Solvent trapping of photochemically generated pyran-4-one-derived oxyallyls: A convenient cyclopentannulation method

Article abstract of DOI:10.1055/s-2001-15067

Fused bicyclic pyran-4-ones 2a - F are readily available via one-step annulation with diketene or diketene equivalents. Irradiation of 2b - E in methanol furnished ring-contracted solvent adducts 4 in moderate yields, whereas irradiation in aqueous H₂SO₄ gave the corresponding glycols 8 and 9. The unusual predominance of cis-fused product 8b appears to result from in situ acid-catalyzed equilibration. Substrate 2f could also be trapped in aqueous acid, and displayed a modest stereoselectivity that may derive from conformational control by the methyl group on the starting material's stereogenic center.

Full text of DOI:10.1055/s-2001-15067

1
268
PAPER
Solvent Trapping of Photochemically Generated Pyran-4-one-Derived
Oxyallyls: A Convenient Cyclopentannulation Method
S
M
olvent Trapping of Ph
i
otoche
k
mically Gen
e
e
rate
d
Pyran-4-on
F
e-Derived
O
x
l
yallylseming, Peter V. Fisher, Gamini U. Gunawardena, Yinghua Jin, Chen Zhang, Wei Zhang, Atta M. Arif,
Frederick G. West*
Department of Chemistry, University of Utah, 315 S. 1400 East, Rm. 2020, Salt Lake City, UT, USA 84112–0850
Fax +1(801)5818433; E-mail: west@chemistry.chem.utah.edu
Received 5 March 2001
Dedicated with best wishes to Professor Howard Zimmerman in recognition of his many important contributions to the field of organic
photochemistry
_
O
+
O
O
O
Abstract: Fused bicyclic pyran-4-ones 2a–f are readily available
via one-step annulation with diketene or diketene equivalents. Irra-
diation of 2b–e in methanol furnished ring-contracted solvent ad-
R
R
R
R
R
R
hν
R
R
Nu:
R
Nu
ducts 4 in moderate yields, whereas irradiation in aqueous H SO
R
R
R
2
4
O
OH
gave the corresponding glycols 8 and 9. The unusual predominance
of cis-fused product 8b appears to result from in situ acid-catalyzed
equilibration. Substrate 2f could also be trapped in aqueous acid,
and displayed a modest stereoselectivity that may derive from con-
formational control by the methyl group on the starting material’s
stereogenic center.
1
O
O
MeO
( )n
R
(
)n
hν
MeOH
R
O
Me
OH Me
2
(n = 0–3)
Key Words: annulations, bicyclic compounds, diols, heterocycles,
photochemistry, ring contractions
Scheme 1
diketene equivalent 2,2,6-trimethyl-1,3-dioxin-4-one6
gave significantly higher yields of 2d while the more
highly substituted 2,2,5,6-tetramethyl-1,3-dioxin-4-one
allowed access to the fully substituted pyranone 2e. In or-
der to examine the effect of a stereogenic center within the
adjacent ring, methyl-substituted example 2f was also pre-
pared, via the pyrrolidine enamine of methylcyclohex-
anone and 2,2,6-trimethyl-1,3-dioxin-4-one.
Pyran-4-ones undergo efficient photochemical ring con-
traction to transient epoxy-fused oxyallyl zwitterions 1
(
Scheme 1), in analogy to the better known 2,5-cyclo-
1
hexadienones. We have shown that these intermediates
can then be trapped by a variety of pendant nucleophiles
to furnish polycyclic products. The short lifetime of the
2
zwitterion suggested that the corresponding intermolecu-
lar processes would not be efficient, with the possible ex-
ception of trapping by nucleophilic solvent. Indeed,
Pavlik and Barltrop demonstrated that alcoholic solvents
could intercept the oxyallyl intermediates derived from
simple polyalkyl pyran-4-ones to give 5-alkoxy-4-hy-
O
O
O
65–70 °C
R
(
)n
( )n
N
O
Me
3
droxy-2-cyclopenten-1-ones. In a preliminary study, we
O
2a (n=0, R=H) 18%
extended this process to fused bicyclic pyran-4-ones 2,
whose intermediate zwitterions could be trapped by sol-
vent methanol to give ring-contracted bicyclic products in
which both bridgehead positions would be oxygenated,
but attempts to accomplish the analogous trapping with
2b (n=1, R=H) 65%
2
2
c (n=2, R=H) 45%
d (n=3, R=H) 45%
Me Me
O
O
Me
O
R
2d (n=3, R=H) 88%
2e (n=1, R=Me) 71%
4
water proceeded in low efficiency. Here we report the
120–130 °C
full details of zwitterion trapping by methanol, as well as
an improved procedure for aqueous trapping of fused bi-
cyclic pyran-4-ones to furnish dihydroxylated products.
The overall procedure functions as a two-step cyclopen-
tannulation method.
Me Me
O
O
O
Me
O
1
20–130 °C
N
O
Me
As described previously, the pyran-4-one substrates 2a–d
could be easily prepared from diketene and the morpho-
line enamines of cyclic ketones following the procedure
Me
2
f 55%
Scheme 2
5
of Hünig (Scheme 2). An alternative method employing
Extended irradiation of cyclopentane-containing pyra-
none 2a in methanol failed to significantly consume the
substrate, a result that we attribute to unacceptable levels
of ring strain in the hypothetical oxyallyl zwitterion 3a
Synthesis 2001, No. 8, 18 06 2001. Article Identifier:
1
437-210X,E;2001,0,08,1268,1274,ftx,en;C02001SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
©

PAPER
Solvent Trapping of Photochemically Generated Pyran-4-one-Derived Oxyallyls
1269
_
O
O
hν
+
X
MeOH
O
Me
O
Me
2a
3a
O
O
O
MeO
hν
MeOH
Me 1.5 equiv H2SO4
0%
OH
1
Me
2b
4b
O
O
O
O
O
MeO
MeO
hν
MeOH
+
+
70%
Me
Me
OH
OH
Me
4
Me
:
OH
2c
4c
5c
7c
:
1
2
O
O
OMe
hν
MeOH
59%
O
Me
OH
Me
2d
4d
O
O
O
MeO
Me
Me
hν
MeOH
Me
OMe
+
Me
40%
O
OH
Me
Me
HO
2e
4e
6e
2
:
3
O
H
H
H
C
hν
MeOH
hν
Norrish type II)
2c
O
7c
(
Me
OH
6c
Scheme 3
that would result (Scheme 3). However, the larger ring Irradiation of pyranones 2 in neutral aqueous solution
substrates 2b–d all gave solvent trapping products, albeit gave complex mixtures, further complicated by the low
in variable yield. The six-membered case 2b provided aqueous solubility of the starting materials. The previous-
only minor amounts of the expected methanol adducts 4b ly noted benefit of catalytic amounts of sulfuric acid in the
and only in the presence of sulfuric acid. Seven- and methanol trapping experiments with 2b suggested further
9
eight-membered substrates 2c,d gave better yields, al- examination of this effect. Prior reports by Barltrop and
10
though the product mixture in the case of 2c was compli- Pavlik indicated that 4-hydroxypyrilium cations, result-
cated by the presence of both diastereomeric methanol ing from protonation of pyran-4-one carbonyl oxygens,
adducts 4c and 5c, as well as the apparent reduction prod- underwent smooth photochemical rearrangement in anal-
uct 7c. Finally, tetrasubstituted pyranone 2e was irradiat- ogy to their neutral counterparts. In the case of substrates
ed and yielded roughly equal amounts of regioisomeric 2b–d, we found that 10% aqueous sulfuric acid provided
methanol adducts 4e and 6e. The preference for trans ad- an effective medium for the desired transformation
dition in these cases parallels previous studies employing (Scheme 4). In contrast to the methanol trapping process
simple monocyclic pyranones, as does the regioselectivity discussed above, significant amounts of both cis- and
in favor of attack at the more substituted terminus of the trans-fused diastereomers 8b–d and 9b–d were isolated,
3
,7
oxyallyl system. The regiochemical mixture seen with and in the case of six-membered substrate 2b, the less
e was expected, since the two termini are equally substi- strained cis-isomer was predominant. The ratio of 8b and
2
tuted. The formation of 7c is most readily explained by 9b was found to be dependent upon the concentration of
competing trapping at the less substituted terminus fol- H SO , suggesting the possibility of in situ isomerization.
2
4
lowed by a secondary Norrish type II cleavage to furnish In fact, trans-fused isomer 9b underwent partial isomer-
8
7
c and formaldehyde. However, we were not able to iso- ization to 8b under the reaction conditions, presumably
via a retro-aldol/aldol mechanism.1
1,12
late any of putative precursor, 6c.
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York

1
270
M. Fleming et al.
PAPER
O
O
O
O
OH
OH
OH
OH
hν
+
1
0% H2SO4
Me
40%
Me
3
Me
2b
8b
9b
:
1
O
O
O
O
O
OH
OH
OH
hν
+
+
OH
Me
1
0% H2SO4
Me
OH
3
44%
Me
2
Me
:
OH
2c
8c
9c
10c
:
1
O
O
O
O
OH
OH
hν
+
1
0% H2SO4
Me
OH
OH
51%
Me
Me
2d
8d
9d
1
:
H+
4
O
OH
O
OH
OH
OH
H+
Me
HO
OH
Me
O
Me
9b
8b
Scheme 4
Definitive stereochemical assignment of cis- and trans- product was a crystalline solid, and x-ray diffraction anal-
13
isomers was challenging. Single crystal x-ray diffraction ysis confirmed that it was the all-cis-isomer 8f. A second
analysis of 4e confirmed the expected trans relationship product was assigned as the other cis-fused isomer 8g,
1
3
1
of the angular hydroxy and methoxy groups, and other based upon H NMR evidence for internal hydrogen
methanol adducts were assigned by analogy. In the cases bonding by the glycol moiety. The third product is pre-
of glycols 8 and 9, the ability to form acetonides 11b, c sumed to be one of the two possible trans-isomers, and we
from 8b, c with no comparable acetonide formation from have tentatively assigned it as 9f. Thus, it appears that the
9
b, c had been used to support a tentative assignment methyl group exerts a modest effect on zwitterion forma-
4
(
Scheme 5). However, we were reluctant to rely on a neg- tion.
ative result and also were concerned about possible acid
catalyzed isomerization under the ketalization conditions
Fused bicyclic pyran-4-ones are easily prepared from
enamines and either diketene or dioxinone, and irradiation
in methanol or aqueous acid leads to ring contraction with
solvent incorporation. This two-step route functions as an
overall cyclopentannulation method, with stereoselectivi-
ty in favor of the trans-isomers 4 and 9 in most cases. A
pre-existing stereocenter in the ring adjacent to the pyra-
none led to a modest selectivity (approx. 2:1) in zwitterion
formation. Intramolecular trapping of similar diastereo-
meric zwitterions is under study and will be reported else-
where.
(
vide supra). Fortunately, a significant difference in the
NMR chemical shifts of the hydroxyl protons could be
used to distinguish the cis- and trans-isomers. In 0.01 M
CDCl solution, cis-isomers 8b–d all displayed one down-
3
field hydroxyl resonance ( = 2.99–3.52 ppm) and a sec-
ond one further upfield (approx. 2.6 ppm), suggestive of
internal hydrogen bonding between the two neighboring
hydroxyls. In contrast, the hydroxyl resonances of 9b, c
both appeared in the typical chemical shift range for iso-
1
4
lated alcohols (1.45–1.83 ppm). X-ray crystallographic
analysis of 8d confirmed the cis ring fusion and the pres-
O
O
OH
O
1
3
ence of an internal hydrogen bond, in support of the
NMR trends described above.
(
)n
MeC(OMe)2Me
cat. TsOH
( )n
Me
Me
Finally, substrate 2f was examined to determine whether
the stereogenic center within the cyclohexyl ring would
exert any influence on ring contraction to the oxyallyl
zwitterion. Assuming that the methyl group adopts a pseu-
doequatorial disposition, formation of zwitterion 3f might
be favorable over that of its diastereomer 3g (Scheme 6).
O
OH
8b,c
Me
OH
Me
1
1b,c
O
( )n
MeC(OMe) Me
2
N. R.
cat. TsOH
OH
9b,c
Me
1
5
In the event, irradiation of 2f in dilute aqueous acid pro-
vided three products in a combined 39% yield. The major
Scheme 5
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent Trapping of Photochemically Generated Pyran-4-one-Derived Oxyallyls
1271
O
O
Me
_
hν
Me
Me
+
O
O
vs.
+
Me
1
0 mol% H
2
SO
4
_
O
Me
39%
O
Me 2f
3f
3g
O
O
O
OH
OH
OH
OH
OH
+
MeOH Me
Me
Me
Me
Me
9f
8f
8g
3
:
1
:
2
Scheme 6
–
1
Reactions were conducted in oven-dried (120°C) or flame-dried
IR (thin film): = 3061, 2920, 1663, 1611 cm .
1H NMR (300 MHz, CDCl3): = 6.05 (q, 1H, J = 0.7 Hz), 2.72 (t,
2
1
glassware under a positive atm of N unless otherwise stated. Trans-
2
fer of anhyd solvents or air-sensitive reagents was accomplished
with oven-dried syringes or cannulae. Solvents were distilled before
use: CH Cl from CaH , Et O and THF from Na-benzophenone
H, J = 5.5 Hz), 2.64 (t, 2H, J = 5.6 Hz), 2.22 (d, 3H, J = 0.7 Hz),
.81 (app. pent., 2H, J = 5.6 Hz), 1.68 (2H, app. p, J = 5.5 Hz), 1.55
2
2
2
2
(
app. p, 2H, J = 5.6 Hz).
ketyl. Commercial reagents and solutions were used as received un-
less otherwise stated. TLC was performed on plates of silica pre-
coated with 0.25 mm Kieselgel 60 F254 (Merck). Flash columns
were packed with 230–400 mesh silica gel (Merck or Baxter). Ra-
dial chromatography was performed on a Harrison Research Chro-
matotron Model 7924T with plates of silica precoated with 1, 2 or 4
mm silica gel 60 F254 containing gypsum (EM Science). Mps were
obtained on a Thomas–Hoover apparatus in open capillary tubes
1
3
C NMR (75 MHz, CDCl ): = 178.4, 167.7, 163.5, 125.8, 112.3,
3
3
3.6, 31.5, 25.8, 24.5, 21.5, 19.4.
Anal. Calcd for C H O : C, 74.13; H, 7.92. Found: C, 74.13; H,
7
1
1
14
2
.93.
Method B: 3-Methyl-2-oxabicyclo[6.4.0]dodeca-3,6(1)-dien-5-
one (2d); Typical Procedure
1
1
open 100-mL round bottom flask equipped with a magnetic stirring
bar. The vigorously stirred mixture was placed in an oil bath pre-
heated to 120–130°C and heated for 1.5 h. After cooling to r.t., the
reaction mixture was diluted with CHCl (200 mL) and washed with
2
(
1
and are uncorrected. H NMR spectra were recorded on a 300 MHz
-Morpholinocyclooctene (4.8 g, 24 mmol) and 2,2,6-trimethyl-
,3-dioxin-4-one (6.4 mL, 49 mmol; 2 equiv.) were mixed in an
1
3
Varian Unity or 500 MHz Varian VXR instrument. C NMR spec-
tra were obtained at 75 MHz (Unity) or at 125 MHz (VXR). IR
spectra were measured with a Mattson FT-IR 3000 spectrophotom-
eter. Mass spectra were determined on a VG Micromass 7050E
mass spectrometer equipped with a VG 2000 data system. Elemen-
tal analyses were carried out at Atlantic Microlabs based in Nor-
cross, Georgia.
3
N NaOH/sat. NaCl (100 mL each). The organic layer was dried
Na SO ), concentrated, and purified by flash chromatography (sil-
2
4
ica gel; 6 cm 15 cm column; Et O–CH Cl –hexanes, 2:1:2) to give
2
2
2
Bicyclic Pyranones 2
4
.1 g (88%) of 2d as a pale yellow crystalline solid.
Mp 89–91°C; R 0.22 (Et O–CH Cl –hexanes, 2:1:2).
IR (KBr): = 1660, 1600 cm–1.
1H NMR (300 MHz, CDCl3): = 6.04 (br s, 1H), 2.66–2.62 (m, 2H),
.57–2.52 (m, 2H), 2.20 (br s, 3H), 1.78–1.70 (m, 2H), 1.67–1.59
Substrates 2a,b were previously described by Hünig and cowork-
5
f
2
2
2
ers. All others were prepared using the Hünig procedure (Method
1
6
A) or the dioxinone procedure (Method B).
Method A: 3-Methyl-2-oxabicyclo[5.4.0]undeca-3,6(1)-dien-5-
one (2c); Typical Procedure
2
(
m, 2H), 1.51–1.38 (m, 4H).
1
-Morpholinocycloheptene (17.3 g, 95 mmol) was placed in a 250
1
3
C NMR (75 MHz, CDCl ): = 178.9, 165.5, 164.4, 123.9, 113.0,
mL 3-neck round bottom flask fitted with magnetic stirring bar, re-
flux condenser with a nitrogen inlet, thermometer and an addition
funnel charged with diketene (15 mL, 190 mmol). The flask was
warmed to 65°C and the diketene was added dropwise over 1 h.
3
3
0.6, 29.0, 29.0, 26.2, 26.1, 22.3, 19.8.
Anal. Calcd for C H O : C, 74.97; H, 8.39. Found: C, 75.09; H,
1
2
16
2
8.44.
(
Caution: do not allow the internal temperature to rise above 75°C.
Rapid addition of diketene can provoke an exotherm with associat-
ed pressure build-up.) Following addition, the reaction was allowed
to stand at 70°C for 2 h, then at ambient temperature for 24 h, after
which the flask was fitted with a distillation head and the red oil was
distilled under reduced pressure (2 mm, 100–160°C). The crude
distillate was diluted with CH Cl (100 mL) and the solution was
washed with 2 N NaOH/sat. NaCl (500 mL each), dried (MgSO4),
filtered, and concentrated to give 14.7 g of yellow solid. Fractional
crystallization (cyclohexane, activated charcoal) gave 7.0 g (41%)
of 2c as a colorless crystalline solid.
3,4-Dimethyl-2-oxabicyclo[4.4.0]deca-3,6(1)-dien-5-one (2e)
Prepared via Method B (71%): colorless crystalline solid, mp 54–
55°C; R = 0.31 (EtOAc–hexanes, 1:1).
f
–
1
IR (thin film): = 2986, 1663, 1605 cm .
1H NMR (300 MHz, CDCl
): = 2.39 (tt, 2H, J = 6.4, 1.5 Hz), 2.32
2
2
3
(tt, 2H, J = 6.2, 1.5 Hz), 2.14 (s, 3H), 1.81 (s, 3H), 1.73–1.63 (m,
2H), 1.63–1.52 (m, 2H).
13
C NMR (75 MHz, CDCl ): = 178.8, 161.9, 159.8, 119.8, 118.8,
3
2
7.0, 21.6, 21.3, 20.6, 17.4, 9.5.
Mp 104–105°C; R 0.49 (EtOAc).
f
Anal. Calcd for C H O : C, 74.13; H, 7.92. Found: C, 73.98; H,
1
1
14
2
7
.97.
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York

1
272
M. Fleming et al.
PAPER
3
,4,10-Trimethyl-2-oxabicyclo[4.4.0]deca-3,6(1)-dien-5-one (2f)
Anal. Calcd for C H O : C, 74.13; H, 7.92. Found: C, 74.01; H,
1
1
14
2
Prepared via Method B, except using 6-methyl-1-pyrrolidinocyclo-
7.93.
hexene (55%): yellow crystalline solid, mp 65–67°C; R = 0.25
f
(EtOAc–hexanes, 1:1).
Solvent Trapping of Pyranones 2
–
1
Photochemical reactions were carried out using a Hanovia 450W
medium pressure Hg lamp in a water-cooled jacket. For small scale
reactions, a quartz tube clamped 10 cm from the outer edge of the
cooling jacket was used, and for large scale reactions an immersion
well was used. All photochemical reaction mixtures were deoxy-
IR (KBr): = 1660, 1605 cm .
1H NMR (500 MHz, CDCl3): = 6.03 (q, 1H, J = 1.0 Hz), 2.70 (dq,
H, J = 13.5, 7.0 Hz), 2.44–2.36 (m, 2H), 2.22 (d, 3H, J = 1.0 Hz),
.91 (dddd, 1H, J = 13.4, 11.0, 5.5, 2.5 Hz), 1.73–1.66 (m, 1H),
.64–1.57 (m, 1H), 1.54–1.48 (m, 1H), 1.24 (d, 3H, J = 7.0 Hz).
1
1
1
genated with a slow stream of dry N for 15–30 min.
2
1
3
C NMR (75 MHz, CDCl ): = 180.1, 166.7, 164.8, 121.6, 112.9,
3
3
2.4, 30.9, 21.6, 20.1, 19.5, 18.9.
Table Photoproducts from Solvent Trapping of 2b–f
Product R /phys. descr. IR (cm ) 1H NMR
–
1
a
13C NMR
b
EA (%)
HRMS (m/z)
f
4b
0.39 (Et O–
3437, 1709, 5.83 (q, 1H, J = 1.5), 3.18 (s, 3H), 2.09 204.5, 175.4,
calcd for C H O
3
2
11 16
CH Cl –hex,
1608
(d, 3H, J = 1.5), 2.10–1.90 (m, 1H),
1.89–1.76 (m, 1H), 1.74–1.62 (m,
127.9, 82.3, 79.5,
51.3, 25.1, 19.6,
18.6, 18.4, 14.2
196.1099. Found:
196.1098
2
2
4:3:3)/ oil
2
H), 1.61–1.36 (m, 5H)
4c
0.40 (hex–
3414, 1688, 5.78 (q, 1H, J = 1.5), 3.15 (s, 3H),
204.4, 176.9,
Calcd for
EtOAc, 1:1)/
solid (mp 111–
1614
2.20–2.0 (m, 1H), 2.09 (d, 3H,
J = 1.5), 1.90–1.50 (m, 10H)
127.1, 85.1, 83.9, C H O : C,
12 18 3
51.4, 29.3, 25.3,
25.0, 24.7, 20.1,
68.54; H, 8.63.
Found: C, 68.68;
H, 8.67
112°C)
1
4.1
5c
7c
4d
4e
6e
0.54 (hex–
EtOAc, 1:1)/ oil 1628
3501, 1707, 5.87 (q, 1H, J = 1.2), 3.87 (d, 1H,
203.5, 181.1,
calcd for C H O
3
210.1256. Found:
210.1263
1
2
18
J = 1.5), 3.37 (s, 3H), 2.20–1.92 (m, 127.6, 82.4, 81.1,
2
(
H), 2.07 (d, 3H, J = 1.2), 1.88–1.76 51.8, 34.5, 30.9,
m, 2H), 1.70–1.20 (m, 6H) 26.8, 22.5, 22.0,
4.0
1
0.33 (hex–
3422, 1696, 3.70 (s, 1H), 2.64–2.50 (m, 1H), 2.55 204.9, 177.5,
EtOAc, 1:1)/ oil 1643 (s, 2H), 2.50–2.36 (m, 1H), 2.36–2.17 142.7, 76.1, 51.4,
m, 2H), 1.85–1.70 (m, 2H), 1.70– 31.8, 27.5, 27.2,
.57 (m, 2H), 1.56–1.45 (m, 2H), 1.43 26.7, 26.6, 23.3
s, 3H)
calcd for C H O
2
1
1
16
180.1158. Found:
180.1154
(
1
(
0.43 (Et O–
3320, 1680, 5.78 (q, 1H, J = 1.4), 3.09 (s, 3H), 2.00 204.6, 178.0,
Calcd for
2
CH Cl –hex,
1610
(d, 3H, J = 1.5), 1.91–1.68 (m, 6H),
1.59–1.19 (m, 7H)
127.2, 82.3, 65.8, C H O : C,
52.1, 30.1, 28.7,
2
2
13 20 3
2:1:1)/ oil
69.61; H, 8.99.
Found: C, 69.63;
H, 9.00
2
2
7.4, 24.0, 23.5,
3.3, 14.5
0.60 (hex–
EtOAc, 1:1)/
solid (mp 136–
3458, 1696, 3.10 (s, 3H), 2.15–1.93 (m, 2H), 1.96 204.7, 166.4,
Calcd for
1632
(q, 3H, J = 1.1), 1.90–1.78 (m, 2H),
1.71 (q, 3H, J = 1.1), 1.70–1.58 (m,
3H), 1.58–1.48 (m, 2H)
134.8, 81.4, 78.7, C H O : C,
51.4, 25.3, 19.6,
18.7, 18.4, 11.5,
12 18 3
68.55; H, 8.63.
Found: C, 68.64;
H, 8.68
137°C)
8
.0
0.42 (hex–
3451, 1703, 3.43 (s, 3H), 2.50–2.25 (m, 2H), 2.20– 204.4, 171.8,
calcd for C H O
3
1
2
18
EtOAc, 1:1)/ oil 1645 2.00 (m, 2H), 1.90 (br s, 1H), 1.80– 135.5, 84.3, 80.7,
210.1256. Found:
210.1262
1
3
.50 (m, 4H), 1.38 (s, 3H), 1.33 (s,
H)
52.6, 22.5, 22.0,
21.9, 21.4, 19.5,
1
5.6
8
9
b
b
0.58 (EtOAc)/ 3401, 1709, 5.87 (q, 1H, J = 1.4), 3.84 (br s, 1H), 207.5, 178.7,
calcd for C H O
3
182.0945. Found:
182.0944
1
0
14
oil
1618
3.65 (br s, 1H), 2.22–2.12 (m, 1H),
127.2, 77.7, 76.9,
32.2, 30.8, 19.9,
19.8, 14.4
2
.07 (d, 3H, J = 1.4), 1.78–1.45 (m,
7
H)
0.50 (EtOAc)/ 3383, 3310, 5.89 (q, 1H, J = 1.5), 2.16–1.94 (m,
205.9, 175.7,
Calcd for
solid (mp 152– 1709, 1607 1H), 2.11 (d, 3H, J = 1.5), 1.83 (br s, 128.4, 79.0, 77.9, C H O : C,
1
0
14
3
153°C)
1Hs), 1.83–1.58 (m, 7H), 1.45 (br s, 24.9, 24.1, 19.6,
H) 18.6, 14.2
65.92; H, 7.74.
Found: C, 65.82;
H, 7.75
1
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent Trapping of Photochemically Generated Pyran-4-one-Derived Oxyallyls
1273
Table Photoproducts from Solvent Trapping of 2b–f (continued)
Product R /phys. descr. IR (cm ) 1H NMR
–
1
a
13C NMR
b
EA (%)
HRMS (m/z)
calcd for C H O
3
196.1099. Found:
196.1103
f
8c
0.49 (hex–
EtOAc, 1:1)/
gum
3410, 1705, 5.93 (q, 1H, J = 1.3), 3.68 (br s, 1H), 208.1, 181.6,
1
1
16
1624
3.24 (br s, 1H), 2.10 (d, 3H, J = 1.3), 127.4, 81.4, 78.6,
2.02 (dd, 1H, J = 13.6, 9.2), 1.85 (dd, 34.9, 34.3, 30.6,
1
1
H, J = 13.6, 8.9), 1.80–1.51 (m, 5H), 22.8, 22.6, 14.5
.45–1.28 (m, 3H)
9c
0.41 (hex–
3399, 3337, 5.80 (q, 1H, J = 1.4), 2.07 (d, 3H,
209.4, 179.9,
Calcd for
EtOAc, 1:1)/
solid (mp 172–
1701, 1618 J = 1.4), 2.05–1.90 (m, 1H), 1.89–1.65 127.5, 84.1, 81.8, C H O : C,
11 16 3
(m, 11H)
29.9, 27.3, 26.4,
26.3, 26.0, 14.1
67.32; H, 8.22.
Found: C, 67.28;
H, 8.20
174°C)
1
8
0c
0.15 (hex–
EtOAc, 1:1)/
solid (mp 98–
3400, 1701, 4.28 (s, 1H), 3.91 (br s, 1H), 3.36 (br 202.9, 176.5,
1638 s, 1H), 2.62 (ddd, 1H, J = 16.3, 8.2, 139.1, 82.1, 79.0,
2.9), 2.48 (ddd, 1H, J = 16.3, 7.9, 3.2), 31.2, 27.3, 26.5,
2.38–2.20 (m, 2H), 1.84–1.70 (m, 26.2, 23.2, 22.6
H), 1.64–1.52 (m, 2H), 1.56–1.40
m, 2H), 1.29 (s, 3H)
calcd for C H O
3
196.1099. Found:
196.1093
1
1
16
101°C)
2
(
d
0.53 (hex–
EtOAc, 1:1)/
gum
3342, 1713 5.87 (q, 1H, J = 1.5), 4.77 (br s, 1H), 206.4, 181.2,
4.02 (br s, 1H), 2.08 (d, 3H, J = 1.5), 127.3, 81.3, 78.9,
1.89–1.80 (m, 2H), 1.73–1.60 (m,
H), 1.54–1.39 (m, 4H), 1.29–1.24
32.6, 28.9, 26.2,
25.6, 24.4, 23.4,
14.1 (125 MHz,
acetone-d6)
4
6
(
m, 2H) (500 MHz, d acetone)
9
8
d
f
0.63 (hex–
EtOAc, 1:1)/
solid (mp 193–
3449, 1699, 5.68 (q, 1H, J = 1.4), 2.05 (d, 3H,
1640
210.1, 181.5,
calcd for C H O
3
210.1256. Found:
210.1253
1
2
18
J = 1.2), 2.01–1.70 (m, 12H), 1.61 (s, 127.2, 82.6, 79.3,
1H), 1.51 (s, 1H)
31.4, 29.3, 29.0,
28.4, 25.2, 24.6,
194°C)
1
4.5
0.50 (hex–
EtOAc, 1:1)/
solid (mp 198–
3590, 1709 5.85 (q, 1H, J = 1.5), 4.83 (br s, 1H), 204.4, 181.2,
3.86 (br s, 1H), 2.17 (d, 3H, J = 1.5), 127.7, 80.8, 79.5,
1.66–1.61 (m, 2H), 1.54–1.48 (m,
41.8, 30.3, 29.4,
201°C)
2H), 1.43–1.28 (m, 2H), 1.15 (d, 3H, 21.3, 16.8, 16.2
J = 6.5), 1.13–1.08 (m, 1H) (500
MHz, d acetone)
(125 MHz, ace-
tone-d6)
6
8
g
0.45 (hex–
3564, 1717 6.00 (q, 1H, J = 1.0), 4.72 (br s, 1H), 204.8, 177.4,
EtOAc, 1:1)/
oil
4.04 (br s, 1H), 2.18–2.13 (m, 1H),
2.10 (d, 3H, J = 1.0), 1.93 (dt, 1H,
J = 13.0, 5.5), 1.72–1.66 (m, 1H),
129.8, 81.7, 77.9,
c
36.7, 29.5, 27.9,
18.2, 17.8, 16.2
(125 MHz, ace-
tone-d6)
1.62–1.58 (m, 1H), 1.53–1.48 (m,
H), 1.32–1.23 (m, 1H), 1.22–1.15
1
(
m, 1H), 0.85 (d, 3H, J = 7.5) (500
6
MHz, d acetone)
9
f
0.45 (hex–
partial spectrum: 5.91 (q, 1H, J = 1.5), 206.2, 181.2,
3.31 (br s, 2H), 2.20 (d, 3H, J = 1.5), 127.3, 79.9, 79.1,
EtOAc, 1:1)/
c
oil
2.20–2.11 (m, 2H), 1.52–1.46 (m,
H), 1.48–1.46 (m, 1H), 1.26–1.22
m, 1H), 1.16 (d, 3H, J = 7.0) (500
MHz, CDCl3)
38.5, 30.1, 29.2,
19.2, 16.5, 16.2
(125 MHz, CDCl3)
1
(
a
b
c
1
All H NMR data were acquired at 300 MHz in CDCl unless otherwise indicated. Coupling constants (J) are given in Hz.
3
13
All C NMR data were acquired at 75 MHz in CDCl unless otherwise indicated.
3
Products 8g and 9f were isolated as an inseparable mixture. Careful iterative chromatography provided an enriched sample of 8g for IR and
NMR analysis. Partial NMR data for 9f were obtained from the mixture.
Methanol Trapping: 1-Hydroxy-8-methoxy-11-methyl-
bicyclo[6.3.0]undec-10-en-9-one (4d); Typical Procedure
Pyranone 2d (105 mg, 0.55 mmol) was dissolved in dry MeOH (95
mL) in a quartz tube equipped with a magnetic stirring bar and rub-
irradiated. Following complete consumption of 2d (1.5 h; deter-
mined by TLC), the reaction mixture was concentrated and the res-
idue was purified by flash chromatography (silica gel; 2 cm 15 cm
column; Et O–CH Cl –hexanes, 2:1:1) to give 72 mg (59%) of 4d
2
2
2
ber septum. The solution was purged with a stream of dry N and
as a pale yellow oil. See Table for characterization data.
2
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York

1
274
M. Fleming et al.
PAPER
Aqueous Trapping: 1,8-Dihydroxy-11-methylbicyclo-
6.3.0]undec-10-en-9-one (9d); Typical Procedure
Pyran-4-one 2d (50 mg, 0.28 mmol) was dissolved in a 10% solu-
(8) For an earlier report of in situ Norrish type II cleavage in a
similar system, see: Keil, E. B.; Pavlik, J. W. J. Heterocycl.
Chem. 1976, 13, 1149.
[
tion of H SO (50 mL) in a polished quartz tube equipped with a
magnetic stirring bar and rubber septum. The solution was purged
(9) Barltrop, J. A.; Barrett, J. C.; Carder, R. W.; Day, A. C.;
Harding, J. R.; Long, W. E.; Samuel, C. J. J. Am. Chem. Soc.
1979, 101, 7510.
2
4
with a stream of dry N and irradiated for 1.5 h. The resulting solu-
2
tion was neutralized with solid Na CO and extracted with EtOAc
(10) Pavlik, J. W.; Spada, A. P.; Snead, T. E. J. Org. Chem. 1985,
50, 3046.
(11) Molecular mechanics calculations (AM1)indicate that cis-
isomer 8b is more stable than trans-isomer 9b by as much as
12 kcal/mol.
2
3
(
(
2
100 mL). The organic layers were combined and dried
MgSO ), then concentrated to give a yellow oil. Purification via ra-
4
dial disk chromatography (silica gel, 1 mm plate; EtOAc–hexanes,
1
8
:4) gave 6 mg (10%) of 9d as a white paste and 24 mg (41%) of
d as a white solid. See Table for characterization data.
(12) In contrast, trans-isomers 9c and 9d did not undergo any
isomerization under the reaction conditions.
(
13) X-ray diffraction data for 4e, 8d and 8f have been deposited
References and Notes
with the Cambridge Crystallographic Data Centre
(
deposition numbers CCDC 158715, CCDC 158907 and
(
1) (a) Zimmerman, H. E.; Lynch, D. C. J. Am. Chem. Soc.
CCDC 158908, respectively).
1985, 107, 7745. (b) Nuss, J. M.; West, F. G. In The
(
(
(
14) Hydroxyl proton assignments were confirmed by D O
2
Chemistry of Dienes and Polyenes; Rappoport, Z., Ed.;
Wiley: Chichester, 1997, 263–324.
exchange. In acetone-d , the hydroxyl protons of both cis-8
and trans-9 all appeared downfield of 4 ppm.
15) Higher concentrations of H SO led to variable product
ratios, presumably via acid-catalyzed isomerization as noted
with 8b/9b.
16) The UV absorbance data for known compounds 2a,b have
6
(
(
2) West, F. G. In Advances in Cycloaddition, Vol. 4; Lautens,
M., Ed.; JAI Press: Greenwich, CT, 1997, 1–40.
3) (a) Barltrop, J. A.; Day, A. C.; Samuel, C. J. J. Am. Chem.
Soc. 1979, 101, 7521. (b) Pavlik, J. W.; Keil, E. B.; Sullivan,
E. L. J. Heterocycl. Chem. 1992, 29, 1829. (c) Pavlik, J.
W.; Kirincich, S. J.; Pires, R. M. J. Heterocycl. Chem. 1991,
2
4
been previously reported: 2a (MeOH):
252 nm ( = 12.6
max
3
–1 –1
5
3
1
0 cm M ); 2b (MeOH):
252 nm ( = 13.6 10
max
28, 537.
–
1
–1
5
3
–1 –1 17
cm M ); 2b (EtOH):
The data for 2c–f are: 2c (MeOH):
1
(
(
(
252 ( = 5.6 10 cm M ).
max
(
(
(
4) West, F. G.; Fisher, P. V.; Gunawardena, G. U.; Mitchell, S.
256 nm ( = 10.2
256 nm
max
Tetrahedron Lett. 1993, 34, 4583.
5) Hünig, S.; Benzing, E.; Hübner, K. Chem. Ber. 1961, 94,
3
–1 –1
0 cm M ); 2d (MeOH):
max
–1 –1
–
5
3
10 M; = 11.4 10 cm M ); 2e (MeOH):
256 nm
max
4
86.
6) (a) Coleman, R. S.; Grant, E. B. Tetrahedron Lett. 1990, 31,
677. (b) Sato, M.; Ogasawara, H.; Kato, K.; Sakai, M.;
–
5
3
–1 –1
10 M; = 11.1 10 cm M ); 2f (EtOH):
262 nm
max
3
–1 –1
= 7.5 10 cm M .
3
(
17) Takeuchi, N.; Nakagawa, H.; Kamisato, M.; Tobinaga, S.
Kato, T. Chem. Pharm. Bull. 1983, 31, 4300.
Chem. Pharm. Bull. 1980, 2460.
(
7) Notably, intermolecular trapping of non-photochemically
generated oxyallyl cations seems to favor attack at the less
substituted terminus: (a) Noyori, R.; Shimizu, F.; Fukuta,
K.; Takaya, H.; Hayakawa, Y. J. Am. Chem. Soc. 1977, 99,
5196. (b) Giese, S.; Kastrup, L.; Stiens, D.; West, F. G.
Angew. Chem. Int. Ed. 2000, 40, 1970. (c) Giese, S.; West,
F. G. Tetrahedron 2000, 56, 10221.
Synthesis 2001, No. 8, 1268–1274 ISSN 0039-7881 © Thieme Stuttgart · New York