, J 7, 5- H3), 1.3–1.6 (2 H,
m, 4-H2), 2.88 (1 H) and 3.53 (1 H) (AB-pair, J 15, 2Ј-H2), 3.74
(1 H, m, 3-H), 3.14 (1 H, br s) and 4.02 (1 H, br s) (2 × OH)
and 7.1–7.3 (4 H, m, ArH); δC (50 MHz) 11.3 (q), 16.8 (q) and
21.8 (q) (3 × Me), 24.6 (t, C-4), 41.3 (s, C-2), 43.5 (t, C-2Ј), 80.1
(d, C-3), 88.0 (s, C-1Ј), 121.9 (d), 123.2 (d), 126.8 (d), 128.9 (d),
142.4 (s) and 148.6 (s) (ArC).
(3S*,1ЈR*)-2-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-2-methylpentan-3-ol 3b. Mp 104–105 ЊC (from hexane)
(Found: C, 76.4; H, 9.2. C14H20O2 requires C, 76.3; H, 9.2%);
νmax/cmϪ1 3300br (OH); δH (200 MHz) 0.69 (3 H, s) and 1.14
(3 H, s) (1-H3 and 2-Me), 1.05 (3 H, t, J 7, 5-H3), 1.4–1.8 (2 H,
m, 4-H2), 3.03 (1 H) and 3.57 (1 H) (AB-pair, J 15, 2Ј-H2), 3.65
(1 H, m, 3-H), 4.27 (1 H, br s) and 5.11 (1 H, br s) (2 × OH)
and 7.1–7.3 (4 H, m, ArH); δC (50 MHz) 11.1 (q), 16.6 (q) and
21.6 (q) (3 × Me), 24.8 (t, C-4), 41.7 (s, C-2), 42.9 (t, C-2Ј), 79.3
(d, C-3), 88.8 (s, C-1Ј), 121.9 (d), 123.5 (d), 127.1 (d), 129.1 (d),
142.4 (s) and 148.4 (s) (ArC).
Scheme 3 Condition: i, 150 ЊC.
Experimental
Mps are uncorrected and bps are oven temperatures in Kugel-
rohr distillation. IR spectra were recorded on a Hitachi 270-50
spectrometer for solutions in CCl4. 1H NMR spectra were
obtained with a Bruker AC 200, a Bruker AC 300-P or a Bruker
AM 400 spectrometer with CDCl3 as a solvent. Tetramethyl-
silane was used as an internal standard and J values are given in
Hz. 13C NMR spectra were measured on a Bruker AC 200 or
a Bruker AC 300-P spectrometer with CDCl3 as a solvent. An
Ushio 100 W high-pressure mercury lamp was used as an
irradiation source. Starting compounds 1a–c were prepared by
the condensation of o-methylisobutyrophenone with the alde-
hyde according to previously described methods.14 Compounds
1d–f were prepared by refluxing 1a–c in acetic anhydride in the
presence of a catalytic amount of hydrochloric acid.
(2S*,1ЈS*)-3-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-3-methylbutan-2-ol 2c. Mp 136–137 ЊC (from hexane)
(Found: C, 75.5; H, 8.7. C13H18O2 requires C, 75.7; H, 8.8%);
νmax/cmϪ1 3400br (OH); δH (300 MHz) 0.74 (3 H, s) and 1.05
(3 H, s) (4-H3 and 3-Me), 1.22 (3 H, d, J 7, 1-H3), 2.98 (1 H) and
3.63 (1 H) (AB-pair, J 15, 2Ј-H2), 3.69 (1 H, br s) and 3.55 (1H,
br s) (2 × OH), 4.19 (1 H, q, J 7, 2-H) and 7.1–7.3 (4 H, m,
ArH); δC (75 MHz) 15.5 (q), 18.4 (q) and 22.0 (q) (3 × Me), 41.4
(s, C-3), 43.9 (t, C-2Ј), 73.9 (d, C-2), 88.4 (s, C-1Ј), 121.9 (d),
123.5 (d), 127.1 (d), 129.3 (d), 142.4 (s) and 148.5 (s) (ArC).
(2S*,1ЈR*)-3-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-3-methylbutan-2-ol 3c. Mp 84–85 ЊC (from hexane) (Found:
C, 75.5; H, 8.7. C13H18O2 requires C, 75.7; H, 8.8%); νmax/cmϪ1
3450br (OH); δH (300 MHz) 0.62 (3 H, s) and 1.15 (3 H, s) (4-H3
and 3-Me), 1.16 (3 H, d, J 7, 1-H3), 3.02 (1 H) and 3.55 (1 H)
(AB-pair, J 15, 2Ј-H2), 3.85 (1 H, br s) and 4.20 (1 H, br s)
(2 × OH), 4.07 (1 H, q, J 7) and 7.1–7.3 (4 H, m, ArH); δC (50
MHz) 15.5 (q), 18.4 (q) and 21.7 (q) (3 × Me), 41.5 (s, C-3), 42.8
(t, C-2Ј), 73.2 (d, C-2), 88.8 (s, C-1Ј), 121.8 (d), 123.5 (d), 127.1
(d), 129.2 (d), 142.4 (s) and 148.3 (s) (ArC).
General procedure for the photolysis of 1a–f
A solution of 1 (600 mg) in methanol (160 cm3) was irradiated
with a 100 W high-pressure mercury lamp through a Pyrex filter
under argon for 2–15 h (see Table 1). The solvent was removed
under reduced pressure, and the residue was chromatographed
on silica gel [hexane–ethyl acetate (6:1 to 22:1)] to give 1,2-
dihydrobenzocyclobutenols 2 and 3 and the cyclopropane-1,2-
diol 4. The physical properties of 4 have already been described
in a previous paper.6
(3S*,1ЈS*)-3-Acetoxy-2-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-2,4-dimethylpentane 2d. Mp 72–73 ЊC (from hex-
ane) (Found: C, 74.0; H, 8.9. C17H24O3 requires C, 73.9; H,
8.8%); νmax/cmϪ1 3500br (OH) and 1720 (C=O); δH (200 MHz)
0.90 (3 H, s) and 1.22 (3 H, s) (1-H3 and 2-Me), 0.96 (3 H, d, J 7)
and 1.01 (3 H, d, J 7) (CHMe2), 2.12 (3 H, s, COMe), 2.0–2.2 (1
H, m, CHMe2), 3.31 (1 H, br s, OH), 2.83 (1 H) and 3.59 (1 H)
(AB-pair, J 15, 2Ј-H2), 5.18 (1 H, d, J 3, 3-H) and 7.1–7.3 (4 H,
m, ArH); δC (50 MHz) 17.7 (q), 18.1 (q), 21.1 (q), 21.3 (q) and
23.3 (q) (5 × Me), 28.7 (d, C-4), 43.2 (s, C-2), 43.4 (t, C-2Ј), 79.9
(d, C-3), 86.1 (s, C-1Ј), 122.1 (d), 123.3 (d), 127.0 (d), 129.1 (d),
(3S*,1ЈS*)-2-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-2,4-dimethylpentan-3-ol 2a. Mp 67–68 ЊC (from hexane)
(Found: C, 77.1; H, 9.3. C15H22O2 requires C, 76.9; H, 9.5%);
νmax/cmϪ1 3400br (OH); δH (300 MHz) 0.78 (3 H, s) and 1.13
(3 H, s) (1-H3 and 2-Me), 0.99 (3 H, d, J 7) and 1.08 (3 H, d, J 7)
(CHMe2), 2.00 (1 H, m, CHMe2), 2.96 (1 H) and 3.60 (1 H)
(AB-pair, J 15, 2Ј-H2), 2.97 (1 H, br s) and 3.90 (2 H, m)
(2 × OH and 3-H) and 7.1–7.3 (4 H, m, ArH); δC (50 MHz) 16.3
(q), 16.9 (q), 21.7 (q) and 23.4 (q) (4 × Me), 29.3 (d, C-4), 42.4
(s, C-2), 43.7 (t, C-2Ј), 80.8 (d, C-3), 89.1 (s, C-1Ј), 121.9 (d),
123.5 (d), 127.1 (d), 129.2 (d), 142.5 (s) and 148.7 (s) (ArC).
143.0 (s) and 148.2 (s) (ArC) and 172.0 (s, C᎐O).
᎐
(3S*,1ЈR*)-2-(1Ј-Hydroxy-1Ј,2Ј-dihydrobenzocyclobuten-1Ј-
yl)-2,4-dimethylpentan-3-ol 3a. Mp 74–75 ЊC (from hexane)
(Found: C, 77.1; H, 9.3. C15H22O2 requires C, 76.9; H, 9.5%);
νmax/cmϪ1 3450br (OH); δH (300 MHz) 0.71 (3 H, s) and 1.25
(3S*,1ЈR*)-3-Acetoxy-2-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-2,4-dimethylpentane 3d. Mp 67–68 ЊC (from hex-
ane) (Found: C, 74.1; H, 8.8. C17H24O3 requires C, 73.9; H,
J. Chem. Soc., Perkin Trans. 1, 2000, 1015–1019
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8.8%); νmax/cmϪ1 3500br (OH) and 1750 (C᎐O); δ (200 MHz)
The same treatment of 1,2-dihydrobenzocyclobutenol 2d–f or
᎐
H
0.90 (3 H, s) and 1.14 (3 H, s) (1-H3 and 2-Me), 0.97 (3 H, d, J 7)
and 0.98 (3 H, d, J 7) (CHMe2), 2.14 (3 H, s, COMe), 2.1–2.3
(1 H, m, CHMe2), 2.67 (1 H, br s, OH), 2.99 (1 H) and 3.66
(1 H) (AB-pair, J 15, 2Ј-H2), 5.14 (1 H, d, J 2, 3-H) and 7.1–7.3
(4 H, m, ArH); δC (50 MHz) 17.4 (q), 20.3 (q), 20.6 (q), 21.2 (q)
and 23.2 (q) (5 × Me), 29.2 (d, C-4), 43.1 (s, C-2), 43.8 (t, C-2Ј),
81.0 (d, C-3), 86.9 (s, C-1Ј), 121.8 (d), 123.4 (d), 127.0 (d), 129.1
3d–f (100 mg) but at 150 ЊC for 20 h gave acetoxy ketone 1d–f,
1,2-dihydrobenzocyclobutenol 2d–f and 3d–f and 4-acetoxy-
3,3-dimethyl-1-phenylbutan-2-one 9a–c. 1,2-Dihydrobenzo-
cyclobutenol 2c or 3c (ca. 10 mg) in benzene-d6 (ca. 0.5 cm3) was
placed in a 5 mm diameter NMR tube and degassed by freeze–
pump–thaw cycles. The tube was heated at 120 ЊC for 80 h. The
1H NMR spectrum of the mixture showed only peaks due to a
1:1 mixture of 2c and 3c.
(d), 142.4 (s) and 148.7 (s) (ArC) and 172.0 (s, C᎐O).
᎐
4-Acetoxy-3,3,5-trimethyl-1-phenylhexan-2-one 9a. Bp 97–
98 ЊC at 0.4 mmHg (Found: C, 73.6; H, 8.8. C17H24O3 requires
C, 73.9; H, 8.8%); νmax/cmϪ1 1740 (ester C᎐O) and 1720 (C᎐O);
(3S*,1ЈR*)-3-Acetoxy-2-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-2-methylpentane 2e. Mp 83–84 ЊC (from hexane)
(Found: C, 73.3; H, 8.6. C16H22O3 requires C, 73.3; H, 8.5%);
νmax/cmϪ1 3500br (OH) and 1720 (C᎐O); δ (200 MHz) 0.82
(3 H, s) and 1.19 (3 H, s) (1-H3 and 2-Me), 0.91 (3 H, t, J 7,
5-H3), 1.66 (2 H, m, 4-H2), 2.11 (3 H, s, COMe), 2.83 (1 H) and
3.58 (1 H) (AB-pair, J 15, 2Ј-H2), 3.55 (1H, br s, OH), 5.17 (1 H,
dd, J 3 and 10, 3-H) and 7.1–7.3 (4 H, m, ArH); δC (50 MHz)
10.8 (q), 17.7 (q), 21.1 (q) and 21.3 (q) (4 × Me), 22.8 (t, C-4),
42.5 (s, C-2), 43.1 (t, C-2Ј), 79.2 (d, C-3), 85.6 (s, C-1Ј), 122.1
(d), 123.2 (d), 126.9 (d), 129.0 (d), 142.8 (s) and 148.1 (s) (ArC)
᎐
᎐
δH (300 MHz) 0.86 (3 H, d, J 7) and 0.89 (3 H, d, J 7) (6-H3 and
5-Me), 1.13 (3 H, s) and 1.22 (3 H, s) (3-Me2), 1.90 (1 H,
d × sept, J 6 and 7, 5-H), 2.09 (3 H, s, COMe), 3.81 (1 H) and
3.88 (1 H) (AB-pair, J 16, 1-H2), 5.20 (1 H, d, J 6, 4-H) and 7.2–
7.4 (5 H, m, ArH); δC (75 MHz) 18.5 (q), 20.1 (q), 20.8 (q), 21.5
(q) and 22.7 (q) (5 × Me), 29.6 (d, C-5), 44.5 (t, C-1), 52.3 (s,
C-3), 80.7 (d, C-4), 126.7 (d), 128.4 (d), 129.6 (d) and 134.3 (s)
(ArC), 170.7 (s, OC᎐O) and 210.4 (s, C᎐O).
᎐
H
᎐
᎐
and 172.1 (s, C᎐O).
᎐
4-Acetoxy-3,3-dimethyl-1-phenylhexan-2-one 9b. Bp 86–88 ЊC
at 0.3 mmHg (Found: C, 73.2; H, 8.5. C16H22O3 requires C, 73.3;
H, 8.5%); νmax/cmϪ1 1740 (ester C᎐O) and 1720 (C᎐O); δH (200
MHz) 0.86 (3 H, t, J 7, 6-H3), 1.16 (3 H, s) and 1.19 (3 H, s)
(3-Me2), 1.4–1.5 (2 H, m, 5-H2), 2.07 (3 H, s, COMe), 3.82 (2 H,
s, 1-H2), 5.25 (1 H, dd, J 5 and 8, 4-H) and 7.2–7.3 (4 H, m,
ArH); δC (50 MHz) 10.8 (q), 20.3 (q), 21.2 (q) and 23.5 (q)
(4 × Me), 20.8 (t, C-5), 44.5 (t, C-1), 52.1 (s, C-3), 78.4 (d, C-4),
126.7 (d), 128.4 (d), 129.6 (d) and 134.4 (s) (ArC), 170.7 (s, ester
(3S*,1ЈS*)-3-Acetoxy-2-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-2-methylpentane 3e. Mp 72–73 ЊC (from hexane)
(Found: C, 73.4; H, 8.5. C16H22O3 requires C, 73.3; H, 8.5%);
νmax/cmϪ1 3500br (OH) and 1750 (C᎐O); δ (200 MHz) 0.85
(3 H, s) and 1.08 (3 H, s) (1-H3 and 2-Me), 0.88 (3 H, t, J 7,
5-H3), 1.67 (2 H, m, 4-H2), 2.11 (3 H, s, COMe), 2.79 (1 H, br s,
OH), 2.96 (1 H) and 3.63 (1 H) (AB-pair, J 15, 2Ј-H2), 5.21 (1 H,
dd, J 1 and 3, 3-H) and 7.1–7.3 (4 H, m, ArH); δC (50 MHz)
10.9 (q), 19.7 (q), 20.3 (q) and 21.2 (q) (4 × Me), 23.7 (t, C-4),
42.5 (s, C-2), 44.2 (t, C-2Ј), 79.9 (d, C-3), 86.5 (s, C-1Ј), 122.0
(d), 123.4 (d), 127.0 (d), 129.2 (d), 142.7 (s) and 148.8 (s) (ArC)
᎐
᎐
᎐
H
C᎐O) and 210.1 (s).
᎐
4-Acetoxy-3,3-dimethyl-1-phenylpentan-2-one 9c. Bp 96–
98 ЊC at 0.4 mmHg (Found: C, 72.7; H, 8.2. C15H22O3 requires
C, 72.6; H, 8.1%); νmax/cmϪ1 1740 (ester C᎐O) and 1720 (C᎐O);
and 171.2 (s, C᎐O).
᎐
᎐
᎐
δH (200 MHz) 1.16 (3 H, d, J 7, 5-H3), 1.17 (3 H, s) and 1.19
(3 H, s) (3-Me2), 1.97 (3 H, s, COMe), 3.79 (2 H, s, 1-H2), 5.26
(1 H, q, J 7, 4-H) and 7.1–7.3 (5 H, m, ArH); δC (50 MHz) 14.9
(q), 19.6 (q), 20.8 (q) and 21.0 (q) (4 × Me), 44.2 (t, C-1), 51.4 (s,
C-3), 74.0 (d, C-4), 126.6 (d), 128.3 (d), 129.5 (d) and 134.2 (s)
(2S*,1ЈS*)-2-Acetoxy-3-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-3-methylbutane 2f. Mp 79–80 ЊC (from hexane)
(Found: C, 72.7; H, 8.2. C15H22O3 requires C, 72.6; H, 8.1%);
νmax/cmϪ1 3630 (OH) and 1750 (C᎐O); δH (200 MHz) 0.89 (3 H,
᎐
s) and 1.13 (3 H, s) (4-H3 and 3-Me), 1.25 (3 H, d, J 7, 1-H3),
2.04 (3 H, s, COMe), 2.88 (1 H) and 3.66 (1 H) (AB-pair, J 15,
2Ј-H2), 3.07 (1 H, br s, OH), 5.34 (1 H, q, J 7, 2-H) and 7.1–7.3
(4 H, m, ArH); δC (50 MHz) 15.6 (q), 17.2 (q), 21.0 (q) and 21.6
(q) (4 × Me), 42.2 (s, C-3), 43.7 (t, C-2Ј), 74.0 (d, C-2), 85.8 (s,
C-1Ј), 122.0 (d), 123.4 (d), 127.1 (d), 129.2 (d), 142.9 (s) and
(ArC), 170.1 (s, ester C᎐O) and 210.1 (s, C᎐O).
᎐
᎐
Pyrolysis of 2a and 3a in the presence of dienophile
A solution of 100 mg of 2a or 3a and 2 equiv. of dimethyl
acetylenedicarboxylate or maleic anhydride in 1 cm3 of benzene
was sealed in a glass tube. The tube was degassed by freeze–
pump–thaw cycles and heated at 120 ЊC for 20 h. The solvent
was removed and the residue was fractionated by chromato-
graphy on silica gel using a 4:1 mixture of hexane and ethyl
acetate. The 1H NMR spectrum of each of the fractions
revealed that 2a and 3a were interconverted, while no adduct of
the dienol arising from 2a or 3a with dienophile was detected.
148.6 (s) (ArC) and 171.0 (s, C᎐O).
᎐
(2S*,1ЈR*)-3-Acetoxy-3-(1Ј-hydroxy-1Ј,2Ј-dihydrobenzocyclo-
buten-1Ј-yl)-3-methylbutane 3f. Bp 96–98 ЊC at 0.3 mmHg
(Found: C, 72.6; H, 8.2. C15H22O3 requires C, 72.6; H, 8.1%);
νmax/cmϪ1 3470br (OH) and 1740 (C᎐O); δ (200 MHz) 0.87
᎐
H
(3 H, s) and 1.10 (3 H, s) (4-H3 and 3-Me), 1.25 (3 H, d, J 7,
1-H3), 2.06 (3 H, s, COMe), 2.74 (1 H, br s, OH), 2.95 (1 H) and
3.64 (1 H) (AB-pair, J 15, 2Ј-H2), 5.22 (1 H, q, J 7, 2-H) and
7.1–7.3 (4 H, m, ArH); δC (50 MHz) 16.0 (q), 19.4 (2q) and 21.4
(q) (4 × Me), 41.8 (s, C-3), 44.1 (t, C-2Ј), 75.2 (d, C-2), 86.2 (s,
C-1Ј), 122.0 (d), 123.3 (d), 126.9 (d), 129.1 (d), 142.5 (s) and
Crystallographic analysis of 2a, 2f and 3d
Data were collected on a MAC Science DIP3000 diffractometer
with Mo-Kα radiation (λ = 0.71073 Å) at 298 K and the
structure was solved by direct methods. Crystal data for 2a:
C15H22O2, M = 234.37, orthorhombic, a = 7.8840(5), b =
12.514(1), c = 14.297(1) Å, V = 1410.6(2) Å3, Z = 4, space group
P212121, µ = 0.067 mmϪ1. The crystal used had dimensions of
0.5 × 0.5 × 0.4 mm. The final cycle of full-matrix least-squares
refinement was based on 1747 observed reflections [I > 3σ(I)]
and 242 variable parameters with R(Rw) = 0.049 (0.062).
Crystal data for 2f: C15H22O3, M = 248.32, monoclinic, a =
11.308(2), b = 9.460(1), c = 13.187(1) Å, V = 1402.4 (3) Å3,
Z = 4, space group P21/n, µ = 0.075 mmϪ1. The crystal used had
dimensions of 0.3 × 0.3 × 0.28 mm. The final cycle of full-
matrix least-squares refinement was based on 1920 observed
148.6 (s) (ArC) and 170.3 (s, C᎐O).
᎐
Pyrolysis of 1Ј,2Ј-dihydrobenzocyclobutenols 2a–f and 3a–f
1Ј,2Ј-Dihydrobenzocyclobutenol 2a–c or 3a–c (100 mg) was
sealed in an 8 mm diameter Pyrex tube under argon. The tube
1
was heated at 120 ЊC for 20 h. The H NMR analysis of the
mixture revealed that interconversion occurred between 2a–c
and 3a–c. The mixture was chromatographed on silica gel and
eluted with a mixture of hexane and ethyl acetate (4:1 to 6:1)
to give two isomeric 1,2-dihydrobenzocyclobutenols 2a–c and
3a–c, hydroxy ketone 1a–c and o-methylisobutyrophenone 5.
1018
J. Chem. Soc., Perkin Trans. 1, 2000, 1015–1019

View Article Online
Can. J. Chem., 1990, 68, 2028; J. L. Charlton and S. Maddaford,
reflections [I > 3σ(I)] and 243 variable parameters with
R(Rw) = 0.053 (0.067). Crystal data for 3d: C17H24O3, M =
276.38, monoclinic, a = 10.106(1), b = 25.218(2), c = 12.298(2)
Can. J. Chem., 1993, 71, 827; J. L. Charlton, S. Maddaford, K. Koh,
S. Boulet and M. H. Saunders, Tetrahedron: Asymmetry, 1993, 4,
645; J. L. Charlton, D. Bogucki and P. Guo, Can. J. Chem., 1995, 73,
1463; D. M. Coltart and J. L. Charlton, Can. J. Chem., 1996, 74, 88.
6 M. Yoshioka, S. Miyazoe and T. Hasegawa, J. Chem. Soc., Perkin
Trans. 1, 1993, 2781.
Å, V = 3134.2(2) Å3, Z = 8, space group P21/n, µ = 0.074 mmϪ1
.
The crystal used had dimensions of 0.15 × 0.15 × 0.15 mm.
The final cycle of full-matrix least-squares refinement was
based on 2941 observed reflections [I > 3σ(I)] and 415 variable
parameters with R(Rw) = 0.054 (0.071).
CCDC reference number 207/396. See http://www.rsc.org/
suppdata/p1/a9/a908326j for crystallographic files in .cif
format.
7 K. Iida, E. Kawata, K. Komada, M. Saito, S. Kumakura and
M. Yoshioka, Acta Crystallogr., Sect. C, 1998, 54, 1938.
8 P. J. Wagner, D. Subrahmanyan and B.-S. Park, J. Am. Chem. Soc.,
1991, 113, 709.
9 R. Haag, J. Wirz and P. J. Wagner, Helv. Chim. Acta, 1977, 60, 2595.
10 K. Iida, M. Saito and M. Yoshioka, J. Org. Chem., 1999, 64, 7407.
11 M. Sobczak and P. J. Wagner, Tetrahedron Lett., 1998, 39, 2523;
P. J. Wagner, M. Sobczak and B.-S. Park, J. Am. Chem. Soc., 1998,
120, 2488.
12 P. J. Wagner, Acc. Chem. Res., 1971, 4, 168.
13 O. L. Chapman, U.-P. E. Tsou and J. W. Johnson, J. Am. Chem. Soc.,
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14 M. Yoshioka, T. Suzuki and M. Oka, Bull. Chem. Soc. Jpn., 1984,
57, 1604; M. Yoshioka, K. Nishizawa, M. Arai and T. Hasegawa,
J. Chem. Soc., Perkin Trans. 1, 1991, 541.
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J. Chem. Soc., Perkin Trans. 1, 2000, 1015–1019
1019