C O M M U N I C A T I O N S
Table 3. Direct Addition of Acetonitrile to Imines Catalyzed by
CpRu(PPh3)(CH3CN)2PF6 (3), DBU, and NaPF6
7 into complex 3 and the Na-alkoxide 9 rather than into 8 (Scheme
2, step ii). Then, 9 would be protonated with DBUH+‚PF6- to afford
2 and regenerate NaPF6. Therefore, the amount of active catalyst 3
and free DBU was sufficient to promote the reaction, resulting in
higher catalyst turnover. In this system, Ru activates acetonitrile,
DBU effects the deprotonation, and the Na cation transfers the
resulting alkoxide, all of these working cooperatively to efficiently
drive the catalytic cycle.
In conclusion, we demonstrated efficient catalytic activation of
acetonitrile as a nucleophile under mild basic conditions with
cooperative catalysis of a cationic Ru complex, DBU, and NaPF6.
Preliminary mechanistic studies suggested a role for each of the
three catalytic components. Further mechanistic studies as well as
exploration of the enantioselective variants are in progress.
entry
R1
R2
time (h)
yield (%)
1a
2
Ph
Boc
Boc
Boc
Boc
P(O)Ph2
P(O)Ph2
4a
4b
4c
4d
4e
4f
24
12
24
48
48
48
84
86
91
79
81
86
o-CH3-C6H4
p-MeO-C6H4
2-naphthyl
o-CH3-C6H4
p-Cl-C6H4
3
4a
5
6
a Performed with 10 mol % DBU.
Scheme 2. Proposed Catalytic Cycle
Acknowledgment. We thank JSPS for financial support. N.K.
is thankful for a JSPS Research Fellowship for Young Scientists.
We thank Dr. M. Kanai and Mr. Y. Suto for useful discussions.
Supporting Information Available: Detailed experimental pro-
cedure and spectroscopic data (PDF). This material is available free of
References
(1) Reviews: (a) Alcaide, B.; Almendros, P. Eur. J. Org. Chem. 2002, 1595.
(b) List, B. Tetrahedron 2002, 58, 5573.
(2) (a) Evans, D. A.; Downey, C. W.; Hubbs, J. L. J. Am. Chem. Soc. 2003,
125. 8706 and references therein. (b) Lalic, G.; Aloise, A. D.;. Shair, M.
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(3) (a) In DMSO. (b) In CH3CN.
(4) (a) Motokura, K.; Nishimura, D.; Mori, K.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. J. Am. Chem. Soc. 2004, 126, 5662. (b) Murahashi, S.-I.;
Takaya, H.; Naota, T. Pure Appl. Chem. 2002, 74, 19. (c) Takaya, H.;
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Yamamoto, Y.; Kubota, Y.; Honda, Y.; Fukui, H.; Asao, N.; Nemoto, H.
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Ito, Y. J. Am. Chem. Soc. 1992, 114, 8295.
(5) Arseniyadis, S.; Kyler, K. S.; Watt, D. S. Org. React. 1984, 31, 1.
(6) Review: Verkade, J. G.; Kisanga, P. Aldrichimica Acta 2004, 37, 3.
(7) (a) CuOtBu: Suto, Y.; Kumagai, N.; Matsunaga, S.; Kanai, M.; Shibasaki,
M. Org. Lett. 2003, 5, 3147. (b) KOtBu: Bunlaksananusorn, T.; Rodriguez,
A. L.; Knochel, P. Chem. Commun. 2001, 745.
(8) Although there are substantial reports on Lewis acidic activation of simple
alkylnitriles as electrophiles (reviews: (a) Kukushkin, V. Y.; Pombeiro,
A. J. L. Chem. ReV. 2002, 102, 1771. (b) Michelin, R. A.; Mozzon, M.;
Bertani, R. Coord. Chem. ReV. 1996, 147, 299.), activation as nucleophiles
is rare (stoichiometric reaction: (c) English. A. D.; Herskovitz. T. J. Am.
Chem. Soc. 1977, 99, 1648. (d) Ittel, S. D.; Tolman, C. A.; English, A.
D.; Jesson, J. P. J. Am. Chem. Soc. 1978, 100, 7577.
(9) For an example of Lewis acid-amine (more than a stoichiometric amount)
cooperative deprotonation of acetonitrile: Sugasawa, T.; Toyoda, T. Synth.
Commun. 1979, 9, 553.
mechanistic studies of the reaction with 1a. A plausible catalytic
cycle is proposed as depicted in Scheme 2. NMR and ESI-MS
analysis13 indicated that Ru coordinated predominantly to aceto-
nitrile, rather than to 1a or HMPA, suggesting that Ru acts as a
Lewis acid to activate acetonitrile for deprotonation.14 Acetonitrile
bound to Ru in 3 was deprotonated by free DBU to afford Ru-
bound metalated nitrile 6.15 The substantial value of the obtained
kinetic isotope effect, kH/kD ) 5.6, and first-order rate dependency
on DBU in initial rate kinetics suggest that this step is rate-
determining.16 Subsequent 1,2-addition of metalated nitrile to 1a
proceeds rapidly to give Ru-alkoxide 7.16 The beneficial effect of
NaPF6 is explained by the following observations. ESI-MS and
NMR studies13 of DBU and 3 in CH3CN without 1a and NaPF6
indicated that DBU can coordinate to the Ru center to afford 8,
although the equilibrium strongly favored 3 rather than 8. On the
other hand, the formation of 8 was facilitated in the presence of 1a
without NaPF6, possibly because the protonation-ligand exchange
(10) Reviews: (a) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem. ReV.
2001, 101, 2067. (b) Slugovc, C.; Ru¨ba, E.; Schmid, R,; Kirchner, K.;
Mereiter, K. Monatsh. Chem. 2000, 131, 1241. An excellent example of
Ru-catalyzed in situ activation of malonate as a nucleophile: (c) Watanabe,
M.; Murata, K.; Ikariya, T. J. Am. Chem. Soc. 2003, 125, 7508.
(11) All three catalytic components are commercially available.
(12) Conditions are supposed to be as mild as Masamune-Roush conditions
for HWE reaction. Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld,
A. P.; Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984,
25, 2183.
-
between 7 and DBUH+‚PF6 would readily afford 8 (Scheme 2,
step i).13,17 Considering the spatial arrangement of ligands in 8,
ligated DBU is positioned too far away to deprotonate intramo-
lecularly. Thus, the accumulation of 8 decreased the concentration
of free DBU available for deprotonation, resulting in a lower
reaction rate and catalytic efficiency. In addition, 8 was unstable
and gradually decomposed to give Ph3PdO and Ru black as
confirmed by 31P NMR. Therefore, the chemical yield was modest
in the absence of NaPF6. An NMR study indicated that NaPF6
effectively suppressed the accumulation of 8,13 allowing the
complete reaction with 5 mol % DBU. Taking into account a
favorable hard-hard interaction between the Na cation and alkox-
ide,18 NaPF6 would accelerate the transformation from Ru-alkoxide
(13) See Supporting Information for details.
(14) NMR chemical shift (CDCl3) of Ru-bound CH3CN was downfield (1H δ
2.12 ppm; 13C δ 3.8 ppm) in comparison with that of free CH3CN (1H δ
1.93 ppm; 13C δ 1.97 ppm).
(15) Fleming, F. F.; Shook B. C. Tetrahedron 2002, 58, 1.
(16) Rate dependencies of reaction on DBU, 3, and 1a were 1.0, 0.64, and 0
order, respectively. See Supporting Information for details.
(17) Dissociative pathway has been suggested for the ligand exchange of CpRu
complex. Therefore, the formation of 8 would be easier from 7 than that
from 3 in which dissociation of acetonitrile is required. Luginbu¨hl, W.;
Zbinden, P.; Pittet, P. A.; Armbruster, T.; Bu¨rgi, H.-B.; Merbach, A. E.;
Ludi, A. Inorg. Chem. 1991, 30, 2355.
(18) Me4NPF6 had no beneficial effect on reaction rate and catalyst turnover.
JA0450509
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