A cationic diruthenium amidinate, [(η5-C5Me 5)Ru(μ2-i-PrN=C(Me)Ni-Pr)Ru(η5-C 5Me5)]+, as an efficient catalyst for the atom-transfer radical reactions

Article abstract of DOI:10.1246/cl.2004.442

A cationic diruthenium amidinate, [(η⁵-C₅Me ₅)Ru(μ₂-i-PrN=C(Me)Ni-Pr)Ru(η⁵-C ₅Me₅)]⁺, is generated by treatment of (η⁵-C₅Me₅)Ru(μ

Full text of DOI:10.1246/cl.2004.442

442
Chemistry Letters Vol.33, No.4 (2004)
A Cationic Diruthenium Amidinate, [(ꢀ5-C5Me5)Ru(ꢁ2-i-PrN=C(Me)Ni-Pr)Ru(ꢀ5-C5Me5)]þ,
as an Efficient Catalyst for the Atom-Transfer Radical Reactions
Yukihiro Motoyama, Mitsuru Gondo, Satoshi Masuda, Yuya Iwashita, and Hideo Nagashimaꢀ
Institute for Materials Chemistry and Engineering, Graduate School of Engineering Sciences, Kyushu University, Kasuga 816-8580
(Received January 14, 2004; CL-040052)
A cationic diruthenium amidinate, [(ꢀ5-C5Me5)Ru(ꢁ2-i-
PrN=C(Me)Ni-Pr)Ru(ꢀ5-C5Me5)]þ, is generated by treatment
of (ꢀ5-C5Me5)Ru(ꢁ2-i-PrN=C(Me)Ni-Pr)Ru(Cl)(ꢀ5-C5Me5)
(3a) with NaPF6 or other metal salts of weakly coordinating
anions, which is active towards catalytic atom transfer radical
cyclization of N-allyl trichloroacetamides and related reactions.
Entry 2). Since reversible generation of cationic species was de-
duced from solution dynamics of 3a in CH2Cl2,4b a solution of
3a exhibited some catalytic activity towards cyclization of 5a
and 5b (Entries 1 and 7). Addition of sodium salts of weakly co-
ordinating anions facilitated the generation of 4. In fact, cycliza-
tion of 5a or its N-tosyl homologue 5b by catalysis of a 1:1 molar
ratio of 3a and NaPF6 or NaBPh4 was complete at room temper-
ature within 30 min to give the corresponding product in quanti-
tative yields (Entries 3, 4, 8, and 9). Catalytic activity of these
cationic catalysts is higher than that using the mononuclear com-
plexes 1 and 2, particularly for the cyclization of 5b (Entries 5, 6,
10, and 11). At 1 mol % loading, this catalyst system afforded 5b
in 92% yield (Entry 12). Application of this new catalyst system
to the cyclization of other N-allyltrichloroacetamides is summa-
rized in Table 1.
Atom-transfer radical reaction has now become one of the
most important carbon–carbon bond-forming reactions which
is utilized for synthetic organic chemistry and polymer synthe-
sis.1 Since our initial discovery of the atom-transfer radical cyc-
lization (ATRC) of allyl trichloroacetates and N-allyltrichloro-
acetamides,2a transition metal-catalyzed ATRC has been
developed for a unique method of carbo- and heterocycles, and
efficient catalysts have been a research target. Among several
transition metal complexes so far reported,1,3 a 1:1 mixture of
CuCl and bipyridine is the most powerful catalyst system for
cyclization of N-protected N-allyltrichloroacetamides to the cor-
responding ꢂ,ꢂ,ꢃ-trichlorinated ꢃ-lactams.2,3 As new catalysts
showing comparable reactivity to the CuCl/bipyridine system,
we have recently reported mononuclear ruthenium amidinates,
(ꢀ5-C5Me5)Ru(amidinate) (1) and (ꢀ5-C5Me5)Ru(amidinate)Cl
(2), to be novel catalysts for the cyclization of N-allyltrichloro-
acetamides.3c It is important that these new catalysts are partic-
ularly efficient for cyclization of a precursor of pyrrolidizine al-
kaloids such as trachelantamidine and pseudoheliotridane, the
activity of which is much higher than that with the CuCl/bipyr-
idine system. The coordinatively unsaturated nature of the ruthe-
nium amidinates leads to this high catalytic activity; however, it
also imposes a drawback in that the ruthenium amidinates are
sensitive to air and moisture and difficult to handle. In this paper,
we wish to report a solution to this synthetic demerit: the finding
that a coordinatively unsaturated species generated in situ from a
stable diruthenium amidinate 3a behaves as a powerful catalyst
for the cyclization of N-allyltrichloroacetamides and its related
reactions.
Cl
Cl
Cl
Cl3C
O
catalyst (10 mol %)
O
N
Z
N
25 °C
Z
5a–d
6a–d
Table 1. Radical cyclization of N-allyltrichloroacetamides 5a–d
Entry Substrate
Catalyst
Solvent
Yield /%
Time /h
1
2
3
4
5
6
7
8
9
10
11
12a
13
14b
5a (Z = Bn)
5a
5a
5a
5a
5a
5b (Z = Ts)
5b
5b
5b
5b
5b
3a
CH2Cl2
4
30
94
>99
>99
85
88
97
>99
>99
31
4 [Y=B(C6F5)4] CH2Cl2
3a + NaPF6
3a + NaBPh4
1
2
3a
3a + NaPF6
3a + NaBPh4
1
0.5
0.5
0.5
4
4
4
0.5
0.5
4
4
3
CH2Cl2
CH2Cl2
toluene
toluene
CH2Cl2
CH2Cl2
CH2Cl2
benzene
benzene
CH2Cl2
CH2Cl2
CH2Cl2
2
0
92
52
>99
3a + NaBPh4
3a + NaPF6
5c (Z = Ph)
1
1
5d (Z = Allyl) 3a + NaPF6
a 1 mol % of catalyst was used. b 2.5 mol % of catalyst was used.
The efficiency of 3a with the aid of NaPF6 or NaBPh4 as the
catalyst eventually led to three important aspects in the ꢃ-lactam
synthesis by ATRC. First, the pyrrolidizine alkaloid precursor
mentioned above was obtained in high yield by this catalyst sys-
tem (Table 2, Entry 1). It is noteworthy that the catalyst efficien-
cy in this particular substrate is much higher than that with the
CuCl/bipyridine system, and comparable to that with 1 or 2,
which are known to be one of the most powerful catalysts for this
type of reaction.
Ru Ru
Ru Ru
X
i-Pr
N
N
i-Pr
N
N
i-Pr
i-Pr
Me
Me
Y
3a: X = Cl
b: X = Br
4:Y
= weakly coordinating anions
Second, high catalytic activity of the in situ-generated cati-
onic diruthenium amidinate was also demonstrated in the cycli-
zation of a N-allyldichloroacetamide 9, which is known as a less
reactive substrate than the trichlorinated homologue. In fact,
with the conventional CuCl/bipy system, it is necessary to apply
high reaction temperatures (>80 ꢁC) or to load large amounts of
the catalyst (ꢂ30 mol %) to obtain the product in good yields.5
As reported previously, isolable coordinatively unsaturated
diruthenium complexes 4 were synthesized by anion exchange
of stable diruthenium amidinates 3.4b The isolated
4
[Y=B(C6F5)4] was found to be active towards the cyclization
of N-allyl-N-benzyltrichloroacetamide 5a; the reaction proceed-
ed smoothly to afford 6a in 94% yield within 30 min (Table 1,
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.4 (2004)
443
Although the neutral complex 3a was not very effective for the
cyclization of 9 (12 h, 25% yield), the cationic diruthenium spe-
cies prepared in situ from 3a and NaBPh4 (10 mol % each) gave
the product 10 in 88% yield, when the reaction was performed at
25 ꢁC for 3 h (Table 3, Entries 1 vs 2). The observed diastereo-
selectivity (trans/cis = 7.0:1) of the reaction with cationic diru-
thenium amidinate was controlled kinetically.6
of an ꢂ-chlorine atom of the dichlorinated lactam, as described
above. Since the catalyst species can be generated in situ from
air- and moisture stable 3a simply by treatment with NaPF6 or
NaBPh4, there is no problem in handling air- and moisture sen-
sitive orgamometallics like 1 and 2. We believe that this catalyst
system can be widely applicable to metal-catalyzed radical reac-
tions, and further studies are now in progress.
Cl
Cl
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
Cl3C
O
Cl
O
H
catalyst (30 mol %)
N
N
7
8
Table 2. Radical cyclization of the cyclic trichloroacetamide 7
References and Notes
Entry
Catalyst
Solvent
Conditions
Yield /%
1
Reviews: a) D. P. Curran, in ‘‘Comprehensive Organic Syn-
thesis,’’ ed. by B. M. Trost and I. Fleming, Pergamon, Oxford
(1991), Vol. 4, p 715. b) J. Iqbal, B. Bhatla, and N. K. Nayyar,
Chem. Rev., 94, 519 (1994). c) K. Matyjaszewski and J. Xia,
Chem. Rev., 101, 2921 (2001). d) M. Kamigaito, T. Ando, and
M. Sawamoto, Chem. Rev., 101, 3689 (2001). e) ‘‘Radicals in
Organic Synthesis,’’ ed. by P. Renaud and M. P. Sibi, Wiley-
VCH, Weinheim (2001). f) A. J. Clark, Chem. Soc. Rev., 31, 1
(2002).
1
2
3
4
rt, 3 h
rt, 13 h
rt, 3 h
90
90
85
97
3a + NaPF6
1
2
CH2Cl2
benzene
benzene
ClCH2CH2Cl
80 °C, 2 h
CuCl / Bipy
Cl
Cl
+
Cl
Cl
HCl2C
catalyst (10 mol %)
O
O
O
N
N
N
Ts
9
Ts
trans-10
Ts
cis-10
2
3
a) H. Nagashima, H. Wakamatsu, K. Ito, Y. Tomo, and J.
Tsuji, Tetrahedron Lett., 23, 2395 (1983). b) H. Nagashima,
H. Wakamatsu, and K. Itoh, J. Chem. Soc., Chem. Commun.,
1984, 652. c) H. Nagashima, N. Ozaki, M. Ishii, K. Seki, M.
Washiyama, and K. Itoh, J. Org. Chem., 58, 464 (1993).
a) Y. Yamaguchi and H. Nagashima, Organometallics, 19,
725 (2000). b) H. Kondo, A. Kageyama, Y. Yamaguchi, M.
Haga, K. Kirchner, and H. Nagashima, Bull. Chem. Soc.
Jpn., 74, 1927 (2001). c) H. Nagashima, M. Gondo, S.
Masuda, H. Kondo, Y. Yamaguchi, and K. Matsubara, Chem.
Commun., 2003, 442. Also see: d) H. Nagashima, H. Kondo,
T. Hayashida, Y. Yamaguchi, M. Gondo, S. Masuda, K.
Miyazaki, K. Matsubara, and K. Kirchner, Coord. Chem.
Rev., 245, 177 (2003).
Table 3. Radical cyclization of the N-allyldichloroacetamide 9
Conditions
25 °C, 12 h
25 °C, 3 h
25 °C, 3 h
trans/cisa
Solvent
Entry Catalyst
Yield /%
25
88
24
95
6.9:1
7.0:1
7.4:1
4.0:1
1
2
3
4
3a
CH2Cl2
3a + NaBPh4 CH2Cl2
CuCl / Bipy CH2Cl2
CuCl / Bipy ClCH2CH2Cl 80 °C, 1 h
a Determined by 1H NMR.
Third, the cationic diruthenium catalytic species is useful for
activation of an ꢂ-chlorine atom of the ꢃ-lactam 6b followed by
intermolecular addition reaction to alkenes. (Table 4). Although
high reaction temperatures are required for the carbon–carbon
bond forming reaction at the ꢂ-position of the 2-pyrroridinone
6b catalyzed by the CuCl/bipy system,6b the reaction of 6b
(0.2 mmol) with 10 equiv. of methylenecyclohexane in the pres-
ence of in situ-generated cationic species (10 mol %) proceeded
even at 25 ꢁC (Entry 1). The diastereomer ratio of the adducts 11
was kinetically controlled (5.7:1); this is in contrast to the fact
that the product ratio obtained by the CuCl/bipy catalyst system
at 83 ꢁC was thermodynamically controlled (>99:1) (Entry 3).6b
4
5
a) H. Kondo, Y. Yamaguchi, and H. Nagashima, J. Am. Chem.
Soc., 123, 500 (2001). b) H. Kondo, K. Matsubara, and H.
Nagashima, J. Am. Chem. Soc., 124, 534 (2002).
a) M. A. Rachita and G. A. Slough, Tetrahedron Lett., 34,
6821 (1993). b) A. J. Clark, D. J. Duncalf, R. P. Filik, D.
M. Haddleton, G. H. Thomas, and H. Wongtap, Tetrahedron
Lett., 40, 3807 (1999). c) A. J. Clark, R. P. Filik, and G. H.
Thomas, Tetrahedron Lett., 40, 4885 (1999). d) A. J. Clark,
R. P. Filik, D. M. Haddleton, A. Radigue, C. J. Sanders, G.
H. Thomas, and M. E. Smith, J. Org. Chem., 64, 8954 (1999).
It is known that equilibrium between the trans- and cis-iso-
mers of this type of compounds easily took place in the pres-
ence of transition metal complexes over 80 ꢁC, and the ther-
modynamically controlled ratio of trans- to cis-10 reached
ca. 4:1: a) G. A. Slough, Tetrahedron Lett., 34, 6825 (1993).
b) S. Iwamatsu, H. Kondo, K. Matsubara, and H. Nagashima,
Tetrahedron, 55, 1687 (1999).
A typical experimental procedure: a trichloroacetamide 5b
(0.2 mmol), 3a (0.02 mmol), and NaBPh4 (0.02 mmol) were
dissolved in freshly distilled, carefully degassed dichlorome-
thane (1.5 mL) under an argon atmosphere. After the solution
was stirred at 25 ꢁC for 30 min, the product 6b was obtained
by silica gel chromatography (CH2Cl2 as an eluent) in quan-
titative yield (Table 1, Entry 9).
Cl
Cl
Cl
Cl
Cl
H
Cl
H
(10 equiv.)
6b
+
O
O
N
N
catalyst (10 mol %)
Ts
Ts
6
7
cis-11
trans-11
Table 4. Reaction of the lactam 6b with methylenecyclohexane
Solvent
Entry Catalyst
Conditions
Yield /%
cis/transa
1
2
3
3a + NaBPh4 CH2Cl2
CuCl / Bipy CH2Cl2
25 °C, 10 h
25 °C, 12 h
57
<5
5.7:1
-
CuCl / Bipy ClCH2CH2Cl 83 °C, 1 h
>99
>99:1
a Determined by 1H NMR.
In summary, we have discovered a new catalyst species,
[(ꢀ5-C5Me5)Ru(ꢁ2-i-PrN=C(Me)Ni-Pr)Ru(ꢀ5-C5Me5)]þ,
which is useful for metal-catalyzed ATRC to access ꢃ-lactams
and its related reaction.7 The catalytic activity is often compara-
ble to the conventional CuCl/bipy catalyst, and even higher in
extreme cases: synthesis of the pyrrolidizine alkaloid skeleton,
cyclization of a N-allyl dichloroactetamide, and the activation
Published on the web (Advance View) March 20, 2004; DOI 10.1246/cl.2004.442