A two-step conversion of α,β-unsaturated ketones to their α-carbalkoxy or α-carbamoyl derivatives

Article abstract of DOI:10.1021/jo020081c

Several enones are converted into their α-iodo derivatives in excellent yields and carbonylated with palladium catalysis in the presence of alcohol or amines to the α-carbonyl enones in satisfactory yields.

Full text of DOI:10.1021/jo020081c

CHART 1
A Tw o-Step Con ver sion of r,â-Un sa tu r a ted
Keton es to Th eir r-Ca r ba lk oxy or
r-Ca r ba m oyl Der iva tives
Fabio E. S. Souza, Hamish S. Sutherland,
Rina Carlini, and Russell Rodrigo*
Guelph-Waterloo Centre for Chemistry and Biochemistry,
Department of Chemistry, University of Waterloo,
Waterloo, Ontario, Canada N2L 3G1
rrodrigo@uwaterloo.ca
Received February 4, 2002
Abstr a ct: Several enones are converted into their R-iodo
derivatives in excellent yields and carbonylated with pal-
ladium catalysis in the presence of alcohol or amines to the
R-carbonyl enones in satisfactory yields.
enone in good yield, we set out to devise a synthetically
useful conversion of 1a to 1d in order to improve the
electrophilicity of the enone double bond. Treatment of
1a with iodine and pyridine in dichloromethane6,7 pro-
duced the R-iodoenone 1b in excellent yield (99%).
Lithium-iodine exchange could not be successfully ac-
complished with n-butyl or tert-butyllithium at temper-
atures between -95 and -78 °C, but the Heck carbalkox-
ylation applied previously to vinyl iodides8 and 5-iodo-
2,3-dihydropyridones9 was an effective alternative. Treat-
ment of 1b with methanol, 2,6-lutidine, palladium acetate
and 1,3-bis(diphenylphosphino)propane (5 mol % each)
in THF under carbon monoxide (750 psi) at 60 °C for 48
h produced a 62% yield of the derived R-carbomethoxy-
enone 1d .10 The reaction was plagued by irreproducible
yields however, and this was eventually traced to the
sodium thiosulfate that was used in the previous step
for destroying excess iodine. Evidently, very small resi-
dues of sulfur compounds, contaminating the iodoenone,
poison the palladium catalyst and reduce its efficacy.
Using ascorbic acid11 in place of the thiosulfate solved
this problem and 1a could be converted to 1d in two steps
in reproducibly good yields (>60%). The Lewis acid
catalyzed cycloaddition of 1d with methyl (E)-4,6-hepta-
dienoate did proceed with the desired regioselectivity to
produce 4d , but in an unacceptably low yield (12-15%)
The notoriously poor dienophilic character of cyclohex-
enones has curtailed their use in natural products
synthesis. This deficiency has been addressed, by Liu and
co-workers in particular, by the placement of an electron-
withdrawing group (EWG) at C-2 of the cycloalkenone.
They have prepared 2-carbalkoxy- and 2-cyanocycloalk-
enones from the corresponding cycloalkanones via enolate
quenching and selenoxide elimination and convincingly
demonstrated their value as dienophiles for the construc-
tion of many terpenoid ring systems.1,2
In the course of synthetic studies related to the
pentacyclic fungal metabolites of the viridin group,3 we
were able to develop a two-step synthesis of the tricycle
1a that represents rings A, B, and E of these compounds.
Although the cyclohexenone moiety of 1a added readily
to reactive isobenzofuranoid dienes and was a valuable
dienophile for the synthesis of pentacyclic marine quino-
nes,4 it was of little use in reactions with simple dienes
with or without Lewis acid catalysis. For example, the
reaction of 1a with methyl (E)-4,6-heptadienoate cata-
lyzed by 10 mol % of aluminum chloride at room tem-
perature for 4 days led to a 7% yield of an adduct whose
structure 2 was confirmed by X-ray crystallography.
Under other conditions with various Lewis acids, solvents
and temperatures the only identifiable product obtained
was dienone 3 (the putative precursor of 2) and its 2,2a
dehydro derivative, with none of the desired adduct 4a
at all (Chart 1).
(6) J ohnson, C. R.; Adams, J . P.; Braun, M. P.; Senanayake, C. B.
W.; Wovkulich, P.; Uskokovic, M. R. Tetrahedron Lett. 1992, 33, 917-
918.
(7) Djuardi, E.; Bovonosombat, P.; McNelis, E. Synth. Commun.
1997, 27, 2497-2503.
(8) (a) Colquhoun, H. M.; Thompson, D. J .; Twigg, M. V. Carbony-
lation: Direct Synthesis of Carbonyl Compounds; Plenum Press: New
York, 1991. (b) Laio, B. Q.; Negishi, E. Heterocycles 2000, 52, 1241-
1249.
(9) Comins, D. L.; J oseph, S. P.; Chen, X. Tetrahedron Lett. 1995,
36, 9141-9144.
(10) The carbomethoxylation of 1b was successfully accomplished
in a pressure bomb equipped with a glass liner, using CO pressures
ranging from 50 to 1000 psi, with the best results being obtained with
750 psi. All other reactions were conducted under the same conditions,
without any optimization for individual substrates.
(11) We thank Rosana Souza for this valuable suggestion. Ascorbic
acid is often used for reducing halogens in water prior to analysis. (a)
Verma, K. K.; J ain, A.; Verma, A. Anal. Chem. 1992, 64, 1484-1489.
(b) Shin, H.-S.; Oh-Shin, Y.-S.; Kim, J .-H.; Ryu, J .-K. J . Chromatogr.
A 1996, 732, 327-333.
Since we were unable to adapt the method5 used for
preparing 1a to the synthesis of an R-EWG substituted
(1) (a) Liu, H.-J .; Tran, D. D. P. Tetrahedron Lett. 1999, 40, 3827-
3830. (b) Liu, H.-J .; Shia, K.-S. Tetrahedron 1998, 54, 13449-13458.
(c) Liu, H.-J .; Shia, K.-S.; Han, Y.; Sun, D.; Wang, Y. Can. J . Chem.
1997, 75, 646-655. (d) Liu, H.-J .; Browne, E. N. C.; Chew, S. Y. Can.
J . Chem. 1988, 66, 2345-2347.
(2) Zhu, J .-L.; Shia, K.-S.; Liu, H.-J . J . Chem. Soc., Chem. Commun.
2000, 1599-1600.
(3) Souza, F. E. S.; Rodrigo, R. J . Chem. Soc., Chem. Commun. 1999,
1947-1948.
(4) Sutherland, H. S.; Higgs, K. C.; Taylor, N. J .; Rodrigo, R.
Tetrahedron 2001, 57, 309-317.
(5) Carlini, R.; Higgs, K.; Older, C.; Randhawa, S.; Rodrigo, R. J .
Org. Chem. 1997, 62, 2330-2331.
10.1021/jo020081c CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/15/2002
6568
J . Org. Chem. 2002, 67, 6568-6570

TABLE 1. Ca r bon yla tion of r-Ha loen on es in th e
The dark mixture was stirred for 3 h at 0 °C, and then diluted
with ether. The ether extract was washed sequentially with cold
HCl (1 M), saturated ascorbic acid solution, and water and then
dried (MgSO4), filtered, and concentrated under reduced pres-
sure. Flash chromatography (1:1 ether-hexane) afforded iodide
1b as a yellow solid (0.148 g, quantitative). Mp: 81-82 °C. IR:
P r esen ce of Alcoh ol a n d Am in e Nu cleop h iles
entry substrate nucleophile product
isolated yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1b
1b
1b
1b
5b
5b
5b
5b
6b
6b
6c
6c
7b
7c
8b
MeOH
1d
1g
1h
1i
5d
5f
62
62
33
55
68
62
64
77
55
58
29
28
42
13
51
HNEt2
n-BuNH2
morpholine
MeOH
n-BuOH
HNEt2
morpholine
MeOH
EtOH
MeOH
EtOH
MeOH
2930, 1700, 1454, 1053 cm-1 1H NMR: 1.25 (s, 3H, R-CH3),
.
1.89-2.08 (m, 2H, H-5), 2.64 (dd, J ) 0.9, 9.2 Hz, 1H, H-8b),
3.02 (m, 1H, H-2a), 3.26 (s, 3H, R-OCH3), 3.78 (dd, J ) 3.1, 8.6
Hz, 1H, H-2), 4.15 (dd, J ) 7.3, 8.6 Hz, 1H, H-2), 5.77 (br s, 2H,
H-3 and H-4), 7.35 (s, 1H, H-6). 13C NMR: 28.1, 37.3, 37.6, 39.5,
51.1, 53.8, 73.0, 98.1, 102.7, 125.6, 129.4, 166.5, 186.3. Anal.
Calcd for C13H15O3I: C, 45.11; H, 4.37. Found: C, 45.23; H, 4.47.
Typ ica l P r oced u r e for th e Am in o- a n d Alk oxyca r bon y-
la tion of r-Ha loen on es: Syn th esis of 7-Ca r bom eth oxy-8a -
m eth oxy-5a-m eth yl-2a,5,5a,8,8a,8b-h exah ydr o-2H-n aph th o-
[1,8-bc]fu r a n -8-on e (1d ). To a solution of iodide 1b (401 mg,
1.16 mmol) in THF (30 mL) were added MeOH (250 µL), 2,6-
lutidine (300 µL), Pd(OAc)2 (14 mg, 0.06 mmol), and dppp (25
mg, 0.06 mmol), and the reaction mixture was placed under a
CO atmosphere (750 psi) in a pressure reactor, which was then
heated at 60 °C for 48 h. The resulting solution was diluted with
Et2O and washed with water. The aqueous layer was extracted
with Et2O, the combined organic phases were dried (Na2SO4),
and the solvent was removed under reduced pressure. Flash
chromatography (50% Et2O in hexane) gave 1d as a light yellow
solid (203 mg, 0.73 mmol, 63% yield). Mp: 80-82 °C. IR: 2952,
5g
5i
6d
6e
6d
6e
7d
7d
8d
MeOH
MeOH
and accompanied by much decomposition. This reaction
could not be used in a viable synthetic route to viridin,
but in view of the amply demonstrated value1,13 of
R-carbalkoxyenones in synthesis we set out to evaluate
the scope of the two step R-carbalkoxylation with several
enone bromides and iodides. The outcome of these
investigations is discussed below and summarized in
Table 1.
1744, 1722, 1436, 1275, 1131 cm-1 1H NMR: 1.25 (s, 3H,
.
R-CH3), 1.80 (br d, J ) 16.7 Hz, 1H, H-5), 2.02 (dd, J ) 4.4,
16.7 Hz, 1H, H-5), 2.57 (dd, J ) 1.3, 9.0 Hz, 1H, H-8b), 2.98 (m,
1H, H-2a), 3.25 (s, 3H, R-OCH3), 3.79 (s, 3H, R-CO2CH3), 3.86
(dd, J ) 1.8, 8.6 Hz, 1H, H-2), 4.13 (dd, J ) 6.6, 8.6 Hz, 1H,
H-2), 5.72 (br s, 2H, H-3 and H-4), 7.60 (s, 1H, H-6). 13C NMR:
27.3, 34.2, 36.4, 36.8, 50.4, 52.3, 53.9, 72.9, 105.2, 124.8, 128.4,
131.3, 163.6, 164.4, 188.3. HRMS (EI) m/z: required for C15H18O5
278.1154, found 278.1150. Anal. Calcd for C15H18O5: C, 64.74;
H, 6.52. Found: C, 64.60; H, 6.39.
Yields of R-haloenones were excellent in the cyclic
examples (5-7) but much less satisfactory with the
acyclic enones.7 Iodides gave better results in the carbon-
ylation than bromides (entries 11, 12, and 14) and
primary amines (entry 3) were inferior to secondary
amines in the reaction (entries 3, 4, 7, and 8). Thiols could
not be used in the reaction; the starting iodoenones were
recovered probably due to poisoning of the palladium
catalyst. The reaction failed with both 2-iodo and 2-iodo-
3-methyl cyclohexenones. Aromatization to phenolic prod-
ucts took place together with deiodination. This seems
to be the usual outcome12 with iodocyclohexenones that
do not contain a quaternary carbon atom in the ring.
Within these limitations our two-step R-carbalkoxylation
appears to be a convenient method that could be used
for improving the reactivity of enones in both cycloaddi-
tion and conjugate addition1a,13 processes. A particularly
good illustration of its value is found in a comparison of
it with the existing five-step method13,14 for converting
cyclopentenones 6a and 7a to their R-esters 6e and 7e,
respectively.
7-Diet h yla m in oca r b on yl-8a -m et h oxy-5a -m et h yl-2a ,5,-
5a ,8,8a ,8b-h exa h yd r o-2H-n a p h th o[1,8-bc]fu r a n -8-on e (1g)
was prepared from iodide 1b as a light brown solid. Mp: 55-58
°C. IR: 2972, 1692, 1635, 1458, 1433, 1049 cm-1. 1H NMR: 1.11
(t, J ) 7.1 Hz, 3H, R2NCH2CH3), 1.18 (t, J ) 7.1 Hz, 3H, R2-
NCH2CH3), 1.27 (s, 3H, R-CH3), 1.96 (br d, J ) 16.5 Hz, 1H,
H-5), 2.04 (br d, J ) 16.5 Hz, 1H, H-5), 2.65 (dd, J ) 0.9, 9.3
Hz, 1H, H-8b), 3.04 (m, 1H, H-2a), 3.20 (q, J ) 7.1 Hz, 2H, R2-
NCH2CH3), 3.32 (s, 3H, R-OCH3), 3.45 (m, 2H, R2NCH2CH3),
3.81 (dd, J ) 3.0, 8.6 Hz, 1H, H-2), 4.15 (dd, J ) 7.2, 8.6 Hz,
1H, H-2), 5.79 (m, 2H, H-3 and H-4), 6.75 (s, 1H, H-6). 13C
NMR: 12.8, 14.2, 28.1, 34.9, 37.2, 37.4, 39.2, 42.7, 50.6, 53.5,
72.9, 103.2, 125.6, 129.7, 136.6, 156.0, 165.4, 188.2. HRMS (EI)
m/z: required for C18H25NO4 319.1784, found 319.1799.
7-Bu tyla m in oca r bon yl-8a -m eth oxy-5a -m eth yl-2a ,5,5a ,8,-
8a ,8b-h exa h yd r o-2H-n a p h th o[1,8-bc]fu r a n -8-on e (1h ) was
prepared from iodide 1b as a light yellow solid. Mp: 61-62 °C.
IR: 3359, 2959, 1694, 1661, 1532, 1458, 1048 cm-1 1H NMR:
.
0.90 (t, J ) 7.3 Hz, 3H, RNH(CH2)3CH3), 1.26 (s, 3H, R-CH3),
1.34 (m, 2H, RNH(CH2)2CH2Me), 1.52 (m, 2H, RNHCH2CH2Et),
1.87 (br d, J ) 16.4 Hz, 1H, H-5), 2.03 (br d, J ) 16.4 Hz, 1H,
H-5), 2.58 (d, J ) 8.9 Hz, 1H, H-8b), 2.98 (m, 1H, H-2a), 3.25 (s,
3H, R-OCH3), 3.31 (m, 2H, RNHCH2Pr), 3.76 (dd, J ) 3.1, 8.5
Hz, 1H, H-2), 4.12 (dd, J ) 7.2, 8.5 Hz, 1H, H-2), 5.74 (m, 2H,
H-3 and H-4), 7.85 (s, 1H, H-6), 8.09 (br s, 1H, RNHBu). 13C
NMR: 13.8, 20.2, 28.1, 31.4, 34.8, 37.2, 37.5, 39.3, 50.5, 52.9,
73.2, 104.4, 125.7, 129.2, 130.0, 162.0, 166.9, 192.2. HRMS (EI)
m/z: required for C18H25NO4 319.1784, found 319.1770.
8a -Meth oxy-5a -m eth yl-7-m or p h olin oca r bon yl-2a ,5,5a ,8,-
8a ,8b-h exa h yd r o-2H-n a p h th o[1,8-bc]fu r a n -8-on e (1i) was
prepared from iodide 1b as a light brown oil. IR: 2963, 1692,
1639, 1435, 1275, 1114 cm-1. 1H NMR: 1.20 (s, 3H, R-CH3), 1.85
(br d, J ) 16.5 Hz, 1H, H-5), 2.01 (br d, J ) 16.5 Hz, 1H, H-5),
2.58 (d, J ) 9.0 Hz, 1H, H-8b), 2.99 (m, 1H, H-2a), 3.21 (s, 5H,
R-OCH3, overlapping RN(CH2CH2)2O), 3.49-3.70 (m, 6H, RCON-
(CH2CH2)2O), 3.75 (dd, J ) 2.8, 8.5 Hz, 1H, H-2), 4.05 (dd, J )
7.2, 8.5 Hz, 1H, H-2), 5.72 (m, 2H, H-3 and H-4), 6.86 (s, 1H,
Exp er im en ta l Section 15
7-I o d o -8a -m e t h o x y -5a -m e t h y l-2a ,5,5a ,8,8a ,8b -h e x a -
h yd r o-2H-n a p h th o[1,8-bc]fu r a n -8-on e (1b). A solution of
naphthofuran 1a (0.094 g, 0.42 mmol) in 10 mL of 1:1 pyridine
and CCl4 was cooled to 0 °C. A solution of iodine (0.453 g, 1.79
mmol) in 5 mL 1:1 pyridine-CCl4 was slowly added dropwise.
(12) J ohnson, C. R.; Adams, J . P.; Collins, M. A. J . Chem. Soc.,
Perkins Trans. 1 1993, 1-2.
(13) Hua, D. H.; Venkataraman, S.; Chan-Yu-King, R.; Paukstelis,
J . V. J . Am. Chem. Soc. 1988, 110, 4741-4748.
(14) (a) Guaciaro, M. A.; Wovkulich, P. M.; Smith, A. B., III.
Tetrahedron Lett. 1978, 4661-4664. (b) Smith, A. B., III; Branca, S.
J .; Guaciaro, M. A.; Wovkulich, P. M.; Korn, A. Org. Synth. 1983, 61,
65-70.
(15) For general experimental details see ref 4. Assignments of 1H
NMR signals were made with the aid of 2D and decoupling methods
and by comparisons with spectra of similar compounds prepared in
our laboratory.
J . Org. Chem, Vol. 67, No. 18, 2002 6569

H-6). 13C NMR: 27.8, 35.0, 37.1, 37.3, 42.2, 47.0, 50.2, 53.2, 66.5,
66.7, 73.0, 103.3, 125.4, 129.4, 135.4, 158.7, 164.3, 187.6. HRMS
(EI) m/z: required for C18H23NO5 333.1576, found 333.1564.
Reaction of 1a with Meth yl (E)-4,6-Heptadien oate. Naph-
thofuranone 1a (0.21 g, 0.93 mmol) was mixed with freshly
distilled methyl (E)-4,6-heptadienoate (1.3 g, 9.3 mmol) in dry
CH2Cl2 (5 mL), and to the resulting solution was added AlCl3
(14 mg, 0.1 mmol). After being stirred at room temperature for
4 days, the reaction was quenched with water, and the products
were extracted into CH2Cl2. The organic extract was washed
with brine, dried (Na2SO4), and concentrated under reduced
pressure. Flash chromatography (20% EtOAc in hexane) led to
the isolation of 3 (51 mg, 29% yield), its 2,2a-dehydro derivative
(15 mg, 8% yield), and adduct 2 (22 mg, 7% yield), all of which
crystallized from ether to give colorless needles, colorless plates,
and shiny plates, respectively. Analytical data for 2: 1H NMR:
1.18 (s, 3H, R-CH3), 1.61 (m, 1H, R-CH2CH2CO2Me), 1.89), 1.61
(m, 1H, R-CH2CH2CO2Me), 1.95 (dd, J ) 6.35, 17.3 Hz, 1H, H-8),
2.01 (dd, J ) 7.0, 15.4 Hz, 1H, H-1), 2.19 (ddd, J ) 2.9, 5.3, 17.3
Hz, 1H, H-8), 2.41 (t, J ) 8.0 Hz, 2H, R-CH2CH2CO2Me), 2.45
(dt, J ) 2.7, 15.4 Hz, 1H, H-1), 2.67 (m, 1H, H-11), 2.88 (ddd, J
) 3.0, 6.5, 9.6 Hz, 1H, H-4), 3.28 (dd, J ) 8.7, 11.4 Hz, 1H,
R-CH2O-R′), 3.65 (s, 3H, R-CO2CH3), 3.91 (t, J ) 8.7 Hz, 1H,
R-CH2O-R′), 5.61 (dt, J ) 3.0, 10.0 Hz, 1H, H-10), 5.81 (m, 1H,
H-9), 5.96 (ddd, J ) 2.8, 6.9, 9.6 Hz, 1H, H-2), 6.16 (ddd, J )
2.9, 6.6, 9.6 Hz, 1H, H-3), 6.20 (d, J ) 10 Hz, 1H, H-6), 6.68 (d,
J ) 10 Hz, 1H, H-7). 13C NMR: 25.1, 29.9, 30.3, 33.4, 36.5, 36.7,
39.6, 51.4, 51.5, 52.1, 70.4, 90.6, 125.6, 126.3, 126.8, 131.1, 132.1,
160.3, 173.9, 193.1. HRMS (EI) m/z: required for C20H24O4
329.1753, found 329.1735. Anal. Calcd for C20H24O4: C, 73.15;
H, 7.37. Found: C, 72.90; H, 7.28. Analytical data for 3. Mp:
2-Diet h yla m in oca r b on yl-4,4-d im et h yl-2-cycloh exen -1-
on e (5g) was prepared from iodide 5b7 as a light brown oil. IR:
1
2964, 1683, 1636, 1430, 1362, 1284 cm-1. H NMR: 1.05 (t, J )
7.1 Hz, 3H, R-CON(CH2CH3)2), 1.14 (t, J ) 7.1 Hz, 3H, R-CON-
(CH2CH3)2), 1.18 (s, 6H, R-CH3), 1.88 (m, 2H, H-5), 2.49 (m, 2H,
H-6), 3.09 (q, J ) 7.1 Hz, 2H, R-CON(CH2CH3)2), 3.40 (q, J )
7.1 Hz, 2H, R-CON(CH2CH3)2), 6.63 (s, 1H, H-3). 13C NMR: 12.9,
14.1, 27.6, 32.9, 34.4, 35.7, 39.2, 43.1, 135.9, 156.4, 166.9, 195.7.
HRMS (EI) m/z: required for C13H21NO2 223.1572, found
223.1557.
4,4-Dim e t h yl-2-m or p h olin oca r b on yl-2-cycloh e xe n -1-
on e (5i) was prepared from iodide 5b7 as a yellow oil. IR: 2960,
1682, 1634, 1434, 1360, 1114 cm-1 1H NMR: 1.20 (s, 6H,
.
R-CH3), 1.90 (t, J ) 6.8 Hz, 2H, H-5), 2.51 (t, J ) 6.8 Hz, 2H,
H-6), 3.20 (t, J ) 4.8 Hz, 2H, RN(CH2CH2)2O), 3.62 (t, J ) 4.8
Hz, 2H, RN(CH2CH2)2O), 3.68 (br s, 4H, RN(CH2CH2)2O), 6.76
(s, 1H, H-3). 13C NMR: 27.4, 33.0, 34.3, 35.5, 42.0, 47.4, 66.6,
66.7, 134.9, 158.4, 165.7, 195.3. HRMS (EI) m/z: required for
C13H19NO3 237.1365, found 237.1364.
2-Ca r bom eth oxy-2-cyclop en ten -1-on e (6d ) was prepared
from either iodide 6b6 or bromide 6c14 as a light yellow oil, and
the 1H NMR spectrum recorded was in complete agreement with
the data reported in the literature.16 1H NMR: 2.50 (m, 2H, H-4),
2.71 (m, 2H, H-5), 3.79 (s, 3H, R-CO2CH3), 8.41 (t, J ) 3.2 Hz,
1H, H-3).
2-Ca r beth oxy-2-cyclop en ten -1-on e (6e) was prepared from
either iodide 6b6 or bromide 6c14 as a yellow oil, and the 1H NMR
spectrum recorded was in complete agreement with the data
reported in the literature.16 1H NMR: 1.35 (t, J ) 6.9 Hz, 3H,
R-CH3), 2.56 (m, 2H, H-4), 2.75 (m, 2H, H-5), 4.30 (q, J ) 6.9
Hz, 2H, R-CO2CH2Me), 8.40 (t, J ) 3.3 Hz, 1H, H-3).
1
86-88 °C. IR: 2878, 1680, 1646, 1130 cm-1. H NMR: 1.28 (s,
2-Ca r bom eth oxy-3-m eth yl-2-cyclop en ten -1-on e (7d ) was
3H, R-CH3), 2.09 (dm, J ) 17.9 Hz, 1H, H-5), 2.32 (dm, J ) 17.9
Hz, 1H, H-5), 3.91 (m, 1H, H-2a), 4.03 (dd, J ) 8.3, 10.3 Hz, 1H,
H-2), 4.84 (dd, J ) 8.3, 9.9 Hz, 1H, H-2), 5.75 (br s, 2H, H-3 and
H-4), 6.20 (d, J ) 9.8 Hz, 1H, H-7), 6.90 (d, J ) 9.8 Hz, 1H,
H-6). 13C NMR: 21.6, 37.8, 39.6, 40.6, 76.2, 125.5, 126.4, 128.5,
139.7, 147.4, 154.9, 177.7. HRMS (EI) m/z: required for C12H12O2
188.0837, found 188.0848. Anal. Calcd for C12H12O2: C, 76.57;
H, 6.43. Found: C, 76.36; H, 6.23. Analytical data for 5a -
m eth yl-5a ,8-d ih yd r o-5H-n a p h th o[1,8-bc]fu r a n -8-on e (2,2a-
prepared either from iodide 7b6 or bromide 7c14 as a yellow oil,
1
and the H NMR spectrum recorded was in complete agreement
with the data reported in the literature.17 1H NMR: 2.39 (s, 3H,
R-CH3), 2.52 (m, 2H, H-4), 2.70 (m, 2H, H-5), 3.85 (s, 3H,
R-CO2CH3).
(Z)-3-Car bom eth oxy-4-ph en yl-3-bu ten -2-on e (8d) was pre-
pared from iodide 8b6 as a light orange oil, and the 1H NMR
spectrum recorded was in complete agreement with the data
reported in the literature.18 1H NMR (200 MHz, CDCl3) δ: 2.42
(s, 3H, R-COCH3), 3.84 (s, 3H, R-CO2CH3), 7.42 (m, 5H, R-C6H5),
7.58 (s, 1H, H-3).
dehydro derivative of 3). IR: 1656, 1446, 1066, 826, 668 cm-1
.
1H NMR: 1.36 (s, 3H, R-CH3), 2.30 (dm, J ) 17.3 Hz, 1H, H-5),
2.46 (ddd, J ) 0.9, 5.8, 17.3 Hz, 1H, H-5), 5.94 (ddd, J ) 2.6,
5.8, 9.7 Hz, 1H, H-4), 6.24 (d, J ) 9.7 Hz, 1H, H-7), 6.54 (ddd, J
) 0.9, 3.0, 9.7 Hz, 1H, H-4), 6.96 (d, J ) 9.7 Hz, 1H, H-6), 7.49
(s, 1H, H-2). 13C NMR: 25.8, 33.4, 36.3, 118.1, 120.8, 127.9,
130.1, 140.7, 144.2, 144.8, 152.7, 174.3. HRMS (EI) m/z: required
for C12H10O2 186.0681, found 186.0686.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada for sup-
port of this work.
2-Ca r bom eth oxy-4,4-d im eth yl-2-cycloh exen -1-on e (5d )
1
was prepared from iodide 5b7 as a colorless oil, and the H NMR
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data for adduct 2 and copies of 1H NMR spectra of
1g-i, 5f,g,i, and the 2,2a-dehydro derivative of 3. This
material is available free of charge via the Internet at
http://pubs.acs.org.
spectrum recorded was in complete agreement with the data
reported in the literature.1d 1H NMR: 1.24 (s, 6H, R-CH3), 1.90
(m, 2H, H-5), 2.54 (m, 2H, H-6), 3.80 (s, 3H, R-CO2CH3), 7.36 (t,
J ) 1.0 Hz, 1H, H-3).
2-Ca r bobu toxy-4,4-d im eth yl-2-cycloh exen -1-on e (5f) was
prepared from iodide 5b7 as a yellow oil. IR: 2961, 1741, 1713,
1690, 1467, 1272 cm-1. 1H NMR: 0.93 (t, J ) 7.2 Hz, 3H, R-CO2-
(CH2)3CH3), 1.22 (s, 6H, R-CH3), 1.42 (m, 2H, R-CO2(CH2)2CH2-
Me), 1.63 (m, 2H, R-CO2CH2CH2Et), 1.88 (m, 2H, H-5), 2.52 (m,
2H, H-6), 4.18 (t, J ) 6.7 Hz, 2H, R-CO2CH2Pr), 7.27 (t, J ) 0.9
Hz, 1H, H-3). 13C NMR: 13.6, 19.0, 27.3, 30.5, 33.3, 35.1, 35.3,
65.0, 130.3, 163.6, 164.9, 194.4. HRMS (EI) m/z: required for
C13H20O3 224.1412, found 224.1409.
J O020081C
(16) Bernardi, A.; Karamfilova, K.; Sanguinetti, S.; Scolastico, C.
Tetrahedron 1997, 53, 13009-13026.
(17) Taber, D. F.; Amedio, J . C., J r.; Sherril, R. G. J . Org. Chem.
1986, 51, 3382-3384.
(18) Bellina, F.; Carpita, A.; Ciucci, D.; De Santis, M.; Rossi, R.
Tetrahedron 1993, 49, 4677-4698.
6570 J . Org. Chem., Vol. 67, No. 18, 2002