Tin-mediated free-radical cyclization of β-allenylbenzoyloximes

Article abstract of DOI:10.1002/(SICI)1099-0690(200001)2000:2<275::AID-EJOC275>3.0.CO;2-R

A set of allene-tethered benzoyloximes (5) has been treated with nBu₃SnH. Depending on their substitution pattern, a wide range of compounds has been obtained. If the stannyl radical adds on the allene, the C-centred radical thus formed undergoes either a 5-exo ring closure to give the cyclopentene derivatives 7 or a 6-endo ring closure onto the N atom to give the dihydropyridines 8. If the stannyl radical adds on the benzoyl moiety, an iminyl radical is formed which leads to the 3H-pyrroles 9 and the alkylidene- pyrrolines 10. Steric effects as well as polar effects are the factors governing the reaction course.

Full text of DOI:10.1002/(SICI)1099-0690(200001)2000:2<275::AID-EJOC275>3.0.CO;2-R

FULL PAPER
Tin-Mediated Free-Radical Cyclization of β-Allenylbenzoyloximes
[a]
[a]
[a]
[a]
¨
Michael Depature, Josef Diewok, Jacques Grimaldi, and Jacques Hatem*
Keywords: Radical reactions / Substituent effects / Nitrogen heterocycles / Dihydropyridines / Pyrrolines
A set of allene-tethered benzoyloximes (5) has been treated
with nBu3SnH. Depending on their substitution pattern, a
wide range of compounds has been obtained. If the stannyl
radical adds on the allene, the C-centred radical thus formed
N atom to give the dihydropyridines 8. If the stannyl radical
adds on the benzoyl moiety, an iminyl radical is formed
which leads to the 3H-pyrroles
9 and the alkylidene-
pyrrolines 10. Steric effects as well as polar effects are the
undergoes either
a
5-exo ring closure to give the
factors governing the reaction course.
cyclopentene derivatives 7 or a 6-endo ring closure onto the
Introduction
Results and Discussion
In the last few decades many examples involving intra-
The structure and functionality of these allenylbenzoy-
molecular addition of free radicals to carbonϪcarbon mul- loximes raise an interesting problem: Two principal posi-
tiple bonds have been reported.[1Ϫ4] Some papers dealing tions are available for attack by stannyl radicals. The first
with an analogous addition to carbonϪnitrogen multiple one is the oxygen atom of the carbonyl group that causes
bonds have appeared as well.[5][6] From this point of view, the formation of the required iminyl radical by addition of
our group has already reported on the nBu3SnH mediated the stannyl radical. The second position is the allene func-
free radical cyclization of allene tethered oxime ethers and tionality. Consequently, the behaviour of allenylbenzoylox-
hydrazones.[7] Thus, we obtained five-membered car- imes towards stannyl radicals strongly depends on the rela-
bocycles bearing a protected amino group and a vinylstan- tive kinetics of the tin radical addition to either position.
nyl functionality. Recently, an increasing number of papers So a systematic structure-reactivity analysis seems to be
deals with the intramolecular addition of nitrogen-centred necessary to determine the factors governing the reaction
radicals onto various acceptors.[5][8] In this area, Zard and pathway.
co-workers have obtained pyrrolines using an iminyl rad-
ical, easily produced by the tributylstannane reduction of
alkene-tethered benzoyloximes.[9] The use of this method
with our allenic compounds would be a good way of ob-
taining stable 3H-pyrroles or alkylidenepyrrolines (see
Scheme 1).
Synthesis of the Radical Precursors 5
A set of β-allenylbenzoyloximes was therefore prepared
in a few steps starting from the corresponding propargylic
alcohols 1 according to Scheme 2.
The β-allenylaldehydes 2 can easily be obtained from the
alcohols 1.[10] Grignard reagent addition to 2, followed by
PCC oxidation[11] of the crude alcohols affords the ketones
3. Cannizzaro reaction with 2b (R1 ϭ R2 ϭ CH3) gives the
corresponding β-allenyl acid[10] which is converted into the
acid chloride. Compound 4 is then obtained by Arbusov
reaction[12] of this acid chloride with triethyl phosphite.
These compounds, 2Ϫ4, can be submitted to oximation and
benzoylation to give the β-allenylbenzoyloximes 5.
Scheme 1. Reaction of β-allenyliminyl radicals
Reaction of Tin Hydrides with the Radical Precursors 5
In this paper, we now describe the first results obtained
in the tributylstannane-mediated cyclization of allene-teth-
ered benzoyloximes.
Depending on their substitution pattern, compounds 5
led to different products (6Ϫ10; Figure 1) when they were
submitted to the action of tin hydrides in radical conditions.
As it seems to be of some importance in the product dis-
tribution, we are going to discuss our results relative to the
nature of the R3 substituent. For R3 ϭ H, 5aϪd were prone
to give the corresponding nitrile and benzoic acid, when
they were heated under reflux in cyclohexane. For that rea-
[a]
´
´
`
´
Laboratoire Structure et Reactivite des Especes Paramagneti-
ques, CNRS UMR 6517: Chimie Biologie et Radicaux Libres.
´
Universites Aix-Marseille I et III,
ˆ
Avenue Escadrille Normandie-Niemen (boıte 541); F-13397
Marseille Cedex 20, France
Fax: (internat.) ϩ 33-4/91988512
E-mail: hatem@srepir1.univ-mrs.fr
Supporting information for this article is available on the WWW
under http://www.wiley-vch.de/home/eurjoc or from the author. son, we treated these compounds with nBu3SnH or Ph3SnH
Eur. J. Org. Chem. 2000, 275Ϫ280
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0102Ϫ275 $ 17.50ϩ.50/0
275

M. Depature, J. Diewok, J. Grimaldi, J. Hatem
FULL PAPER
With the particular substitution pattern of the allenes we
used, the stannyl radical adds only onto the diagonal car-
bon atom (see Scheme 3). The subsequent 5-exo-trig cycli-
zation onto the CϭN bond, and H abstraction from tin
hydride by the obtained aminyl radical affords 7.
Scheme 3. Mechanistic pathway for obtaining 7
These reactions were relatively slow when nBu3SnH was
used and were stopped after 48 hours (Table 1). The bulkier
R1 and R2 the lower the yield of cyclized product 7. For 5a
and 5c the cyclization afforded an unseparable mixture of
two stereoisomers (69:31 and 75:25, respectively). The
major isomer in both cases is where the methyl group and
the amino group are cis.[14] The use of Ph3SnH was tested
on 5d and allowed us to obtain 7Јd in excellent yield despite
the high steric hindrance of R1 and R2. Actually, Ph3SnH
is a better reducing agent than nBu3SnH.[15] Thus, it likely
means that the stannyl radical addition onto the allene, and
the 5-exo cyclization are both reversible processes, the H
abstraction being the kinetically determining step. It is wor-
thy to note that no product resulting from the formation of
an iminyl radical has been detected in the crude products.
For R3 ϭ CH3 (5eϪh), we used nBu3SnH/AIBN in re-
fluxing cyclohexane (Table 1). For 5e and 5f we obtained
the vinyltin derivatives 7eϪf in good yield; the carbocycle
7e was isolated as an unseparable mixture of two stereoiso-
mers (60:40) in which the major isomer has the methyl
group and the amino function in cis relative confor-
mation.[14] Compared with the behaviour of 5f, the corre-
sponding allylallene (2,3,3,6-tetramethylhepta-1,4,5-triene)
gave 6-endo cyclization as the major process.[16] As we have
discussed earlier, however,[17] this difference in the two be-
haviours is not surprising when the polarity of the CϭN
bond is considered.
Scheme 2. Synthesis of radical precursors 5aϪm
Figure 1. Products obtained from the tin hydride reaction on 5
(in one case) in the presence of triethylborane, to avoid this
thermal decomposition.[13] Thereby, as it is shown in Table
1, we only obtained the five-membered cyclized products
7aϪd and 7Јd.
Table 1. Tin hydride reaction of radical precursors 5a؊h
1
5
Reaction conditions
Reaction Recovered
Yield of
With 5g and 5h, no cyclization occurred. In fact the H-
time [h]
5 (%)
7 (%)
NMR analysis of the crude products did not show any sig-
nal in the 3Ϫ6 ppm area; indicating that neither 7gϪh nor
8gϪh nor 6gϪh were significantly present in the mixtures.
In both cases, starting material was totally degraded after
48 hours and gave an unidentifiable mixture of compounds.
The use of Ph3SnH instead of nBu3SnH did not give bet-
ter results.
a
b
c
d
d
e
f
nBu3SnH/Et3B, 25°C
nBu3SnH/Et3B, 40°C
nBu3SnH/Et3B, 40°C
nBu3SnH/Et3B, 40°C
Ph3SnH/Et3B, 25°C
nBu3SnH/AIBN, 80°C
nBu3SnH/AIBN, 80°C
nBu3SnH/AIBN, 80°C
nBu3SnH/AIBN, 80°C
48
48
48
48
2.4
8
13
22
20
31
71
75
65
48
91 (7Јd)
81
8
75
g
h
48
48
For R3 ϭ Ph (5iϪl) and, in one case, R3 ϭ P(O)(OEt)2
(5m), the reaction evolution is slightly more complex. De-
276
Eur. J. Org. Chem. 2000, 275Ϫ280

Tin-Mediated Free-Radical Cyclization of β-Allenylbenzoyloximes
FULL PAPER
pending on the substituents R1 and R2 a mixture of 6 and
7 or a mixture of 8, 9, and 10 was obtained (Table 2).
Table 2. Reaction of radical precursors 5i؊m with tributyltin hy-
dride (AIBN, c-C6H12, reflux)
5
Reaction time [h]
Recovered
5 (%)
% of isolated products
6
7
8
9 ϩ 10
i
13
5.5
30
20
6
19
44
j
82
42
17
55
< 10
48
43
k
l
m
12
Submitted to our experimental conditions, the radical
precursor 5i gave a small amount of the linear product 6i
(19%) and the five-membered cyclized product 7i (44%).
The latter was isolated as a mixture of two stereoisomers in
a 9:1 ratio in which the major isomer has the methyl group
and the amino function in cis relative orientation.[14]
For 5jϪl, a mixture of 8jϪl, 9jϪl, and 10jϪl were ob-
tained. In these three examples, 9 and 10 were obtained in
approximately equal ratio. We must observe that the yield
of 8 decreases when the steric hindrance of R1 and R2 in-
creases; at the same time, the yield of both 9 and 10 in-
creases. When R3 ϭ P(O)(OEt)2 (5m), compound 8m was
the sole product of the reaction. It was obtained in a quasi-
quantitative yield for the crude product. So, the 55% yield
in isolated 8m seems to be the result of its degradation on
silica gel during its purification.
Scheme 4. Tentative mechanism for obtaining compounds 6؊10
centred radical onto a nitrogen atom of a CϭN bond has
been reported (Scheme 5).[18]
Discussion
As is shown in Tables 1 and 2, a wide range of products
can be obtained from the reaction of tin hydride on radical
precursors 5aϪm. Depending on the substitution pattern of
the starting compound, 5, cyclopentene derivatives 7, 2,5-
dihydropyridines 8, 3H-pyrroles 9, and alkylidenepyrrolines
10 are the main products of the reaction. In Scheme 4 we
show a tentative mechanism to explain all our results.
Starting from 5, the addition of the stannyl radical to the
Scheme 5. Radical cyclization of 5-benzeneselenylalkylimines
In this case, the 5-exo ring closure is normally the major
allene seems to be the favoured process. The obtained rad- process, for stereoelectronic effects as well as for polar ef-
ical 11 undergoes a 5-exo cyclization leading to 7 when the fects.[18][19] With a methyl group on C-1, the increasing
substitution pattern is not hindered as in the case of 5aϪf steric hindrance is not enough to slow down the 5-exo ring
(Table 1) and 5i (Table 2). In this latter case the bulky phe- closure, contrary to the 5-hexenyl radical cyclization.[20] On
nyl group slows down the 5-exo cyclization, thus the H ab- the other hand, the increasing polarity of the CϭN bond
straction from tin hydride can compete to give 6i, since the due to the methyl group favours this cyclization process. In
secondary radical 11i is not too bulky. For 5jϪm the radical our case, the formation of 12 in a 5-exo cyclization mode
11 undergoes a 6-endo cyclization onto the nitrogen atom. would be also the favoured process. That is indeed the case
Subsequent debenzoylation from the so-obtained radical 13 starting from 5aϪf and 5i. Starting from 5gϪh, the overall
leads to the 2,5-dihydropyridines 8jϪm. When R3 ϭ Ph substitution hindrance is probably too large and slows
(5jϪl), the formation of iminyl radical 14 competes with the down the 5-exo ring closure as it is normally expected; but
formation of 13 and a mixture of 9 and 10 is also obtained that does not allow the 6-endo ring closure to be competi-
(via the allylic radical 15).
tive. It means that the formation of 8jϪm by an effective 6-
Starting from 11, the two possible courses of the reaction, endo ring closure of the nucleophilic C-centred radical 11
5-exo or 6-endo ring closure, deserve some comments. To onto the nitrogen atom of the CϭN bond cannot only be
our knowledge, only one case of 6-endo ring closure of a C- explained by stereoelectronic or steric effects as is the case
Eur. J. Org. Chem. 2000, 275Ϫ280
277

M. Depature, J. Diewok, J. Grimaldi, J. Hatem
FULL PAPER
in 5-hexenyl radical.[20] Similar observations have been re-
ported by Komatsu[21] in the ring closure of 6-aza-7-hep-
tadien-2-yl system. Moreover, as we have previously
shown,[17] that cannot be explained by π delocalization of
radical 13. On the other hand, it is well-known that the
attack of a nucleophilic radical onto an olefin is strongly
favoured by the polar effect induced by an electron-with-
drawing substituent at the carbon atom which is not at-
tacked (β-substituent effect).[22] From a similar point of
view, we assume that the presence of an electron-with-
drawing group [R3 ϭ Ph, P(O)(OEt)2] at the carbon atom
of the carbonϪnitrogen double bond is necessary to make
the nitrogen atom more attractive towards nucleophilic rad-
icals.
(200 MHz): δ ϭ 1.16 [s, 6 H, C(CH3)2], 1.70 [d, J ϭ 2.8 Hz, 6 H,
(CH3)2CϭC], 2.13 (s, 3 H, CH3CϭO), 4.98 (m, J ϭ 2.8 Hz, 1 H,
CHϭC) Ϫ 13C NMR (50 MHz): δ ϭ 19.8 (CH3), 23.9 (CH3), 24.5
(CH3), 48.1 [C(CH3)2], 95.3 (CϭCϭCH), 97.9 (CϭCϭCH), 200.8
(CϭCϭCH), 210.6 (CϭO).
2,2,5-Trimethyl-1-phenylhexa-3,4-dienone (3j): 64% yield, colourless
1
oil. Ϫ IR (CCl4): ν˜ ϭ 1965 cmϪ1 (CϭCϭC), 1680 (CϭO). Ϫ H
NMR (200 MHz): δ ϭ 1.37 [s, 6 H, C(CH3)2], 1.65 [d, J ϭ 2.9 Hz,
6 H, (CH3)2CϭC], 5.23 (m, J ϭ 2.9 Hz, 1 H, CHϭC), 7.36Ϫ7.46
(m, 3 H, Ph), 7.92Ϫ7.98 (m, 2 H, Ph). Ϫ 13C NMR (50 MHz): δ ϭ
20.0 (CH3), 26.8 (CH3), 48.1 [C(CH3)2], 96.9 (CϭCϭCH), 99.0
(CϭCϭCH), 127.8 129.3 and 131.5 (CH, Ph), 137.1 (C, Ph), 200.9
(CϭCϭCH), 205.0 (CϭO).
Preparation of the β-Allenyl Phosphonate 4: Under argon, 20 mL of
a 2  solution of oxalyl chloride in CH2Cl2 was added to a solution
of the β-allenyl acid (3.08 g, 20 mmol)[10] in 5 mL of anhydrous
CH2Cl2 at 0°C. The reaction mixture was stirred at 20°C for 1 h,
and excess oxalyl chloride was then removed under reduced press-
ure. The residual acid chloride was cooled to 0°C and of P(OEt)3
(3.5 mL, 20 mmol) was added dropwise. The reaction mixture was
stirred at 20°C for 1 h. Distillation of the mixture gave 4.
Conclusion
In summary, in this work, we have shown that the action
of tributyltin hydride on a wide range of β-allenylbenzoy-
loximes mainly occurs on the allenic sp-carbon atom. De-
pending on the type of substitution on the carbon atom of
the oxime function, the reaction gives either the cyclopen-
tene derivatives 7 or 2,5-dihydropyridines 8, both bearing a
tributyltin group. Starting from the unsubstituted or
methyl-substituted benzoyloximes 5, cyclopentenes 7 are
obtained from a 5-exo ring closure. With methyl-substituted
benzoyloximes, this reaction fails when the allene is over-
crowded. When the benzoyloxime substituent is an electron-
withdrawing group [Ph, P(O)(OEt)2], a 6-endo ring closure
takes place onto the nitrogen atom of the CϭN bond, lead-
ing to the 2,5-dihydropyridines 8. Iminyl radical formation
competes with the latter process when the steric hindrance
at the terminal, trigonal carbon atom increases. In this way,
3H-pyrroles 9 and alkylidenepyrrolines 10 are obtained. At
last, we succeeded in chemoselective formation of 9 and 10
using a radical precursor other than 5.[23]
1-Diethylphosphonato-2,2,5-trimethylhexa-3,4-dienone (4): 52%
yield, colourless oil, b.p. 105Ϫ110°C/0.1 Torr.
Ϫ
1H NMR
(200 MHz): δ ϭ 1.26 [s, 6 H, C(CH3)2], 1.28 and 1.29 (2t, J ϭ
7.2 Hz, 6 H, OCH2CH3), 1.64 [d, J ϭ 2.9 Hz, 6 H, (CH3)2CϭC],
4.13 and 4.14 (2quin, J ϭ 7.2 Hz, 4 H, OCH2CH3), 5.18 (m, 1 H,
CHϭC). Ϫ 13C NMR (50 MHz): δ ϭ 16.2 and 16.3 (OCH2CH3),
20.1 (CH3), 23.3 (CH3), 50.1 [d, J ϭ 55.4 Hz, C(CH3)2], 63.3 and
63.4 (OCH2CH3), 92.7 (CϭCϭCH), 98.8 (CϭCϭCH), 202.4 (Cϭ
CϭCH), 211.7 (d, J ϭ 154.0 Hz, CϭO).
General Procedure for the Preparation of the β-Allenylbenzoyloximes
5: To a stirred mixture of CH2Cl2 (10 mL), pyridine (10 mL), and
˚
hydroxylamine hydrochloride (2.09 g, 30 mmol) was added 4-A mo-
lecular sieves and 15 mmol of 2, 3, or 4. The reaction was moni-
tored by TLC (for the compounds 3a؊h the reaction was com-
pleted after 1 h; for the compounds 3i؊m and 4 the reaction mix-
ture was heated under reflux overnight). The mixture was diluted
with 70 mL of Et2O, filtered, and washed with 40 mL of water. The
organic layer was then extracted with a 5% aqueous CuSO4 solu-
tion to remove pyridine. The solvent was dried with MgSO4 and
concentrated under reduced pressure giving crude β-allenyl oximes.
To a solution of the so-obtained oximes (10 mmol) in a mixture of
20 mL of Et2O and 2 mL of pyridine, 2 mL of benzoyl chloride was
added dropwise. After 2 h, 3 mL of water and then 70 mL of an
aqueous saturated Na2CO3 solution were added. The reaction mix-
ture was stirred overnight. The aqueous phase was extracted with
Et2O and the combined organic layers were washed with a 5%
aqueous CuSO4 solution. The solvent was dried with MgSO4 and
concentrated under reduced pressure giving crude β-allenylbenzoy-
loximes which were purified by silica-gel column chromatography
(eluent: Et2O/pentane).
Experimental Section
Presented are selected data; a complete Experimental Section is
available on the WWW under http://www.wiley-vch.de/home/eurjoc
or from the author.
General: Melting points are uncorrected. Ϫ 1H- and 13C- NMR
spectra were performed in CDCl3 with tetramethylsilane as internal
reference, and recorded with Bruker AC 200 and AMX 400 spec-
trometers. Ϫ IR: Mattson 1000 FT-IR. Ϫ Merck silica gel 60
(230Ϫ400 mesh) was used for column chromatography. Ϫ Solvents
and reagents were purified according to standard laboratory tech-
niques. Ϫ Abbreviation used: AIBN ϭ 2,2Ј-azobis(2-methylpro-
pionitrile).
2,2,5-Trimethylhexa-3,4-dienal O-Benzoyloxime (5b): 75% yield,
white crystals (pentane), m.p. 32Ϫ34°C. Ϫ IR (KBr): ν˜ ϭ 1972
1
cmϪ1 (CϭCϭC), 1735 (CϭO). Ϫ H NMR (200 MHz): δ ϭ 1.31
General Procedure for the Preparation of the β-Allenyl Ketones 3:
The β-allenyl ketones 3 were obtained in the standard manner, first
by the action of methyl- or phenylmagnesium iodide on the β-al-
lenyl aldehydes 2,[10] and then by oxidation of the resulting β-al-
lenyl alcohols by PCC.[11] The crude ketones were purified by silica-
gel column chromatography (eluent: Et2O/pentane).
[s, 6 H, C(CH3)2], 1.70 [d, J ϭ 2.9 Hz, 6 H, (CH3)2CϭC], 5.02
(sept, J ϭ 2.9 Hz, 1 H, CHϭC), 7.39Ϫ7.57 (m, 3 H, Ph), 7.75 (s,
1 H, CHN), 8.02Ϫ8.07 (m, 2 H, Ph). Ϫ 13C NMR (50 MHz): δ ϭ
20.5 (CH3), 25.3 (CH3), 38.6 [C(CH3)2], 95.6 (CϭCϭCH), 97.0
(CϭCϭCH), 128.0 128.9 and 133.1 (CH, Ph), 131.1 (C, Ph), 164.1
(CϭO), 165.4 (HCϭN), 200.1 (CϭCϭCH).
Ϫ C16H19NO2
3,3,6-Trimethylhepta-4,5-dien-2-one (3f): 66% yield, colourless oil.
(257.33): calcd. C 74.68, H 7.44, N 5.44; found C 74.66, H 7.47,
Ϫ IR (neat): ν˜ ϭ 1965 cmϪ1 (CϭCϭC), 1710 (CϭO). Ϫ 1H NMR N 5.36.
278
Eur. J. Org. Chem. 2000, 275Ϫ280

Tin-Mediated Free-Radical Cyclization of β-Allenylbenzoyloximes
3,3,6-Trimethylhepta-4,5-dien-2-one O-Benzoyloxime (5f): 76%
FULL PAPER
4-(Benzoyloxyamino)-3,3,4,5,5-pentamethyl-1-(tri-n-butylstannyl)-
cyclopentene (7f): Obtained from 5f in 75% yield, colourless oil. Ϫ
yield, white crystals (pentane), m.p. 47Ϫ48°C. Ϫ IR (KBr): ν˜ ϭ
1
1967 cmϪ1 (CϭCϭC), 1745 (CϭO). Ϫ H NMR (200 MHz): δ ϭ IR (CCl4): ν˜ ϭ 1751 cmϪ1 (CϭO). 1H NMR (200 MHz): δ ϭ
1.32 [s, 6 H, C(CH3)2], 1.71 [d, J ϭ 2.8 Hz, 6 H, (CH3)2CϭC], 2.04
0.83Ϫ0.93 (m, 15H, SnCH2CH2CH2CH3), 1.08 (s, 3 H, CH3), 1.09
(s, 3 H, CH3CϭN), 4.99 (sept, J ϭ 2.8 Hz, 1 H, CHϭC), 7.44Ϫ7.56 (s, 3 H, CH3), 1.16 (s, 3 H, CH3), 1.18 (s, 3 H, CH3), 1.19 (s, 3 H,
(m, 3 H, Ph), 8.02Ϫ8.07 (m, 2 H, Ph). Ϫ 13C NMR (50 MHz): δ ϭ CH3), 1.24Ϫ1.52 (m, 12 H, SnCH2CH2CH2CH3), 5.44 (s, 1 H,
13.1 (NϭCCH3), 20.4 (CH3), 25.4 (CH3), 42.7 [C(CH3)2], 96.2 (Cϭ
CϭCH), 98.4 (CϭCϭCH), 128.4 129.4 and 133.0 (CH, Ph), 163.8
CHϭC), 7.39Ϫ7.56 (m, 3 H, Ph), 7.95Ϫ8.00 (m, 2 H, Ph), 8.04 (s,
1 H, Ph). Ϫ 13C NMR (50 MHz): δ ϭ 10.0 (SnCH2), 13.7
(CϭO), 171.7 (CϭN), 201.0 (CϭCϭCH). Ϫ C17H21NO2 (271.36): (SnCH2CH2CH2CH3), 18.8 (CH3), 25.5 (CH3), 26.2 (CH3), 27.4
calcd. C 75.25, H 7.80, N 5.16; found C 75.24, H 7.68, N 5.14.
(CH2), 29.2 (CH2), 52.1 [C(CH3)2], 56.3 [C(CH3)2], 70.7 (CHNH),
128.6 129.2 and 133.1 (CH, Ph), 128.7 (C, Ph), 148.5 (CHϭC),
150.4 (CHϭC), 166.4 (CϭO). Ϫ C29H49NO2Sn (562.41): calcd. C
61.93, H 8.78, N 2.49; found C 61.85, H 8.83, N 2.45.
2,2,5-Trimethyl-1-phenylhexa-3,4-dienone O-Benzoyloxime (5j):
66% yield, white needles (pentane), m.p. 104Ϫ106°C. Ϫ IR (KBr):
1
ν˜ ϭ 1965 cmϪ1 (CϭCϭC), 1753 (CϭO). Ϫ H NMR (200 MHz):
δ ϭ 1.38 [s, 6 H, C(CH3)2], 1.59 [d, J ϭ 2.8 Hz, 6 H, (CH3)2CϭC],
5.12 (sept, J ϭ 2.8 Hz, 1 H, CHϭC), 7.15Ϫ7.60 (3 m, 10 H, Ph).
Ϫ
Cyclization of 5i gave a mixture of 6i and 7i.
13C NMR (50 MHz): δ ϭ 20.2 (CH3), 26.1 (CH3), 42.7
[C(CH3)2], 96.2 (CϭCϭCH), 98.7 (CϭCϭCH), 127.2 127.7 128.2
128.3 129.2 and 129.4 (CH, Ph), 132.9 and 133.5 (C, Ph), 163.7
(CϭO), 174.0 (CϭN), 201.4 (CϭCϭCH). Ϫ C22H23NO2 (333.43):
calcd. C 79.25, H 6.95, N 4.20; found C 79.18, H 6.95, N 4.12.
2,2-Dimethyl-1-phenyl-4-(tri-n-butylstannyl)hex-3-enone O-Benzoyl-
oxime (6i): 19% yield, colourless oil. Ϫ IR (CCl4): ν˜ ϭ 1719 cmϪ1
(CϭO). Ϫ 1H NMR (400 MHz): δ ϭ 0.80Ϫ1.00 (m, 15H,
SnCH2CH2CH2CH3), 1.02 (t,
J ϭ 7.5 Hz, 3 H, CH2CH3),
1.24Ϫ1.33 (m, 6 H, CH2), 1.41Ϫ1.47 (m, 6 H, CH2), 1.50 [s, 6 H,
C(CH3)2], 2.62 (qd, J ϭ 7.5 Hz and 2.2 Hz, 2 H, CH2CH3), 5.30
(d, J ϭ 2.2 Hz, 1 H, CHϭC), 7.17Ϫ7.62 (m, 10 H, Ph). Ϫ 13C
NMR (100 MHz): δ ϭ 10.1 (SnCH2), 13.7 (SnCH2CH2CH2CH3),
14.7 (CH3), 26.8 (CH2), 27.4 (CH2), 28.4 (CH3), 29.1 (CH2), 44.9
[C(CH3)2], 127.5 127.6 128.3 129.4 and 132.8 (CH, Ph), 129.3 and
134.0 (C, Ph), 142.3 (CHϭC), 153.8 (CHϭC), 163.8 (CϭO), 173.8
(CϭN). Ϫ C33H49NO2Sn (610.45): calcd. C 64.93, H 8.09, N 2.29;
found C 65.01, H 8.11, N 2.26.
1-Diethylphosphonato-2,2,5-trimethylhexa-3,4-dienone O-Ben-
zoyloxime (5m): 23% yield, colourless oil. Ϫ H NMR (200 MHz):
1
δ ϭ 1.22 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3), 1.46 [s, 6 H, C(CH3)2],
1.67 [d, J ϭ 2.8 Hz, 6 H, (CH3)2CϭC], 4.13 (m, 4 H, OCH2CH3),
5.40 (m, J ϭ 2.8 Hz, 1 H, CHϭC), 7.40Ϫ7.56 (m, 3 H, Ph),
8.14Ϫ8.19 (m, 2 H, Ph). Ϫ 13C NMR (50 MHz): δ ϭ 16.3 and
16.4 (OCH2CH3), 18.6 (CH3), 26.5 (CH3), 26.6 CH3), 43.3 (d, J ϭ
21.1 Hz, [C(CH3)2], 62.6 and 62.7 (OCH2CH3), 95.5 (CϭCϭCH),
98.7 (CϭCϭCH), 128.6 130.1 and 133.5 (CH, Ph), 134.6 (C, Ph),
163.2 (CϭO), 166.8 (d, J ϭ 141.9 Hz, CϭN), 201.6 (CϭCϭCH).
Ϫ C20H28NO5P (393.42): calcd. C 61.06, H 7.17, N 3.56; found C
61.00, H 7.11, N 3.47.
4-(Benzoyloxyamino)-3,3,5-trimethyl-4-phenyl-1-(tri-n-butyl-
stannyl)cyclopentene (7i): 44% yield, pale yellow oil. Ϫ IR (CCl4):
ν˜ ϭ 1720 cmϪ1 (CϭO). Ϫ The 1H-NMR and 13C-NMR spectra
were recorded on a mixture of both isomers (9:1 ratio). Only the
major isomer could be fully described. Major isomer: 1H NMR
(200 MHz): δ ϭ 0.56 (s, 3 H, CH3), 0.85Ϫ0.96 (m, 15 H,
SnCH2CH2CH2CH3), 1.19 [d, J ϭ 7.4 Hz, 3 H, CH(CH3)],
1.21Ϫ1.36 (m, 6 H, CH2), 1.35 (s, 3 H, CH3), 1.37Ϫ1.51 (m, 6 H,
CH2), 3.77 [qd, J ϭ 7.4 Hz and 2.3 Hz, 1 H, CH(CH3)], 5.70 (d,
J ϭ 2.3 Hz, 1 H, CHϭC), 7.25Ϫ7.79 (3m, 10 H, Ph), 8.16 (s, 1 H,
General Procedure for the Tin-Mediated Radical Cyclization of the
Compounds 5a؊d (Table 1): A hexane solution of Et3B (1.0 ,
1.0 mL, 1.0 mmol) and 20 mL of air were added portionwise for 48
h to a solution of tin hydride (1.2 mmol) and 5a؊d (1.0 mmol) in
cyclohexane (50 mL) under argon. The solvent was evaporated un-
der reduced pressure and the crude mixture was purified by silica-
gel column chromatography (eluent: Et2O/pentane).
NH).
Ϫ δ ϭ 9.6 (SnCH2), 13.8
13C NMR (50 MHz):
4-(Benzoyloxyamino)-3,3,5,5-tetramethyl-1-(tri-n-butylstannyl)
cyclopentene (7b): 75% yield, colourless oil. Ϫ IR (CCl4): ν˜ ϭ 1721
cmϪ1 (CϭO). Ϫ 1H NMR (200 MHz): δ ϭ 0.83Ϫ0.96 (m, 15 H,
SnCH2CH2CH2CH3), 1.08 (s, 3 H, CH3), 1.11 (s, 3 H, CH3), 1.22
(s, 3 H, CH3), 1.24 (s, 3 H, CH3), 1.26Ϫ1.54 (m, 12 H,
SnCH2CH2CH2CH3), 3.25 (d, J ϭ 7.4 Hz, 1 H, CHNH), 5.48 (s,
1 H, CHϭC), 7.41Ϫ7.57 (m, 3 H, Ph), 8.00Ϫ8.05 (m, 2 H, Ph),
8.18 (d, J ϭ 7.4 Hz, 1 H, CHNH). Ϫ 13C NMR (50 MHz): δ ϭ
9.7 (SnCH2), 13.7 (SnCH2CH2CH2CH3), 23.3 (CH3), 24.0 (CH3),
27.4 (CH2), 29.2 (CH2), 30.2 (CH3), 31.1 (CH3), 49.2 [C(CH3)2],
53.3 [C(CH3)2], 77.0 (CHNH), 128.6 129.2 and 133.2 (CH, Ph),
128.7 (C, Ph), 148.8 (CHϭC), 151.1 (CHϭC), 166.5 (CϭO). Ϫ
C28H47NO2Sn (548.38): calcd. C 61.33, H 8.64, N 2.55; found C
61.38, H 8.59, N 2.54.
(SnCH2CH2CH2CH3), 15.5 (CH3), 22.7 (CH3), 26.2 (CH3), 27.4
(CH2), 29.3 (CH2), 51.1 (CH), 53.3 [C(CH3)2], 76.9 (CNH), 127.1
127.6 128.0 128.4 129.2 and 132.9 (CH, Ph), 128.9 and 140.5 (C,
Ph), 145.1 (CHϭC), 150.1 (CHϭC), 165.7 (CϭO). Ϫ Minor iso-
1
mer: H NMR (200 MHz) (incomplete description): δ ϭ 3.26 [qd,
J ϭ 7.2 Hz and 2.8 Hz, 1 H, CH(CH3)], 5.82 (d, J ϭ 2.8 Hz, 1 H,
CHϭC). Ϫ 13C NMR (50 MHz) (incomplete description): δ ϭ 9.8
(SnCH2), 13.8 (SnCH2CH2CH2CH3), 27.4 (CH2), 29.3 (CH2), 54.3
(CH), 78.8 (CNH), 133.2 (CH, Ph), 139.8 (C, Ph), 146.6 (CHϭC),
152.4 (CHϭC), 166.3 (CϭO). Ϫ C33H49NO2Sn (610.45): calcd. C
64.93, H 8.09, N 2.29; found C 64.89, H 8.06, N 2.26.
Cyclization of 5j afforded a mixture of 8j, 9j, and 10j.
General Procedure for the Tin-Mediated Radical Cyclization of the
Compounds 5e؊m (Tables 1 and 2): Bu3SnH (1.2 equiv.) and AIBN
(0.2 equiv.) were added to a cyclohexane solution (0.02 ) of the
compounds 5e؊m. After this solution was degassed with a stream
2,2,5,5-Tetramethyl-6-phenyl-3-(tri-n-butylstannyl)-2,5-dihydro-
pyridine (8j): 82% yield, colourless oil. Ϫ IR (CCl4): ν˜ ϭ 1679 cmϪ1
(CϭN). Ϫ 1H NMR (400 MHz): δ ϭ 0.88Ϫ0.97 (m, 15H,
SnCH2CH2CH2CH3), 1.14 (s, 6 H, CH3), 1.31Ϫ1.38 (m, 6 H, CH2),
of argon, the mixture was heated under reflux, and monitored by 1.32 (s, 6 H, CH3), 1.47Ϫ1.55 (m, 6 H, CH2), 5.55 (s, 1 H, CHϭ
TLC until the starting material had disappeared. After evaporation
of the solvent, the crude mixture was purified by silica-gel column
chromatography (Et2O/pentane starting from 5e؊l; CH2Cl2/ethyl
acetate starting from 5m).
C), 7.30 (m, 5 H, Ph). Ϫ 13C NMR (100 MHz): δ ϭ 10.5 (SnCH2),
13.7 (SnCH2CH2CH2CH3), 27.4 (CH2), 28.7 (CH3), 29.1 (CH2),
32.0 (CH3), 35.0 (CϪCϭN), 60.5 (CϪNϭC), 127.6 127.8 and 127.9
(CH, Ph), 141.2 (C, Ph), 141.7 (CHϭC), 144.3 (CHϭC), 171.1 (Cϭ
Eur. J. Org. Chem. 2000, 275Ϫ280
279

M. Depature, J. Diewok, J. Grimaldi, J. Hatem
M. Ramaja, Tetrahedron 1987, 43, 3541Ϫ3676.
FULL PAPER
[1]
[2]
N). Ϫ C27H45NSn (502.36): calcd. C 64.56, H 9.03, N 2.79; found
B. Giese, Radicals in Organic Synthesis: Formation of Car-
bonϪCarbon Bonds, Pergamon, New York, 1986.
W. B. Motherwell, D. Crich, Free-Radical Chain Reactions in
Organic Synthesis, Academic Press, London, 1992.
J. Fossey, D. Lefort, J. Sorba, Free Radicals in Organic Chemis-
try, John Wiley & Sons, Inc., New York, 1995.
A. G. Fallis, I. M. Brinza, Tetrahedron 1997, 53, 17543Ϫ17593.
T. Naito, Heterocycles 1999, 50, 505Ϫ541.
C 64.49, H 9.01, N 2.75.
[3]
[4]
3,3-Dimethyl-2-phenyl-5-isopropyl-3H-pyrrole (9j): 4% yield,
1
colourless oil. Ϫ H NMR (200 MHz): δ ϭ 1.26 [d, J ϭ 6.7 Hz, 6
H, CH(CH3)2], 1.40 [s, 6 H, C(CH3)2], 2.80 [septd, J ϭ 6.7 Hz and
1.4 Hz, 1 H, CH(CH3)2], 5.74 (d, J ϭ 1.4 Hz, 1 H, CHϭC),
7.25Ϫ7.44 (m, 3 H, Ph), 7.90Ϫ8.00 (m, 2 H, Ph). Ϫ 13C NMR
(50 MHz): δ ϭ 21.2 (CH3), 22.9 (CH3), 29.5 [CH(CH3)2)], 55.8
[C(CH3)2], 127.8 128.4, 128.9 and 129.7 (CH, vinyl), 133.6 (C, Ph),
159.7 (CϪN), 183.0 (CϭN). Ϫ C15H19N (213.32): calcd. C 84.46,
H 8.98, N 6.57; found C 84.31, H 8.97, N 6.45.
[5]
[6]
[7]
J. MarcoϪContelles, G. Balme, D. Bouyssi, C. Destabel, C. D.
Henriet-Bernard, J. Grimaldi, J. M. Hatem, J. Org. Chem. 1997,
62, 1202Ϫ1209 and references therein.
[8]
J. L. Esker, M. Newcomb, Adv. Heterocycl. Chem. 1993, 58,
1Ϫ45.
[9]
S. Zard, Synlett 1996, 1148Ϫ1154.
[10]
[11]
4,4-Dimethyl-2-isopropylidene-5-phenyl-3,4-dihydro-2H-pyrrole
(10j): 5% yield, colourless oil. Ϫ 1H NMR (200 MHz): δ ϭ 1.44 [s,
6 H, C(CH3)2], 1.77 (m, 3 H, CH3), 2.12 (m, 3 H, CH3), 2.60 (m,
2 H, CH2), 7.36Ϫ7.40 (m, 3 H, Ph), 7.92Ϫ7.97 (m, 2 H, Ph). Ϫ
13C NMR (50 MHz): δ ϭ 19.4 (CH3), 20.8 (CH3), 27.7 (CH3), 45.5
(CH2), 48.9 [C(CH3)2], 123.1 (CϭCϪN), 128.3 and 129.5 (CH, Ph),
134.7 (C, Ph), 147.5 (CϪN), 177.8 (CϭN). Ϫ C15H19N (213.32):
calcd. C 84.46, H 8.98, N 6.57; found C 84.39, H 9.06, N 6.44.
R. S. Bly, S. U. Koock, J. Am. Chem. Soc. 1969, 91, 3292Ϫ3298.
S. Agarwal, H. P. Tiwari, J. P. Sharma, Tetrahedron 1990, 46,
4417Ϫ4420.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
A. J. Kirby, S. G. Warren, The Organic Chemistry of Phosphorus,
Elsevier Publishing Company, Amsterdam, 1967, p. 60.
K. Nozaki, K. Oshima, K. Utimoto, Tetrahedron 1989, 45,
923Ϫ933.
The structure of both isomers was analysed from the mixture
using NOESY experiment.
J. A. Howard, K. U. Ingold, J. Am. Chem. Soc. 1968, 90,
1055Ϫ1058.
Cyclization of 5m gave 8m.
F. El Gueddari, J. R. Grimaldi, J. M. Hatem, Tetrahedron Lett.
1995, 6685Ϫ6688.
6-Diethylphosphonato-2,2,5,5-tetramethyl-3-(tri-n-butylstannyl)-2,5-
dihydropyridine (8m): 55% yield, colourless oil. Ϫ 1H NMR
(400 MHz): δ ϭ 0.84Ϫ0.91 (m, 15 H, SnCH2CH2CH2CH3), 1.23
[s, 6 H, C(CH3)2], 1.27Ϫ1.34 (m, 6 H, CH2), 1.29 [s, 6 H, C(CH3)2],
1.31 (t, J ϭ 7.2 Hz, 6 H, OCH2CH3), 1.41Ϫ1.48 (m, 6 H, CH2),
4.14 (q, J ϭ 7.2 Hz, 4 H, OCH2CH3), 5.45 (d, J ϭ 9.7 Hz, 1 H,
CHϭC). Ϫ 13C NMR (100 MHz): δ ϭ 10.4 (SnCH2), 13.6
(SnCH2CH2CH2CH3), 16.3 (CH3), 27.3 (CH2), 27.8 (CH3), 29.1
(CH2), 31.5 (CH3), 34.9 (d, J ϭ 29.0 Hz, CϪCϭN), 61.3 (d, J ϭ
23.0 Hz, OCH2CH3), 62.8 (CϪN), 141.8 (CHϭC), 142.6 (CHϭC),
168.7 (d, J ϭ 204.2 Hz, CϭN). Ϫ C25H50NO3PSn (514.35): calcd.
C 53.40, H 8.96, N 2.49; found C 53.44, H 8.92, N 2.43.
M. Depature, D. Siri, J. Grimaldi, J. Hatem, R. Faure, Tetra-
hedron Lett. 1999,4547Ϫ4550.
W. R. Bowman, P. T. Stephenson, N. K. Terett, A. R. Young,
Tetrahedron 1995, 51, 7959Ϫ7980.
I. Ryu, K. Matsu, S. Minakata, M. Komatsu, J. Am. Chem.
Soc. 1998, 120, 5838Ϫ5839 and references cited.
A. L. J. Beckwith, Tetrahedron 1981, 37, 3073Ϫ3100.
I. Ryu, S.-i. Ogura, S. Minaka, M. Komatsu, Tetrahedron Lett.
1999, 1515Ϫ1518.
[20]
[21]
[22]
[23]
H. Fischer in Substituent Effects in Radical Chemistry (Eds.: H.
G. Viehe et al.), NATO ASI Series, Series C: Mathematical and
Physical Sciences, 1986, vol. 189, p. 123Ϫ142.
M. Depature, J. Grimaldi, J. Hatem, to be published.
Received June 18, 1999
[O99373]
280
Eur. J. Org. Chem. 2000, 275Ϫ280