Radical cyclisation reactions leading to polycyclics related to the amaryllidaceae and erythrina alkaloids

Article abstract of DOI:10.1016/S0040-4020(00)00646-3

Novel radical cyclisation reactions, mediated by tributyltin hydride, samarium(II) iodide or manganese(III) acetate, have been explored to form tri- and tetra-cyclic ring systems related to the Amaryllidaceae or Erythrina family of alkaloids. Haloethanamide precursors possessing a cyclohexenone ring have been shown to form octahydroindolones, and erythrinane-type systems can be formed from precursors bearing unsaturated side-chains in tandem cyclisations. An octahydroindolone has been converted to the ring skeleton of γ-lycorane using samarium(II) iodide while reaction with manganese(III) acetate has been shown to yield a novel tetracyclic ring system bearing a 7-membered ring. Finally, a new tandem cyclisation of a cyclohexenone aryl halide has been shown to provide a quick approach to a 5,5,6,6-tetracycle related to erythrinane natural products. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00646-3

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7217–7228
Radical Cyclisation Reactions Leading to Polycyclics Related
to the Amaryllidaceae and Erythrina Alkaloids
*
Andrew F. Parsons and David A. J. Williams
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Received 10 May 2000; revised 7 July 2000; accepted 24 July 2000
Abstract—Novel radical cyclisation reactions, mediated by tributyltin hydride, samarium(II) iodide or manganese(III) acetate, have been
explored to form tri- and tetra-cyclic ring systems related to the Amaryllidaceae or Erythrina family of alkaloids. Haloethanamide precursors
possessing a cyclohexenone ring have been shown to form octahydroindolones, and erythrinane-type systems can be formed from precursors
bearing unsaturated side-chains in tandem cyclisations. An octahydroindolone has been converted to the ring skeleton of g-lycorane using
samarium(II) iodide while reaction with manganese(III) acetate has been shown to yield a novel tetracyclic ring system bearing a
7-membered ring. Finally, a new tandem cyclisation of a cyclohexenone aryl halide has been shown to provide a quick approach to a
5,5,6,6-tetracycle related to erythrinane natural products. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
A number of very recent synthetic approaches to these types
of alkaloid have centred on the formation of the tetracyclic
skeleton using a radical cyclisation reaction in the key
step.2–8 In 1996, Schultz and co-workers2 reported the first
asymmetric synthesis of (ϩ)-lycorine 1 using a key 6-endo-
trig cyclisation of an aryl radical and a similar approach was
reported (in the same year) by Rigby and Mateo to form
a-lycorane.3 The first total synthesis of (Ϫ)-g-lycorane 2,
which employed both a 5-endo-trig and a 6-exo-trig radical
cyclisation (mediated by tributyltin hydride), was reported
in 1998 by Ikeda and co-workers.4 Since then, Zard and co-
workers5,6 have developed two radical approaches to
racemic g-lycorane 2; the first approach centred on a
5-endo-trig cyclisation (mediated by Ni/AcOH), followed
by a 6-endo-trig cyclisation (mediated by tributyltin
hydride), while the second approach exploited a tandem
cyclisation of an amidyl radical to construct the tetracyclic
ring system. Finally, Cossy and co-workers7 have recently
employed an aminyl radical cyclisation (mediated by CuCl/
CuCl2) as a key step in a racemic synthesis of 2. In this
paper, we report the development of some novel radical
cyclisation reactions, mediated by tributyltin hydride,
samarium(II) iodide or manganese(III) acetate, which
provide a short approach to polycyclic ring systems related
to the Amaryllidaceae or Erythrina family of alkaloids.
The synthesis of Amaryllidaceae and Erythrina alkaloids
has attracted considerable synthetic attention in recent
years.1 This can be attributed to the wide range of biological
properties that these compounds exhibit (including emetic
behaviour, inhibition of protein and DNA synthesis in
certain cells; antineoplastic, antiviral, short-term hypo-
tensive and insect antifeedant activity) and the synthetic
challenge of constructing the polycyclic ring systems asso-
ciated with these compounds. These ring systems generally
consist of four (two carbocyclic and two heterocyclic)
contiguous rings as illustrated by the Amaryllidaceae alka-
loids lycorine 1, g-lycorane 2 (a degradation product of
lycorine-type alkaloids) and sternbergine 3, and the
Erythrina alkaloids cocculine 4 and erysotrine 5.
Results and Discussion
Our initial studies investigated the formation of a 5,6-bi-
cyclic ring system by radical cyclisation of dichloroethan-
amides 6a–d (Scheme 1, Table 1). These were prepared on
acylation of the imine/enamine derived from 1,2-cyclo-
hexanedione and the appropriate benzylamine, in a one-
pot reaction. Reaction with 2.2 equiv. of tributyltin hydride
Keywords: radicals and radical reactions; cyclisation; alkaloids; enamides.
* Corresponding author. Tel.: ϩ44-1904-432608; fax: ϩ44-1904-432516;
e-mail: afp2@york.ac.uk
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00646-3

7218
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
Scheme 1.
in boiling toluene or benzene resulted in 5-endo-trig cycli-
sation leading to the formation of octahydroindolones 7a–d
in 63–85% (isolated) yield. It was found that the best
cyclisation yields were obtained when 1.1 equiv. of tri-
butyltin hydride were added to the dichloride over 5 h
(rather than 1 h); the second equivalent (of tributyltin
hydride) can then be added in one portion to reduce the
remaining carbon–chlorine bond. In all cases separable
mixtures of cis- and trans-ring junction isomers, in the
1
ratio 3.3–5.1:1, were formed as indicated by the H and
13C NMR spectra. For example, for the doublet signals
1
due to H7a in the H NMR spectra, coupling constants of
ca. 8 and 11 Hz were assigned to the (major) cis- and
(minor) trans-isomers, respectively. This assignment was
substantiated by base-induced equilibration experiments.
Thus, heating the trans-isomer of 7a with (catalytic) DBU
in toluene for 5 h resulted in epimerisation to give only the
thermodynamically more stable cis-isomer. These results
contrast with radical cyclisation of a related N-(S)-1-phenyl-
ethyl-iodoethanamide precursor by Ikeda and co-workers,
for which only the cis-ring junction isomer was reported.4
Given the possible trapping of the a-amino keto radical 10
with molecular oxygen, it was envisaged that radicals
similar to 10 could also be trapped by a (second) carbon–
carbon double bond in an intramolecular tandem cyclisation
reaction. This could allow the formation of erythrinane-type
ring systems. Indeed, reaction of the N-but-3-enyl and N-4-
ethoxycarbonylbut-3-enyl dichloroethanamides 12a–b with
tributyltin hydride resulted in tandem cyclisation to form
tricycles 13 and 14 in 58 and 64% yield, respectively
(Scheme 2). The exclusive formation of 5,6,6-tricycle 13
(as a single diastereomer) can be explained by a 5-endo/
6-endo cyclisation mechanism and the formation of the
6-membered ring is presumably due to the stability† of the
intermediate captodative radical (of type 10); this promotes
a reversible cyclisation leading to the thermodynamic
(6-ring) product.11 In contrast, a 5-endo/5-exo tandem cycli-
sation was observed for 12b because the ester substituent is
able to stabilise the radical produced on 5-exo cyclisation;
the second cyclisation is no longer reversible and so the
kinetic (5-ring) product 14 is formed (as a 1:1 mixture of
diastereomers). Steric effects may also be important as indi-
cated by the reaction of the N-2-(cyclohex-1-enyl)ethyl
precursor 15 (Scheme 3). Following reaction with tributyltin
hydride, the desired erythrinane-type 5,6,6,6-tetracycle 16
was isolated in only 19% yield (as a single diastereomer)
together with octahydroindolone 17 in 38% yield (as a 4.7:1
mixture of cis-:trans-isomers). The lower yield for 16
compared to 13 may be attributed to steric effects. Indeed,
cyclisation of a related monochloroethanamide, without the
ketone group, has been shown to lead to a similar tetracycle
in 44% yield.10 In order to reduce the rate of hydrogen-atom
Interestingly, when the related monochloroethanamide 8
was reacted with 1.1 equiv. of tributyltin hydride, added
over 1 h, in addition to the formation of 7a in 29% yield
(as a 3.7:1 mixture of cis-/trans-isomers), the hydroxy
derivative 9 was also obtained (as a single diastereoisomer)
in 22% yield. The unexpected formation of 9 could arise
from reaction of molecular oxygen with the intermediate
(captodative) a-amino ketone radical 10.9 However, it is
unclear why related alcohols were not isolated from reaction
of dichloroethanamides 6a–d with tributyltin hydride under
similar conditions. It should also be noted that the position
of the ketone group influences the efficiency of the 5-endo
cyclisation. Thus, when chloroethanamide 11, bearing a
ketone group at C-3 (rather than C-6), was reacted with
tributyltin hydride (added over 5 h) only 16% yield of the
octahydroindolone was isolated (together with the ethana-
mide derived from simple reduction in 52% yield). This
presumably reflects the relative stability of the intermediate
radicals produced on 5-endo cyclisation—the ketone can
only (mesomerically) stabilise the radical derived from
5-endo cyclisation when positioned at C-6.
Table 1. Tributyltin hydride-mediated cyclisation of dichloroethanamides
6a–d
6
R1
R2 Bu3SnH addition time/h Yield of 7 (%) cis:trans
a
b
b
c
H
H
H
H
MeO
MeO
1
1
5
5
5
63
65
85
74
71
4.2:1
4.8:1
3.3:1
5.1:1
4.6:1
†
Stabilisation of the radical by the ketone group is important as cyclisation
OCH2O
of the corresponding chloroethanamide, without the ketone group,
produced a mixture of 5,5,6- and 5,6,6-tricycles in a 1.2:1 ratio (Ref. 10).
d
F
H

A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
7219
Scheme 2.
Scheme 3.
trapping of the (sterically hindered) a-amino keto radical
leading to 17, the bulkier triphenyltin hydride was reacted
with 15 (in place of tributyltin hydride). Gratifyingly, this
resulted in an improved yield of 37% for 16 while the yield
of 17 was reduced slightly (to 32%).
Friedel–Crafts reaction in which the samarium(II) iodide
acts as a Lewis acid to promote nucleophilic attack at the
ketone. All the spectroscopic data for 19 were consistent
with the structure shown, although the diene (m/z 290,
MϩHϩ) was sensitive to aerial oxidation to give the corre-
sponding benzene ring as indicated by the mass spectrum
(m/z 288, MϩHϩ). The successful formation of the desired
lycorane-type ring system then led us to explore the cycli-
sation of octahydroindolones 7b and 7d bearing different
substituents [namely 4-methoxy (electron-donating) and
3-fluoro (electron-withdrawing) groups] on the acceptor
benzene ring. Unfortunately, reaction of these substrates
with samarium(II) iodide/DMPU lead to the formation of
many products (as evidenced by TLC), the major products
of which were the alcohols 20a–b (isolated in 24% and 33%
yield, respectively), and the formation of the desired tetra-
cycles was only tentatively assigned, in Ͻ9% yield, from
the NMR and mass spectra.
The elaboration of N-benzyl-octahydroindolones 7b–d was
then investigated with a view to forming the fourth ring of
the lycorane or the erythrinane-type ring system. This
requires the formation of a new carbon–carbon bond
between the benzene ring and position 7 or 7a of the octa-
hydroindolone ring. Initially, it was envisaged that the
lycorane ring system could be accessed from reaction of
7b–d with samarium(II) iodide. Reaction with the ketone
group was expected to lead to the formation of a ketyl
radical which could then cyclise on to the substituted
benzene ring.12 Hence, reaction of cis-7c with 3.3 equiv.
of samarium(II) iodide and 8 equiv. of DMPU in tetra-
hydrofuran, resulted in the isolation of alcohol 18 in 17%
yield (as a 2.6:1 mixture of isomers) and tetracycle 19 in
17% yield (together with 4% unreacted starting material)
(Scheme 4). The unexpected formation of the cyclohexa-
diene 19 (as a single diastereomer) could result from radical
cyclisation on to the benzene ring to give a cyclohexadienyl
radical, which is subsequently reduced by samarium(II)
iodide to give an anion which is protonated on workup.
Alternatively, 19 could be formed by an intramolecular
The cyclisation of cis-7c, to form a 5,5,6,6-tetracyclic
analogue of the erythrinane ring system, was then investi-
gated using manganese(III) acetate. It was envisaged that
reaction of the ketone group with manganese(III) acetate
would lead to generation of an a-amino ketone radical (of
type 10) which could then cyclise on to the benzene ring to
form a new 5-membered ring.13 Hence, cis-7c was reacted
with 4 equiv. of manganese(III) acetate in boiling benzene.
Scheme 4.

7220
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
This yielded the 6-acetoxy ketone 2114 in 18% yield (as a
2.7:1 mixture of isomers) together with two inseparable
regioisomeric tetracycles, 22 and 23, in the ratio 2.8:1, in
34% yield. The formation of 21 and tetracycles 22–23,
which possess a novel ring system, presumably results
from radical generation at C-6 (rather than C-7a). Cyclisa-
tion of this radical on to the two possible positions of the
benzene ring produces the observed 7-membered rings and
the predominance of 22 over 23 can be attributed to steric
effects. Activation of the benzene ring is required for
reasonable yields of cyclisation because when the corre-
sponding N-benzyl-octahydroindolone 7a was reacted with
manganese(III) acetate, p10% yield of the cyclised product
was isolated. The major product was the 6-acetoxy ketone
(as a 2.1:1 mixture of isomers) in 52% yield. Interestingly,
reaction of manganese(III) acetate with trans-7c only
produced the 7a-acetoxy adduct in poor yield (7%) together
with recovered starting material (43%). The ring strain asso-
ciated with the trans-ring junction presumably prevents
radical cyclisation to form a 7-membered ring.
could, however, be prepared using an alternative radical
cyclisation strategy (Scheme 5). Hence, reaction of aryl
bromide 24 (prepared from allylamine, 2-bromobenzoyl
chloride and 1,2-cyclohexanedione in a one-pot reaction)
with tributyltin hydride (added over 1 h) resulted in the
formation of tricycle 25 in 15% yield (as a 1.6:1 mixture
of trans-/cis-isomers) and the desired tetracycle 26 in 41%
yield. Tetracycle 26 was isolated as a mixture of 4 isomers
in the ratio 17.8:5.0:2.3:1 (from the 1H NMR spectra) and 25
and 26 were isolated in similar yields and diastereomer
ratios when tributyltin hydride or triphenyltin hydride
were added to 24 over 5 h. The initial aryl radical can
cyclise in a 6-endo fashion to form 25, while the formation
of 26 can be explained by a competitive 5-exo/5-exo tandem
cyclisation. Of particular note is the construction of the
hindered quaternary centre in 26 by the (initial) 5-exo cycli-
sation. The predominance of 5-exo over 6-endo cyclisation
was also observed using substrates for which a second
radical cyclisation is impossible. For example, cyclisation
of the related N-2-hydroxyethyl precursor 27 produced
tetracycles 28 and 29 in 30% and 40% yield (as single
diastereomers), respectively (Scheme 6). The major
product, 29, is derived from 5-exo cyclisation of the aryl
radical while 28 is formed from a competitive 6-endo cycli-
sation. Both cyclisation pathways lead to tricycles, which
then react to form the observed hemiacetals 28 and 29,
presumably on (silica) column chromatography.
This work has demonstrated a number of novel radical
cyclisation reactions leading to tri- and tetra-cyclic ring
systems related to the lycorane and erythrinane-type
skeletons. Haloethanamide precursors possessing a cyclo-
hexenone ring have been shown to form octahydro-
indolones, and erythrinane-type systems can be formed
from precursors bearing unsaturated side-chains in tandem
cyclisations. An octahydroindolone has been converted to
the ring skeleton of lycorane using samarium(II) iodide
while reaction with manganese(III) acetate has been
shown to yield a novel tetracyclic ring system bearing a
7-membered ring. Finally, a novel tandem (5-exo/5-exo)
The 5,5,6,6-tetracyclic (erythrinane-type) ring system
Scheme 5.
Scheme 6.

A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
7221
cyclisation of an unsaturated aryl halide has been shown to
provide a quick 2-step approach to a 5,5,6,6-ring system
related to the erythrinane natural products.
108 (20); Found: MϩHϩ, 312.0552. C15H1535Cl2NO2
requires for MϩHϩ, 312.0558.
N-(4-Methoxybenzyl)-N-(6-oxocyclohex-1-enyl)-2,2-dichloro-
ethanamide 6b. 58%; Solid; mp 121–124ЊC (Found: C,
56.44; H, 5.05; N, 4.04. C16H17Cl2NO3 requires C, 56.16;
H, 5.01; N, 4.09%); Rf 0.35 (ethyl acetate-petroleum ether,
1:1); nmax (CHCl3)/cmϪ1 3031 (w), 3009 (w), 2958 (w),
2937 (w), 1696 (br, s), 1612 (w), 1513(m), 1400 (w),
1250 (m), 1209 (w), 1177 (w), 1112 (w) and 1035 (w); dH
(270 MHz, CDCl3) 7.09 (2H, d, Jˆ8.5 Hz, 2×
CHCHCOMe), 6.80 (2H, d, Jˆ8.5 Hz, 2×CHCOMe), 6.64
(1H, t, Jˆ4 Hz, CHvC), 5.87 (1H, s, CHCl2), 5.20 (1H, d,
Jˆ14 Hz, NCHAHBAr), 3.98 (1H, d, Jˆ14 Hz,
NCHAHBAr), 3.76 (3H, s, OCH3), 2.51–2.34 (4H, m,
CH2CO and CH2CH) and 2.06–1.92 (2H, m, CH2CH2CH2);
dC (67.5 MHz, CDCl3) 194.4 (CH2CO), 163.6 (NCO), 159.2
(COMe), 151.8 (CHvC), 136.4 (CvCH), 130.4
(CHCHCOMe), 127.7 (CvCH), 113.8 (CHCOMe), 64.8
(CHCl2), 55.1 (OCH3), 51.3 (NCH2Ar), 38.0 (CH2CO),
25.9 (CH2CH) and 22.0 (CH2CH2CH2); m/z (CI, NH3) 361
Experimental
IR spectra were recorded on an ATI Mattson Genesis FTIR
1
spectrometer. H and 13C NMR spectra were recorded on a
Jeol EX 270 spectrometer. The carbon spectra were
assigned using DEPT experiments. Coupling constants (J)
were recorded in Hertz to the nearest 0.5 Hz. Mass spectra
were recorded on a Fisons Instruments VG Analytical
Autospec Spectrometer system. Thin layer chromatography
was performed on Merck aluminium-backed silica gel
plates. Melting points were recorded on a Gallenkamp
melting point apparatus. The Chemical Analytical Services
Unit, University of Newcastle performed microanalyses
using a Carlo Erba 1106 Elemental Analyser. Compounds
were visualised under a UV lamp, using alkaline potassium
permanganate solution and/or acidic cerium(IV) sulfate-
molybdic acid solution. Column chromatography was
performed using silica gel (Matrex Silica 60, 70–200
micron Fisons or ICN flash silica 60, 32–63 mm). Petroleum
ether refers to the fraction with bp 40–60ЊC.
(
37,35MϩNHϩ4 , 20%), 359 (35MϩNHϩ4 , 30), 325 (35), 308
(15), 291 (10), 274 (25), 138 (35) and 121 (100); Found:
MϩNHϩ4 , 359.0930. C16H1735Cl2NO3 requires for MϩNH4ϩ,
359.0929.
N-(3,4-Methylenedioxybenzyl)-N-(6-oxocyclohex-1-enyl)-
2,2-dichloroethanamide 6c. 63%; Solid; mp 110–116ЊC;
Rf 0.25 (ethyl acetate-petroleum ether, 2:3); nmax (CHCl3)/
cmϪ1 2935 (w), 2893 (w), 1693 (s), 1490 (m), 1444 (w),
1403 (w), 1244 (m), 1192 (w), 1124 (w) and 1040 (m); dH
(270 MHz, CDCl3) 6.74 (1H, t, Jˆ4 Hz, CHvC), 6.73 (1H,
d, Jˆ1.5 Hz, CCHCO), 6.71 (1H, d, Jˆ8 Hz, CHCHCO),
6.61 (1H, dd, Jˆ8, 1.5 Hz, CHCHCO), 5.95 (2H, s,
OCH2O), 5.90 (1H, s, CHCl2), 5.21 (1H, d, Jˆ14.5 Hz,
NCHAHBAr), 3.93 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 2.59–
2.42 (4H, m, CH2CO and CH2CH) and 2.10–1.98 (2H, m,
CH2CH2CH2); dC (67.5 MHz, CDCl3) 194.3 (CH2CO),
163.7 (NCO), 151.8 (CHvC), 147.8, 147.2 (CHCHCO
and CCHCO), 136.5 (CvCH), 129.5 (NCH2C), 122.6
(CHCHCO), 109.2, 108.0 (CHCHCO and CCHCO), 101.1
(OCH2O), 64.7 (CHCl2), 51.7 (NCH2Ar), 38.1 (CH2CO),
25.9 (CH2CH) and 22.1 (CH2CH2CH2); m/z (CI, NH3) 375
General procedure for the preparation of 6a–d, 8, 12a,
15 and 24
To a stirred solution of 1,2-cyclohexanedione (0.35–2.5 g,
3.12–22.30 mmol) in benzene or toluene (50–100 cm3) at
room temperature was added the amine (0.28–3.36 g,
1.1 equiv., 3.43–24.53 mmol). The solution was heated at
reflux in a Dean–Stark water separator until TLC indicated
that no starting material remained (approx. 3 h). After
cooling to 0ЊC, the acid halide (0.81–3.62 g, 1.1 equiv.,
3.43–24.53 mmol) was added dropwise. Pyridine or triethyl-
amine (0.27–2.48 g, 1.1 equiv., 3.43–24.53 mmol) was
then added and the solution allowed to warm to room
temperature. After stirring overnight, the solution was
washed with water, brine, dried (magnesium sulfate) and
the solvent evaporated under reduced pressure to afford
the crude alkene, which was purified by column chroma-
tography (silica) (0.77–4.39 g, 48–65%).
(
(
37,35MϩNHϩ4 , 55%), 373 (35MϩNHϩ4 , 85), 358
37,35MϩHϩ, 25), 357 (25), 356 (35MϩHϩ, 30), 355 (25),
339 (45), 322 (15), 286 (30), 152 (20) and 135 (100); Found:
MϩNHϩ4 , 373.0719. C16H1535Cl2NO4 requires for MϩNH4ϩ,
373.0722.
N-Benzyl-N-(6-oxocyclohex-1-enyl)-2,2-dichloroethan-
amide 6a. 49%; White solid; mp 120–122ЊC; Rf 0.4 (ethyl
acetate-petroleum ether, 2:3); nmax (CHCl3)/cmϪ1 3064 (w),
3031(w), 3007 (m), 2952 (w), 2936 (w), 1689 (s), 1655 (s),
1613 (s), 1495 (w), 1451 (w), 1394 (s), 1342 (m), 1233 (w)
and 1188 (w); dH (270 MHz, CDCl3) 7.35–7.16 (5H, m,
aromatics), 6.68 (1H, t, Jˆ4 Hz, CHvC), 5.90 (1H, s,
CHCl2), 5.32 (1H, d, Jˆ14.5 Hz, NCHAHBPh), 4.05 (1H,
d, Jˆ14.5 Hz, NCHAHBPh), 2.57–2.31 (4H, m, CH2CO
and CH2CH) and 2.08–1.92 (2H, m, CH2CH2CH2); dC
(67.5 MHz, CDCl3) 194.4 (CH2CO), 163.9 (NCO), 151.7
(CHvC), 136.8, 135.9 (CvCH and CvCH), 129.1,
128.6, 128.0 (3×CHvC), 64.8 (CHCl2), 52.0 (NCH2Ph),
38.2 (CH2CO), 26.0 (CH2CH) and 22.1 (CH2CH2CH2);
m/z (CI, NH3) 331 (37,35MϩNH4ϩ, 15%), 329 (35MϩNH4ϩ,
25), 314 (37,35MϩHϩ, 15), 312 (35MϩHϩ, 20), 295 (10), 278
(25), 259 (20), 244 (80), 242 (100), 200 (10), 185 (15) and
N-(3-Fluorobenzyl)-N-(6-oxocyclohex-1-enyl)-2,2-dichloro-
ethanamide 6d. 63%; Solid; mp 79–83ЊC; Rf 0.2 (diethyl
ether–petroleum ether, 3:2); nmax (CHCl3)/cmϪ1 3038 (w),
3030 (w), 3023 (w), 3007 (w), 2957 (w), 2936 (w), 1697 (br,
s), 1632 (w), 1616 (w), 1592 (w), 1488 (w), 1452 (w), 1399
(w), 1358 (w), 1343 (w), 1301 (w), 1256 (w), 1232 (w) and
1216 (w); dH (270 MHz, CDCl3) 7.29 (1H, dt, Jˆ6, 8 Hz,
CHCHCF), 7.01–6.93 (3H, m, CCHCF, CHCHCF and
CHCCHCF), 6.80 (1H, t, Jˆ4 Hz, CHvC), 5.93 (1H, s,
CHCl2), 5.27 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 4.05 (1H,
d, Jˆ14.5 Hz, NCHAHBAr), 2.63–2.38 (4H, m, CH2CO
and CH2CH) and 2.11–1.99 (2H, m, CH2CH2CH2); dC
(67.5 MHz, CDCl3) 194.4 (CH2CO), 164.1 (NCO), 162.8
1
3
(d, JCFˆ248 Hz, CF), 151.8 (CHvC), 138.4 (d, JCFˆ

7222
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
3
8 Hz, CCHCF), 136.8 (CvCH), 130.2 (d, JCFˆ8 Hz,
CH2CH2CO), 1.96–1.83 (4H, m, CH2CvCH and
CH2CHvCCH2) and 1.64–1.47 (4H, m, CH2CH2CvCH
and CH2CH2CHvCCH2); dC (67.5 MHz, CDCl3) 194.4
(CH2CO), 163.4 (NCO), 150.6 (COCvCH), 137.7
(COCvCH), 134.0 (CH2CvCH), 123.3 (CH2CvCH),
64.6 (CHCl2), 47.2 (NCH2), 38.1 (CH2CO), 35.5
(NCH2CH2), 28.0, 25.9, 25.1 (CH2CHvCCO, CH2CvCH
and CH2CHvCCH2), 22.6 and 22.1 (CH2CH2CO,
CH2CH2CHvCCH2 and CH2CH2CvCH); m/z (CI, NH3)
332 (37,35MϩHϩ, 65%), 330 (35MϩHϩ, 100), 296 (15) and
260 (25); Found: MϩHϩ, 330.1022. C16H2135Cl2NO2
requires for MϩHϩ, 330.1028.
4
CHCHCF), 124.5 (d, JCFˆ3 Hz, CHCCHCF), 115.7 (d,
2JCFˆ22 Hz, CHCF), 114.9 (d, JCFˆ22 Hz, CHCF), 64.7
2
(CHCl2), 51.6 (NCH2Ar), 38.1 (CH2CO), 26.0 (CH2CH) and
22.1 (CH2CH2CH2); m/z (CI, NH3) 349 (37,35MϩNH4ϩ,
65%), 347 (35MϩNH4ϩ, 100), 332 (37,35MϩHϩ, 10), 330
(35MϩHϩ, 15), 313 (15), 277 (15), 260 (20) and 218 (15);
Found: MϩNHϩ4 , 347.0727. C15H1435Cl2FNO2 requires for
MϩNHϩ4 , 347.0729.
N-Benzyl-N-(6-oxocyclohex-1-enyl)-2-chloroethanamide
8. 65%; Oil; Rf 0.3 (ethyl acetate-petroleum ether, 1:1); nmax
(CHCl3)/cmϪ1 3032 (w), 3009 (m), 2955 (w), 2934 (w),
2889 (w), 2873 (w), 1691 (br s), 1632 (w), 1496 (w),
1455 (w), 1428 (w), 1408 (w), 1361 (w), 1344 (w),
1253(w), 1233 (w), 1219 (w), 1191 (w), 1152 (w), 1123
(w) and 1080 (w); dH (270 MHz, CDCl3) 7.36–7.20 (5H,
m, aromatics), 6.69 (1H, t, Jˆ4.5 Hz, CHvC), 5.32 (1H, d,
Jˆ14.5 Hz, NCHAHBPh), 4.05 (1H, d, Jˆ14.5 Hz,
NCHAHBPh), 3.92 (2H, s, CH2Cl), 2.57–2.37 (4H, m,
CH2COC and CH2CH) and 2.07–1.98 (2H, m,
CH2CH2CH2); dC (67.5 MHz, CDCl3) 194.5 (CH2COC),
166.0 (NCO), 150.7 (CHvC), 137.0, 136.0 (2×CvCH),
128.5, 128.1, 127.3 (3×CHvC), 50.9 (NCH2Ph), 41.4
(CH2Cl), 37.8 (CH2COC), 25.5 (CH2CH) and 21.8
(CH2CH2CH2); m/z (CI, NH3) 280 (37MϩHϩ, 35%), 278
(35MϩHϩ, 100), 244 (75), 200 (50) and 91 (20); Found:
MϩHϩ, 278.0945. C15H1635ClNO2 requires for MϩHϩ,
278.0948.
N-Allyl-N-(6-oxocyclohex-1-enyl)-2-bromobenzamide 24.
51%; Oil; Rf 0.2 (petroleum ether–diethyl ether–dichloro-
methane, 5:4:1); nmax (CHCl3)/cmϪ1 3016 (m), 2955 (w),
2930 (w), 1689 (s), 1656 (s), 1629 (m), 1592 (w), 1471 (w),
1430 (w), 1399 (m), 1358 (w), 1297 (w), 1237 (w), 1121 (w)
and 1027 (w); dH (270 MHz, CDCl3) 7.48 (1H, dd, Jˆ7.5,
1.5 Hz, CHCBr), 7.24–7.10 (3H, m, aromatics), 7.05 (1H,
br t, Jˆ4.5 Hz, CHvC), 5.88 (1H, ddt, Jˆ17, 10, 6.5 Hz,
CHvCH2), 5.26–5.15 (2H, m, CHvCH2), 4.77–4.73 (1H,
br m, NCHAHB), 3.85–3.72 (1H, br m, NCHAHB), 2.45–
2.05 (4H, br m, CH2CO and CH2CH2CH), 1.93–1.74 (1H,
br m, CH2CHAHBCH2) and 1.63–1.45 (1H, br m,
CH2CHAHBCH2); dC (67.5 MHz, CDCl3) 194.9 (CH2CO),
168.1 (NCO), 149.0 (CHvC), 138.3, 138.1 (CvCBr and
CvCH), 132.7, 132.1, 129.9, 127.6, 126.8 (4×CHvC and
CHvCH2), 119.3 (CBr), 118.2 (CHvCH2), 49.5 (NCH2),
37.9 (CH2CO), 25.6 (CH2CH2CH) and 21.8 (CH2CH2CH2);
m/z (CI, NH3) 336 (81MϩHϩ, 100%), 334 (79MϩHϩ, 95),
300 (15), 256 (40), 228 (15), 185 (15), 183 (15) and 150
(40); Found: MϩHϩ, 334.0437. C16H1679BrNO2 requires for
MϩHϩ, 334.0443.
N-(But-3-enyl)-N-(6-oxocyclohex-1-enyl)-2,2-dichloro-
ethanamide 12a. 56%; Oil: Rf 0.1 (diethyl ether–petroleum
ether, 1:1); nmax (CHCl3)/cmϪ1 3035 (w), 3011(w), 2955
(w), 2938 (w), 1698 (br, s), 1633 (w), 1403 (w), 1346 (m),
1231 (w), 1216 (w), 1198 (w) and 1117 (w); dH (270 MHz,
CDCl3) 7.21 (1H, t, Jˆ4 Hz, CHvC), 5.95 (1H, s, CHCl2),
5.74 (1H, ddt, Jˆ17, 10.5, 7 Hz, CHvCH2), 5.10–5.02 (2H,
m, CHvCHAHB and CHvCHAHB), 3.88 (1H, dt, Jˆ13.5,
7.5 Hz, NCHAHB), 3.20 (1H, dt, Jˆ13.5, 7.5 Hz, NCHAHB),
2.69–2.59 (4H, m, CH2CO and CH2CHvC), 2.32–2.22
(2H, appt quintet, Jˆ7 Hz, NCH2CH2) and 2.15 (2H, appt
quintet, Jˆ6.5 Hz, CH2CH2CH2); dC (67.5 MHz, CDCl3)
194.4 (CH2CO), 163.3 (NCO), 151.1 (CHvC), 137.1
(CvCH), 134.2 (CHvCH2), 116.6 (CHvCH2), 64.4
(CHCl2), 47.8 (NCH2), 37.7 (CH2CO), 31.3
(NCH2CH2), 25.6 (CH2CHvC) and 21.7 (CH2CH2CH2);
m/z (CI, NH3) 280 (37MϩHϩ, 10%), 278 (37,35MϩHϩ,
65), 276 (35MϩHϩ, 100), 242 (30), 234 (20), 206 (90),
166 (20), 164 (35) and 124 (45); Found: MϩHϩ,
276.0557. C12H1535Cl2NO2 requires for MϩHϩ,
276.0558.
N-(2-Hydroxyethyl)-N-(6-oxocyclohex-1-enyl)-2-bromo-
benzamide 27. Following the general procedure 1,2-cyclo-
hexanedione (0.35 g, 3.12 mmol) in toluene (70 cm3) was
reacted with 2-(tert-butyldimethylsilyloxy)ethylamine
(0.60 g, 3.43 mmol), 2-bromobenzoyl chloride (0.45 cm3,
3.43 mmol) and triethylamine (0.48 cm3, 3.43 mmol).
Column chromatography (silica; diethyl ether–petroleum
ether, 3:2) afforded the silyl protected alcohol (0.86 g,
61%) as a white crystalline solid: mp 92–95 ЊC; Rf 0.3
(diethyl ether–petroleum ether, 3:2); nmax (CHCl3)/cmϪ1
3009 (w), 2954 (w), 2931 (w), 2888 (w), 2857 (w), 1688
(s), 1654 (s), 1632 (m), 1591 (w), 1472 (w), 1429 (w), 1401
(w), 1349 (w), 1311 (w), 1257 (w), 1228 (w), 1102 (w) and
1085 (w); dH (270 MHz, d8-toluene, 80 ЊC) 7.38–6.84 (5H,
m, aromatics and CHvC), 4.15–3.80 (4H, br m, NCH2 and
CH2OSi), 2.20–2.00 (2H, br m, CH2CO or CH2CH), 2.00–
1.80 (2H, br m, CH2CO or CH2CH), 1.30–1.55 (2H, br m,
CH2CH2CH2), 1.12 [9H, s, SiC(CH3)3] and 0.25 [6H, s,
Si(CH3)2]; dC (67.5 MHz, CDCl3) 195.0 (CH2CO), 168.6
(NCO), 148.6 (CHvC), 139.7, 138.6 (CvCBr and
CvCH), 132.2, 129.9, 127.9, 126.8 (4×CvC), 119.5
(CBr), 61.0 (CH2OSi), 50.0 (NCH2), 38.1 (CH2CO), 25.8
[SiC(CH3)3], 25.7 (CH2CH), 22.0 (CH2CH2CH2), 18.1
[SiC(CH3)2] and Ϫ5.4 [Si(CH3)2]; m/z (CI, NH3) 454
(81MϩHϩ, 100%), 452 (79MϩHϩ, 95), 396 (35), 394 (30),
374 (70), 372 (55), 322 (20), 320 (20), 240 (15), 185 (15)
and 183 (15); Found: MϩHϩ, 452.1258. C21H3079BrNO3Si
requires for MϩHϩ, 452.1257.
N-[2-(Cyclohex-1-enyl)ethyl]-N-(6-oxocyclohex-1-enyl)-
2,2-dichloroethanamide 15. 48%; Oil; Rf 0.2 (diethyl
ether–petroleum ether, 3:2); nmax (CHCl3)/cmϪ1 3023 (m),
3011 (m), 2934 (s), 2891 (m), 2860 (m), 2837 (m), 1692 (br,
s), 1632 (m), 1449 (m), 1438 (m), 1405 (m), 1346 (m), 1307
(w), 1235 (w), 1216 (w), 1186 (w), 1154 (w) and 1123 (m);
dH (270 MHz, CDCl3) 7.14 (1H, t, Jˆ4 Hz, COCvCH),
5.87 (1H, s, CHCl2), 5.41 (1H, br s, CHvCCH2), 3.95
(1H, dt, Jˆ13.5, 7.5 Hz, NCHAHB), 3.14 (1H, dt, Jˆ13.5,
7.5 Hz, NCHAHB), 2.65–2.58 (4H, m, CH2CO
and CH2CHvCCO), 2.18–2.09 (4H, m, NCH2CH2 and

A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
7223
p-Toluenesulfonic acid (0.13 g, 0.71 mmol) was added to a
solution of the protected alcohol (3.19 g, 7.06 mmol) in
THF–water (20:1; 21 cm3) at room temperature. The
solution was stirred overnight, ethyl acetate was added
and the solution was washed with water, brine, dried
(magnesium sulfate) and the solvent evaporated under
reduced pressure. Column chromatography (silica; ethyl
acetate) afforded alcohol 27 (1.38 g, 58%) as a colourless
oil: Rf 0.2 (ethyl acetate); nmax (CHCl3)/cmϪ1 3470 (br w,
OH), 3025 (w), 3009 (w), 2951 (w), 2826 (w), 1685 (s),
1655 (s), 1629 (s), 1592 (w), 1473 (w), 1428 (m), 1404
(m), 1365 (w), 1347 (w), 1307 (w), 1229 (w), 1208 (w),
1123 (w), 1070 (w) and 1044 (w); dH (270 MHz, d8-toluene,
80ЊC) 7.55–6.94 (5H, br m, aromatics and CHvC), 4.10–
3.00 (5H, br m, NCH2, CH2OH and CH2OH), 2.09 (2H, br s,
CH2CO or CH2CH), 1.95 (2H, br s, CH2CO or CH2CH) and
1.45 (2H, br s, CH2CH2CH2); dC (67.5 MHz, d8-toluene,
80ЊC) 196.3 (CH2COC), 170.1 (NCO), 149.2 (CHvC),
141.1, 140.7 (CvCBr and CvCH), 133.5, 131.0, 129.9,
128.0 (4×CHvC), 121.1 (CBr), 61.8 (CH2OH), 52.6
(NCH2), 39.3 (CH2COC), 26.8 (CH2CH) and 23.3
(CH2CH2CH2); m/z (CI, NH3) 340 (81MϩHϩ, 50%), 338
(79MϩHϩ, 50), 322 (95), 320 (100), 260 (35), 258 (35),
242 (100), 240 (55), 214 (40), 186 (30), 138 (35) and 136
(35); Found: MϩHϩ, 338.0391. C15H1679BrNO3 requires for
MϩHϩ, 338.0392.
48.0 (NCH2), 38.0 (CH2COC), 30.1 (NCH2CH2), 25.9
(CH2CHvC), 22.0 (CH2CH2CH2) and 14.1 (CO2CH2CH3);
m/z (CI, NH3) 367 (37,35MϩNH4ϩ, 65%), 365 (35MϩNH4ϩ,
100), 350 (37,35MϩHϩ, 45), 348 (35MϩHϩ, 30), 321 (35),
319 (55), 314 (30), 304 (40), 302 (60), 278 (70), 264 (15),
236 (45), 234 (30), 190 (15), 137 (15), 124 (95) and 81 (70);
Found: MϩNHϩ4 , 365.1018. C15H1935Cl2NO4 requires for
MϩNHϩ4 , 365.1035.
General procedure for radical cyclisation of precursors
6a–d, 8, 12a–b, 15, 24, 27
A 0.014 (or 0.028) mol dmϪ3 solution containing tributyl- or
triphenyl-tin hydride (0.09–2.66 g, 1.1–1.3 equiv., 0.32–
7.59 mmol) and azobisisobutyronitrile (10–270 mg, 0.2–
0.3 equiv.) in degassed toluene or benzene (23–230 cm3)
was added dropwise over 1 or 5 h via a syringe pump to a
0.024 (or 0.048) mol dmϪ3 solution of the alkene (0.1–
2.0 g, 0.29–5.84 mmol) in boiling degassed toluene or
benzene (12–122 cm3) whilst the latter was stirred under
nitrogen. The solution was heated at reflux for a further
3 h and, when using dichloroamides, more tributyl- or
triphenyl-tin hydride (0.09–2.25 g, 1.1 equiv.) and azobis-
isobutyronitrile (10–190 mg, 0.2 equiv.) were added imme-
diately and the solution heated at reflux for a further 2 h.
Diethyl ether (10–15 cm3) and aqueous potassium fluoride
solution (10%, 10–15 cm3) were added to the residue and
the mixture was stirred for 2 h. The organic layer was sepa-
rated, washed with water, brine, dried (magnesium sulfate),
evaporated and purified by column chromatography (silica)
to afford cyclic products (0.11–1.11 g, 57–85%).
Ethyl (E)-5-[N-(6-oxocyclohex-1-enyl)-2,2-dichloroethan-
amido]pent-2-enoate 12b. A mixture of diene 12a (0.30 g,
1.09 mmol) and osmium tetroxide (one crystal) in dioxane–
water (2:1, 10 cm3) was stirred while sodium periodate
(0.51 g, 2.39 mmol) was added portionwise over 0.3 h.
After stirring for 1 h at room temperature the solution was
extracted with ethyl acetate (×3) and the combined organic
extracts were washed with water, dried (magnesium sulfate)
and evaporated to afford the crude aldehyde, N-(2-formyl-
ethyl)-N-(6-oxocyclohex-1-enyl)-2,2-dichloroethanamide:
dH (270 MHz, CDCl3) 9.72 (1H, t, Jˆ1 Hz, CHO), 7.15
(1H, t, Jˆ4 Hz, CHvC), 5.79 (1H, s, CHCl2), 3.79 (2H, t,
Jˆ6.5 Hz, NCH2), 2.85 (2H, dt, Jˆ1, 6.5 Hz, NCH2CH2),
2.65–2.58 (4H, m, CH2COC and CH2CHvC) and 2.20–
2.09 (2H, m, CH2CH2CH2). This was dissolved in dichloro-
methane (8 cm3) and (carbethoxymethylene)triphenylphos-
phorane (0.57 g, 1.63 mmol) was added portionwise. The
mixture was stirred for 4 h and further dichloromethane
(20 cm3) added. After washing with water, the solvent was
evaporated and purification of the crude product by column
chromatography (silica; diethyl ether) afforded 12b (0.26 g,
68%) as a colourless oil: Rf 0.3 (diethyl ether); nmax
(CHCl3)/cmϪ1 3026 (w), 3011 (w), 2958 (w), 2939 (w),
1700 (br, s), 1602 (w), 1321 (w), 1310 (w), 1279 (w),
1233 (w), 1196 (w), 1124 (w), 1097 (w) and 1042 (w); dH
(270 MHz, CDCl3) 7.16 (1H, t, Jˆ4 Hz, CHvC), 6.84 (1H,
dt, Jˆ16, 7 Hz, CHvCHCO2Et), 5.88 (1H, s, CHCl2), 5.85
(1H, dt, Jˆ16, 1.5 Hz, CHvCHCO2Et), 4.18 (2H, q,
Jˆ7 Hz, CO2CH2CH3), 3.86 (1H, dt, Jˆ13.5, 7.5 Hz,
NCHAHB), 3.36 (1H, dt, Jˆ13.5, 7 Hz, NCHAHB), 2.66–
2.59 (4H, m, CH2CO and CH2CHvC), 2.53–2.42 (2H, m,
NCH2CH2), 2.15 (2H, appt quintet, Jˆ6.5 Hz, CH2CH2CH2)
and 1.28 (3H, t, Jˆ7 Hz, CO2CH2CH3); dC (67.5 MHz,
CDCl3) 194.5 (CH2COC), 165.9 (OCO), 163.7 (NCO),
151.0 (CHvC), 144.4 (CHvCHCO2Et), 137.8 (CvCH),
123.4 (CHvCHCO2Et), 64.5 (CHCl2), 60.2 (CO2CH2CH3),
1-Benzyloctahydroindole-2,7-dione 7a. 63% (d.r. 4.2–
3.7:1); (3aRء,7aSء) — Major diastereomer: oil; Rf 0.3
(ethyl acetate–petroleum ether, 4:1); nmax (CHCl3)/cmϪ1
3006 (m), 2938 (m), 2873 (w), 1708 (s), 1691 (s), 1449
(m), 1417 (s), 1357 (w), 1305 (w), 1247 (m), 1143 (w)
and 1124 (w); dH (270 MHz, CDCl3) 7.32–7.19 (5H, m,
aromatics), 5.18 (1H, d, Jˆ15 Hz, NCHAHBPh), 4.18 (1H,
d, Jˆ15 Hz, NCHAHBPh), 3.78 (1H, d, Jˆ8.5 Hz,
COCHN), 2.96–2.82 (1H, m, NCHCH), 2.44 (1H, dd, Jˆ
16.5, 8 Hz, CHAHBCON), 2.23 (2H, t, Jˆ6.5 Hz, CH2COC),
2.12 (1H, dd, Jˆ16.5, 10.5 Hz, CHAHBCON) and 1.97–1.62
(4H, m, CH2CH2CH and CH2CH2CH2); dC (67.5 MHz,
CDCl3) 209.5 (CH2COC), 173.7 (NCO), 136.2 (CvCH),
128.5, 128.1, 127.4 (3×CHvC), 64.5 (COCHN), 45.8
(NCH2Ph), 39.5 (CH2COC), 36.8 (NCHCH), 35.1
(CH2CON), 26.5 and 22.1 (CH2CH2CH and CH2CH2CH2);
m/z (CI, NH3) 244 (MϩHϩ, 100%); Found: MϩHϩ,
244.1335. C15H17NO2 requires for MϩHϩ, 244.1338.
(3aRء,7aRء) — Minor diastereomer: oil; Rf 0.35 (ethyl
acetate-petroleum ether, 4:1); nmax (CHCl3)/cmϪ1 3008
(w), 2948 (w), 1695 (br s), 1448 (w), 1394 (w), 1328 (w)
and 1136 (w); dH (270 MHz, CDCl3) 7.25–7.11 (5H, m,
aromatics), 5.12 (1H, d, Jˆ14.5 Hz, NCHAHBPh), 4.37
(1H, d, Jˆ14.5 Hz, NCHAHBPh), 3.50 (1H, d, Jˆ11 Hz,
COCHN), 2.53–2.42 (1H, m, CHAHBCON), 2.27–1.94
(6H, m, CHAHBCON, NCHCH, CH2COC and CH2CH2CH
or CH2CH2CH2) and 1.81–1.43 (2H, m, CH2CH2CH or
CH2CH2CH2); dC (67.5 MHz, CDCl3) 205.4 (CH2COC),
174.5 (NCO), 136.3 (CvCH), 128.7, 128.7, 127.6
(3×CHvC), 67.9 (COCHN), 44.9 (NCH2Ph), 43.8
(NCHCH), 39.7, 37.5 (CH2COC and CH2CON), 27.9 and

7224
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
27.4 (CH2CH2CH and CH2CH2CH2); m/z (CI, NH3) 261
(MϩNHϩ4 , 45%) and 244 (MϩHϩ, 100); Found: MϩHϩ,
244.1334. C15H17NO2 requires for MϩHϩ, 244.1338.
(COCHN), 45.6 (NCH2Ar), 39.5 (CH2COC or CH2CON),
36.7 (NCHCH), 35.2 (CH2COC or CH2CON), 26.6 and 22.1
(CH2CH2CH and CH2CH2CH2); m/z (CI, NH3) 288 (MϩHϩ,
100%) and 135 (20); Found: MϩHϩ, 288.1236. C16H17NO4
requires for MϩHϩ, 288.1236. (3aRء,7aRء) — Minor
diastereomer: solid; mp 119–121ЊC (Found: C, 66.67; H,
6.03; N, 4.46%. C16H17NO4 requires C, 66.89; H, 5.96; N,
4.88%); Rf 0.2 (ethyl acetate–petroleum ether, 7:3); nmax
(CHCl3)/cmϪ1 3007 (w), 2950 (w), 1727 (m), 1691 (s),
1490 (m), 1446 (m), 1394 (w), 1245 (m), 1136 (w) and
1042 (m); dH (270 MHz, CDCl3) 6.71 (1H, d, Jˆ8 Hz,
CHCHCO), 6.69 (1H, d, Jˆ1.5 Hz, CCHCO), 6.64 (1H,
dd, Jˆ8, 1.5 Hz, CHCHCO), 5.93 (2H, s, OCH2O), 5.08
(1H, d, Jˆ14 Hz, NCHAHBAr), 4.34 (1H, d, Jˆ14 Hz,
NCHAHBAr), 3.59 (1H, d, Jˆ11.5 Hz, COCHN), 2.60–
2.48 (1H, m, CHAHBCON), 2.36–2.02 (6H, m,
CHAHBCON, NCHCH, CH2COC and CH2CH2CH or
CH2CH2CH2) and 1.88–1.52 (2H, m, CH2CH2CH or
CH2CH2CH2); dC (67.5 MHz, CDCl3) 205.9 (CH2COC),
175.0 (NCO), 148.3, 147.5 (CHCHCO and CCHCO),
130.6 (NCH2C), 122.6 (CHCHCO), 109.5, 108.7
(CHCHCO and CCHCO), 101.5 (OCH2O), 68.2
(COCHN), 45.1 (NCH2Ar), 44.1 (NCHCH), 40.2, 38.0
(CH2COC and CH2CON), 28.4 and 27.9 (CH2CH2CH and
CH2CH2CH2); m/z (CI, NH3) 288 (MϩHϩ, 100%), 154 (10)
and 135 (20); Found: MϩHϩ, 288.1234. C16H17NO4
requires for MϩHϩ, 288.1236.
1-(4-Methoxybenzyl)octahydroindole-2,7-dione 7b. 65–
85%(d.r. 3.3–4.8:1); (3aRء,7aSء) — Major diastereomer:
solid; mp 101–104ЊC; Rf 0.35 (ethyl acetate–petroleum
ether, 4:1); nmax (CHCl3)/cmϪ1 3007 (w), 2935 (w), 1720
(m), 1686 (s), 1612 (w), 1513 (m), 1448 (w), 1415 (w), 1303
(w), 1246 (w), 1177 (w) and 1035(m); dH (270 MHz,
CDCl3) 7.14 (2H, d, Jˆ8.5 Hz, 2×CHCHCOMe), 6.84
(2H, d, Jˆ8.5 Hz, 2×CHCOMe), 5.08 (1H, d, Jˆ14.5 Hz,
NCHAHBAr), 4.12 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 3.79–
3.75 (4H, m, OCH3 and COCHN), 2.92–2.80 (1H, m,
NCHCH), 2.42 (1H, dd, Jˆ16.5, 8 Hz, CHAHBCON),
2.35–2.13 (3H, m, CH2COC and CHAHBCON) and 2.04–
1.60 (4H, m, CH2CH2CH and CH2CH2CH2); dC (67.5 MHz,
CDCl3) 209.6 (CH2COC), 173.7 (NCO), 158.9 (COMe),
129.6 (CHCHCOMe), 128.2 (NCH2C), 113.9 (CHCOMe),
64.4 (COCHN), 55.1 (OCH3), 45.3 (NCH2Ar), 39.5
(CH2COC or CH2CON), 36.7 (NCHCH), 35.4 (CH2COC
or CH2CON), 26.6 and 22.2 (CH2CH2CH and
CH2CH2CH2); m/z (CI, NH3) 274 (MϩHϩ, 100%) and 121
(15); Found: MϩHϩ, 274.1441. C16H19NO3 requires for
MϩHϩ, 274.1443. (3aRء,7aRء) — Minor diastereomer:
solid; mp 98–101 ЊC; Rf 0.4 (ethyl acetate–petroleum
ether, 4:1); nmax (CHCl3)/cmϪ1 3007 (w), 2952 (w), 1726
(m), 1691 (s), 1611 (w), 1513 (m), 1391 (w), 1247 (m), 1178
(w), 1137 (w) and 1035 (w); dH (270 MHz, CDCl3) 7.12
(2H, d, Jˆ8.5 Hz, 2×CHCHCOMe), 6.81 (2H, d, Jˆ
8.5 Hz, 2×CHCOMe), 5.12 (1H, d, Jˆ14.5 Hz, NCHAHBAr),
4.37 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 3.78 (3H, s, OCH3),
3.55 (1H, d, Jˆ11.5 Hz, COCHN), 2.60–2.46 (1H, m,
CHAHBCON), 2.34–1.98 (6H, m, NCHCH, CHAHBCON,
CH2COC, CH2CH2CH or CH2CH2CH2) and 1.88–1.50
(2H, m, CH2CH2CH or CH2CH2CH2); dC (67.5 MHz,
CDCl3) 206.0 (CH2COC), 175.0 (NCO), 159.5 (COMe),
130.5 (CHCHCOMe), 128.9 (NCH2C), 114.4 (CHCOMe),
68.3 (COCHN), 55.6 (OCH3), 44.7 (NCH2Ar), 44.1
(NCHCH), 40.2, 38.0 (CH2COC and CH2CON), 28.4 and
28.3 (CH2CH2CH and CH2CH2CH2); m/z (CI, NH3) 274
(MϩHϩ, 100%) and 121 (25); Found: MϩHϩ, 274.1438.
C16H19NO3 requires for MϩHϩ, 274.1443.
1-(3-Fluorobenzyl)octahydroindole-2,7-dione 7d. 71%
(d.r. 4.6:1); (3aRء,7aSء) — Major diastereomer: oil; Rf 0.2
(diethyl ether); nmax (CHCl3)/cmϪ1 3037 (w), 3022 (w),
3007 (w), 2939 (w), 2874 (w), 1701 (s), 1689 (s), 1616
(w), 1592 (w), 1488 (w), 1451 (w), 1416 (m), 1352 (w),
1306 (w), 1256 (m), 1228 (w), 1206 (w) and 1139 (w); dH
(270 MHz, CDCl3) 7.28 (1H, dt, Jˆ6, 8 Hz, CHCHCF),
7.02–6.89 (3H, m, CCHCF, CHCHCF and CHCCHCF),
5.16 (1H, d, Jˆ15 Hz, NCHAHBAr), 4.18 (1H, d,
Jˆ15 Hz, NCHAHBAr), 3.84 (1H, d, Jˆ8.5 Hz, COCHN),
3.03–2.83 (1H, m, NCHCH), 2.45 (1H, dd, Jˆ16.5, 8 Hz,
CHAHBCON), 2.38–2.32 (2H, m, CH2COC), 2.19 (1H, dd,
Jˆ16.5, 11 Hz, CHAHBCON) and 2.05–1.64 (4H, m,
CH2CH2CH and CH2CH2CH2); dC (67.5 MHz, CDCl3)
1
209.4 (CH2COC), 173.8 (NCO), 162.7 (d, JCFˆ246 Hz,
3
3
CF), 138.9 (d, JCFˆ7 Hz, CCHCF), 130.0 (d, JCFˆ8 Hz,
4
1-(3,4-Methylenedioxybenzyl)octahydroindole-2,7-dione
7c. 74% (d.r. 5.1:1); (3aRء,7aSء) — Major diastereomer:
solid; mp 103–105 ЊC; (Found: C, 66.95; H, 5.94; N,
4.83%. C16H17NO4 requires C, 66.89; H, 5.96; N, 4.88%);
Rf 0.2 (ethyl acetate-petroleum ether, 7:3); nmax (CHCl3)/
cmϪ1 3006 (m), 2940(m), 1720 (s), 1690 (s), 1491 (m), 1444
(m), 1418 (m), 1369 (w), 1246 (s), 1195 (w) and 1042 (m);
dH (270 MHz, CDCl3) 6.74 (1H, d, Jˆ8 Hz, CHCHCO),
6.71 (1H, d, Jˆ1.5 Hz, CCHCO), 6.66 (1H, dd, Jˆ8,
1.5 Hz, CHCHCO), 5.94 (2H, s, OCH2O), 5.06 (1H, d, Jˆ
14.5 Hz, NCHAHBAr), 4.08 (1H, d, Jˆ14.5 Hz, NCHAHBAr),
3.80 (1H, d, Jˆ8.5 Hz, COCHN), 2.97–2.82 (1H, m,
NCHCH), 2.42 (1H, dd, Jˆ16.5, 8 Hz, CHAHBCON), 2.33
(2H, appt t, Jˆ6 Hz, CH2COC), 2.18 (1H, dd, Jˆ16.5,
11 Hz, CHAHBCON) and 2.03–1.62 (4H, m, CH2CH2CH
and CH2CH2CH2); dC (67.5 MHz, CDCl3) 209.6
(CH2COC), 173.6 (NCO), 147.8, 146.9 (CHCHCO and
CCHCO), 130.0 (NCH2C), 121.6 (CHCHCO), 108.5,
108.1 (CHCHCO and CCHCO), 100.9 (OCH2O), 64.3
CHCHCF), 123.5 (d, JCFˆ3 Hz, CHCCHCF), 114.6 (d,
2JCFˆ22 Hz, CHCF), 114.2 (d, JCFˆ21 Hz, CHCF), 64.4
2
(COCHN), 45.3 (NCH2Ar), 39.4 (CH2COC or CH2CON),
36.7 (NCHCH), 34.7 (CH2COC or CH2CON), 26.3 and 22.0
(CH2CH2CH and CH2CH2CH2); m/z (CI, NH3) 262 (MϩHϩ,
100%); Found: MϩHϩ, 262.1237. C15H16FNO2 requires for
MϩHϩ, 262.1243. (3aRء,7aRء) — Minor diastereomer:
solid; mp 89–92 ЊC; Rf 0.2 (diethyl ether); nmax (CHCl3)/
cmϪ1 3054 (w), 3040 (w), 3021 (w), 3006 (w), 2950 (w),
2871 (w), 1706 (br, s), 1616 (w), 1592 (w), 1488 (w), 1451
(w), 1432 (w), 1399 (m), 1340 (w), 1257 (w), 1228 (w),
1206 (w), 1167 (w), 1138 (w) and 1079 (w); dH
(270 MHz, CDCl3) 7.30–7.22 (1H, dt, Jˆ6, 8 Hz,
CHCHCF), 6.99–6.88 (3H, m, CCHCF, CHCHCF and
CHCCHCF), 5.11 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 4.47
(1H, d, Jˆ14.5 Hz, NCHAHBAr), 3.62 (1H, d, Jˆ12 Hz,
COCHN), 2.62–2.49 (1H, m, CHAHBCON) and 2.37–2.02
(6H, m, CHAHBCON, NCHCH, CH2COC and CH2CH2CH
or CH2CH2CH2), 1.93–1.53 (2H, m, CH2CH2CH or

A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
7225
CH2CH2CH2); dC (67.5 MHz, CDCl3) 205.3 (CH2COC),
171.6, 171.4, 171.1 (OCO and NCO), 79.7, 78.1 (COCN),
61.1 (CO2CH2CH3), 45.5, 44.0 (NCCH), 42.2, 41.1 (NCH2
or CH2COC), 39.9 (CHCH2CO2Et), 39.7, 38.9, 38.8
(CH2CO2Et and NCH2 or CH2COC), 37.0 (CHCH2CO2Et),
35.5, 35.3, 32.1, 32.0 (CH2CON and NCH2CH2), 25.7, 25.3
(CH2CH2CH2CO), 21.7, 20.1 (CH2CH2CH2) and 14.2
(CO2CH2CH3); m/z (CI, NH3) 280 (MϩHϩ, 100%);
Found: MϩHϩ, 280.1544. C15H21NO4 requires for
MϩHϩ, 280.1549.
1
174.6 (NCO), 162.9 (d, JCFˆ246 Hz, CF), 138.9 (d,
3
3JCFˆ7 Hz, CCHCF), 130.2 (d, JCFˆ8 Hz, CHCHCF),
4
2
124.2 (d, JCFˆ3 Hz, CHCCHCF), 115.4 (d, JCFˆ22 Hz,
2
CHCF), 114.6 (d, JCFˆ22 Hz, CHCF), 67.9 (COCHN),
44.5 (NCH2Ar), 43.8 (NCHCH), 39.7, 37.4 (CH2COC and
CH2CON), 27.9 and 27.4 (CH2CH2CH and CH2CH2CH2);
m/z (CI, NH3) 262 (MϩHϩ, 100%); Found: MϩHϩ,
262.1235. C15H16FNO2 requires for MϩHϩ, 262.1243.
1-Benzyl-7a-hydroxyoctahydroindole-2,7-dione 9. 22%;
Oil; Rf 0.4 (ethyl acetate–petroleum ether, 4:1); nmax
(CHCl3)/cmϪ1 3474 (br w, OH), 3009 (w), 2953 (m), 2870
(w), 1702 (br s), 1449 (w), 1398 (m), 1334 (w), 1236 (w),
1136 (w), 1105 (m) and 1066 (w); dH (270 MHz, CDCl3)
7.28–7.18 (5H, m, aromatics), 4.96 (1H, s, COH exchange-
able), 4.75 (1H, d, Jˆ15 Hz, NCHAHBPh), 3.77 (1H, d,
Jˆ15 Hz, NCHAHBPh), 2.94 (1H, dd, Jˆ17, 7 Hz,
CHAHBCON), 2.51–2.43 (1H, m, NCCH) and 2.23–1.25
(7H, m, CHAHBCON, CH2COC, CH2CH2CH and
CH2CH2CH2); dC (67.5 MHz, CDCl3) 208.2 (CH2COC),
176.2 (NCO), 136.9 (CvCH), 129.1, 128.6, 127.6
(3×CHvC), 90.2 (COH), 43.8 (NCHCH), 42.7
(NCH2Ph), 37.3, 36.4 (CH2COC and CH2CON), 30.1 and
23.4 (CH2CH2CH and CH2CH2CH2); m/z (CI, NH3) 260
(MϩHϩ, 100%), 244 (65), 242 (35), 189 (15), 106 (25)
and 91 (35); Found: MϩHϩ, 260.1284. C15H17NO3 requires
for MϩHϩ, 260.1287.
(4aRء,9aSء,13aSء,13bRء)-Tetradecahydro-6H-indolo-
[7a,1-a]isoquinoline-1,6-dione 16. 19–37%; Solid; mp
124–127ЊC; Rf 0.2 (diethyl ether-dichloromethane, 4:1);
nmax (CHCl3)/cmϪ1 3006 (m), 2932 (s), 2857 (m), 1703
(s), 1673 (s), 1449 (m), 1434 (m), 1419 (m), 1366 (w),
1301 (w), 1268 (w), 1250 (w), 1237 (w), 1216 (w), 1199
(w), 1175 (w), 1125 (w) and 1105 (w); dH (270 MHz,
CDCl3) 4.10 (1H, ddd, Jˆ13, 5.5, 1.5 Hz, NCHAHB), 3.41
(1H, ddt, Jˆ3.5, 1.5, 13 Hz, NCHAHB), 2.69–2.22 (5H, m,
CH2CO, CH2CON and CHCH2CON) and 2.08–0.83 (16H,
m, NCH2CH2CH, NCH2CH2CHCH, 4×CH2CH2CH and
3×CH2CH2CH2);
dC
(67.5 MHz,
CDCl3)
212.2
(CH2COC), 172.3 (NCO), 70.9 (COCN), 53.5
(NCH2CH2CHCH), 42.5 (NCH2 or CH2COC or
CH2CON), 42.1 (CHCH2CON), 39.1, 35.4 (two from
NCH2, CH2COC or CH2CON), 35.0 (NCH2CH2CH), 34.3,
32.4, 29.4, 27.6, 27.1, 25.8 and 19.4 (4×CH2CH2CH and
3×CH2CH2CH2); m/z (CI, NH3) 262 (MϩHϩ, 100%);
Found: MϩHϩ, 262.1805. C16H23NO2 requires for
MϩHϩ, 262.1807.
(7aRء,11aSء)-Decahydro-6H-pyrido[2,1-i]indole-6,11-
dione 13. 58%; Solid; mp 104–106ЊC (Found: C, 69.67; H,
8.52; N, 6.73. C12H17NO2 requires C, 69.54; H, 8.27; N,
6.76%); Rf 0.2 (ethyl acetate); nmax (CHCl3)/cmϪ1 3035
(w), 3025 (m), 3006 (s), 2947 (s), 2863 (m), 1717 (s),
1688 (s), 1461 (m), 1449 (m), 1431 (m), 1414 (s), 1365
(w), 1292 (m), 1252 (m), 1243 (w), 1207 (w), 1163 (w),
1147 (w), 1123 (w) and 1052 (w); dH (270 MHz, CDCl3)
4.06 (1H, dd, Jˆ13, 4.5 Hz, NCHAHB), 3.29 (1H, ddt,
Jˆ3.5, 1.5, 13 Hz, NCHACHB), 2.63–1.68 (12H, m,
CH2CO, CH2CON, NCCH, CH2CH2CH, CH2CH2CO,
NCCH2 and NCH2CHAHB) and 1.52–1.26 (3H, m,
NCH2CHAHB and NCH2CH2CH2); dC (67.5 MHz, CDCl3)
212.0 (CH2COC), 172.0 (NCO), 69.9 (COCN), 45.5
(NCCH), 38.5, 38.0 (NCH2 and CH2COC), 33.4, 32.8
(CH2CON and NCCH2), 24.1, 23.4, 22.0 and 19.5
(NCH2CH2, CH2CH2CH, CH2CH2CO and NCH2CH2CH2);
m/z (CI, NH3) 208 (MϩHϩ, 100%), 179 (15), 150 (25) and
137 (10); Found: MϩHϩ, 208.1337. C12H17NO2 requires for
MϩHϩ, 208.1338.
1-[2-(Cyclohex-1-enyl)ethyl]octahydroindole-2,7-dione
17. 32–38% (d.r. 4.7–5.3:1); Oil; (3aRء,7aSء) — Major
diastereomer: Rf 0.2 (diethyl ether-dichloromethane, 4:1);
nmax (CHCl3)/cmϪ1 3020 (w), 3010 (w), 2937 (m), 2872 (w),
2861 (w), 1698 (br s), 1449 (w), 1408 (m), 1366 (w), 1349
(w), 1236 (w), 1217 (w) and 1176 (w); dH (270 MHz,
CDCl3) 5.44–5.40 (1H, br m, CHvC), 4.03 (1H, d,
Jˆ8.5 Hz, COCHN), 3.95 (1H, dt, Jˆ14, 7.5 Hz, NCHAHB),
3.06 (1H, dt, Jˆ14, 7 Hz, NCHAHB), 2.97–2.83 (1H, m,
NCHCH), 2.41 (2H, appt t, Jˆ6.5 Hz, CH2COC), 2.36
(1H, dd, Jˆ16.5, 8 Hz, CHAHBCON) and 2.20–1.41 (15H,
m,
CHAHBCON,
NCH2CH2,
CH2CH2CH2CvCH,
CH2CHvC, CH2CH2CO, CH2CH2CH2CO, CH2CH2CHvC,
CH2CH2CH2CvCH); dC (67.5 MHz, CDCl3) 209.4
(CH2COC), 173.8 (NCO), 134.8 (CvCH), 123.0
(CHvC), 65.6 (COCHN), 40.5, 39.5 (NCH2 and
CH2COC), 36.8 (NCHCH), 35.5, 35.5 (CH2CON and
NCH2CH2),
27.8,
26.8,
25.2
(CH2CHvC,
CH2CH2CH2CvCH and CH2CH2CH2CO), 22.8, 22.4 and
22.2 (3×CH2CH2CH2); m/z (CI, NH3) 262 (MϩHϩ, 100%)
and 154 (15); Found: MϩHϩ, 262.1801. C16H23NO2
requires for MϩHϩ, 262.1807. (3aRء,7aRء) — Minor
diastereomer: oil; Rf 0.3 (diethyl ether-dichloromethane,
4:1); nmax (CHCl3)/cmϪ1 3024 (w), 3009 (w), 2940 (m),
2867 (w), 1702 (br s), 1449 (w), 1405 (m), 1372 (w),
1351 (w), 1234 (w), 1220 (w) and 1175 (w); dH
(270 MHz, CDCl3) 5.41 (1H, br s, CHvC), 3.98 (1H, d,
Jˆ11 Hz, COCHN), 3.81 (1H, dt, Jˆ13.5, 7.5 Hz,
NCHAHB), 3.52 (1H, dt, Jˆ13.5, 7 Hz, NCHAHB), 2.51–
2.34 (3H, m, CH2COC and CHAHBCON or NCHCH) and
2.23–1.45 (16H, m, CHAHBCON or NCHCH, CHAHBCON,
NCH2CH2, CH2CH2CH2CvCH, CH2CHvC, CH2CH2CO,
(1RءSء,6aRء,10aRء)-1-[(Ethoxycarbonyl)methyl]octa-
hydro-1H,5H-pyrollo[2,1-i]indole-5,10-dione 14. 64%
(d.r. 1:1); Solid; mp 105–109ЊC; Rf 0.2 (ethyl acetate-
dichloromethane, 4:1); nmax (CHCl3)/cmϪ1 3036 (w), 3025
(w), 3005 (w), 2951 (w), 1725 (s), 1685 (s), 1476 (w), 1417
(m), 1381 (w), 1314 (w), 1241 (w), 1233 (w), 1220 (w),
1207 (w), 1194 (w), 1177 (w), 1166 (w) and 1027 (w); dH
(270 MHz, CDCl3) (mixture of diastereomers) 4.24–4.14
(2H, m, CO2CH2CH3), 3.64–3.28 (2H, m, NCH2), 2.93–
1.66 (14H, m, CH2CO, CH2CON, NCCH, CHCH2CO2Et,
CH2CO2Et, CH2CH2CH2CO, CH2CH2CO, NCH2CH2) and
1.32–1.26 (3H, m, CO2CH2CH3); dC (67.5 MHz, CDCl3)
(mixture of diastereomers) 211.5, 210.9 (CH2COC), 172.0,

7226
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
CH2CH2CH2CO, CH2CH2CHvC, CH2CH2CH2CvCH);
dC (67.5 MHz, CDCl3) 205.5 (CH2COC), 174.3 (NCO),
135.4 (CvCH), 123.1 (CHvC), 69.3 (COCHN), 44.3
(NCHCH), 39.9, 39.6, 37.5, 35.8 (NCH2, CH2COC,
CH2CON and NCH2CH2), 28.3, 27.9, 27.6, 25.4, 22.9 and
22.4 (CH2CHvC, CH2CH2CH2CvCH, CH2CH2CH2CO
and 3×CH2CH2CH2); m/z (CI, NH3) 262 (MϩHϩ, 100%)
and 154 (10); Found: MϩHϩ, 262.1804. C16H23NO2
requires for MϩHϩ, 262.1807.
19: Oil; Rf 0.2 (ethyl acetate); nmax (CHCl3)/cmϪ1 3571 (br
w, OH), 3021 (w), 3007 (w), 2939 (w), 2867 (w), 1683 (s),
1445 (w), 1418 (w), 1384 (w), 1373 (w), 1321 (w), 1301
(w), 1268 (w), 1241 (w), 1227 (w), 1187 (w), 1160 (w),
1037 (w) and 1016 (w); dH (270 MHz, CDCl3) 5.77–5.74
(1H, m, CHvC), 5.70–5.68 (2H, m, OCH2O), 4.43 (1H, d,
Jˆ14.5 Hz, NCHAHB), 3.40–3.34 (2H, m, NCHAHB and
COHCHN), 3.27 (1H, br t, Jˆ8 Hz, COHCHCH2), 3.01–
2.92 (2H, m, COHCHCH2), 2.60–2.48 (1H, m, NCHCH),
2.45 (1H, dd, Jˆ16, 6 Hz, CHAHBCON), 2.01 (1H, d,
Jˆ16 Hz, CHAHBCON) and 1.73–1.03 (6H, m, CH2COH,
CH2CH2CH and CH2CH2CH2); dC (67.5 MHz, CDCl3)
175.9 (NCO), 134.3, 131.2, 129.6 (CvCH and 2×CvC),
121.5 (CHvC), 99.5 (OCH2O), 72.3 (COH), 63.1
(COHCHN), 47.8 (COHCHCvCH), 46.5 (NCH2Ar), 40.3
(CH2CON), 31.2 (NCHCH), 29.2, 29.0 (CH2CvC and
CH2COH), 24.8 (CH2CH2CH) and 19.3 (CH2CH2CH2);
m/z (CI, NH3) 290 (MϩHϩ, 100%), 154 (15), 136 (25) and
134 (20); Found: MϩHϩ, 290.1390. C16H19NO4 requires for
MϩHϩ, 290.1392.
Treatment of (3aRء,7aSء)-1-(3,4-methylenedioxybenzyl)-
octahydroindole-2,7-dione 7c with samarium(II) iodide
in the presence of DMPU
To a solution of octahydroindolone 7c (0.15 g, 0.52 mmol)
in anhydrous THF (15 cm3) was added DMPU (0.51 cm3,
4.18 mmol) and the solution was stirred for 0.25 h. SmI2
solution (0.1 mol dmϪ3 in THF; 11.50 cm3, 1.15 mmol)
was added dropwise over 1 h via a syringe pump and the
solution was stirred for a further 3 h, after which TLC
indicated that starting material remained. Further SmI2
solution (5.75 cm3, 0.57 mmol) was added and the solution
stirred for a further 1 h. The solution was filtered through
Celite and the solvent removed under reduced pressure.
Column chromatography (silica; ethyl acetate) afforded
(3aRء,11cSء)-11b-hydroxy-9,10-methylene-dioxy-1,2,3,3a,4,
5,11,11a,11b,11c-decahydro-7H-pyrollo[3,2,1-de]phenan-
thridin-5-one 19 (25 mg, 17%) as a single diastereomer and
(3aRء,7RءSء,7aSء)-7-hydroxy-1-(3,4-methylenedioxybenzyl)-
octahydroindol-2-one 18 (26 mg, 17%) as an inseparable
2.6:1 mixture of diastereomers.
Treatment of (3aRء,7aSء)-1-(3,4-methylenedioxybenzyl)-
octahydroindole-2,7-dione 7c with manganese(III)
acetate dihydrate
To a solution of octahydroindolone 7c (0.11 g, 0.38 mmol)
in degassed benzene (15 cm3) was added manganese(III)
acetate dihydrate (0.41 g, 1.53 mmol). The solution was
heated overnight at reflux under nitrogen, cooled, filtered
through Celite, washed with water, brine, dried (magnesium
sulfate) and the solvent evaporated under reduced pressure.
Column chromatography (silica; ethyl acetate) afforded
11,12-methylene-dioxy-2,3,3a,4,5,6,7,7a-octahydro-6,1-([1,2]-
benzenomethano)indole-2,7-dione 22 and 12,13-methylene-
dioxy-2,3,3a,4,5,6,7,7a-octahydro-6,1-([1,2]benzenomethano)-
indole-2,7-dione 23 (37 mg, 34%) as an inseparable 2.8:1
mixture and (3aRء,6RءSء,7aSء)-6-acetoxy-1-(3,4-methylene-
dioxybenzyl)octahydroindole-2,7-dione 21 (24 mg, 18%) as
an inseparable 2.7:1 mixture of diastereomers.
18 (Major diastereomer): solid; mp 131–134ЊC; Rf 0.25
(ethyl acetate); nmax (CHCl3)/cmϪ1 3615 (w, OH), 3019
(w), 2938 (w), 2901 (w), 1673 (s), 1504 (w), 1490 (m),
1444 (m), 1421 (m), 1371 (w), 1246 (m), 1224 (m), 1098
(w) and 1042 (w); dH (270 MHz, CDCl3) 6.78–6.74 (3H, m,
aromatics), 5.93 (2H, s, OCH2O), 4.93 (1H, d, Jˆ14.5 Hz,
NCHAHBAr), 4.31 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 3.68
(1H, ddd, Jˆ10.5, 7.5, 4 Hz, CHOH), 3.18 (1H, t, Jˆ
7.5 Hz, CHOHCHN), 2.63–2.25 (4H, m, NCHCH,
CH2CON and CHOH) and 1.88–1.17 (6H, m, CH2CHOH,
CH2CH2CH and CH2CH2CH2); dC (67.5 MHz, CDCl3)
174.7 (NCO), 147.8, 146.8 (CHCHCO and CCHCO),
131.1 (NCH2C), 121.5 (CHCHCO), 108.6, 108.2
(CHCHCO and CCHCO), 100.9 (OCH2O), 73.3 (CHOH),
63.1 (CHOHCHN), 45.7 (NCH2Ar), 35.3 (CH2CHOH or
CH2CON), 34.0 (NCHCH), 32.5 (CH2CHOH or
CH2CON), 25.8 (CH2CH2CH) and 18.8 (CH2CH2CH2);
m/z (CI, NH3) 290 (MϩHϩ, 100%), 156 (10) and 135 (30);
Found: MϩHϩ, 290.1391. C16H19NO4 requires for MϩHϩ,
290.1392. Minor diastereomer: the presence of this was
indicated by: dH (270 MHz, CDCl3) 5.95 (2H, s, OCH2O),
4.76 (1H, d, Jˆ15 Hz, NCHAHBAr), 4.08 (1H, d, Jˆ15 Hz,
NCHAHBAr), 4.03–3.98 (1H, br m, CHOH), 3.27 (1H, dd,
Jˆ7, 4 Hz, CHOHCHN); dC (67.5 MHz, CDCl3) 176.9
(NCO), 148.0, 147.0 (CHCO), 130.9 (NCH2C), 121.3
(CHCHCO), 108.4, 108.3 (CHCHCO and CCHCO), 101.1
(OCH2O), 65.6 (CHOH), 60.0 (CHOHCHN), 44.7
(NCH2Ar), 36.4 (CH2CHOH or CH2CON), 32.3
(NCHCH), 29.4 (CH2CHOH or CH2CON), 25.7
(CH2CH2CH) and 14.5 (CH2CH2CH2).
21: Oil; Major diastereomer: Rf 0.4 (ethyl acetate); nmax
(CHCl3)/cmϪ1 3007 (w), 2928 (m), 1741 (s), 1691 (s),
1491 (m), 1445 (m), 1418 (w), 1372 (w), 1243 (s) and
1042 (m); dH (270 MHz, CDCl3) 6.75–6.63 (3H, m,
aromatics), 5.94 (2H, s, OCH2O), 5.16 (1H, d, Jˆ15 Hz,
NCHAHBAr), 5.12–5.03 (1H, m, COOCH), 4.04–3.94
(2H, m, NCHAHBAr and COCHN), 3.02–2.82 (1H, m,
NCHCH), 2.35 (1H, dd, Jˆ17, 8 Hz, CHAHBCON) and
2.24–1.89 (8H, m, CHAHBCON, CH3COO, CH2CHCO
and CH2CH2CH); dC (67.5 MHz, CDCl3) 203.1
(CHCOCH), 172.9 (NCO), 169.7 (CH3COO), 147.9, 147.0
(CHCHCO and CCHCO), 129.7 (NCH2C), 121.5
(CHCHCO), 108.9, 108.3 (CHCHCO and CCHCO), 100.9
(OCH2O), 74.6 (COOCH), 64.2 (COCHN), 45.7 (NCH2Ar),
37.5 (NCHCH), 33.7 (CH2CON), 27.5 (CH2CHCO), 22.5
(CH2CH2CH) and 20.3 (CH3COO); m/z (CI, NH3) 346
(MϩHϩ, 100%), 286 (MϪCH3COO, 40) and 135 (25);
Found: MϩHϩ, 346.1290. C18H19NO6 requires for
MϩHϩ, 346.1291. Minor diastereomer: the presence of
this was indicated by: dH (270 MHz, CDCl3) 5.93 (2H, s,
OCH2O), 4.96 (1H, d, Jˆ14.5 Hz, NCHAHBAr), 3.89 (1H,
d, Jˆ14.5 Hz, NCHAHBAr), 2.77–2.66 (1H, m, NCHCH)
and 2.47 (1H, dd, Jˆ16.5, 7.5 Hz, CHAHBCON); dC

A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
7227
(67.5 MHz, CDCl3) 202.9 (CHCOCH), 174.4 (NCO), 169.8
(CH3COO), 74.9 (COOCH), 65.6 (COCHN), 45.2
(NCH2Ar), 36.0 (NCHCH) and 20.4 (CH3COO).
(1H, ddt, Jˆ15, 4.5, 1.5 Hz, NCHAHB), 4.42 (1H, dd,
Jˆ13, 1 Hz, COCHN), 4.19 (1H, ddt, Jˆ15, 9, 1 Hz,
NCHAHB), 3.30–3.20 (1H, br m, NCHCH), 2.75–2.32
(4H, m, CH2CO and CH2CHAr) and 2.02–1.80 (2H, m,
CH2CH2CH2); dC (67.5 MHz, CDCl3) 206.7 (CH2CO),
164.9 (NCO), 137.9 (CvCH), 132.9, 132.3, 128.5, 128.2,
126.9, 123.3 (4×CH, CvCH and CHvCH2), 118.9
(CHvCH2), 66.8 (COCHN), 45.9 (NCH2), 44.1
(NCHCHAr), 41.2 (CH2CO), 27.6 and 27.5 (CH2CH2CH
and CH2CH2CH2); m/z (CI, NH3) 256 (MϩHϩ, 100%);
Found: MϩHϩ, 256.1329. C16H17NO2 requires for
MϩHϩ, 256.1338. (4aRء,10bSء) — Minor diastereomer:
Rf 0.2 (diethyl ether); nmax (CHCl3)/cmϪ1 3008 (m), 2957
(m), 2929 (m), 2874 (w), 1724 (s), 1650 (s), 1603 (w), 1466
(m), 1445 (w), 1427 (w), 1417 (w), 1379 (w), 1359 (w),
1315 (w), 1289 (w), 1252 (w) and 1237 (w); dH
(270 MHz, CDCl3) 8.15 (1H, dd, Jˆ7.5, 1.5 Hz, CHvC),
7.47 (1H, dt, Jˆ7.5, 1.5 Hz, CHCHCH), 7.35 (1H, dt,
Jˆ7.5, 1 Hz, CHCHCH), 7.21 (1H, br d, Jˆ7.5 Hz,
CHvC), 5.86 (1H, dddd, Jˆ17, 10, 7.5, 5 Hz, CHvCH2),
5.27–5.19 (2H, m, CHvCH2), 4.95 (1H, ddt, Jˆ15.5, 5,
2 Hz, NCHAHB), 4.21 (1H, d, Jˆ6.5 Hz, COCHN), 3.93–
3.90 (1H, br m, NCHCHAr), 3.49 (1H, ddt, Jˆ15.5, 7.5,
1 Hz, NCHAHB), 2.75–2.65 (1H, m, CHAHBCO or
CHAHBCHAr), 2.47–2.17 (3H, m, CHAHBCHAr and
CH2CO or CHAHBCO and CH2CHAr), 2.09–1.76 (2H, m,
CH2CH2CH2); dC (67.5 MHz, CDCl3) 206.3 (CH2CO),
164.2 (NCO), 135.8 (CvCH), 133.7, 132.1, 130.1, 129.2,
127.5, 123.8 (4×CHvC, CvCH and CHvCH2), 117.8
(CHvCH2), 65.9 (COCHN), 49.0 (NCH2), 41.0
(NCHCHAr), 40.5 (CH2CO), 25.8 (CH2CHAr) and 22.3
(CH2CH2CH2); m/z (CI, NH3) 256 (MϩHϩ, 100%) and
150 (10); Found: MϩHϩ, 256.1337. C16H17NO2 requires
for MϩHϩ, 256.1338.
22: Oil; Rf 0.3 (ethyl acetate); nmax (CHCl3)/cmϪ1 3024 (w),
3007 (w), 2955 (w), 2923 (w), 1692 (s), 1487 (m), 1452 (w),
1410 (w), 1320 (w), 1237 (m) and 1043 (w); dH (270 MHz,
CDCl3) 6.69 (1H, s, aromatic), 6.54 (1H, s, aromatic), 5.93
(2H, s, OCH2O), 4.97 (1H, d, Jˆ16.5 Hz, NCHAHBAr), 4.18
(1H, d, Jˆ8 Hz, COCHN), 3.92 (1H, d, Jˆ16.5 Hz,
NCHAHBAr), 3.61 (1H, t, Jˆ8.5 Hz, COCHAr), 3.04–2.97
(1H, m, NCHCH), 2.88 (1H, dd, Jˆ16.5, 3 Hz, CHAHBCON),
2.39–2.22 (1H, m, CHAHBCHCO or CH2CHAHBCH), 2.16
(1H, d, Jˆ16.5 Hz, CHAHBCON), 2.00–1.85, 1.82–1.66
and 1.54–1.47 (3×1H, m, CHAHBCHCO and CH2CH2CH
or CH2CHAHBCH and CH2CHCO); dC (67.5 MHz, CDCl3)
209.3 (CHCOCH), 174.9 (NCO), 147.0, 146.6 (CCHCO),
131.1, 127.2 (NCH2C and NCH2CC), 110.1, 108.9
(CCHCO), 101.3 (OCH2O), 67.9 (COCHN), 55.5
(COCHAr), 45.1 (NCH2Ar), 37.9 (CH2CON), 34.5
(NCHCH), 30.6 (CH2CHCO) and 26.6 (CH2CH2CH); m/z
(CI, NH3) 286 (MϩHϩ, 100%) and 256 (10); Found:
MϩHϩ, 286.1076. C16H15NO4 requires for MϩHϩ,
286.1079.
23: The presence of this was indicated by: dH (270 MHz,
CDCl3) 6.72 (1H, d, Jˆ8 Hz, aromatic), 6.65 (1H, d,
Jˆ8 Hz, aromatic), 5.98 (1H, d, Jˆ1.5 Hz, OCHAHBO),
5.91 (1H, d, Jˆ1.5 Hz, OCHAHBO), 5.00 (1H, d,
Jˆ16.5 Hz, NCHAHBAr), 4.21 (1H, d, Jˆ8 Hz, COCHN),
3.98 (1H, t, Jˆ8 Hz, COCHAr), 3.90 (1H, d, Jˆ16.5 Hz,
NCHAHBAr) and 2.85 (1H, dd, Jˆ16.5, 3 Hz, CHAHBCON);
dC (67.5 MHz, CDCl3) 209.1 (CHCOCH), 174.8 (NCO),
146.1, 146.0 (CHCHCO and CCCO), 128.3 (NCH2C or
NCH2CC), 121.7 (CHCHCO), 119.6 (NCH2C or
NCH2CC), 107.0 (CHCHCO), 101.0 (OCH2O), 68.2
(COCHN), 48.3 (COCHAr), 45.0 (NCH2Ar), 37.9
(CH2CON), 34.9 (NCHCH), 28.5 (CH2CHCO) and 26.3
(CH2CH2CH).
26 Diastereomer 1: Rf 0.2 (diethyl ether); nmax (CHCl3)/
cmϪ1 3007 (m), 2963(m), 2880 (w), 1720 (s), 1692 (s),
1611 (w), 1466 (m), 1374 (m), 1348 (w), 1311 (w) and
1238 (w); dH (270 MHz, CDCl3) 7.82–7.78 (1H, m,
CHvC), 7.61–7.52 (2H, m, CHvC and CHCHCH), 7.47
(1H, dt, Jˆ1.5, 7.5 Hz, CHCHCH), 4.17 (1H, dd, Jˆ12,
7.5 Hz, NCHAHB), 3.00–2.85 (1H, m, NCCH), 2.83 (1H,
dd, Jˆ12, 8 Hz, NCHAHB), 2.71–2.51 (3H, m, CH2CO
and CH2CHAHBCH or CH2CH2CH and CHAHBCO), 2.30–
2.00 (3H, m, CH2CH2CH2 and CH2CHAHBCH or
CHAHBCO), 1.75–1.62 (1H, m, CHCH3) and 1.06 (3H, d,
Jˆ7 Hz, CHCH3); dC (67.5 MHz, CDCl3) 205.8 (CH2CO),
170.8 (NCO), 144.8 (CvCH), 132.7 (CvCH), 132.0,
129.0, 124.7, 121.4 (4×CH), 80.9 (COCN), 48.7 (NCH2),
48.2, 39.9 (NCCH and CHCH3), 37.2 (CH2CO), 23.0, 22.8
(CH2CH2CH and CH2CH2CH2) and 14.9 (CHCH3); m/z (CI,
NH3) 256 (MϩHϩ, 100%); Found: MϩHϩ, 256.1329.
C16H17NO2 requires for MϩHϩ, 256.1338. Diastereomer
2: The presence of this was indicated by: dH (270 MHz,
CDCl3) 3.63 (1H, dd, Jˆ11.5, 8.5 Hz, NCHAHB), 3.29
(1H, dd, Jˆ11.5, 8.5 Hz, NCHAHB), 1.87–1.81 (1H, m,
CHCH3) and 1.09 (3H, d, Jˆ7 Hz, CHCH3); dC
(67.5 MHz, CDCl3) 204.4 (CH2CO), 170.3 (NCO), 143.0
(CvCH), 133.2 (CvCH), 131.5, 129.3, 124.8, 121.5
(4×CH), 81.6 (COCN), 52.9 (NCCH), 47.8 (NCH2), 40.4
(CH2CO), 37.6 (CHCH3), 22.2, 22.2 (CH2CH2CH and
CH2CH2CH2) and 16.7 (CHCH3). Diastereomer 3: The
presence of this was indicated by: Rf 0.3 (diethyl ether);
Treatment of N-allyl-N-(6-oxocyclohex-1-enyl)-2-
bromobenzamide 24 with Bu3SnH
Tributyltin hydride (0.21 g, 0.73 mmol) and azobisisobutyro-
nitrile (28 mg) in degassed toluene (52 cm3) were added to
diene 24 (0.18 g, 0.56 mmol) in degassed toluene (23 cm3)
over 1 h following the general cyclisation procedure.
Column chromatography (silica; diethyl ether) afforded
5-allyl-1,2,3,4,4a,5,6,10b-octahydrophenanthridine-4,6-
dione 25 (20 mg, 15%) as a separable 1.6:1 mixture of two
diastereomers and 5-methyl-2,3,4,4a,5,6-hexahydro-1H,
8H-isoindolo[3,2-i]indole-1,8-dione 26 (56 mg, 41%) as a
17.8:5.0:2.3:1 mixture of four diastereomers (obtained as
two fractions of two inseparable diastereomers) as oils.
25 (4aRء,10bRء) — Major diastereomer: Rf 0.4 (diethyl
ether); nmax (CHCl3)/cmϪ1 3031 (w), 3008 (w), 2958 (w),
2931 (w), 2873 (w), 1724 (m), 1658 (s), 1603 (w), 1518(w),
1486 (w), 1463 (w), 1417 (w), 1379 (w), 1351 (w), 1286 (w)
and 1237 (w); dH (270 MHz, CDCl3) 8.18 (1H, dd, Jˆ8,
1.5 Hz, CHvC), 7.52–7.38 (2H, m, 2×CHCHCH), 7.33
(1H, br d, Jˆ8 Hz, CHvC), 5.73 (1H, dddd, Jˆ17, 10, 9,
4.5 Hz, CHvCH2), 5.18–5.07 (2H, m, CHvCH2), 5.03

7228
A. F. Parsons, D. A. J. Williams / Tetrahedron 56 (2000) 7217–7228
nmax (CHCl3)/cmϪ1 3009 (w), 2963 (w), 2930 (w), 2875 (w),
1758 (w), 1698 (s), 1605 (w), 1467 (w), 1381 (w), 1360 (w),
1342 (w), 1329 (w), 1235 (w), 1157 (w), 1138 (w), 1102 (w)
and 1030 (w); dH (270 MHz, CDCl3) 7.82–7.78 (1H, m,
CHvC), 7.53 (1H, dt, Jˆ1.5, 7.5 Hz, CHCHCH), 7.46
(1H, dt, Jˆ1, 7.5 Hz, CHCHCH), 7.24 (1H, br d,
Jˆ7.5 Hz, CHvC), 4.09 (1H, dd, Jˆ12, 6.5 Hz, NCHAHB),
2.98–1.20 (9H, m, NCHAHB, NCCH, CH2CO, CH2CH2CH,
CH2CH2CH2 and CHCH3) and 1.04 (3H, d, Jˆ7 Hz,
CHCH3); dC (67.5 MHz, CDCl3) 213.1 (CH2CO), 174.2
(NCO), 147.2, 132.8 (2×CvCH), 132.7, 129.0, 124.6,
121.1 (4×CH), 80.2 (COCN), 49.8 (NCH2), 44.7, 39.1
(NCCH and CHCH3) and 11.1 (CHCH3); m/z (CI, NH3)
256 (MϩHϩ, 100%) and 185 (10); Found: MϩHϩ,
256.1334. C16H17NO2 requires for MϩHϩ, 256.1338. Dia-
stereomer 4: The presence of this was indicated by: dH
(270 MHz, CDCl3) 4.24 (1H, dd, Jˆ12, 7.5 Hz, NCHAHB)
and 1.13 (3H, d, Jˆ7 Hz, CHCH3); dC (67.5 MHz, CDCl3)
212.0 (CH2CO), 173.4 (NCO), 146.9 (CvCH), 79.4
(COCN), 51.0 (NCH2), 45.6, 39.6 (NCCH and CHCH3)
and 14.3 (CHCH3).
1414 (w), 1365 (w), 1353 (w), 1285 (w), 1207 (w), 1144
(w) and 1064 (w); dH (270 MHz, CDCl3) 7.73 (2H, appt t,
Jˆ7.5 Hz, aromatics), 7.51 (1H, dt, Jˆ7.5, 1 Hz, aromatic),
7.39 (1H, t, Jˆ7.5 Hz, aromatic), 4.26–4.09 (2H, m,
NCHAHB and NCH2CHAHBOC), 3.73 (1H, dd, Jˆ11,
5 Hz, NCHAHB or NCH2CHAHBOC), 3.35 (1H, dt, Jˆ5,
12.5 Hz, NCHAHB or NCH2CHAHBOC), 3.08 (1H, br s,
COH), 2.47 (1H, dt, Jˆ13, 5 Hz, CHAHBCOH or
CHAHBCN) and 2.17–1.56 (7H, m, CHAHBCN or
CHAHBCOH, CHAHBCOH, CHAHBCN, CH2CH2CN and
CH2CH2COH); dC (67.5 MHz, CDCl3) 166.8 (NCO),
147.3 (CvCH), 132.9 (CvCH), 130.9, 128.3, 124.1,
122.9 (4×CH), 96.1 (COH), 66.3 (NCAr), 58.6 (NCH2),
37.0, 35.6, 31.4 (NCH2CH2OC, CH2COH and CH2CAr),
22.0 and 21.8 (CH2CH2CAr and CH2CH2COH); m/z (CI,
NH3) 260 (MϩHϩ, 100%), 245 (10), 242 (15) and 200
(10); Found: MϩHϩ, 260.1285. C15H17NO3 requires for
MϩHϩ, 260.1287.
Acknowledgements
Treatment of N-(2-hydroxyethyl)-N-(6-oxocyclohex-1-
enyl)-2-bromobenzamide 27 with Bu3SnH
We thank the EPSRC for a research studentship and Pfizer
for financial contributions.
To a solution of alkene 27 (0.30 g, 0.89 mmol) in degassed
toluene (37 cm3) was added tributyltin hydride (0.34 g,
1.15 mmol) and azobisisobutyronitrile (44 mg) in toluene
(82 cm3) over 5 h according to the general procedure.
Column chromatography (silica; ethyl acetate) afforded
3a-hydroxy-1,2,3,3a,5,6,12b,12c-octahydro-8H-[1,4]oxazino-
[2,3,4-de]phenanthridin-8-one 28 (70 mg, 30%) and 4a-
hydroxy-2,3,4,4a,6,7-hexahydro-1H,9H-isoindolo[2,3-d][1,4]-
benzoxazin-9-one 29 (92 mg, 40%) as single diastereomers.
References
1. For recent reviews see: (a) Lewis, J. R. Nat. Prod. Rep. 1999,
16, 389. (b) Bentley, K. W. Nat. Prod. Rep. 1999, 16, 367.
2. Schultz, A. G.; Holoboski, M. A.; Smyth, M. S. J. Am. Chem.
Soc. 1996, 118, 6210.
3. Rigby, J. H.; Mateo, M. E. Tetrahedron 1996, 52, 10569.
4. Ikeda, M.; Ohtani, S.; Sato, T.; Ishibashi, H. Synthesis 1998,
1803.
28: solid; mp 188–191ЊC; Rf 0.3 (ethyl acetate); nmax
(CHCl3)/cmϪ1 3586 (w, OH), 3017 (w), 3006 (m), 2948
(m), 2888 (w), 2868 (w), 1688 (w), 1644 (s), 1603 (w),
1461 (w), 1447 (w), 1424 (w), 1349 (w), 1285 (w), 1253
(w), 1231 (w), 1220 (w), 1208 (w), 1126 (w), 1106 (w),
1075 (w) and 1056 (w); dH (270 MHz, CDCl3) 8.13 (1H,
dd, Jˆ7.5, 1 Hz, CHvC), 7.47 (1H, dt, Jˆ7.5, 1.5 Hz,
CHCHCH), 7.40–7.25 (2H, m, CHvC and CHCHCH),
4.30–4.08 (2H, m, NCHAHB and NCH2CHAHBOC), 3.80–
3.48 (1H, m, NCHAHB or NCH2CHAHBOC), 3.28–3.03 (2H,
m, NCHAHB or NCH2CHAHBOC and COHCHN), 2.52–
2.48 (1H, br m, CHAHBCOH or CHAHBCHAr) and
2.10–1.20 (6H, m, CHAHBCOH or CHAHBCHAr and
CHAHBCOH, CHAHBCHAr, CH2CH2COH, CH2CHAr
and CH2CH2CH2); dC (67.5 MHz, CDCl3) 166.1 (NCO),
139.9 (CvCH), 132.4, 128.4 (2×CHvC), 127.4
(CvCH), 126.6, 123.5 (2×CHvC), 94.1 (COH), 63.4
(NCHCH), 58.6 (NCH2), 41.0, 36.1 (NCH2CH2OC and
CH2COH), 35.2 (NCHCH), 27.2 (CH2CH) and 21.4
(CH2CH2CH2); m/z (CI, NH3) 260 (MϩHϩ, 45%), 242
(100), 240 (50), 230 (15) and 213 (15); Found: MϩHϩ,
260.1287. C15H17NO3 requires for MϩHϩ, 260.1287.
5. Cassayre, J.; Zard, S. Z. Synlett 1999, 501.
6. Hoang-Cong, X.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett.
1999, 40, 2125.
7. (a) Cossy, J.; Tresnard, L.; Pardo, D. G. Eur. J. Org. Chem.
1999, 1925. (b) Cossy, J.; Tresnard, L.; Pardo, D. G. Tetrahedron
Lett. 1999, 40, 1125.
8. Cassayre, J.; Quiclet-Sire, B.; Saunier, J.-B.; Zard, S. Z.
Tetrahedron Lett. 1998, 39, 8995.
9. For a related example see: Goodall, K.; Parsons, A. F.
Tetrahedron Lett. 1997, 38, 491.
10. Sato, T.; Nakamura, N.; Ikeda, K.; Okada, M.; Ishibashi, H.;
Ikeda, M. J. Chem. Soc., Perkin Trans. 1 1992, 2399.
11. For a related example see: Baker, S. R.; Burton, K. I.; Parsons,
A. F.; Pons, J.-F.; Wilson, M. J. Chem. Soc., Perkin Trans. 1 1999,
427.
12. Shiue, J.-S.; Lin, C.-C.; Fang, J.-M. Tetrahedron Lett. 1993,
34, 335.
13. (a) Snider, B. B.; Cole, B. M. J. Org. Chem. 1995, 60, 5376.
(b) Snider, B. B.; Kiselgof, E. Y. Tetrahedron 1996, 52, 6073. (c)
Bhowmik, D. R.; Venkateswaran, R. V. Tetrahedron Lett. 1999,
40, 7431.
14. For related acetoxylations see: (a) Williams, G. J.; Hunter,
N. R. Can. J. Chem. 1976, 54, 3831. (b) Demir, A. S.; Jeganathan,
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Jeganathan, A. Synthesis 1992, 235.
29: solid; mp 192–196ЊC; Rf 0.2 (ethyl acetate); nmax
(CHCl3)/cmϪ1 3582 (w, OH), 3005 (w), 2929 (m), 2873
(w), 2857 (w), 1682 (s), 1488 (w), 1470 (w), 1452 (w),