Oxidative radical cyclization on enamide systems using n-Bu3SnH and dilauroyl peroxide

Article abstract of DOI:10.1016/S0040-4020(03)00764-6

Efficient 5-endo and 6-endo oxidative radical cyclizations on enamide systems are described using nBu₃SnH and dilauroyl peroxide both as initiator and oxidant. Dibenzoyl peroxide and dicumyl peroxide were also tested in the same reaction and the product yields were very similar to those obtained with dilauroyl peroxide. The erythrina ring system was constructed in a two-step sequence featuring this novel process.

Full text of DOI:10.1016/S0040-4020(03)00764-6

Tetrahedron 59 (2003) 4953–4958
Oxidative radical cyclization on enamide systems using
n-Bu3SnH and dilauroyl peroxide
*
Miguel A. Guerrero, Raymundo Cruz-Almanza and Luis D. Miranda
´ ´ ´ ´ ´
Instituto de Quımica, Universidad Nacional Autonoma de Mexico, Circuito Exterior S.N., Ciudad Universitaria, Coyoacan, Mexico,
D.F. 04510, Mexico
Received 28 November 2002; revised 5 May 2003; accepted 12 May 2003
Abstract—Efficient 5-endo and 6-endo oxidative radical cyclizations on enamide systems are described using nBu3SnH and dilauroyl
peroxide both as initiator and oxidant. Dibenzoyl peroxide and dicumyl peroxide were also tested in the same reaction and the product yields
were very similar to those obtained with dilauroyl peroxide. The erythrina ring system was constructed in a two-step sequence featuring this
novel process. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
a-halo amides or by an halogen transfer/thermal elimination
process.2s,8
The 5-endo-trig cyclization of carbamoylmethyl radicals of
enamides has been extensively explored, most notably by
Ishibashi and co-workers.1–5 This unusual 5-endo cycliza-
tion, reported as a highly efficient process, has been applied
to the synthesis of various natural products and related
compounds. Several methods have been devised to effect
such cyclizations, most of them being n-Bu3SnH-mediated
reactions, whereby the stabilized radical intermediate 3 is
ultimately reduced affording saturated g-lactams 4
(Scheme 1).2 In contrast, oxidative termination of the
radical sequence has also been accomplished using metallic
Ni-,3 Mn(III)-4 and Cu(II)-based reagents.5
The many synthetic applications of tin based radical
chemistry, drew our attention to the possible use of an
organic peroxide in a tin-mediated radical cyclization onto
enamide systems. Thus, we wondered if using n-Bu3SnH
and a stoichiometric amount of DLP as the initiator, rather
than AIBN, oxidized products would be obtained. Addition-
ally, such experiments might yield information to clarify the
oxidative role of the DLP in the xanthate mediated reaction
(Scheme 1).6 This publication describes the results of such
an investigation (Scheme 3, path ii).
Recently, Zard’s group6 reported an unexpected oxidative
radical cyclization on the enamide 1a using xanthates as the
radical source and dilauroyl peroxide (DLP) as the initiator.
The olefin mixture 7a–8a formed in good yield from 1a
(Scheme 1) was suggested to arise by either a xanthate
transfer/thermal elimination process (Scheme 3, path ii) or
by direct oxidation by DLP (Scheme 1, path i). In an
apparently similar process, lactams 7b–9b (Scheme 1) were
recently isolated in moderate yields (11–54%) from the
radical cyclization of chloroacetamide 1b using n-Bu3SnH
and a large excess (5 equiv.) of n-Bu3SnX (X¼F, OAc, Cl,
or I).2s In the absence of a formal oxidant, the products were
proposed to be formed by either a single electron transfer
mechanism from the a-amidoyl radical 3 to the starting
2. Results and discussion
Chloroacetamides 1b2s and 1c6 were synthesized by the
previously reported method. Thus a mixture of n-Bu3SnH/
DLP in benzene was then added slowly (over a four-hour
period) to a solution of chloroacetamide 1b in refluxing
benzene. As expected, a mixture of two isomeric lactams 7a
and 8a (8:2) was isolated in 92% yield together with traces
of isomer 9a (Table 1, entry 1), similar to that reported
before using xanthate chemistry.6 Longer reaction periods
gave increasingly larger amounts of the most stable
compound 9a. This substance was also produced thermally
from a mixture of 7a and 8a. A similar result was obtained
starting with 1c under the same reaction conditions (Table 1,
entry 2).
In the light of the above observations, the effectiveness of
dibenzoyl peroxide (DBP)9 and dicumyl peroxide (DCP)10
in this process, was also examined (Table 1). The combined
product yields were very similar to those obtained with
Keywords: dilauroyl peroxide; radical cyclization; oxidation; enamide;
erythrina.
*
Corresponding author. Tel.: þ52-55-56-22-44-40; fax: þ52-55-56-16-
22-17; e-mail: mirandald@correo.unam.mx
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00764-6

4954
M. A. Guerrero et al. / Tetrahedron 59 (2003) 4953–4958
Scheme 2.
also observed. Generally, the product yields were better than
those obtained in reactions performed with n-Bu3SnX
(X¼F, OAc, Cl, or I), described before.2s
Fast consumption of the starting material was observed
using dibenzoyl peroxide. Indeed, acetamide 1b was
entirely consumed before addition of the n-Bu3SnH/DLP
mixture was completed. This observation led us speculate
that the process could be carried out by using dibenzoyl
peroxide in absence of the tin reagent. In this case,
abstraction of chlorine atom from 1 by the phenyl radical
would generate the stabilized radical 2 (Scheme 2), a
process which is expected to be very favorable.11 Thus,
upon a portionwise addition of dibenzoyl peroxide to a
solution of either chloroacetamides 1b or 1c in toluene (at
958C), lactams 9a and 9b respectively were isolated in good
yield (Table 1, entry 7, 8). On the other hand, a competition
between the oxidant (peroxide) and the relatively high
concentration of the reductant (tin reagent), was observed in
the process when, an excess of tin hydride (1.5 equiv.) was
utilized in the reaction (Table 1, entry 9). Saturated lactam
4b was afforded in 35% yield, together with 23% yield of
the mixture 7b–8b along with a considerable amount of
recovered starting material (35%).
Scheme 1.
lauroyl peroxide but, the product distribution was rather
different in the reaction mediated by dibenzoyl peroxide
(Table 1, entry 3,4). The tendency for the latter reaction to
give mainly the most stable olefin 9 may be explicable by a
faster conversion of 7 and 8 into 9 by the more acidic
benzoic acid produced in this reaction. The DCP-mediated
reactions (Table 1, entry 5,6) were performed in refluxing
chlorobenzene (1328C),10 and good yields of 7 and 8 were
Table 1. Radical cyclization of a-halo amides 1b–c
Entry Amide
R
Cond. Peroxide
Yield (%)
7þ8a
9
4
1
2
3
4
5
6
7
8
9
1b
1c
1b
1c
1b
1c
1c
1b
1c
(CH2)2Ph
CH2Ph
(CH2)2Ph
CH2Ph
(CH2)2Ph
CH2Ph
CH2Ph
(CH2)2Ph
CH2Ph
A
A
A
A
A
A
B
B
C
DLPb
DLPb
DBPc
DBPc
DCPd
DCPd
DBP
92
93
5
Traces
Traces
86
6
88
89
88
5
5
23
Traces
Traces
89
87
Traces 35
DBP
DLP
10Conditions: A. n-Bu3SnH (1.1 equiv.), organic peroxide (2.0 equiv.).
B. Dibenzoyl peroxide (1.5 equiv.), toluene, 958C, 2 h. C. n-Bu3SnH
(1.5 equiv.), dilauroyl peroxide (0.9 equiv.), C6H6, reflux, 2 h.
a
b
c
d
1
Ratio (,8:2) based on the H NMR spectrum of an isolated mixture.
In benzene, reflux.
In toluene at 958C.
In chlorobenzene, reflux, 4 h.
Scheme 3. Proposed mechanism for the oxidative radical cyclization under
n-Bu3SnH/DLP conditions.

M. A. Guerrero et al. / Tetrahedron 59 (2003) 4953–4958
4955
afford the carboxylate 14 and the carboxyl radical which
by loss CO2 would produce the intermediate radical 11 to
continue the chain (Scheme 3). Consistent with this
mechanism, lauric acid, which comes from the protona-
tion of 14, was isolated in yields ranging between 1 and
1.2 equiv. in DLP-mediated reactions. In addition,
benzoic acid and 2-phenyl propan-2-ol were produced
in similar yields (120 and 110%) in the dibenzoyl and
dicumyl mediated reactions. In the light of the above
observations, it is likely that a similar mechanism is
involved in the DLP mediated xanthate reactions where
oxidized products are obtained (Scheme 1, path i).6 The
ability of the DLP to effect oxidation of stabilized
radicals to cations has been recently invoked in radical
additions onto aromatic systems.7
The above observations opened up the possibility for a very
short entry to the pharmacologically important erythrina
alkaloids.12 The skeleton of these alkaloids could be
assembled combining oxidative radical cyclization with
intramolecular in situ Friedel–Crafts type cyclization of the
intermediate iminium ion as described recently by Zard
et al.6 (Scheme 4). Thus, chloroacetamide 17 was prepared
in a two-step process from commercially available ketone
15 and amine 16. For reasons which we do not understand,
the dibenzoyl peroxide mediated reaction failed to effect
cyclization of 17, in the absence of n-Bu3SnH (Condition B,
Table 1). However, erythrina derivative 18 was ultimately
isolated in 74% yield upon addition of a catalytic amount of
p-toluenesulfonic acid to the reaction mixture after 17 had
been consumed in the n-Bu3SnH/DLP mediated radical
cyclization. There was no need to isolate the mixture of the
isomeric, intermediate, unsaturated lactams 7c and 8c since
they both give the same iminium ion in the presence of acid.
The dioxolane protective group was lost under these acidic
reaction conditions. This sequence represents one of the
shortest routes to an erythrina alkaloid derivative published
to date.
Scheme 4. Short synthesis to the erythrina framework alkaloids.
Conditions: (i) toluene, reflux, then chloroacetylchloride, pyridine
CH2Cl2, rt, (ii) n-Bu3SnH (1.1 equiv.), DLP (2.0 equiv.) benzene, reflux,
4 h, then catalytic p-toluenesulfonic acid.
The new n-Bu3SnH/DLP oxidative radical cyclization
process was extended to an aryl bromide. Thus, bromide
21 was prepared in two steps from the piperonal derived
amine 203d in moderate yield. Reaction of 21 under the
above-described oxidative radical conditions afforded the
thermodynamically stable olefin 22, exclusively in good
yield. The phenanthridine system present in this product is
found in many alkaloids, some of which exhibit interesting
pharmacological activity (Scheme 5).13
Scheme 5. Conditions: (i) toluene, reflux, then benzoyl chloride, pyridine
CH2Cl2, rt, (ii) n-Bu3SnH (1.1 equiv.), DLP (2.0 equiv.) benzene, reflux,
4 h.
A
reasonable mechanism for the n-Bu3SnH/DLP
mediated-reaction is depicted in Scheme 3. The reaction
is initiated by the well-known thermal fragmentation/
homolytic decarboxylation process of the peroxide 10,
affording two radicals 11 which produce the stannyl
radical 12 by reacting with tin hydride (Scheme 3). The
results described herein support a mechanism in which
the organic peroxide functions as the oxidant generating
the iminium ion 6 by a single electron transfer from
radical 3 (Scheme 3). The generation of 6 by a chlorine
atom transfer mechanism is expected to be difficult given
that the cyclization of chloroacetamide 1c under nBu3-
SnH/AIBN conditions gave mainly the reduced product
4b (Scheme 1).2a Peroxyl radical-anion 13 formed in the
process would undergo a heterolytic fragmentation to
3. Conclusions
Novel and efficient oxidative radical cyclizations are
described using n-Bu3SnH and an organic peroxide
which serves both as the initiator and the oxidant in
cyclizations onto enamide systems. This novel process
opens up new applications in tin hydride-mediated free
radical reactions, and the present route to the erythrina
ring system and the phenanthridine derivative 22, under-
scores its synthetic potential. Extension to more complex
structures using this methodology is currently under
investigation.

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M. A. Guerrero et al. / Tetrahedron 59 (2003) 4953–4958
4. Experimental
5.5.46 (m, 1H), 4.09 (s, 2H),3.99 (s, 4H), 3.87 (s, 3H), 3.85
(s, 3H), 3.65–3.71 (m, 2H), 2.83 (dd, J1¼J2¼7.8 Hz, 2H),
2.34–2.25 (m, 4H), 1.85 (t, J¼6.3 Hz, 2H). 13C NMR
(75 MHz, CDCl3) d 166.0, 149.2, 147.8, 137.8, 131.4,
125.9, 120.9, 120.8, 112.3, 111.5, 106.9, 64.8, 56.17, 56.12,
48.0, 41.9, 35.4, 33.6, 31.2, 29.97. IR (cm21) n: 2960.2,
2936.5, 2838.7, 1731.7, 1654.9, 1515.3, 1462.7, 1446.37,
1415.5, 1260.9, 1154.4, 1119.6, 1030.7. MS (EI) m/z¼164
(100% Mþ 2Cl), 395 (Mþ weak).
4.1. General
Proton magnetic resonance spectra were recorded at 200 and
300 MHz as CDCl3 solutions and are reported in ppm
(Varian Unity instrument) downfield from internal tetra-
methylsilane. IR spectra were obtained on a Nicolet FT-IR
Magna 750 spectrometer. Chromatography was carried out
using silica gel. Mass spectra were recorded at JEOEL
JEM-AX505HA instrument at voltage of 70 eV.
4.2. Cyclization reaction
4.1.1. N-(6-Bromo-benzo[1,3]dioxol-5-ylmethyl)-N-
cyclohex-1-enyl-benzamide (21) (general procedure). A
solution of cyclohexanone (0.5 g, 5.1 mmol), and amine
(1.17 g, 5.1 mmol) in toluene was heated to reflux for 4 h in
a Dean–Stark apparatus. After evaporation of the solvent,
the residue was dissolved in dry toluene and cooled to 08C.
Triethylamine (0.62 g, 6.1 mmol) was added, followed by a
dropwise addition of benzoyl chloride (0.72 g, 5.1 mmol).
The solution was then stirred for 3 hours at room
temperature. Water was added and the resulting mixture
extracted with ether, the organic layer was dried over
magnesium sulfate and concentrated in vacuum. The residue
was purified by silica gel column chromatography to give
Conditions A (general procedure): a solution of dilauroyl
peroxide (2.0 equiv.) (0.038 mmol/mL of benzene),
Bu3SnH (1.1equiv) in benzene was added dropwise (syringe
pump) to a degassed solution of the chloride (1 equiv.) in
refluxing benzene (0.025 mmol/mL) over 4 h. The reaction
mixture was then cooled and the solvent removed under
reduced pressure. The residues were partitioned between
hexane (10 mL) and acetonitrile (15 mL). The polar layer
was washed with hexane (4£10). The solvent was
evaporated and the crude product was purified by silica
gel column chromatography (hex/AcOEt) to furnish a
mixture of isomers.
1
1.26 g (60%) of the benzamide 21. H NMR (300 MHz,
Reaction with dibenzoyl peroxide was carried out in toluene
at 958C. Procedure was identical to that described for the
DLP-mediated reaction; however, the reaction mixture was
washed with a saturated aqueous solution of NaHCO3
before solvent was removed in the workup.
CDCl3) d 7.54–7.49 (m, 2H), 7.39–7.29 (m, 3H), 7.04 (s,
1H), 6.97 (s, 1H), 5.96 (s, 2H), 5.32–5.26 (m, 1H), 4.88 (s,
2H), 2.0–1.88 (m, 2H), 1.86–1.77 (m, 2H), 1.86–1.77 (m,
2H), 1.54–1.42 (m, 2H), 1.4–1.3 (m, 2H). 13C NMR
(50 MHz) d 170.60, 147.58, 147.48, 138.39, 136.77, 130.38,
130.05, 129.60, 128.45, 127.72, 127.43, 112.36, 109.66,
101.69, 49.76, 28.62, 24.70, 22.48, 21.16. IR (cm21) n:
2938, 1704, 1661.9, 15515.8, 1479.4. MS (EI) m/z¼254
(100%), 413 (Mþ weak), 415 (Mþþ2), HRMS (FABþ):
calcd for C21H21O3NBr: 414.0709, found: 414.0705.
Reaction with dicumyl peroxide was carried out in refluxing
chlorobenzene, and the procedure was identical to that
described for the DLP-mediated reaction.
Conditions B: a solution of dibenzoyl peroxide (1.5 equiv.)
in benzene was added dropwise to a degassed solution of the
chloride 1b or 1c (1 equiv.) in toluene at 958C over 3 h. The
reaction mixture was then cooled and washed with a
saturated aqueous solution of NaHCO3. Solvent was
removed under reduced pressure and crude product was
purified by a silica gel column chromatography (Hep/
AcOEt) to furnish olefin isomers (7–9).
Chloroacetamides 1b–c and 17 were synthesized according
to the procedure described previously (see text).
4.1.2. 2-Chloro-N-cyclohex-1-enyl-N-phenethyl-ceta-
mide (1b). Spectra data were identical with those reported
previously.6 1H NMR (300 MHz, CDCl3) d 7.31–7.17 (m,
5H), 5.61–5.58 (m, 1H), 4.08 (s, 2H), 3.65–3.60 (m, 2H),
2.87 (dd, J1¼J2¼7.9 Hz, 2H), 2.14–2.04 (m, 4H),
1.76–1.68 (m, 2H), 1.63–1.59 (m, 2H). 13C NMR
(75 MHz, CDCl3) d 21.3, 22.6, 24.7, 27.6, 33.8, 41.7,
47.6, 126.3, 128.4, 128.7, 137.9, 138.0, 165.6. IR (cm21) n:
2942.1, 2863.14, 2840.2, 1641.8, 1451.5, 1409.1, 1356.6,
1140.4. MS (EI) m/z¼242 (100%; Mþ 2Cl), 277 (Mþ
weak).
Conditions C: A solution of dilauroyl peroxide (0.136 g,
0.34 mmol), and Bu3SnH (0.16 g, 0.568 mmol) in benzene
(9 mL) was added dropwise (syringe pump) to a degassed
solution of the chloride 1c (0.1 g, 0.38 mmol) in refluxing
benzene (15 mL) over 4.5 h. Workup was identical to that
described for conditions A. Affording 0.029 g of 4b (35%)
and 0.020 g of the mixture 7b–9b (23%), along with 0.035
of recovered starting material g (35%).
4.1.3. N-Benzyl-2-chloro-N-(cyclohex-1-enyl)acetamide
(1c). The NMR spectra data were identical with those
reported before.2s 1H NMR (300 MHz, CDCl3) d 7.26–7.30
(m, 5H), 5.47 (br s, 1H), 4.63 (s, 2H), 4.13 (s, 2H), 2.03 (br s,
4H), 1.52–1.70 (m, 4H). 13C NMR (67.8 MHz, CDCl3) d
165.8, 137.4, 137.1, 129.3, 128.7, 128.3, 127.4, 49.9, 41.7,
27.9, 24.7, 22.6, 21.3.
4.2.1. cis-1-Benzyl-octahydroindol-2-ona (4b).2s The
NMR spectra data were identical with those reported
previously. H NMR (300 MHz, CDCl3) d 7.21–7.33 (m,
5H), 4.93 (d, 1H, J¼15 Hz), 3.97 (d, 1H, J¼15 Hz), 3.39 (q,
1H, J¼5.6 Hz), 2.19–2.47 (m, 3H), 1.56–1.72 (m, 3H),
1.23–1.52 (m, 5H).
1
4.1.4. 2-Chloro-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-N-
(1,4-dioxa-spiro[4.5]dec-7-en-8-yl)-acetamide (17).6 1H
NMR (300 MHz, CDCl3) d 6.81–6.72 (m, 3H), 5.48–
4.2.2. 1-Phenethyl-1,3,3a,4,5,6-hexahydro-indol-2-one
(7a).6 This product was very sensitive to isomerization
and was fully characterized as its more stable isomer 9.6

M. A. Guerrero et al. / Tetrahedron 59 (2003) 4953–4958
4957
Isomer 7a: 1H NMR (300 MHz, CDCl3) d 7.3–7.1 (m, 5H),
4.85 (m, 1H, C¼C–H), 3.81 (ddd, 1H, J¼6.9 Hz, 9.4 Hz,
13.5 Hz, NCH–H), 3.51 (ddd, 1H, J¼6.9 Hz, 9.4 Hz,
13.5 Hz, NCH–H), 2.8–2.9 (m, 2H, PhCH2), 2.75–1.5
(m, 8H). MS (EI): Mþ m/z¼241.
4.41–4.35 (m, 1H), 3.88 (s, 3H, OMe), 3.86 (s, 3H, OMe),
3.15–2.93 (m, 4H), 2.77–2.59 (m, 3H), 2.49–2.08 (m, 4H).
13C NMR (75 MHz, CDCl3): 210.0, 172.11, 148.4, 148.2,
134.3, 125.4, 111.7, 107.2, 62.4, 56.3, 55.9, 53.4, 43.2, 37.7,
37.4, 35.2, 34.7, 33.5, 27.5. IR (cm21) n: 2956, 2939, 2850,
1718, 1680, 1514, 1463, 1424, 1285. EM: Mþ m/z¼315.
HRMS (IE): calcd for C18H21O4N: 315.1471, found:
315.1458.
Isomer 8a This product was very sensitive to isomerization
as well and was observed only in mixtures with the other
isomers. It was fully characterized as its more stable isomer
9a.
Acknowledgements
Isomer 9a The NMR spectra data were identical with
those reported previously.6 1H NMR (300 MHz, CDCl3) d
7.20–7.30 (m, 5H), 3.90 (ddd, J¼14.0, 8.4, 6.7 Hz, 1H,
NCH–H), 3.54–3.27 (m, 1H, NCH), 3.33 (ddd, J¼14.0,
8.4, 6.8 Hz, 1H, NCH–H), 2.91–2.84 (m, 2H, PhCH2),
2.67–2.73 (m, 1H), 1.78–2.34 (m, 4H), 1.40–1.10 (m, 2H),
1.0–0.92 (m, 1H). 13C NMR (75 MHz, CDCl3) d 7171.5,
161.9, 139.1, 128.8, 128.5, 126.4, 62.3, 41.6, 35.3, 33.1,
28.3, 27.4, 23.08. IR (cm21) n: 2941.7, 2861.3, 1670.3,
1449.8, 1411.9, 1327.9. EM: Mþ m/z¼241.
Financial support from DGAPA (PAPIIT-IN205901) and
CONACYT (37312-E) is gratefully acknowledged. Also we
thank Professor J. M. Muchowski for helpful discussions
´
and R. Patin˜o, J. Perez, L. Velasco, H. Rios, N. Zavala and
A. Pen˜a, for technical support.
References
4.2.3. Isomer 7b and 8b. This products were very sensitive
to isomerization and was observed only in mixtures. It was
characterized as its more stable isomer 9b.
1. For a recent review on 5-endo cyclization see: Ishibashi, H.;
Sato, T.; Ikeda, M. Synthesis 2002, 695.
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4.2.4. 1-Benzyl-1,4,5,6,7,7a-hexahydroindol-2-one (9b).
Spectra data were identical with those reported previously.2s
1H NMR (300 MHz, CDCl3) d 7.37–7.21 (m, 5H), 5.80 (s,
1H), 4.99 (d, J¼15.1 Hz, 1H), 4.17 (d, J¼15.1 Hz, 1H), 3.58
(dd, J¼11.2, 5.9 Hz, 1H), 2.72 (br d J¼11.2 Hz, 1H), 1.39–
1.17 (m, 4H), 1.43–1.19 (m, 2H), 1.11–0.92 (m, 1H).
4.2.5. Phenyl-(2,3,4,6-tetrahydro-1H-[1,3]dioxolo[4,5-
1H
j]phenanthridin-5-yl)-methanone
(22).
NMR
(300 MHz, CDCl3) d 8.03–7.93 (m, 2H), 7.61–7.49 (m,
3H), 6.89 (s, 1H), 5.96 (dd, J1¼1.47 Hz, J2¼6.9 Hz, 2H),
5.30 (d, J¼17.58 Hz, 1H), 4.30 (d, J¼17.5 Hz, 1H),
2.82–2.75 (m, 1H), 2.49–2.38 (m, 2H), 2.1–1.9 (m, 3H),
1.81–1.57 (m, 2H), 1.41–1.15 (m, 2H). 13C (75 MHz,
CDCl3) d 165.81, 150.47, 147.47, 146.40, 131.89, 130.82,
128.28, 127.49, 125.53, 124.19, 123.98, 106.19, 103.13,
101.14, 40.98, 28.91, 25.41, 22.08, 19.02. IR (cm21) n:
2932.5, 1678, 1486, 1042. EM: Mþ m/z¼333. HRMS (IE):
calcd for C21H19O3N: 333.1365, found: 333.1362.
4.2.6. Erythrina derivative (18). A solution of dilauroyl
peroxide (0.18 g, 0.45 mmol) and Bu3SnH (0.08 g,
0.27 mmol) in benzene was added dropwise to a benzene
solution of the chloride (0.10 g, 0.25 mmol) in refluxing
benzene over a 4 h period. After no more starting material
was detected by TLC a catalytic amount of p-toluene-
sulphonic acid was added to the reaction mixture. After
additional 40 min reflux, the reaction mixture was cooled to
room temperature and solvent removed under reduced
pressure, the residues were partitioned between hexane
(10 mL) and acetonitrile (15 mL). The polar layer was
washed with hexane (4£10 mL). The solvent was evapor-
ated and the crude product was purified by silica gel column
chromatography (AcOEt) to furnish 59 mg (74%)of the
product as a solid with mp: 162–1648C (lit. 162–1658C).
Spectra data were identical with those reported previously.6
1H NMR (300 MHz, CDCl3) d 6.69 (s, 1H), 6.58 (s, 1H),
3. For nickel-mediated 5-endo cyclizations, see: (a) Quiclet-Sire,
B.; Saunier, J.-B.; Zard, S. Z. Tetrahedron Lett. 1996, 37,
1397. (b) Cassayre, J.; Quiclet-Sire, B.; Saunier, J. B.; Zard,
S. Z. Tetrahedron 1998, 54, 1029. (c) Cassayre, J.; Quiclet-
Sire, B.; Saunier, J. B.; Zard, S. Z. Tetrahedron Lett. 1998, 39,
8995. (d) Cassayre, J.; Zard, S. Z. Synlett 1999, 501.
(e) Cassayre, J.; Zard, S. Z. J. Am. Chem. Soc. 1999, 121,
6072. (f) Cassayre, J.; Dauge, D.; Zard, S. Z. Synlett 2000, 471.

4958
M. A. Guerrero et al. / Tetrahedron 59 (2003) 4953–4958
4. For Mn(III)-mediated 5-endo cyclizations, see: (a) Davies,
Tetrahedron Lett. 1998, 39, 7295. (e) Ly, T.-M.; Quiclet-Sire,
B.; Sortais, B.; Zard, S. Z. Tetrahedron Lett. 1999, 40, 2533.
8. For a similar atom transfer reaction, see: Miranda, L. D.; Cruz-
Almanza, R.; Pavon, M.; Romero, Y.; Muchowski, J. M.
Tetrahedron Lett. 2000, 41, 10181.
D. T.; Kapur, N.; Parsons, A. F. Tetrahedron Lett. 1998, 39,
4397. (b) Davies, D. T.; Kapur, N.; Parsons, A. F. Tetrahedron
2000, 56, 3941. (c) Ishibashi, H.; Toyao, A.; Takeda, Y.
Synlett 1999, 1468. (d) Toyao, A.; Chikaoka, S.; Takeda, Y.;
Tamura, O.; Muraoka, O.; Tanabe, G.; Ishibashi, H.
Tetrahedron Lett. 2001, 42, 1729.
9. We thank a referee for suggest this experiment.
10. At reaction temperature selected, each peroxide has
t1/2¼,1.5 h Motherwell, W. B.; Crich, D. Free Radical
Chain Reaction in Organic Synthesis; Academic: London,
1992.
5. For Cu(I)-mediated 5-endo cyclisations, see: (a) Davies, D. T.;
Kapur, N.; Parsons, A. F. Tetrahedron Lett. 1999, 40, 8615.
(b) Clark, A. J.; Dell, C. P.; Ellard, J. M.; Hunt, N. A.;
McDonagh, J. P. Tetrahedron Lett. 1999, 40, 8619. (c) Clark,
A. J.; Filik, R. P.; Haddleton, D. M.; Radigue, A.; Sanders,
C. J.; Thomas, G. H.; Smith, M. E. J. Org. Chem. 1999, 64,
8954. (d) Bryans, J. S.; Chessum, N. E. A.; Parsons, A. F.;
Ghelfi, F. Tetrahedron Lett. 2001, 42, 2901.
11. For an example of similar production a carbamoylmethyl
radical from the iodine derivative using DLP see: Ollivier, C.;
Bark, T.; Renaud, P. Synthesis 1997, 1598.
12. For a review of Erythrina alkaloids, see:Tsuda, Y.; Sano, T.
The Alkaloids; Cordell, G. A., Ed.; Academic: San Diego,
1996; Vol. 48, pp 249–337.
6. Miranda, L. D.; Zard, S. Z. Organic Lett. 2002, 4, 1135.
7. (a) Kaoudi, T.; Quiclet-Sire, B.; Seguin, S.; Zard, S. Z. Angew.
Chem. Int. Ed. 2000, 39, 732. (b) Axon, J.; Boiteau, L.; Boivin,
J.; Forbes, J. E.; Zard, S. Z. Tetrahedron Lett. 1994, 35, 1719.
(c) Liard, A.; Quiclet-Sire, B.; Saicic, R. N.; Zard, S. Z.
Tetrahedron Lett. 1997, 38, 1759. (d) Cholleton, N.; Zard, S. Z.
13. (a) Martin, S. F. The Alkaloids; Brossi, A., Ed.; Academic:
New York, 1987; Vol. 30, pp 251–376. (b) Hoshino, O. The
Alkaloids; Cordell, G. A., Ed.; Academic: San Diego, 1998;
Vol. 51, pp 323–424.