A coordinatively unsaturated ruthenium methoxide as a highly effective catalyst for the halogen atom-transfer radical cyclization of N-allyl dichloroacetamides and related reactions

Article abstract of DOI:10.1016/j.tet.2006.01.011

Atom-transfer radical cyclization (ATRC) catalyzed by coordinatively unsaturated ruthenium alkoxides 4, [(η⁵-C₅Me ₅)Ru(OR)]₂, is investigated, and ruthenium methoxide 4a (R=Me) is found to exhibit excellent cata

Full text of DOI:10.1016/j.tet.2006.01.011

Tetrahedron 62 (2006) 2779–2788
A coordinatively unsaturated ruthenium methoxide as a highly
effective catalyst for the halogen atom-transfer radical cyclization
of N-allyl dichloroacetamides and related reactions
*
Yukihiro Motoyama, Shiori Hanada, Kazuya Shimamoto and Hideo Nagashima
Graduate School of Engineering Science, Institute for Materials Chemistry and Engineering,
Kyushu University, Kasuga, Fukuoka 816-8580, Japan
Received 30 November 2005; revised 29 December 2005; accepted 6 January 2006
Available online 7 February 2006
Abstract—Atom-transfer radical cyclization (ATRC) catalyzed by coordinatively unsaturated ruthenium alkoxides 4, [(h5-C5Me5)-
Ru(OR)]2, is investigated, and ruthenium methoxide 4a (RZMe) is found to exhibit excellent catalytic activity for the cyclization of N-allyl-
a,a-dichloroacetamides at ambient temperature. Addition of some amounts of two-electron donor ligands such as pyridine and
triphenylphosphine improves the catalyst efficiency to afford the corresponding g-lactams in high yields. The high catalytic activity of this
catalyst system enables to control the diastereoselectivity of this 5-exo cyclization kinetically. The present 4a/pyridine system is also
effective for the 4-exo cyclization of N-vinylacetamides to afford the corresponding b-lactams in quantitative yields. The 4a/pyridine system
is also active towards the ATRP of methyl methacrylate (MMA) at room temperature to afford the poly(MMA) with narrow molecular weight
distributions (Mw/MnZ1.2) at the initial stage.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
the fact that these substituents lower the LUMO of
a-halogenated acetyl moiety and facilitate abstraction of a
halogen atom by transition metal catalysts. On the other
hand, several reactive catalyst systems, which can promote
the reaction at low temperature, were developed; in
particular, catalyst systems composed of CuCl and bidentate
diamines4c and isolable coordinatively unsaturated ruthe-
nium amidinates 1–3 were found to be one of the most
effective catalysts for ATRR (Fig. 1).6c,7 Thus, combination
of the selection of appropriate substrates, which have
suitable electronic structures for ATRR, with powerful
catalyst systems realized the cyclization of N-allyl-a,a,a-
trichloroacetamides below room temperature within a few
hours. However, the cyclization of less reactive substrates
such as N-allyl-a,a-dichloroacetamides is slow even using
CuCl/bipyridine and ruthenium amidinates as the catalyst
and it is necessary to apply high reaction temperatures
(O80 8C) to obtain the product in good yield.4e,7,8 This
indicates the requirement to seek for catalysts more
powerful enough to activate a carbon–chlorine bond of
N-allyl dichloroacetamides with ease to afford the corre-
sponding g-lactams.
Atom-transfer radical reaction (ATRR) has now become
one of the most important carbon–carbon bond-forming
reactions, being utilized for synthetic organic chemistry and
polymer synthesis.1–3 In particular, our discovery of copper-
catalyzed cyclizations of allyl a,a,a-trichloroacetates4a and
N-allyl-a,a,a-trichloroacetamides4b offered a research field
of transition metal-catalyzed atom-transfer radical cycliza-
tion (ATRC), which has afforded powerful synthetic
methods for carbo- and heterocycles including macrolide
and alkaloid skeletons.5 From the synthetic point-of-view, it
should be noted that requirement of high reaction
temperatures is a general disadvantage of ATRR, especially
in the reactions involving activation of less reactive carbon–
halogen bonds. In our earliest report on the cyclization of
a-halogenated N-allylacetamides, either RuCl2(PPh3)3 or
CuCl catalyst was effective at 140 8C.4b Later elaboration to
improve the reaction conditions revealed that the reaction
was facilitated by increasing the halogen atom at the
a-position and/or introduction of electron-withdrawing
group on the nitrogen atom.4e,f This is presumably due to
For the development of highly reactive new catalysts, we
have been interested in use of coordinatively unsaturated
transition metal complexes. ATRC is generally explained by
the catalytic cycle shown in Scheme 1. The atom-transfer
Keywords: Coordinatively unsaturated complex; Polymerization; Radical
cyclization; Ruthenium.
*
Corresponding author. Tel.: C81 92 583 7819; fax: C81 92 583 7819;
e-mail: nagasima@cm.kyushu-u.ac.jp
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.011

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Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
Figure 1. Ruthenium amidinate complexes 1–3.
Scheme 2. ATRC of N-allyl-a,a-dichloroacetamides 5.
Treatment of a,a-dichloroacetamide 5a (0.2 mmol) with
4a (10 mol% of Ru) in dichloromethane for 4 h under an
argon atmosphere afforded the cyclic product 6a in 50%
isolated yield with a trans/cis ratio of 86:14 (Table 1,
entry 1). The alkoxy group on the ruthenium apparently
affected the catalytic activity; the ethoxy complex 4b gave 6a
in34% yield (entry2), whereasnoproduct wasobtainedbythe
use of trifluoroethyl and t-butyl derivatives (4c and 4d) as
catalysts (entries 3 and 4). It is noteworthy that ruthenium
halidecomplexessuchas[Cp*RuIICl]4 and[Cp*RuIIICl2]2 are
not effectiveforthiscyclizationatambient temperature(!5%
yields). These results showed that the sterically less-hindered
alkoxide ligand plays a crucial role in enhancing the reactivity
of the ruthenium complexes towards organic halides via the
one-electron redox process, which may be related to the
p-donation by alkoxide lone pairs. Among the solvents
examined, dichloromethaneprovedtobethemosteffectivefor
both chemical yield and trans/cis ratio of the product (entries
5–8).
Scheme 1. Atom-transfer reaction with transition metal complex.
reaction of organic halides (R–X) with transition metals (M)
proceeds via the redox mechanism involving a [R–X/M]
complex as an intermediary species, and the formal oxidation
state of the metal species is increased by one, and M–X is
formed by the halogen abstraction.9 In the [R–X/M]
complex, M has to be coordinatively unsaturated, and thus,
use of isolated coordinatively unsaturated complexes as the
catalyst could facilitate the production of [R–X/M], which
subsequently undergoes atom-transfer process to produce the
radical species (R%) to initiate the reaction. If M has
appropriate redox potentials, the catalytic cycle illustrated
in Scheme 1 could be successfully operated.
Table 1. Radical cyclization of 5a with [Cp*Ru(OR)]2 4a–da
In fact, ruthenium amidinate complexes 1–3 showed a
coordinatively unsaturated nature, and actually behaved as
efficient catalysts for ATRR as described in our previous
papers.6c,7 For further studies in this line, we were interested
in isolable ruthenium alkoxides [(h5-C5Me5)Ru(OR)]2 4,
which exist in solution as coordinatively unsaturated dimers
having 32 valence electrons and reversibly forms monomers
in contact with appropriate ligands.10 The formed monomer,
which was stabilized by the ligand, is still coordinatively
unsaturated (16 valence electrons), being able to accept the
coordination of R–X for its activation.10c,11 In this paper, we
wish to report that coordinatively unsaturated ruthenium
alkoxides actually behave as the catalyst for the cyclization
of N-allyl-a,a-dichloroacetamides 5 and related reactions.
The scope of these ruthenium alkoxides as catalysts for
ATRC is described in relation to the low-temperature
activation of organic halides and stereochemical outcomes
of the reactions, and their performance is compared with
that for atom-transfer radical polymerization (ATRP)
(Scheme 2).
Entry
Cat.
Solvent
Time (h)
Yield (%) trans/cisb
1
2
3
4
5
6
7
8c
4a
4b
4c
4d
4a
4a
4a
4a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Benzene
MeCN
Et2O
4
4
4
50
34
0
86:14
85:15
—
4
0
64
33
32
—
16
16
16
16
86:14
83:17
82:18
78:22
!10
a All reactions were carried out using 0.2 mmol of 5a, 0.01 mmol of 4 in
1.5 mL of solvent at room temperature.
b Determined by 1H NMR analysis.
c 0.03 mmol (30 mol% Ru) was used.
Despite the high catalytic activity for the cyclization of
dichloroacetamide 5a, a disadvantage of 4a is its short
lifetime as shown in the reaction profiles (Fig. 2, left; a); the
reaction was terminated after some of the starting materials
were consumed (w80%, TON%8). Although the catalytic
activity (initial reaction rate) was slightly decreased,
addition of pyridine to the reaction mixture depresses
inactivation of the catalyst (Fig. 2, left; b). The effects of
pyridine and other ligands, which affect the catalytic
efficiency in the reaction of 5a with 4a in dichloromethane
at ambient temperature, are summarized in Table 2.
2. Results and discussion
2.1. Atom-transfer radical cyclization
As we expected, [Cp*Ru(OMe)]2 4a was effective for the
activation of a C–Cl bond at ambient temperature.

Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
2781
determined to be 3,4-trans by X-ray diffraction (Fig. 3, left).
The 3,4-trans stereochemistry of major products 6a–c was
assigned by the similarity seen in the H NMR spectra to
1
those reported by Slough8a and Gelfi.8b
Table 3. Radical cyclization of various N-allyldichloroacetamides 5a–da
Figure 2. The plots of formed 6a (%) versus time (h): (a) catalyzed by 4a
(B); (b) catalyzed by 4a/pyridine (C); (c) catalyzed by 3 (,);
(d) catalyzed by CuCl/bipyridine (!).
Entry
Substrate
Time (h)
Yield (%)
Trans/cisb
1
2
3
5a (ZZTs)
5b (ZZAllyl)
5c (ZZBn)
5c
5d (ZZPh)
5e (ZZH)
4
5
20
7
17
4
92
95
76
O99
90
87:13
80:20
81:19
82:18
83:17
—
Table 2. Additive effects in the reaction of 5a with 4aa
Entry
Additive
Additive/Ru Yield (%)
Trans/cisb
4c
5d
6
1
2
3
4
5
6
7
8
—
PPh3
—
50
95
91
O99
O99
O99
89
86:14
87:13
89:11
87:13
87:13
87:13
87:13
87:13
0.5
0.5
0.5
1.0
2.0
3.0
0.25
!1
DMAP
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
a All reactions were carried out using 0.2 mmol of 5, 0.01 mmol of 4a
and 0.01 mmol of pyridine in 1.5 mL of CH2Cl2 at room temperature.
b Determined by 1H NMR analysis.
c In dichloroethane at 40 8C.
d 0.03 mmol of 4a (30 mol% Ru) and 0.03 mmol of pyridine were used.
O99
a All reactions were carried out using 0.2 mmol of 2, 0.01 mmol of 4a and
additive in 1.5 mL of CH2Cl2 at room temperature for 4 h.
1
b Determined by H NMR analysis.
Remarkable improvement in the catalytic efficiency was
achieved by the addition of donor ligands (0.5 equiv for Ru),
and pyridine proved to be the most effective for this catalyst
system (entries 1 vs 2–4). We also found that the addition of
0.25–2.0 equiv of pyridine for Ru resulted in satisfactory
yields within 4 h (entries 4–8). It is noteworthy that both the
catalytic activity and efficiency of the present
[Cp*Ru(OMe)]2/pyridine system exceeds those of either
the CuCl/bipyridine or the cationic diruthenium amidinate
systems; the conventional Cu-catalyzed cyclization of
dichloroacetamide is very slow at that temperature (2 h,
20% yield). The reaction catalyzed by the ruthenium
complex 3, which is the most effective catalyst for this
type of cyclization, was faster than that with the CuCl/
bypridine system but slower than that with 4a, but
terminated before reaching completion (3 h, 88% yield)
(Fig. 2, right).
Figure 3. The ORTEP drawings of 3,4-trans-6d (left) and 3,4-trans-10a
(right). For clarify, only H atoms at the C3 and C4 positions are shown.
The efficiency of [Cp*Ru(OMe)]2/pyridine system eventually
led to three important aspects in the ATRC. First, the reaction
of N-tosyl-a,a-dichloroacetamides 7a and 7b bearing sub-
stituted allyl groups such as prenyl and methallyl moieties,
which are less reactive substrates than the N-allyl homologue
5a,8e proceeded even at ambient temperature to afford the
corresponding g-lactams 10a and 10b in good yields (Table 4,
entries 1 and 2). The relative stereochemistry of the major
product 10a was determined to be 3,4-trans by X-ray
diffraction (Fig. 3, right). It is noteworthy that the
diastereoselectivity of the reaction of methallyl derivative
7b reaches to 93:7. The 3,4-trans configuration of the major
product 10b was determined by difference NOE experiments;
no NOEs were obtained between the methine proton (H3) at
the 3-position and the methyl protons at the 4-position (4-Me)
for the major isomer, whereas 6.7% NOE to 4-Me by
irradiation of H3 and 10.7% NOE to H3 by irradiation of
4-Me for the minor isomer. This catalyst system was also
effective for the cyclization of a-monobromoacetamide 8 and
the corresponding brominated g-lactam 11 was obtained in
98% yield (entry 3). Application of this catalyst system to
b-lactam synthesis is also possible; 4-exo cyclization
predominantly proceeded by the reaction of N-vinylaceta-
mides 9a and 9b to give the corresponding b-lactams 12a and
12b inquantitative yieldsas the soleproducts (entries 4 and 5).
Table 3 summarizes the results obtained for the reaction of
various N-allyl-a,a-dichloroacetamides 5a–e catalyzed by
5 mol% of [Cp*Ru(OMe)]2 4a (i.e., 10 mol% Ru) and
5 mol% of pyridine (Ru/pyridineZ0.5) in dichloromethane
(1.5 mL). In all reactions, the product was formed in high
yields, except in the case of the N–H congener 5e (entry 6).
High catalytic activity of the present catalyst system was
also demonstrated in the cyclization of N-benzyl and
N-phenyl derivatives 5c and 5d, which are both known as
less reactive substrates than 5a and 5b.4f,12 Although the
reaction of 5c with this catalyst system was not so fast at
room temperature (20 h; 76% yield), the reaction at 40 8C
for 7 h gave the product 6c in quantitative yield (entries 3
and 4). In the reaction of 5d, the cyclic product 6d was
obtained in 90% isolated yield by the use of 30 mol% Ru at
room temperature for 17 h (entry 5). In all cases, the trans/
cis ratio of the product was controlled as ca. 4:1. The
relative stereochemistry of the major isomer of 6d was

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Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
Table 4. Radical cyclization of various acetamides 9–11a
isomers is observed in the presence of the catalyst at room
temperature. These results suggest that the reaction of a,a-
dichloroacetamides 5 by the 4a/pyridine catalyst is
controlled kinetically, which is similar to the cationic
diruthenium amidinate 3 reported previously.7 Interestingly,
MO calculations indicate that there is no substantial energy
difference (!0.1 kcal/mol)14 between trans-10b and cis-
10b in the case of the reaction of 7b. Furthermore,
activation energies of both pathways via the free radical
mechanism are almost the same (ca. 5 kcal/mol).15 Never-
theless, higher trans-selectivity of the cyclization of 7b (N-
methallyl:trans/cisZca. 13.3:1) was observed than that of
5a (N-allyl:trans/cisZca. 6.7:1). This may be explained by
the Ru-coordinated transition states (Fig. 4). Both 3,4-cis-6a
and 3,4-cis-10b are obtained via the transition states A and
B. In the transition state B, the steric repulsion between the
methyl substituent of 7b and bulky h5-C5Me5 ligand on the
Ru is expected to be more important than that between H
and h5-C5Me5 ligand in A. Therefore, the cyclization of 7b
proceeds through the transition state C, which affords the
3,4-trans isomer.
Entry
1c
Substrate
Time (h) Product (trans/cis)b Yield (%)
4
80
7a
7b
10a (80:20)
10b (93:7)
2
16
70
3d
4
4
98
8
11
4
O99
9a
12a
5
4
O99
9b
12b
a All reactions were carried out using 0.02 mmol of substrate, 0.03 mmol of
4a and 0.03 mmol of pyridine in 1.5 mL of CH2Cl2 at room temperature.
b Determined by 1H NMR analysis.
c 0.02 mmol of 4a (20 mol% Ru) and 0.02 mmol of pyridine were used.
d 0.01 mmol of 4a (10 mol% Ru) and 0.01 mmol of pyridine were used.
The advantage of the coordinatively unsaturated
[Cp*Ru(OMe)]2 complex 4a is its easy preparation by the
literature method10b–d and the redox properties suitable for
the ATRC of N-allyl dichloroacetamides. It is known that
there are some relations between the redox properties and
the efficiency of the catalyst in the conventional CuCl/
bipyridine catalyst system and the coordinatively unsatu-
rated diruthenium amidinate 3 active for ATRC.7b The
redox potentials for CuCl/bipyridine in THF is EpaZ
C0.03 V, EpcZK0.13 V [CuI/CuII], whereas that of 3 is
EpaZK0.002 V, EpcZK0.05 V [RuII/RuIII]. In contrast,
cyclic voltammogram of 4a (RZMe) in THF shows a quasi-
reversible one-electron oxidation wave (EpaZK0.13 V,
EpcZK0.20 V versus Ag/AgC at the scan rate of 0.1 V/s)
due to the RuII/RuIII oxidation process. These data showed
that the ruthenium methoxide 4a is a stronger electron donor
than the CuCl/bipyridine and the diruthenium amidinate 3,
and reasonably explain facile activation of a C–Cl bond in
N-allyl dichloroacetamides, less reactive substrates than
N-allyl trichloroacetamides.
Figure 4. Proposed transition states.
It is well known that radical cyclization of u-olefinic
haloamides at low temperatures has a problem of low
yields of the product due to high rotational barrier
(16–22 kcal/mol) of the Ccarbonyl–N.4f,12 As shown in
Scheme 3, there are two possible rotamers, anti-5 and syn-
5, and anti-5 is the rotamer unfavorable for the cyclization.
1
From the H NMR spectra of amides 5a (ZZTs) and 5d
(ZZPh), single set of signals is observed. However, the
spectrum of 5c (ZZBn) shows two sets of signals (ca. 1:1)
due to the rotational isomers around the Ccarbonyl–N bond.
Preliminary DFT caluculations14 suggest that there is no
substantial energy difference between two rotamers of 5a
An interesting feature of the 4a-catalyzed cyclization of
N-allyl dichloroacetamides is its stereoselectivity. It is
known that equilibrium between the trans- and cis-isomers
of the g-lactams 6 formed from a,a-dichloroacetamides 5
took place easily in the presence of transition metal
complexes over 80 8C.13 For example, the thermodynami-
cally controlled ratio of trans-6a to cis-6a reached ca. 4:1;
this is in accord with that the ab initio study predicts energy
difference between two isomers to be ca. 3 kcal/mol.14 The
diastereomer ratio of 6a obtained by the present catalyst
system is ca. 6.7:1, and no equilibrium between the two
Scheme 3. The conformation of 5a–d in solution.

Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
2783
(!0.3 kcal/mol) and 5c (0.7 kcal/mol), whereas anti-5d
(4.3 kcal/mol) is the stable conformer for the other one. We
have previously reported that the rotation barrier of the
N-tosylated acetamides was much lower than that of the
N-benzyl derivatives; syn–anti interconversion of the tosyl-
protected amides was first in the NMR time scale, leading to
the appearance of a single set of sharp signals.4f,12d Two
apparent reasons of higher reactivity of 5a than that of 5c
and 5d are the introduction of the electron-withdrawing
substituent on the N atom, which lowers the LUMO of the
a-C–Cl bond described above, and facile formation of the
rotamer favorable for the cyclization by the amide rotation.
While in the case of 5c and 5d, high population of the
undesired rotamer makes the reaction slower, but the
reactivity of the catalyst is high enough to provide
the product under milder conditions (!40 8C) than the
cyclization catalyzed by the conventional CuCl/bipyridine
catalyst. Such high reactivity may be explained by the
oxophilic nature of the coordinatively unsaturated ruthe-
nium methoxide, which could provide its interaction with
the oxygen atom of amide 5. As shown in Scheme 4, the
coordination makes syn-D a more favorable conformation
than anti-D because of the steric repulsion between the Cl
atom at the a-position and the substituent (Z) on the N atom.
Scheme 5. Proposed reaction mechanisms for ATRC catalyzed by
4a/pyridine system.
4a having appropriate redox potentials for ATRC in the
presence of pyridine. The success of these studies prompted
us to extend catalysis of the coordinatively unsaturated
ruthenium methoxide to ATRP. As described in our
previous paper,7b coordinatively unsaturated species facili-
tates the initial step of ATRC, cleavage of a C–X bond of the
substrate, which is the most important point for the catalytic
cycle as shown in Scheme 1. In contrast, the catalyst for
ATRP has to play important roles not only for the activation
of the organic halide initiators to start the polymerization
but also the reactivation of a C–X bond at the terminal of the
intermediate polymer (the dormant species) as shown in
Scheme 6. The coordinatively unsaturated species should be
advantageous to take part in the facile activation of the
organic halide initiators and the dormant species. In
contrast, a possible drawback deduced from our results of
ATRC is instability of the coordinatively unsaturated
species, which makes the reactivation of dormant species
ineffective in the time running. The deactivation of the
catalyst should affect the polymerization behavior. Sawa-
moto and coworker reported a coordinatively unsaturated
ruthenium complex, Ru(Cp*)Cl(PCy3), catalyzes rapid but
‘ill-controlled’ polymerization of methyl methacrylate
(MMA) to give poly(MMA) with quite broad molecular
weight distributions (Mw/MnZ2.8–6.2).16 In sharp contrast,
we found that the coordinatively unsaturated ruthenium
amidinate 3 can effectively activate a C–X bond of organic
halides resulting in the formation of poly(MMA) having a
halogen atom end group with narrow molecular weight
distributions (Mw/Mn%1.3), but the polymerization is
terminated before complete conversion of monomers.7b
Scheme 4. The conformation of Cp*Ru(OMe)/5 in the cyclization.
One of the most interesting questions in this cyclization is
what is a net catalyst species in solution. As noted above, the
ruthenium alkoxides 4 exist as a dimer in crystal
structures,10c,d whereas they are possibly dissociated to the
corresponding monomer in contact with appropriate ligand.
In fact, the several coordinatively unsaturated Cp*Ru(OR)L
were isolated and characterized by Caulton and
coworkers.10g Since the addition of auxiliary ligands is
important for efficient catalytic reactions, a probable answer
is the reaction proceeding through a monomeric active
species. Although clear evidence for the complexation
between [Cp*Ru(OMe)]2 4a and pyridine was not visible on
1
the H NMR spectrum of a mixture of 4a and pyridine, in
which only dimeric 4a and free pyridine were observed, we
consider at present stage that the coordination can take place
reversibly, and a small amount of active catalyst stabilized
by pyridine promote the cyclization. In other words, the
success of 4a/pyridine system for the ATRC is provided by
the stabilization of the coordinatively unsaturated,
unstable monomeric Cp*Ru(OMe) species with pyridine
(Scheme 5, E). The ATRC of 5 proceeds via the complex E
to afford the product 6. Then the stable dimer 4a and free
pyridine are regenerated, as shown in Scheme 5.
2.2. Atom-transfer radical polymerization
In the above sections, we have demonstrated high catalytic
reactivity of the coordinatively unsaturated [Cp*Ru(OMe)]2
Scheme 6. Proposed mechanisms for ATRP.

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Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
Table 5. Radical polymerization of MMA with 4aa
stable enough to achieve the complete conversion of the
monomers.
Additiveb Yield (%)c Mn
Mw/Mn
d
d
Entry Initiator
1
2
3
4
5
6
CCl4
CCl4
Cl3CCO2Me
Cl3CCO2Me
Cl2HCCO2Et
Cl2HCCO2Et
—
Pyridine
—
Pyridine
—
Pyridine
16
20
21
20
17
18
3900
3100
5500
4000
9600
7000
1.3
1.2
1.4
1.2
1.6
1.3
3. Conclusion
In our examinations for the coordinatively unsaturated
ruthenium alkoxide, [(h5-C5Me5)Ru(OMe)]2 4a, as the
ATRC and ATRP catalyst, we found that 4a can effectively
activate a C–X bond of organic or macromolecular halides
at low temperature (room temperature).21 In the cyclization
reaction, the 4a/pyridine system is useful for the synthesis of
both b- and g-lactams under mild conditions. The catalytic
activity of the present system is even higher than the
conventional CuCl/bipyridine catalyst and the diruthenium
amidinate complex 3. This clearly shows an advantage of
coordinatively unsaturated complexes in catalyst efficiency
for the halogen abstraction at the initial stage of the catalytic
cycle, which especially contributes to rapid ATRC and
controlling the relative stereochemistry of newly formed
stereocenters. This catalyst system is also active towards
polymerization of methacrylate using poly(THF)-derived
macroinitiator, giving poly(THF)–poly(MMA) block copo-
lymer with narrow molecular weight distributions; however,
the polymerization is often accompanied by the catalyst
deactivation leading to low conversion of the monomer. In
other words, the present coordinatively unsaturated
polymerization catalyst has a strong point in the efficiency
but not in the durability. Consequently, the results presented
in this paper demonstrate that the use of coordinatively
unsaturated species is a reasonable strategy for the
development of good catalysts for ATRC. For their
application to ATRP, the polymerization is well-controlled
at the initial stage, however, durability has somehow to be
added to the catalyst to achieve high conversion of the
monomer. These findings provide important aspects in
catalyst search for atom-transfer radical reactions.
a All reactions were carried out using 9.5 mmol of 4a, 9.5 mmol of MMA,
and 38 mmol of initiator in 2 mL of ethyl acetate at 60 8C for 12 h.
b 0.5 equiv for Ru was used.
c Determined by 1H NMR analysis.
d Determined by GPC analysis of the crude product.
A mixture of [Cp*Ru(OMe)]2 4a (9.5 mmol), MMA (1 mL,
9.5 mmol), and initiator (38 mmol) was stirred at 60 8C for
12 h (Table 5). The reaction using carbon tetrachloride as an
initiator produced poly(MMA) with MnZ3900; Mw/MnZ
1.3 in 16% yield as shown in entry 1. The molecular weight
distribution of formed polymer was slightly improved
(Mw/MnZ1.2) by the addition of pyridine (0.5 equiv for
Ru), but the averaged molecular weight (Mn) decreased
(entries 1 vs 2). The polymerization was also achieved by
the use of a,a,a-trichloro- and a,a-dichloroacetates as
initiators (entries 3–6). In all cases, the present polymer-
ization was terminated within 3 h, showing that 4a is
reactive; but has a short lifetime.17
We also examined the activation of a carbon–halogen bond
of macroinitiators, which is known to be less reactive than
that of commonly used organic initiators. Matyjaszewski
reported the polymerization of MMA with CuBr/dNbipy
[dNbipyZ4,40-di(5-nonyl)-2,20-bipyridine]
using
poly(THF)-derived bromopropionate as the initiator, in
which a temperature over 90 8C (24 h, O97% conversion)
was required for the reaction.18a The ruthenium methoxide
4a catalyzed the polymerization of MMA using the
macroinitiator 1318,19 derived from polybutylene oxides,
[poly(THF)], bearing a 2-bromoisobutyl group at the
polymer terminal (MnZ3800; Mw/MnZ1.2)7b at 25 8C for
4 h to form the polymer of MnZ35,000 and Mw/MnZ1.4;
4. Experimental
1
4.1. General methods
the H NMR spectrum of the obtained copolymer revealed
that the product contains both poly(THF) and poly(MMA)
segments (Scheme 7).20 In the conversion of this particular
polymerization, the chain growth was terminated after 47%
of MMA was consumed (42% isolated yield). These results
clearly showed that 4a acts as an efficient catalyst for the
activation of a C–Br bond of less reactive macromolecule
initiator at low temperature, but the catalyst system is not
All reactions were carried out under a nitrogen or argon
atmosphere. Solvents were distilled under an inert gas
atmosphere from CaH2 (dichloromethane, acetonitrile and
dichloroethane) or sodium/benzophenone (benzene and
ether) prior to use. Carbon tetrachloride was purchased from
Wako Pure Chemical Ind., Ltd. Methyl trichloroacetate
and ethyl dichloroacetate were purchased from Tokyo
Chemical Industry Co., Ltd. 1H and 13C NMR spectra were
measured on JEOL ECA 400 (400 MHz) and ECA 600
1
(600 MHz) spectrometers. Chemical shifts for H NMR are
described in parts per million downfield from tetramethylsi-
lane as an internal standard (dZ0) in CDCl3, unless otherwise
noted. Chemical shifts for 13C NMR are expressed in parts per
million in CDCl3 as an internal standard (dZ77.1), unless
otherwise noted. IR spectra were measured on a JASCO FT/
IR-550 spectrometer. Column chromatography was per-
formed with silica gel (Merck, Art 7734). Elemental analysis
was performed by the Elemental Analysis Center, Faculty of
Science, Kyushu University. HRMS analysis was performed
by the Analytical Center in Institute for Materials Chemistry
Scheme 7. Polymerization of MMA using macroinitiator 13.

Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
2785
and Engineering, Kyushu University. Analytical thin-layer
chromatography (TLC) was performed on glass plates and
aluminum sheets precoated with silica gel (Merck, Kieselgel
60 F254, layer thickness 0.25 and 0.2 mm, respectively).
Visualization was accomplished by UV light (254 nm),
anisaldehyde, and phosphomolybdic acid. GPC analyses of
the polymers were performed with a JASCO DG-1580-83
degasser, PU-980 HPLC pump, UV-970 UV/vis detector, RI-
930 RI detector, and CO-2065-plus column oven (at 40 8C)
using a Shodex GPC-KF-804L connected with a GPC KF-
805L in THF. Calibration was carried out on the basis of
retention time of a standard sample of poly(methyl methacryl-
ate)(Shodex Standard M-75) 7 samples (Mw/MnZ1.02–1.09),
of which the Mn range is 1.84!103–1.99!106. [(h5-
C5Me5)Ru(OR)]2 complexes 4a–d10b–d were prepared by the
literature methods. Acetamide derivatives 5, 7–9 were
prepared according to the literature methods.4,8 Macroinitiator
13 was prepared by our method.7b,19a
5.72 (ddt, JZ17.0, 10.4, 6.0 Hz, 1H); 13C NMR (150 MHz,
CDCl3): dZ43.5, 44.8, 45.9, 47.0, 56.6, 119.2, 131.1, 168.3.
1
cis-Isomer. H NMR (600 MHz, CDCl3): dZ2.92 (tdt, JZ
8.2, 7.1, 6.6 Hz, 1H), 3.28 (dd, JZ9.9, 8.2 Hz, 1H), 3.47
(dd, JZ9.9, 7.1 Hz, 1H), 3.62 (dd, JZ11.0, 8.2 Hz, 1H),
3.80 (dd, JZ11.0, 6.6 Hz, 1H), 3.88–4.00 (m, 2H), 4.46 (d,
JZ6.0 Hz, 1H), 5.20–5.27 (m, 2H), 5.72 (m, 1H); 13C NMR
(150 MHz, CDCl3): dZ40.7, 42.0, 45.5, 48.1, 57.6, 118.9,
131.1, 169.0.
4.2.3. 3-Chloro-4-chloromethyl-1-benzyl-pyrrolidin-2-
one (6c).4e,8b Diastereomer ratio was determined by
capillary GLC analysis: TC-17 (30 M), column temperature
240 8C, ditection FID, tRZ20.3 min (trans), 21.2 min (cis).
trans-Isomer. 1H NMR (400 MHz, CDCl3): dZ2.82 (ddddd,
JZ9.0, 8.1, 7.1, 6.1, 4.9 Hz, 1H), 3.17 (dd, JZ10.0, 7.1 Hz,
1H), 3.43 (dd, JZ10.0, 8.1 Hz, 1H), 3.66 (dd, JZ11.7,
6.1 Hz, 1H), 3.70 (dd, JZ11.7, 4.9 Hz, 1H), 4.40 (d, JZ
9.0 Hz, 1H), 4.43 (d, JZ14.6 Hz, 1H), 4.58 (d, JZ14.6 Hz,
1H), 7.19–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3): dZ
43.5, 44.9, 47.0, 47.5, 56.8, 128.2, 128.3, 129.0, 135.2, 168.6.
4.2. General procedure for the atom-transfer radical
cyclization of N-allyl-a-halogenated acetamies catalyzed
by [(h5-C5Me5)Ru(OMe)]2/bipyridine system
1
In a typical example, [(h5-C5Me5)Ru(OMe)]2 (4a, 5.3 mg,
0.01 mmol, 10 mol% Ru) was measured into a flask, then
freshly distilled, carefully degassed dichloromethane
(1.5 mL) and pyridine (0.8 mL, 0.5 equiv for Ru) were
added. This catalyst solution was transferred to the reaction
flask in which contains N-allyl-N-tosyl-2,2-dichloroaceta-
mide (5a, 64.4 mg, 0.2 mmol). After the resulting solution
was stirred at ambient temperature for 4 h, the reaction
mixture was filtered through a pad of Celite and Florisil, and
then the filtrate was concentrated under reduced pressure.
Purification by silica gel chromatography (1:1 hexane/ether)
gave the product (6a) in 92% yield (59.3 mg): the cis/trans
cis-Isomer. H NMR (400 MHz, CDCl3): dZ2.87 (ddddd,
JZ8.1, 7.8, 7.1, 6.8, 6.3 Hz, 1H), 3.16 (dd, JZ10.0, 8.1 Hz,
1H), 3.36 (dd, JZ10.0, 7.1 Hz, 1H), 3.57 (dd, JZ11.2,
7.8 Hz, 1H), 3.77 (dd, JZ11.2, 6.8 Hz, 1H), 4.43 (d, JZ
14.6 Hz, 1H), 4.51 (d, JZ6.3 Hz, 1H), 4.57 (d, JZ14.6 Hz,
1H), 7.19–7.41 (m, 5H); 13C NMR (100 MHz, CDCl3): dZ
40.8, 42.0, 47.1, 48.0, 57.7, 128.1, 128.2, 129.0, 135.3,
169.4.
4.2.4. 3-Chloro-4-chloromethyl-1-phenyl-pyrrolidin-2-
one (6d). trans-Isomer. White solid; mp 113–114 8C;
elemental Anal. Calcd (%) for C11H11Cl2NO: C, 54.12; H,
1
1
4.54; N, 5.74. Found: C, 53.79; H, 4.57; N, 5.70; H NMR
ratio was determined by H NMR analysis.
(600 MHz, CDCl3): dZ2.99 (ddddd, JZ8.8, 8.2, 7.7, 6.6,
3.8 Hz, 1H), 3.82 (dd, JZ11.5, 6.6 Hz, 1H), 3.83 (dd, JZ
9.9, 7.7 Hz, 1H), 3.87 (dd, JZ11.5, 3.8 Hz, 1H), 4.00 (dd,
JZ9.9, 8.2 Hz, 1H), 4.54 (d, JZ8.8 Hz, 1H), 7.22 (t, JZ
7.1 Hz, 1H), 7.41 (dd, JZ8.2, 7.1 Hz, 2H), 7.63 (d, JZ
8.2 Hz, 2H); 13C NMR (150 MHz, CDCl3): dZ43.1, 44.4,
48.6, 57.4, 120.0, 125.6, 129.1, 138.4, 167.4.
4.2.1. 3-Chloro-4-chloromethyl-1-(p-toluenesulfonyl)-
pyrrolidin-2-one (6a).8a trans-Isomer. 1H NMR
(600 MHz, CDCl3): dZ2.46 (s, 3H), 2.82 (m, 1H), 3.68–
3.78 (m, 3H), 4.11 (dd, JZ10.2, 8.1 Hz, 1H), 4.34 (d, JZ
9.3 Hz, 1H), 7.34 (d, JZ8.3 Hz, 2H), 7.94 (d, JZ8.3 Hz,
2H); 13C NMR (150 MHz, CDCl3): dZ21.8, 42.3, 44.2,
47.0, 56.1, 128.3, 130.0, 134.3, 146.1, 166.7.
cis-Isomer. 1H NMR (600 MHz, CDCl3): dZ3.08 (m, 1H),
3.73 (dd, JZ11.5, 8.2 Hz, 1H), 3.80–3.91 (m, 3H), 4.63 (d,
JZ6.0 Hz, 1H), 7.22 (m, 1H), 7.41 (m, 2H), 7.63 (m, 2H);
13C NMR (150 MHz, CDCl3): dZ40.3, 41.9, 49.8, 58.7,
120.2, 125.7, 129.1, 138.4, 167.4.
1
cis-Isomer. H NMR (600 MHz, CDCl3): dZ2.46 (s, 3H),
2.95 (ddddd, JZ8.3, 7.6, 7.3, 6.8, 6.1 Hz, 1H), 3.53 (dd, JZ
11.5, 7.6 Hz, 1H), 3.66 (dd, JZ10.3, 8.3 Hz, 1H), 3.71 (dd,
JZ11.5, 6.8 Hz, 1H), 4.13 (dd, JZ10.3, 7.3 Hz, 1H), 4.44
(d, JZ6.1 Hz, 1H), 7.37 (d, JZ8.3 Hz, 2H), 7.92 (d, JZ
8.3 Hz, 2H); 13C NMR (150 MHz, CDCl3): dZ21.8, 40.4,
41.0, 47.9, 57.6, 128.2, 130.0, 134.0, 146.0, 166.8.
4.2.5. 3-Chloro-4-chloroisopropyl-1-(p-toluenesulfonyl)-
pyrrolidin-2-one (10a). trans-Isomer. Elemental Anal.
Calcd (%) for C14H17Cl2NO3S: C, 48.01; H, 4.89; N,
4.00. Found: C, 47.96; H, 4.90; N, 4.00; 1H NMR
(600 MHz, CDCl3): dZ1.60 (s, 3H), 1.72 (s, 3H), 2.45 (s,
3H), 2.67 (ddd, JZ8.8, 8.2, 7.7 Hz, 1H), 3.85 (dd, JZ10.4,
7.7 Hz, 1H), 4.10 (dd, JZ10.4, 8.8 Hz, 1H), 4.51 (d, JZ
8.2 Hz, 1H), 7.36 (d, JZ8.8 Hz, 2H), 7.95 (d, JZ8.8 Hz,
2H); 13C NMR (150 MHz, CDCl3): dZ21.7, 31.1, 31.4,
46.4, 52.9, 56.0, 69.6, 128.4, 129.9, 134.2, 146.0, 167.2.
4.2.2. 3-Chloro-4-chloromethyl-1-allyl-pyrrolidin-2-one
(6b). IR (neat): nZ1705 cmK1; HRMS. Calcd for
C8H11Cl2NO: [M]Z207.0218. Found: [M]Z207.0211;
1
trans-Isomer. H NMR (600 MHz, CDCl3): dZ2.87 (ttd,
JZ8.2, 6.6, 4.4 Hz, 1H), 3.28 (dd, JZ9.9, 6.6 Hz, 1H), 3.53
(dd, JZ9.9, 8.2 Hz, 1H), 3.72 (dd, JZ11.5, 6.6 Hz, 1H),
3.76 (dd, JZ11.5, 4.4 Hz, 1H), 3.91 (dd, JZ14.8, 6.0 Hz,
1H), 3.97 (dd, JZ14.8, 6.0 Hz, 1H), 4.37 (d, JZ8.2 Hz,
1H), 5.24 (d, JZ17.0 Hz, 1H), 5.26 (d, JZ10.4 Hz, 1H),
1
cis-Isomer. H NMR (600 MHz, CDCl3): dZ1.53 (s, 3H),
1.62 (s, 3H), 2.42 (s, 3H), 2.91 (ddd, JZ9.9, 6.6, 5.0 Hz,

2786
Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
1H), 3.92 (dd, JZ10.4, 9.9 Hz, 1H), 4.20 (dd, JZ10.4,
6.6 Hz, 1H), 4.34 (d, JZ5.0 Hz, 1H), 7.30 (d, JZ8.7 Hz,
2H), 7.74 (d, JZ8.7 Hz, 2H); 13C NMR (150 MHz, CDCl3):
dZ25.5, 30.6, 31.7, 41.0, 50.1, 57.0, 67.0, 127.1, 128.1,
134.0, 143.3, 166.7.
4.4. Electrochemical measurements
Cyclic voltammetric studies were carried out using a BAS
50B/W electrochemical analyzer in a globe box filled with
purified nitrogen. The measurement was performed at room
temperature using a ruthenium or copper complex
(0.0015 mmol) in THF (5 mL) containing Bu4NPF6
(0.1 M) as a supporting electrolyte. A three-electrode cell
was used, which was equipped with a platinum disk working
electrode, a platinum wire counter electrode, and a silver
reference electrode comprised of a silver wire in count with
AgNO3 (0.01 M) and Bu4NPF6 (0.2 M) in acetonitrile.
4.2.6. 3-Chloro-4-chloromethyl-4-methyl-1-(p-toluene-
sulfonyl)-pyrrolidin-2-one (10b). Elemental Anal. Calcd
(%) for C13H15Cl2NO3S: C, 46.44; H, 4.50; N, 4.17. Found:
C, 46.69; H, 4.58; N, 4.13. Major isomer. 1H NMR
(600 MHz, CDCl3): dZ1.13 (s, 3H), 2.46 (s, 3H), 3.52 (d,
JZ11.5 Hz, 1H), 3.56 (d, JZ11.5 Hz, 1H), 3.72 (d, JZ
10.4 Hz, 1H), 3.88 (d, JZ10.4 Hz, 1H), 4.52 (s, 1H), 7.36
(d, JZ8.8 Hz, 2H), 7.93 (d, JZ8.8 Hz, 1H); 13C NMR
(150 MHz, CDCl3): dZ18.5, 21.7, 43.9, 47.7, 52.8, 61.0,
128.1, 129.92, 134.2, 145.91, 166.4.
4.5. X-ray structure determination and details
of refinement
1
X-ray-quality crystals of 5a, 6d and 10a were grown from a
mixture of CH2Cl2 and hexane, and mounted in a glass
capillary. All measurements were made on a Rigaku RAXIS
RAPID imaging plate area detector with graphite mono-
Minor isomer. H NMR (600 MHz, CDCl3): dZ1.31 (s,
3H), 2.46 (s, 3H), 3.37 (d, JZ11.5 Hz, 1H), 3.54 (d, JZ
11.5 Hz, 1H), 3.63 (d, JZ10.4 Hz, 1H), 4.00 (d, JZ
10.4 Hz, 1H), 4.18 (s, 1H), 7.36 (d, JZ8.8 Hz, 2H), 7.93 (d,
JZ8.8 Hz, 1H); 13C NMR (150 MHz, CDCl3): dZ20.7,
21.7, 42.9, 47.3, 53.2, 63.3, 128.1, 129.86, 134.1, 145.89,
166.6.
˚
chromated Cu Ka radiation; lZ1.54187 A for 5a, and on a
Rigaku Saturn CCD area detector with graphite mono-
˚
chromated Mo Ka radiation; lZ0.71070 A. The crystal-to-
detector distance was 127.40 mm for 5a, 45.09 mm for 6d,
and 45.07 mm for 10a. The data were collected at 123(1) K
to a maximum 2q value of 136.58 for 5a, and of 55.08 for 6d
and 10a. The structures were solved by direct methods,25
and expanded using Fourier techniques.26 The non-
hydrogen atoms were refined anisotropically. Hydrogen
atoms were refined using the riding model. The final cycle
of full-matrix least-squares refinement on F2 was based on
2393 observed reflections and 185 variable parameters for
5a, on 2502 observed reflections and 148 variable
parameters for 6d, and on 3461 observed reflections and
207 variable parameters for 10a. Neutral atom scattering
factors were taken from Cromer and Waber.27 All
calculations were performed using the CrystalStructure28,29
crystallographic software package. The numbering schemes
employed are shown in Figure 3 (3,4-trans-6a and 3,4-
trans-10a) and Supporting information (5a), which were
drawn with ORTEP at 50% probability elipsoids. Crystallo-
graphic data (excluding structure factors) for the structure
has been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-
290147 for 5a, CCDC-290148 for 3,4-trans-6d, and
CCDC-290149 for 3,4-trans-10a. Copies of the data can
be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: C44 1223 336
033; e-mail: deposit@ccdc.cam.ac.uk).
4.2.7. 3,3-Dimethyl-4-bromomethyl-1-(p-toluenesulfo-
nyl)-pyrrolidin-2-one (11).8c 1H NMR (600 MHz,
CDCl3): dZ0.89 (s, 3H), 1.16 (s, 3H), 2.44 (s, 3H), 2.45
(dddd, JZ9.9, 8.8, 7.7, 4.4 Hz, 1H), 3.20 (t, JZ9.9 Hz, 1H),
3.43 (dd, JZ9.9, 4.4 Hz, 1H), 3.46 (dd, JZ10.4, 8.8 Hz,
1H), 4.15 (dd, JZ10.4, 7.7 Hz, 1H), 7.34 (d, JZ8.2 Hz,
2H), 7.91 (d, JZ8.2 Hz, 2H); 13C NMR (150 MHz, CDCl3):
dZ17.8, 21.7, 23.4, 29.7, 45.0, 45.4, 48.8, 128.0, 129.7,
134.8, 145.3, 176.8.
4.2.8. 3,3-Dichloro-4-(1-chloroisopropyl)-1-benzyl-azeti-
din-2-one (12a).23 1H NMR (600 MHz, CDCl3): dZ1.74 (s,
3H), 1.81 (s, 3H), 4.23 (s, 1H), 4.33 (d, JZ14.9 Hz, 1H),
4.98 (d, JZ14.9 Hz, 1H), 7.20–7.43 (m, 5H); 13C NMR
(150 MHz, CDCl3): dZ26.2, 29.0, 46.2, 68.5, 77.8, 81.2,
128.3, 128.5, 128.9, 133.9, 161.7.
4.2.9. 3,3-Dimethyl-4-(1-bromoisopropyl)-1-benzyl-aze-
tidin-2-one (12b).24 1H NMR (600 MHz, CDCl3): dZ
1.27 (s, 3H), 1.39 (s, 3H), 1.80 (s, 3H), 1.81 (s, 3H), 3.60 (s,
1H), 4.23 (d, JZ15.4 Hz, 1H), 4.92 (d, JZ15.4 Hz, 1H),
7.27–7.36 (m, 5H); 13C NMR (150 MHz, CDCl3): dZ17.9,
24.0, 31.3, 32.6, 45.0, 55.3, 65.1, 72.8, 127.6, 128.5, 128.6,
136.1, 174.7. HRMS. Calcd for C15H20BrNO: [M]Z
309.0728. Found: [M]Z309.0725.
4.3. Polymerization of MMA using macroinitiator 13
Acknowledgements
A mixture of [Cp*Ru(OMe)]2 4a (5 mg, 9 mmol), MMA
(1 mL, 9.5 mmol), and macroinitiator 13 [MnZ3800, Mw/
MnZ1.2] (68 mg, 18 mmol) was placed in a glass tube. The
mixture was degassed three times, and sealed in vacuo.
After it was stirred at 25 8C for 4 h, the reaction mixture was
concentrated under reduced pressure. The residue was
dissolved in THF and was purified by precipitation by
adding methanol gave the block copolymer in 42% yield.
The GPC analysis showed MnZ36,000, Mw/MnZ1.4.
We are grateful to Mr. Taisuke Matsumoto and Ms. Keiko
Ideta (Analytical Center in Institute for Materials Chem-
istry and Engineering, Kyushu University) for their help in
the X-ray and NOE analyses. This work was supported by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan.

Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
2787
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Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2006.01.
011. Tables of crystal structure parameters and details of
data correction, bond angles and distances, and atomic
positional and thermal parameters of 5a, 3,4-trans-6d and
3,4-trans-10a.
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and the diruthenium amidinate 3 as the polymerization catalyst
is observed in the end group of the formed polymer. ATRP by
3 afforded the polymer having halogen atom at the end group,
which undergoes reactivation by 3 to regenerate the active
radical species at the polymer end. In contrast, post-
polymerization of MMA from poly(MMA) (MnZ4000;
Mw/MnZ1.2), which was obtained by the reaction shown in
Table 5, entry 4 proceeded even at 25 8C to afford the
poly(MMA) of MnZ40,000, but some of the starting
macroinitiator remained. 1H NMR spectra of polymers formed
by 4a showed two broad signals at d 6.15 and 5.42 ppm, which
are assignable to the vinylic protons at the polymer end. These
results suggest that the poly(MMA) formed by the present
catalyst system contained both the terminal chloride (F) and
the exo-methylene moiety (G). This may be attributed to the
fact that 3 has a cationic species, which act as a Lewis acid,
whereas 4d is a metal alkoxide, which can behave as a base.
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Y. Motoyama et al. / Tetrahedron 62 (2006) 2779–2788
narrow Mw/Mns; this strongly suggests interaction of the
radical species at the polymer end with the metallic species
leading to abstraction of the halogen atom from the M–X
species by the polymer radical. As a consequence of the first
and the second points, ATRC should also be promoted by the
redox mechanism not involving the free radical chain process.
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temperature using poly(THF)-derived initiator 13 is not clear at
present. We assumed that the polyether moiety of both the
initiator 13 and the dormant chain might effectively stabilize the
highly reactive ruthenium alkoxide 4a with an oxophilic nature.
21. For the metal-catalyzed atom-transfer reactions, the redox
mechanisms shown in Scheme 1 are often proposed. Although
possible involvement of free radical chain processes cannot be
completely excluded in the ATRC and ATRP reactions
presented in this paper, the following points strongly support
the redox mechanism. First, the same coordinatively unsatu-
rated complex catalyzes the both ATRC and ATRP; this
suggests that these reactions proceed through similar mech-
anisms. Second, free radical polymerization generally
provides polymers with wide molecular weight distributions,
and termination process is disproportionation (Ref. 22). In
contrast, the ATRP presented in this paper achieves the
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