X=Y-ZH Systems as potential 1,3-dipoles. Part 52: Fused-ring forming electrophile induced oxime→nitrone→cycloaddition cascades

Article abstract of DOI:10.1016/S0040-4020(01)00661-5

Electrophile induced cyclisation of oximes onto endocyclic alkenes and exo-methylene cycloalkanes occurs stereo- and regio-specifically generating cis-fused bicyclic nitrones in good yield. Subsequent facially selective cycloaddition with N-methylmaleimid

Full text of DOI:10.1016/S0040-4020(01)00661-5

TETRAHEDRON
Pergamon
Tetrahedron 57 32001) 7035±7045
XˆY±ZH Systems as potential 1,3-dipoles. Part 52:
Fused-ring forming electrophile induced
oxime!nitrone!cycloaddition cascadesq
H. Ali Dondas, Ronald Griggp and Sylvie Thibault
School of Chemistry, The University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK
Received 24 April 2001;revised 24 May 2001;accepted 14 June 2001
AbstractÐElectrophile induced cyclisation of oximes onto endocyclic alkenes and exo-methylene cycloalkanes occurs stereo- and regio-
speci®cally generating cis-fused bicyclic nitrones in good yield. Subsequent facially selective cycloaddition with N-methylmaleimide occurs
in good yield. The sequence may be carried out as a one-pot procedure and results in the formation of 4 bonds, 2 rings and 6 stereocentres.
q 2001 Elsevier Science Ltd. All rights reserved.
1. Background
2. Cyclisation ofoximes onto endocyclic alkenes
As part of an ongoing research program developing new
cascade reactions we have recently reported a range
of electrophile induced oxime!nitrone!cycloaddition
cascades2 involving stereo- and regio-speci®c spiro- and
bridged-ring forming cyclisation of oximes onto proximate
alkenes.3,4
Aldehyde 32a) was prepared by the literature procedure5
whilst aldehydes 32b±e) were prepared as outlined in
Scheme 1.6 Aldehydes 32a±e) were converted to their
oximes 33a±e) which were obtained as 1:1 mixtures of
E/Z-isomers 3Scheme 2). The reaction of 33a) with PhSeBr
3MeCN, rt, 1 h.) gave the nitrone salt 34a EˆPhSe). The
nitrone was liberated from the salt by treatment with Hunig's
base and trapped in situ in a 1,3-dipolar cycloaddition reac-
tion with N-methylmaleimide 3NMM) 3MeCN, rt, 10 h).
The cycloaddition occured with high facial selectivity and
the product comprised a separable 1:1 mixture 370%) of the
exo-35a) and endo-36a) cycloadducts whose stereochemistry
We now report that oximes cyclise onto endocyclic alkenes
and exo-methylene cycloalkanes in the presence of electro-
philes such as PhSeBr and N-bromosuccinimide 3NBS) to
generate cis-fused bicyclic nitrones which can be trapped in
1,3-dipolar cycloaddition reactions.
Scheme 1. 3i) NBS/AIBN;3ii) Mg/THF;3iii) 3-bromocycloalkene/rt/3 h;3iv) 2N H 2SO4/3:1 v/v CH3CN±H2O/rt/20 h.
q See Ref. 1 for Part 51.
Keywords: cycloalkenes; exo- and endo-trig cyclisation;onium ions;cyclic nitrones;1,3-dipolar cycloaddition;facial selectivity.
Corresponding author. Tel./fax: 144-113-2336501;e-mail: r.grigg@chem.leeds.ac.uk
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020301)00661-5

7036
H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
Scheme 2.
was assigned from n.O.e data and 2D-COSY studies. Both
cycloadducts arise from cycloaddition to the less hindered
outer surface of the bowl-shaped nitrone i.e. syn to the ring
junction H-atoms. The PhSe groups of the cycloadducts 35a)
and 36a) were removed using Bu3SnH/AIBN affording 37a)
and 38a) in 79±81% yield 3Scheme 2).
2.1. Br1 as electrophile
The reaction of 33a) with NBS 3CH2Cl2, 258C, 2 h) afforded
the nitrone free base of 34a, EˆBr) in essentially quantita-
tive yield with the succinimide acting as a proton scavenger.
Cycloaddition 3NMM, benzene, 608C, 13 h) furnished a 1:1
mixture 361%) of exo-35f) and endo-36f) cycloadducts as a
separable mixture. Their respective stereochemistries were
assigned from n.O.e data and 2D-COSY studies.
Oximes 33b±e) reacted with PhSeBr under same reaction
conditions to give the nitrone salts 34b±e, EˆPhSe) from
which the nitrones were liberated with K2CO3 and similarly
trapped in situ in 1,3-dipolar cycloaddition reactions using
NMM as the dipolarophile 3MeCN, 808C, 16 h) to produce
exo-cycloadducts 35b±e) in moderate to good yield
3Scheme 2) together, in the case of 33b) and 33d), with a
trace amount 3,5%) of 36b) and 36d). The stereochemistry
of 35b±e) was determined on the basis of n.O.e data and
2D-COSY studies. Thus the longer tether in these latter
cases imposes high exo-selectivity on the facially selective
cycloaddition.
3. Cyclisation ofoximes onto exo-methylene
cycloalkanes
32-Methylenecyclohexyl) acetaldehyde 39) was prepared
from methyl cyclohexen-1-carboxylate via hydride reduc-
tion, vinyl transeteri®cation and Claisen rearrangement as
outlined in Scheme 37 and was converted into oxime 310)
which comprised a 1:1 E/Z-mixture of isomers.
Scheme 3. 3i) NaAlH23OCH2CH2OCH3)2, benzene, N2, rt, 24 h;3ii) CH 2vCHOCH2CH3, Hg3Oac)2, N2, re¯ux, 6 h;3iii) Sealed tube, 200 8C, N2, 1 h;
3iv) NH2OH´HCl, CH3CO2Na, MeCN/H2O, rt, 6 h.

H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
7037
3.1. PhSe1 as electrophile
In summary, the electrophile-induced cyclisation of oximes
onto proximate endocyclic alkenes or exo-methylene
cycloalkenes creates cis-fused bicyclic nitrones which
undergo facially selective 1,3-dipolar cycloaddition to
N-methylmaleimide. The sequence may be carried out as
a one-pot procedure and results in a considerable increase
in molecular complexity with the formation of four bonds,
two rings and six stereocentres.
The reaction of E/Z-310) with PhSeBr 3MeCN, rt, 1 h) gave
the nitrone salt 311). The free nitrone was liberated in situ
and trapped in a 1,3-dipolar cycloaddition reaction with
NMM 3MeCN, rt, Hunig's base, 10 h) to produce a 1:1
mixture 372%) of diastereoisomeric exo-cycloadducts 312)
and 313), in 37 and 35% overall yield from 310), respec-
tively. The stereochemistries of 312) and 313) were assigned
from n.O.e data and 2D-COSY studies.
4. Experimental
4.1. General
Nuclear magnetic resonance spectra and decoupling experi-
ments were determined at 300 MHz on a Q.E 300 instru-
ment and at 400 MHz on a Bruker AM400 spectrometer as
speci®ed. Chemical shifts are given in parts per million 3d)
down®eld from tetramethylsilane as internal standard.
Spectra were determined in deuteriochloroform except
where otherwise stated. The following abbreviations are
used;s ˆsinglet, dˆdoublet, tˆtriplet, qˆquartet, mˆmulti-
plet, brˆbroad and brsˆbroad singlet. Flash column
chromatography was performed using silica gel 60 3230±
400 mesh). Kieselgel columns were packed with silica gel
GF254 3Merck 7730). Petroleum ether refers the fraction
with bp 40±608C unless otherwise speci®ed. Melting points
were determined on a Ko¯er hot stage apparatus and are
uncorrected. Microanalyses were obtained using a Carlo±
Erba Model 1106 instrument. Mass spectra were recorded at
70 eV on a VG Autospec mass spectrometer. All calcu-
lations for selenium were based on its most abundant
isotope 80Se. Solvents were puri®ed according to procedures
given in Puri®cation of Laboratory Chemicals, D. D. Perrin,
W. L. F. Armanego, D. R. Perrin, Pergamon Press, 1980.
3.2. Br1 as electrophile
The reaction of the 1:1 mixture of E/Z-isomers 310) with
NBS 3CH2Cl2, 258C, 2 h) afforded a 1:1 mixture of oxazine
314) and nitrone 315) re¯ecting the E/Z-ratio of the starting
oxime 33). In this case the succinimide acts as the proton
scavenger. Treating the mixture with NMM 3C6H6, 608C,
13 h) afforded a 1:1 mixture of diastereoisomeric cyclo-
adducts 316) and 317) in 73% yield relative to E-310)
together with unchanged 314), [42% relative to Z-310)].
The stereochemistries of the cycloadducts were assigned
from n.O.e data and 2D-COSY studies.
4.1.1. 2-12-Cyclopent-2-enylethyl)-1,3-dioxolane 11b). A
solution of 2-32-bromoethyl)-1,3-dioxolane 31.81 g, 1.3
equiv.) in THF 32 mL) was added dropwise to a suspension
of magnesium turnings 30.244 g, 1.3 equiv.) in THF
310 mL). After dissolution of all the magnesium, a solution
of 3-bromocyclopentene 31.17 g, 8.0 mmol) in THF 32 mL)
was slowly added to the Grignard reagent over 20 min. The
solution was stirred at room temperature for 3 h, poured into
ice-water 350 mL) and the product extracted with diethyl
ether 33£50 mL). The combined organic layers were
washed with saturated aq. NH4Cl, water, and brine, dried
3MgSO4) and concentrated to afford the product 31.26 g,
94%) as a colourless oil, bp 458C/0.1 mmHg. 3Found
3HRMS): 168.1141, C10H16O2 requires: 168.1150); d
3300 MHz): 5.68 3m, 2H, CHvCH), 4.85 3t, 1H, Jˆ
5.0 Hz, CH±O), 4.00±3.82 3m, 4H, 2£CH2±O) and 2.69±
1.35 3m, 9H, cyclopentyl and alkyl); m/z 3%): 168 3M1, 1),
106 319), 99 327), 80 379), 73 3100), 67 337), 45 334) and 41
319).
4.1.2. 2-12-Cyclohex-2-enylethyl)-1,3-dioxolane 11c). A
solution of 2-32-bromoethyl)-1,3-dioxolane 39.05 g, 1.2
equiv.) in THF 315 mL) was added dropwise to a suspension
of magnesium turnings 31.22 g, 1.2 equiv.) in THF 340 mL).
After dissolution of all magnesium, a solution of 3-bromo-
cyclohexene 36.44 g, 40.0 mmol) in THF 35 mL) was slowly
added to the Grignard reagent over 45 min. The solution

7038
H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
was stirred at room temperature for 3 h, poured into ice-
water 3200 mL) and the product extracted with diethyl
ether 33£200 mL). The combined organic layers were
washed with saturated aq. NH4Cl, water, and brine, dried
3MgSO4) and concentrated to afford the product 36.82 g,
94%) as a colourless oil, bp 508C/0.1 mmHg. 3Found: C,
trated to afford the product 30.25 g, 68%) as a colourless
oil. d 3300 MHz): 9.78 3t, 1H, Jˆ2.0 Hz, CHO), 5.77±
5.62 3m, 2H, CHvCH) and 2.78±1.38 3m, 9H, cyclopentyl
and alkyl); m/z 3%): 124 3M1, 5), 107 316), 80 368), 67
3100), 55 326) and 41 312).
72.3;H, 9.85, C 11H18O2 requires: C, 72.55;H, 9.9%);
d
4.1.6. 3-1Cyclohex-2-enyl)-propionaldehyde 12c). 2N
H2SO4 310 mL) was added to a stirred solution of acetal
31c) 30.55 g, 3.0 mmol) in a 3:1 v/v mixture of aceto-
nitrile±water 330 mL) and stirring was continued at room
temperature for 6 h. 8% Aq. NaHCO3 350 mL) was then
added, the product extracted with diethyl ether 33£
50 mL), the combined organic layers dried 3MgSO4) and
concentrated to afford the product 30.36 g, 88%) as a colour-
less oil. d 3300 MHz): 9.78 3t, 1H, Jˆ1.5 Hz, CHO), 5.69
3m, 1H, CH2±CHv), 5.52 3dd, 1H, Jˆ2.0 and 10.0 Hz,
CH±CHv), 2.48 3dt, 2H, Jˆ1.5 and 7.5 Hz, CH2±CHO)
and 2.14±1.16 3m, 9H, cyclohexyl and alkyl); m/z 3%): 138
3M1, 3), 94 3100), 81 393), 79 399), 67 327), 53 326) and 41
339).
3300 MHz): 5.66 3dt, 1H, Jˆ3.0 and 10.0 Hz, CH2±
CHv), 5.57 3dd, 1H, Jˆ1.5 and 10.0 Hz, CH±CHv),
4.85 3t, 1H, Jˆ4.5 Hz, CH±O), 3.99±3.82 3m, 4H, 2£
CH2±O), 2.07 3m, 1H, CH) and 1.98±1.17 3m, 10H, cyclo-
hexyl and alkyl); m/z 3%): 182 3M1, 4), 121 351), 99 329), 94
362), 81 3100), 73 397), 67 319), 57 321), 45 344) and 41 333).
4.1.3. 2-12-Cyclohept-2-enylethyl)-1,3-dioxolane 11d). A
solution of 2-32-bromoethyl)-1,3-dioxolane 31.84 g, 1.2
equiv.) in THF 32 mL) was added dropwise to a suspension
of magnesium turnings 30.244 g, 1.2 equiv.) in THF
310 mL). After dissolution of all magnesium, a solution of
3-bromocycloheptene 31.41 g, 8.0 mmol) in THF 32 mL)
was slowly added to the Grignard reagent over 20 min.
The solution was stirred at room temperature for 3 h, poured
into ice-water 350 mL) and the product extracted with
diethyl ether 33£50 mL). The combined organic layers
were washed with saturated aq. NH4Cl, water, and brine,
dried 3MgSO4) and concentrated to afford the product
31.51 g, 96%) as a colourless oil, bp 608C/0.1 mmHg.
3Found HRMS: 196.1457, C12H20O2 requires: 196.1463);
d 3300 MHz): 5.77 3m, 1H, CH2±CHv), 5.54 3dd, 1H,
Jˆ3.0 and 11.0 Hz, CH±CHv), 4.85 3t, 1H, Jˆ4.5 Hz,
CH±O), 3.98±3.81 3m, 4H, 2£CH2±O) and 2.28±1.21 3m,
13H, cycloheptyl and alkyl); m/z 3%): 196 3M1, 4), 134 316),
108 379), 99 355), 93 339), 86 322), 79 328), 73 3100), 67
319), 45 331) and 41 320).
4.1.7. 3-1Cyclohept-2-enyl)-propionaldehyde 12d). 2N
H2SO4 310 mL) was added to a stirred solution of acetal
31d) 30.61 g, 3.1 mmol) in a 3:1 v/v mixture of aceto-
nitrile±water 330 mL) and stirring was continued at room
temperature for 20 h. 8% Aq. NaHCO3 350 mL) was then
added, the product extracted with diethyl ether 33£50 mL),
the combined organic layers dried 3MgSO4) and concen-
trated to afford the product 30.45 g, 95%) as a colourless
oil. 3Found HRMS: 152.1203, C10H16O requires:
152.1201); d 3300 MHz): 9.78 3t, 1H, Jˆ1.5 Hz, CHO),
5.80 3m, 1H, CH2±CHv), 5.51 3dd, 1H, Jˆ3.5 and
11.0 Hz, CH±CHv) and 2.50±1.22 3m, 13H, cycloheptyl
and alkyl); m/z 3%): 152 3M1, 3), 108 3100), 93 369), 79
348), 67 345) and 55 322); nmax 3®lm): 2910 3C±H), 2830
3CHO), 2710 3CHO), 1720 3CvO), 1440 3CH2±CHO), 735
4.1.4. 2-12-Cyclooct-2-enylethyl)-1,3-dioxolane 11e). A
solution of 2-32-bromoethyl)-1,3-dioxolane 35.44 g, 1.2
equiv.) in THF 35 mL) was added dropwise to a suspension
of magnesium turnings 30.731 g, 1.2 equiv.) in THF
320 mL). After dissolution of all magnesium, a solution of
3-bromocyclooctene 34.53 g, 24.0 mmol) in THF 35 mL)
was slowly added to the Grignard reagent over 30 min.
The solution was stirred at room temperature for 3 h, poured
into ice-water 3100 mL) and the product extracted with
diethyl ether 33£100 mL). The combined organic layers
were washed with saturated aq. NH4Cl, water, and brine,
dried 3MgSO4) and concentrated to afford the product
34.89 g, 97%) as a colourless oil, bp 748C/0.1 mmHg.
3Found HRMS: 210.1614, C13H22O2 requires: 210.1620);
d 3300 MHz): 5.65 3q, 1H, Jˆ8.5 Hz, CH2±CHv), 5.20
3t, 1H, Jˆ8.5 Hz, CH±CHv), 4.85 3t, 1H, Jˆ4.5 Hz,
CH±O), 3.99±3.81 3m, 4H, 2£CH2±O) and 2.50±1.08 3m,
15H, cyclooctyl and alkyl); m/z 3%): 210 3M1, 2), 181 33),
148 35), 122 322), 109 311), 99 373), 73 3100), 67 334), 55
320), 45 340) and 41 334).
and 690 cm21
.
4.1.8. 3-1Cyclooct-2-enyl)-propionaldehyde 12e). 2N
H2SO4 310 mL) was added to a stirred solution of acetal
31e) 30.65 g, 3.0 mmol) in a 3:1 v/v mixture of aceto-
nitrile±water 330 mL) and stirring was continued at room
temperature for 20 h. 8% Aq. NaHCO3 350 mL) was then
added, the product extracted with diethyl ether 33£50 mL),
the combined organic layers dried 3MgSO4) and concen-
trated to afford the product 30.43 g, 84%) as a colourless
oil. 3Found HRMS: 166.1360, C11H18O requires:
166.1358); d 3300 MHz): 9.78 3t, 1H, Jˆ1.7 Hz, CHO),
5.70 3q, 1H, Jˆ9.5 Hz, CH2±CHv), 5.16 3t, 1H, Jˆ
9.5 Hz, CH±CHv) and 2.52±1.12 3m, 15H, cyclooctyl
and alkyl); m/z 3%): 166 3M1, 11), 122 3100), 107 339),
93 357), 79 361), 67 391), 55 352) and 41 383); nmax 3®lm):
2920 3C±H), 2850 3CHO), 1720 3CvO), 1445 3CH2±
CHO), 750 and 710 cm21
.
4.1.9. 2-1Cyclopent-2-en)-1-acetaldoxime 13a). A solution
of aldehyde 32a) 310 g, 90.9 mmol) in acetonitrile 3200 mL)
was added to a solution of hydroxylamine hydrochloride
36.95 g, 1.1 equiv.) and sodium acetate 38.95 g, 1.2 equiv.)
in water 3100 mL). The resulting solution was stirred at
ambient temperature for 6 h and then extracted with chloro-
form 32£300 mL). The combined organic layer was dried
3MgSO4), concentrated under reduced pressure and the
4.1.5. 3-1Cyclopent-2-enyl)-propionaldehyde 12b). 2N
H2SO4 310 mL) was added to a stirred solution of acetal
31b) 30.51 g, 3.0 mmol) in a 3:1 v/v mixture of aceto-
nitrile±water 330 mL) and stirring was continued at room
temperature for 20 h. 8% Aq. NaHCO3 350 mL) was then
added, the product extracted with diethyl ether 33£50 mL),
the combined organic layers dried 3MgSO4) and concen-

H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
7039
residue subjected to column chromatography on silica,
eluting with 1:1 v/v petroleum ether±ether. The product
39.8 g, 86%) was obtained as a colourless thick oil, which
comprised a 1:1 mixture of E- and Z-isomers. 3Found: C,
66.7;H, 8.55;N, 10.95, C 7H11NO requires: C, 67.15;H,
8.85, N, 11.2%); d 3300 MHz): 9.8 and 9.47 3br, 1H, OH,
isomers), 7.43 3t, 1H, E-CHvN), 6.77 3t, 1H, Z-CHvN),
5.77 3brs, 1H, CHvC, isomers), 5.66 3brs, 1H, CHvC,
isomers) and 2.88±1.44 3m, 7H). m/z 3%);125 3M 1, 2), 108
314), 91 36), 80 314), 67 3100), 59 312), 41 314) and 39 310).
3Found: C, 71.75;H, 10.0;N, 8.35, C 10H17NO requires: C,
71.85;H, 10.15, N, 8.4%); d 3300 MHz): 8.92 and 8.47 3br,
1H, OH, isomers), 7.44 3t, 1H, Jˆ6.0 Hz, E-CHvN), 6.74 3t,
1H, Jˆ5.5 Hz, Z-CHvN), 5.77 3m, 1H, CHvC, isomers),
5.55 3m, 1H, CHvC, isomers) and 2.47±1.19 3m, 13H); m/z
3%): 167 3M1, 4), 150 349), 135 319), 121 314), 109 396), 95
345), 93 347), 79 362), 67 3100), 59 338) and 55 337).
4.1.13. 3-1Cyclooct-2-enyl)-propionaldoxime 13e). A solu-
tion of aldehyde 32e) 30.53 g, 3.2 mmol) in acetonitrile
320 mL) was added to a solution of hydroxylamine hydro-
chloride 30.24 g, 1.1 equiv.) and sodium acetate 30.32 g,
1.2 equiv.) in water 310 mL). The resulting solution was
stirred at ambient temperature for 4 h and then extracted
with dichloromethane 33£20 mL). The combined organic
layer was dried 3MgSO4), concentrated under reduced
pressure and the residue subjected to column chroma-
tography on silica, eluting with 1:2 v/v ether±hexane. The
product 30.53 g, 92%) was obtained as a colourless oil,
which comprised a 1:1 mixture of E- and Z-isomers.
3Found: C, 72.8;H, 10.7;N, 7.75, C 11H19NO requires: C,
72.95;H, 10.05, N, 7.75%); d 3300 MHz): 8.82 and 8.43 3br,
1H, OH, isomers), 7.43 3t, 1H, Jˆ6.0 Hz, E-CHvN), 6.73
3t, 1H, Jˆ5.5 Hz, Z-CHvN), 5.67 3q, 1H, Jˆ9.0 Hz,
CHvC, isomers), 5.17 3q, 1H, Jˆ9.0 Hz, CHvC, isomers)
and 2.53±1.09 3m, 15H); m/z 3%): 181 3M1, 3), 164 388),
149 311), 123 323), 107 318), 93 332), 81 377), 67 3100), 55
354) and 41 396).
4.1.10. 3-1Cyclopent-2-enyl)-propionaldoxime 13b). A
solution of aldehyde 32b) 30.17 g, 1.3 mmol) in acetonitrile
315 mL) was added to a solution of hydroxylamine hydro-
chloride 30.10 g, 1.1 equiv.) and sodium acetate 30.13 g,
1.2 equiv.) in water 37.5 mL). The resulting solution was
stirred at ambient temperature for 4 h and then extracted
with dichloromethane 33£20 mL). The combined organic
layer was dried 3MgSO4), concentrated under reduced
pressure and the residue subjected to column chroma-
tography on silica, eluting with 1:2 v/v ether±hexane. The
product 30.12 g, 65%) crystallised from ether±hexane as
colourless needles, mp 65±678C, which comprised a 1:1
mixture of E- and Z-isomers. 3Found: C, 68.9;H, 9.4;N,
10.0, C8H13NO requires: C, 69.1;H, 9.35, N, 10.05%); d
3300 MHz): 9.2 and 8.8 3br, 1H, OH, isomers), 7.44 3t, 1H,
Jˆ6.0 Hz, E-CHvN), 6.74 3t, 1H, Jˆ5.5 Hz, Z-CHvN),
5.75 3m, 1H, CHvC, isomers), 5.64 3m, 1H, CHvC,
isomers) and 2.72±1.36 3m, 9H); m/z 3%): 139 3M1, 10),
122 313), 106 310), 93 323), 79 354), 67 3100) and 53 312).
4.1.14. exo-2-Methyl-7-phenylselenyl-octahydro-8-oxa-
2,7b-diaza-dicyclopenta[a,e]pentalene-1,3-dione 15a) and
endo-2-methyl-7-phenylselanyl-octahydro-8-oxa-2,7b-
diaza-dicyclopenta[a,e]pentalene-1,3-dione 16a). Phenyl-
selenyl bromide 31.32 g, 1.2 equiv.) was added to a solution
of oxime 33a) 30.5 g, 4.0 mmol) in dry acetonitrile 350 mL).
The resulting solution was stirred at ambient temperature for
1 h and NMM 30.48 g, 1 equiv.) and diisopropylethylamine
3Hunig's base) 30.84 mL, 1.2 equiv.) were added. The
resulting mixture was stirred at 258C for 10 h. The solvent
was then evaporated and the residue was subjected to
column chromatography on silica, eluting with 3:1 v/v
petroleum ether±ether to afford the product 31.12 g, 70%)
as a 1:1 mixture of endo- and exo-isomers 35a) and 36a).
4.1.11. 3-1Cyclohex-2-enyl)-propionaldoxime 13c).
A
solution of aldehyde 32c) 31.04 g, 7.5 mmol) in acetonitrile
350 mL) was added to a solution of hydroxylamine hydro-
chloride 30.58 g, 1.1 equiv.) and sodium acetate 30.75 g,
1.2 equiv.) in water 325 mL). The resulting solution was
stirred at ambient temperature for 4 h and then extracted
with dichloromethane 33£50 mL). The combined organic
layer was dried 3MgSO4), concentrated under reduced
pressure and the residue subjected to column chroma-
tography on silica, eluting with 1:2 v/v ether±hexane. The
product 30.91 g, 79%) crystallised from ether±hexane as
colourless needles, mp 60±628C, which comprised a 1:1
mixture of E- and Z-isomers. 3Found: C, 70.65;H, 10.1;
N, 9.25, C9H15NO requires: C, 70.6;H, 9.8, N, 9.15%); d
3300 MHz): 8.82 and 8.38 3br, 1H, OH, isomers), 7.43 3t, 1H,
Jˆ6.0 Hz, E-CHvN), 6.73 3t, 1H, Jˆ5.5 Hz, Z-CHvN),
5.69 3m, 1H, CHvC, isomers), 5.56 3m, 1H, CHvC, isomers)
and 2.47±1.17 3m, 11H); m/z 3%): 153 3M1, 2), 135 318),
120 310), 107 326), 95 360), 81 3100), 67 355) and 53 331).
Compound 35a): Obtained 335%) as colourless prisms from
ether±petroleum ether, mp 119±1218C. 3Found: C, 55.35;
H, 5.1;N, 7.0, C 18H20N2O3Se requires: C, 55.25;H, 5.15;N,
7.15%); d 3400 MHz): 7.52±7.19 3m, 5H, ArH), 4.70 3d,
1H, Jˆ7.0 Hz, Ha), 4.0 3dd, 1H, Jˆ5.5 and 8.0 Hz, He),
3.72 3dd, 1H, Jˆ6.5 and 10.5 Hz, Hc), 3.43 3d, 1H, Jˆ
7.0 Hz, Hb), 3.23 3m, 1H, Hd), 2.97 3s, 3H, NMe), 2.80 3m,
1H, Hf) and 2.24±1.211 3m, 6H); m/z 3%): 392 3M1, 28), 281
312), 264 334), 235 399), 233 354), 207 35) and 184 313).
4.1.12. 3-1Cyclohept-2-enyl)-propionaldoxime 13d). A
solution of aldehyde 32d) 30.30 g, 2.0 mmol) in acetonitrile
315 mL) was added to a solution of hydroxylamine hydro-
chloride 30.15 g, 1.1 equiv.) and sodium acetate 30.19 g,
1.2 equiv.) in water 37.5 mL). The resulting solution was
stirred at ambient temperature for 4 h and then extracted
with dichloromethane 33£20 mL). The combined organic
layer was dried 3MgSO4), concentrated under reduced
pressure and the residue subjected to column chroma-
tography on silica, eluting with 1:2 v/v ether±hexane. The
product 30.25 g, 75%) was obtained as a colourless viscous
oil, which comprised a 1:1 mixture of E- and Z-isomers.

7040
H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
eluting with 2:1 v/v ether±hexane to afford the exo-cyclo-
adduct 35b) 30.16 g, 71%) contaminated with trace amount
3,5%) of endo-isomer 36b).
Compound 35b): Obtained as colourless amorphous solid,
mp 104±1068C. 3Found: C, 56.3;H, 5.7;N, 6.7,
C19H22N2O3Se requires: C, 56.3;H, 5.45;N, 6.9%);
d
3400 MHz), 3C6D6): 7.59±7.02 3m, 5H, ArH), 4.07 3d, 1H,
Jˆ7.5 Hz, Ha), 3.53 3dt, 1H, Jˆ6.0 and 9.2 Hz, Hd), 3.23
3dt, 1H, Jˆ5.0 and 7.5 Hz, Hc), 3.09 3t, 1H, Jˆ6.0 Hz, He),
2.59 3s, 3H, NMe), 2.42 3dd, 1H, Jˆ5.0 and 7.5 Hz, Hb),
2.05 3m, 2H, Hf and aliphatic) and 1.80±0.72 3m, 7H); m/z
3%): 406 3M1, 19), 284 3100), 249 365), 221 357), 198 355),
157 360), 111 342), 79 385), 67 368), 54 359) and 41 367).
Compound 36a): Obtained 335%) as colourless needles from
ether±petroleum ether, mp 117±1198C. 3Found: C, 55.35;
H, 5.2;N, 7.15, C 18H20N2O3Se requires: C, 55.25;H, 5.15;
N, 7.15%); d 3400 MHz): 7.47±7.19 3m, 5H, ArH), 4.75 3d,
1H, Jˆ8.5 Hz, Ha), 3.90 3m, 1H, Hc), 3.61 3t, 1H, Jˆ8.5 Hz,
Hb), 3.57±3.54 3m, 1H, Hd), 3.48 3dd, 1H, Jˆ4.0 and
8.0 Hz, He), 2.82 3s, 3H, NMe), 2.65 3m, 1H, Hf), 2.35
3m, 1H, CH2) and 1.98±1.27 3m, 5H); m/z 3%): 392 3M1,
34), 264 349), 235 3100), 223 378), 157 344), 143 354), 108
360), 67 369), 54 364) and 41 354).
4.1.16. exo-8-Methyl-1-phenylselenyl-decahydro-10-oxa-
8,10a-diaza-pentaleno[2,1-a]-naphthalene-7,9-dione 15c).
Phenylselenyl bromide 30.21 g, 1.0 equiv.) was added to a
stirred solution of oxime 33c) 30.14 g, 0.9 mmol) in dry
acetonitrile 310 mL) and stirring was continued at ambient
temperature for 2 h. Anhydrous potassium carbonate
30.14 g, 1.1 equiv.) was then added and the solution stirred
at ambient temperature for an additional 1 h. NMM 30.13 g,
1.2 equiv.) was added and the resulting mixture was boiled
under re¯ux for 16 h. The solvent was then evaporated and
the residue subjected to column chromatography on silica,
eluting with 2:1 v/v ether±hexane to afford the exo-cyclo-
adduct 35c) 30.27 g, 71%) which crystallised from ether±
hexane as colourless needles, mp 162±1648C. 3Found: C,
57.2;H, 5.85;N, 6.45, C 20H24N2O3Se requires: C, 57.3;H,
5.75;N, 6.7%); d 3400 MHz), 3DMSO, 37.38C): 7.63±7.38
3m, 5H, ArH), 4.86 3d, 1H, Jˆ7.0 Hz, Ha), 3.84 3dt, 1H,
Jˆ4.0 and 8.0 Hz, Hd), 3.67 3m, 1H, Hc), 3.55 3dd, 1H,
Jˆ4.0 and 7.0 Hz, Hb), 3.20 3dd, 1H, Jˆ4.0 and 8.0 Hz,
He), 2.97 3s, 3H, NMe), 2.31 3m, 1H, Hf) and 2.35±1.49
3m, 10H); m/z 3%): 420 3M1, 30), 309 313), 292 325), 263
378), 250 323), 221 3100), 212 320), 169 313), 157 349), 134
350), 111 346), 91 361), 79 370), 77 375), 67 350) and 54 360).
4.1.15. exo-7-Methyl-1-phenylselenyl-octahydro-9-oxa-
7,9a-diaza-cyclopenta[b]-as-indacene-6,8-dione
15b).
Phenylselenyl bromide 30.14 g, 1.0 equiv.) was added to a
stirred solution of oxime 33b) 30.08 g, 0.5 mmol) in dry
acetonitrile 310 mL) and stirring was continued at ambient
temperature for 2 h. Anhydrous potassium carbonate
30.09 g, 1.1 equiv.) was then added and the solution stirred
at ambient temperature for an additional 1 h. NMM 30.08 g,
1.2 equiv.) was added and the resulting mixture was boiled
under re¯ux for 16 h. The solvent was then evaporated and
the residue subjected to column chromatography on silica,

H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
7041
4.1.18. Cycloadduct 15e). Phenylselenyl bromide 30.14 g,
1.0 equiv.) was added to a stirred solution of oxime 33e)
30.11 g, 6.0 mmol) in dry acetonitrile 310 mL) and stirring
was continued at ambient temperature for 2 h. Anhydrous
potassium carbonate 30.09 g, 1.1 equiv.) was then added and
the solution stirred at ambient temperature for an additional
1 h. NMM 30.08 g, 1.2 equiv.) was added and the resulting
mixture was boiled under re¯ux for 16 h. The solvent was
then evaporated and the residue subjected to column
chromatography on silica, eluting with 2:1 v/v ether±
hexane to afford the exo-cycloadduct 35e) 30.08 g, 32%) as
a colourless amorphous solid, mp 192±1948C. 3Found: C,
59.1;H, 6.2;N, 6.05, C 22H28N2O3Se requires: C, 59.1;H,
6.25;N, 6.25%); d 3400 MHz), 3DMSO, 608C): 7.59±7.37
3m, 5H, ArH), 4.87 3d, 1H, Jˆ7.0 Hz, Ha), 4.08 3m, 1H,
Hd), 3.92 3m, 1H, Hc), 3.75 3dd, 1H, Jˆ10.0 and 4.5 Hz,
He), 3.41 3d, 1H, Jˆ7.0 Hz, Hb), 2.97 3s, 3H, NMe), 2.21
3m, 1H, Hf) and 1.95±1.41 3m, 14H); m/z 3%): 448 3M1,
34), 320 38), 291 363), 221 3100), 208 327), 180 37), 157
340), 91 321), 77 333), 67 341) and 55 336).
4.1.17. Cycloadducts 15d) and 16d). Phenylselenyl bromide
30.17 g, 1.1 equiv.) was added to a stirred solution of oxime
33d) 30.11 g, 0.6 mmol) in dry acetonitrile 310 mL) and
stirring was continued at ambient temperature for 2 h.
Anhydrous potassium carbonate 30.11 g, 1.2 equiv.) was
then added and the solution stirred at ambient temperature
for an additional 1 h. NMM 30.09 g, 1.3 equiv.) was added
and the resulting mixture was boiled under re¯ux for 16 h.
The solvent was then evaporated and the residue subjected
to column chromatography on silica, eluting with 2:1 v/v
ether±hexane to afford the exo-cycloadduct 35d) 30.16 g,
58%) contaminated with trace amount 3,5%) of endo-
isomer 36d).
Compound 35d): Obtained as a colourless amorphous solid,
mp 52±548C. 3Found: C, 58.05;H, 6.05;N, 6.45,
C21H26N2O3Se requires: C, 58.25;H, 6.0;N, 6.45%);
d
3400 MHz), 3C6D6): 7.53±6.95 3m, 5H, ArH), 4.05 3d, 1H,
Jˆ7.0 Hz, Ha), 3.70 3m 1H, Hc), 3.60 3m, 1H, Hd), 3.29 3m,
1H, He), 2.70 3s, 3H, NMe), 2.52 3dd, 1H, Jˆ3.0 and 7.0 Hz,
Hb), 2.14 3m, 1H), 1.99 3m, 1H, Hf) and 1.59±0.86 3m,
11H); m/z 3%): 434 3M1, 29), 306 348), 277 3100), 226
388), 221 392), 157 344), 132 361), 119 328), 111 355), 106
356), 91 348), 79 353), 78 368), 77 365), 67 352), 54 360) and
41 355).

7042
H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
4.1.19.
exo-2-Methyl-octahydro-8-oxa-2,7b-diaza-di-
cyclopenta[a,e]pentalene-1,3-dione 17a). Tri-n-butyltin
hydride 3Bu3SnH) 30.57 mL, 1.2 equiv.) and 2,20-azobis-
32-methylpropionitrile) 3AIBN) 30.0294 g, 10 mol%) were
added to a stirred solution of cycloadduct 35a) 30.7 g,
1.79 mmol) in toluene 370 mL) at room temperature. The
reaction mixture was stirred and heated at re¯ux under N2
for 4 h. After removing toluene under reduced pressure the
residue was subjected to column chromatography on silica,
eluting with 1:3 v/v petroleum ether±diethyl ether to afford
the product 30.337 g, 79%) as colourless prisms. mp 124±
1268C. 3Found: C, 61.15;H, 6.85;N, 11.85, C 12H16N2O3
requires: C, 61.0;H, 6.85;N, 11.85%) d 3400 MHz): 4.69
3d, 1H, Jˆ7.0 Hz, Ha), 4.0 3dd, 1H, Jˆ14.5 and 8.0 Hz, He),
3.70 3t, 1H, Jˆ8.5 Hz, Hc), 3.44 3d, 1H, Jˆ7.0 Hz, Hb),
2.94 3s, 3H, NMe), 2.73 3m, 1H, Hf) and 2.05±1.17 3m,
8H); m/z 3%): 236 3M1, 61), 125 374), 112 317), 108 338),
67 3100), 59 325), 54 325) and 41 339).
4.1.21. exo-7-Bromo-2-methyl-octahydro-8-oxa-2,7b-di-
aza-dicyclopenta[a,e]pentalene-1,3-dione 15f) and endo-
7-bromo-2-methyl-octahydro-8-oxa-2,7b-diaza-dicyclo-
penta[a,e]pentalene-1,3-dione 16f). A solution of oxime
33a) 30.4 g, 3.2 mmol) and NBS 3recrystallised) 30.57 g,
3.2 mmol) in dry DCM 340 mL) was stirred at room
temperature for 3 h. The DCM was removed under reduced
pressure and the residue was taken up in benzene 340 mL),
NMM 30.35 g, 3.2 mmol) added and the mixture heated at
608C for 13 h. After cooling the benzene was evaporated
under reduced pressure to leave a yellow brown oil which
comprised a 1:1 mixture of 35f) and 36f). Flash column
chromatography eluting with 1:1 v/v ethyl acetate±hexane
afforded the separated exo- and endo-isomers 35f) and 36f)
30.61 g, 61% combined yield).
Compound 35f): Obtained as a pale yellow solid, mp 163±
1658C. 3Found: C, 45.7;H, 4.55;N, 8.7;Br, 25.55,
C12H15N2O3Br requires: C, 45.7;H, 4.8;N, 8.85, Br,
25.4%); d 3400 MHz): 4.78 3d, 1H, Jˆ7.5 Hz, Ha), 4.19
3dd, 1H, Jˆ8.0 and 3.5 Hz, He), 4.10 3m, 1H, Hd), 3.67
3m, 1H, Hc), 3.46 3d, 1H, Jˆ7.5 Hz, Hb), 3.05 3m, 1H,
Hf), 3.02 3s, 3H, NMe) and 2.23±1.34 3m, 6H); m/z 3%):
316 3M1, 87), 314 389), 235 3100), 203 350), 123 330), 108
341), 79 362), 67 392), 53 360) and 41 389).
4.1.20. endo-2-Methyl-octahydro-8-oxa-2,7b-diaza-di-
cyclopenta[a,e]pentalene-1,3-dione 18a). Tri-n-butyltin
hydride 3Bu3SnH) 30.32 mL, 1.2 equiv.) and 2,20-azobis-
32-methyl propionitrile) 3AIBN) 30.017 g, 10 mol%) were
added to a stirred solution of cycloadduct 36a) 30.4 g,
1.02 mmol) in toluene 340 mL) at room temperature. The
reaction mixture was stirred and boiled under re¯ux under
N2 for 4 h. After removing toluene under reduced pressure
the residue was subjected to column chromatography on
silica, eluting with 1:3 v/v petroleum ether±ether to afford
the product 30.34 g, 81%) as colourless prisms, mp 121±
1238C. 3Found: C, 60.95;H, 6.8;N, 11.75, C 12H16N2O3
requires: C, 61.0;H, 6.85;N, 11.85%); d 3400 MHz): 4.78
3d, 1H, Jˆ8.0 Hz, Ha), 3.86 3m, 1H, Hc), 3.67 3t, 1H,
Jˆ8.0 Hz, Hb), 3.48 3m, 1H, He), 2.92 3s, 3H, NMe), 2.46
3m, 1H, Hf) and 2.26±1.39 3m, 8H); m/z 3%): 236 3M1, 29),
125 379), 108 338), 95 316), 86 317), 80 338), 67 3100), 54
341), 53 330) and 41 348).

H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
7043
oil, which comprised a 1:1 mixture of E- and Z-isomers.
3Found: C, 70.3;H, 9.9;N, 9.05, C 9H15NO requires: C,
70.55;H, 9.9;N, 9.1%); d 3300 MHz): 9.92 3br, 1H, OH,
isomers), 7.44 3t, 1H, E-CHvN), 6.72 3t, 1H, Z-CHvN)
4.69 and 4.57 32£brs, 2H, vinyl-H, isomers) and 2.66±1.20
3m, 11H); m/z 3%): 153 3M1, 8), 136 312), 121 342), 95
3100), 67 357), 55 329) and 41 332).
4.1.23. Cycloadducts 112) and 113). Phenylselenyl bromide
30.462 g, 1.2 equiv.) was added to a solution of oxime 310)
30.25 g, 1.63 mmol) in dry acetonitrile 325 mL). The
resulting solution was stirred at ambient temperature for
1 h when NMM 30.181 g, 1 equiv.) and diisopropylethyl-
amine 3Hunig's base) 30.34 mL, 1.2 equiv.) were added.
The resulting mixture was stirred at 258C for 10 h, then
the solvent was evaporated. The residue was subjected to
column chromatography on silica, eluting with 3:2 v/v
petroleum ether±diethyl ether to afford the product
30.49 g, 72%) as a 1:1 mixture of diastereoisomers 312)
and 313) in 35% and 37% yield respectively.
Compound 36f): Obtained as colourless colourless prisms,
mp 159±1618C. 3Found: C, 45.9;H, 4.5;N, 8.6, Br;25.45,
C12H15N2O3Br requires: C, 45.7;H, 4.8;N, 8.85, Br;
25.4%); d 3400 MHz): 4.88 3d, 1H, Jˆ8.0 Hz, Ha), 4.31
3brs, 1H, He), 3.95 3m, 1H, Hc), 3.65±3.61 3m, 2H, Hb
and Hd), 3.02 3s, 3H, NMe) and 2.73±1.04 3m, 7H); m/z
3%): 316 3M1, 53), 314 355), 235 373), 203 356), 155 361),
145 336), 112 330), 108 335), 67 392) and 41 3100).
4.1.24. 2-Methyl-7a-phenylselanylmethyl-octahydro-8-
oxa-2,7b-diaza-cyclopenta[a,e]-pentalene-1,3-dione 112).
Obtained as pale yellow thick oil. 3Found: C, 57.05;H, 5.8;
N, 6.55 C20H24N2O3Se requires: C, 57.25;H, 5.75;N,
6.7%); d 3400 MHz): 7.50±7.15 3m, 5H, ArH), 4.84 3d,
1H, Jˆ7.5 Hz Ha), 3.99±3.94 3m, 1H, Hc), 3.43 3dd, 1H,
Jˆ3.0 and 7.5 Hz, Hb), 3.04 32£d, 2H, Jˆ12.0 Hz, Hd),
2.93 3s, 3H, NMe) and 2.35±1.27 3m, 11H); m/z 3%): 421
3M11, 37), 263 323), 249 3100), 171 33), 137 344), 134 36),
93 38) and 79 35).
4.1.22. 2-Methylenecyclohexyl acetaldoxime 110). A
solution of aldehyde 39) 35 g, 36.2 mmol) in acetonitrile
3130 mL) was added to a solution of hydroxylamine hydro-
chloride 32.77 g, 1.1 equiv.) and sodium acetate 33.56 g,
1.2 equiv.) in water 350 mL). The resulting solution was
stirred at ambient temperature for 6 h, and extracted with
chloroform 32£200 mL). The combined organic layers were
dried 3MgSO4) and concentrated under reduced pressure.
The residue was subjected to column chromatography on
silica eluting with 1:1 v/v petroleum ether±ether. The
product 34.81 g, 87%) was obtained as a colourless thick
4.1.25. exo-2-Methyl-7a-phenylselanylmethyl-octahydro-
8-oxa-2,7b-diaza-cyclopenta[a,e]-pentalene-1,3-dione 113).
Obtained as colourless prisms from ether±petroleum ether
360±808C), mp 194±1968C. 3Found: C, 57.45;H, 5.5;N,
6.55 C20H24N2O3Se requires: C, 57.25;H, 5.75;N, 6.7%); d
3300 MHz), 3C6D6): 7.62±6.96 3m, 5H, ArH), 4.11 3d, 1H,
Jˆ7.4 Hz, Ha), 3.89±3.84 3m, 1H, Hc), 3.52 3d, 1H, Jˆ
12.0 Hz, Hd), 3.14 3d, 1H, Jˆ12.0 Hz, Hd), 2.66 3d, 1H,
Jˆ7.4 Hz, Hb), 2.49 3s, 3H, NMe) and 2.31±0.51 3m,

7044
H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
11H); m/z 3%): 421 3M11, 49), 263 321), 249 3100), 134 38),
109 313), 95 320) and 67 321).
Compound 316): Obtained 318%) as colourless prisms from
ether±petroleum ether, mp 197±1998C. 3Found: C, 49.2;
H, 5.6;N, 8.2, C 14H19BrN2O3 requires: C, 40.0;H, 5.6;N,
8.15%); d 3400 MHz): 4.86 3d, 1H, Jˆ7.5 Hz, Ha), 3.14±
4.09 3m, 1H, Hc), 3.84 3d, 1H, Jˆ11.0 Hz, Hd1), 3.62 3d,
1H, Jˆ11.0 Hz, Hd2), 3.47 3d, 1H, Jˆ7.5 Hz, Hb), 3.02 3s,
3H, NMe), 2.60 3m, 1H, He), 2.35 3m, 1H, CH2), 1.90 3m,
1H, CH2) and 2.32±0.95 3m, 8H); m/z 3%): 344 3M1, 4),
249 3100), 152 321), 138 311), 111 310), 95 322) and 41
321).
4.1.26.
8a-Bromomethyl-4a,5,6,7,8,8a-hexahydro-4H-
benzo[e][1,2]oxazine114), exo-7a-bromomethyl-2-methyl-
octahydro-8-oxa-2,7b-diaza-cyclopenta[a,e]-pentalene-
1,3-dione116) and 7a-bromomethyl-2-methyl-octahydro-
8-oxa-2,7b-diaza-cyclopenta[a,e]-pentalene-1,3-dione
117). A solution of oxime 310) 30.25 g, 1.63 mmol) and NBS
3recrystallised) 30.29 g, 1.63 mmol) in dry DCM 330 mL)
was stirred at room temperature for 4 h. Then DCM was
removed under reduced pressure, the residue taken up in
benzene 330 mL), NMM 30.181 g, 1.63 mmol) added and
the mixture heated at 608C for 13 h. After cooling, the
benzene was evaporated under reduced pressure to leave a
yellow-brown oily mixture which was separated by ¯ash
column chromatography eluting with 1:1 v/v ethyl acetate±
hexane, to give 314), 316) and 317).
Compound 314): Obtained 342%) as a pale yellow thick oil
3Found: C, 46.8;H, 6.2;N, 6.1;Br, 34.35 C
9H14BrNO
requires: C, 46.55;H, 6.1;N, 6.05;Br, 34.4%); d 7.26 3d,
1H, Jˆ4.0 Hz, Ha), 3.48 3d, 1H, Jˆ10.7 Hz, Hb), 3.24 3d,
1H, Jˆ10.7 Hz, Hb), 2.40 3m, 1H, He), 2.15 3m, 1H, Hc),
1.68 3m, 1H, Hd) and 1.83±0.88 3m, 8H); m/z 3%): 232
3M11, 3), 151 390), 137 388), 106 375), 92 393), 67 370),
55 3100) and 41 386).
Compound 317): Obtained 322%) as a pale yellow thick oil
which solidi®ed from petroleum ether±ether as an amor-
phous solid, mp 169±1718C. 3Found: C, 48.85;H, 5.55;
N, 7.9. C14H19BrN2O3 requires: C, 49.0, H, 5.6;N,
8.15%); d 3400 MHz), 3C6D6): 4.18 3d, 1H, Jˆ7.5 Hz,
Ha), 3.74±3.70 3m, 1H, Hc), 2.94 and 2.91 32d, 2H, Jˆ
11.0 Hz, Hd), 2.65 3dd, 1H, Jˆ7.5 and 2.0 Hz, Hb), 2.54
3s, 3H, NMe) and 1.85±0.88 3m, 11H); m/z 3%): 344 3M1,

H. A. Dondas et al. / Tetrahedron 57 )2001) 7035±7045
7045
Markandu, J.;Kennewell, P.;Thornton-Pett, M. Tetrahedron
2001, 57, 1119±1128.
5), 279 32), 262 33), 249 3100), 149 310), 122 37), 108 35) and
41 38).
2. Frederickson, M.;Grigg, R.;Markandu, J.;Redpath, J. J. Chem.
Soc., Chem. Commun. 1994, 2225±2226. Grigg, R.;Hadji-
soteriou, M.;Kennewell, P.;Markandu, J.;Thornton-Pett, M.
J. Chem. Soc., Chem. Commun. 1992, 1388±1389. Grigg, R.;
Hadjisoteriou, M.;Kennewell, P.;Markandu, J. J. Chem. Soc.,
Chem. Commun. 1993, 1340±1342. Grigg, R.;Hadjisoteriou,
M.;Kennewell, P.;Markandu, J.
Commun. 1992, 1537±1538.
J. Chem. Soc., Chem.
3. Dondas, H. A.;Grigg, R.;Frampton, C. S. Tetrahedron Lett.
1997, 38, 5719±5722.
4. Dondas, H. A.;Grigg, R.;Hadjisoteriou, M.;Markandu, J.;
Thomas, W. A.;Kennewell, P.
10 087±10 096.
Tetrahedron 2000, 56,
5. Oppolzer, W.;Siles, S.;Snowden, R. L.;Bakker, B. H.;
Petrzilka, M. Tetrahedron 1985, 3497±3509. Omura, K.;
Swern, D. Tetrahedron 1978, 34, 1651±1660. Collins, I.;Fox,
M. E.;Holmes, A. B.;Williams, S. F.;Baker, R.;Forbes, I. J.;
Thompson, M. J. Chem. Soc., Perkin Trans. 1 1991, 175±182.
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Acknowledgements
We thank Mersin University 3Turkey) 3H. A. D.) for leave of
absence and Leeds University for support.
7. McAndrew, B. A. J. Chem. Soc., Perkin Trans. 1 1979, 1837±
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References
1. Part 51: Dondas, H. A.;Grigg, R.;Hadjisoteriou, M.;