Ruthenium-catalyzed ring-closing metathesis accelerated by long-range steric effect

Article abstract of DOI:10.1039/c1cc13304g

Ruthenium-based metathesis catalysts with a N-heterocyclic carbene ligand bearing 2,3,4,5-tetraphenylphenyl moieties (1-TPPh and 1-TPPh*) are developed. The highly active catalyst system has been realized in THF by the combination of 1-TPPh* and CuCl as a phosphine scavenger. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc13304g

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 9699–9701
www.rsc.org/chemcomm
COMMUNICATION
Ruthenium-catalyzed ring-closing metathesis accelerated by long-range
steric effectw
Tetsuaki Fujihara, Yoshikazu Tomike, Toshiyuki Ohtake, Jun Terao and Yasushi Tsuji*
Received 3rd June 2011, Accepted 14th July 2011
DOI: 10.1039/c1cc13304g
Ruthenium-based metathesis catalysts with a N-heterocyclic
carbene ligand bearing 2,3,4,5-tetraphenylphenyl moieties
(1-TPPh and 1-TPPh*) are developed. The highly active
catalyst system has been realized in THF by the combination
of 1-TPPh* and CuCl as a phosphine scavenger.
arranged oligo(ethylene glycol) chains.7 Besides them, parti-
cularly efficient is 2,3,4,5-tetraphenylphenyl (TPPh) moiety
which has rigid and widely spread structure.8 TPPh moieties
provoke steric effect at long range and realize extremely
active catalytic activity in Pd-catalyzed air oxidation of
alcohol8a and kinetic resolution of racemic vinyl ethers.8b In
the Ru-catalyzed RCM reaction, we anticipate that NHC
ligands having TPPh at long range facilitate the phosphine
dissociation and shield the resulting 14-electron catalyst
species against decompositions,9 such as dimerization
(Fig. 2). In this communication, we report synthesis and
catalytic activity of Ru catalysts bearing NHC ligands with
TPPh and methylated TPPh (TPPh*) substituents (1-TPPh
and 1-TPPh* in Fig. 1) in RCM. 1-TPPh shows much higher
catalytic activity than the conventional catalysts such as 1-Me.
Moreover, 1-TPPh* maintains high catalytic activity even
when PCy3 is scavenged by added CuCl.
Ring-closing metathesis (RCM) is one of the most important
synthetic reactions for formation of cyclic compounds
containing carbon–carbon double bonds.1 In the reaction,
the Grubbs second-generation catalyst (1-Me in Fig. 1)2a,b
is widely used and shows much higher catalytic activity
than the earlier
Grubbs first-generation catalyst
(2:(PCy3)2Cl2RuQCHPh).2b–d Mechanistic investigations3
indicate that dissociation3e of the tricyclohexylphophine
(PCy3) to the four-coordinate 14-electron species
(LCl2RuQCHPh)3b is crucial. However, surprisingly, 1-Me
only dissociates PCy3 less efficiently than 2.3c,d Therefore, in an
effort to enhance the catalytic activity of 1-Me, phosphine-free
catalysts were prepared by replacing PCy3 with 3-bromopyridine
ligand4a or with intramolecular coordination of an isopropoxy
substituent of the alkylidene ligand (Hoveyda catalyst:
1-O-Me in Fig. 1).4c However, the 3-bromopyridine catalyst
decomposes faster4b and 1-O-Me might be reluctant to
dissociate the intramolecular coordination. Furthermore,
these alterations and other alkylidene modifications4d–f only
provide, in principle, the same active catalytic species as from
1-Me after a single turnover with olefinic substrates. In
contrast, variation of the N-heterocyclic carbene (NHC)
moiety5 must be capable, since it can directly amend the nature
of the 14-electron species to enhance catalytic activity or even
realize asymmetric reactions with chiral NHCs.
1-TPPh was synthesized from 2-bromo-5-iodo-m-xylene
(See ESIw).10 Unfortunately, X-ray analysis of 1-TPPh was not
successful. But, the corresponding Hoveyda-type complex
(1-O-TPPh) derived from 1-TPPh and 2-isopropoxystryrene4b
afforded good crystals. The molecular structure of 1-O-TPPh
determined by X-ray structural analysis (Fig. S2w) clearly shows
that the TPPh moiety on the NHC ligand spatially spreads out
and shields the Ru coordination sphere at long-range. The Ru–C
(NHC) bond length of 1-O-TPPh (1.973(5) A) is quite similar to
that of 1-O-Me (1.981(5) A),4b implying the TPPh moieties do not
obstruct the metal center. 1-Ph was also prepared similarly.10
We recently developed highly active catalyst systems
utilizing steric effects at long range (long-range steric effect).6–8
To exploit such an effect, ligands bearing steric bulk apart
(41 nm) from a coordination cite are requisite. We have
already developed very efficient ligands of this nature, i.e.,
bowl-shaped phosphines6 and phosphines bearing peripherally
Department of Energy and Hydrocarbon Chemistry, Graduate School
of Engineering, Kyoto University, Kyoto 615-8510, Japan.
E-mail: ytsuji@scl.kyoto-u.ac.jp; Fax: +81-75-383-2514;
Tel: +81-75-383-2515
w Electronic supplementary information (ESI) available. CCDC
825592. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1cc13304g
Fig. 1 Structures of catalysts.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 9699–9701 9699

View Article Online
When 0.10 mol% of PCy3 was added to entry 1 in Table 1
(where 1.0 mol% of 1-TPPh was employed as catalyst), the
catalyst was still active to provide 4a in 94% yield (entry 1,
Table 2). In sharp contrast, the addition of the same amount
(0.10 mol%) of PCy3 to entry 2 in Table 1 (employing
1.0 mol% of 1-Me), the catalytic activity significantly
decreased and 4a was afforded in 38% yield (entry 2). The
TPPh moiety on the NHC ligand might suppress re-coordination
of PCy3 more efficiently than 1-Me and secure the good
catalytic activity under these conditions. On the other hand,
the addition of the double amount (0.20 mol%) of PCy3 to the
1-TPPh catalyst systems resulted in considerable catalyst
deactivation providing 4a in 39% (entry 3) as observed in
entry 4. With the larger amount of the added PCy3, even
1-TPPh lowered its catalytic activity.
Fig. 2 Ru metathesis catalyst activated by the long-range steric effect.
The RCM of diolefins (3) was carried out in toluene or
CH2Cl2 at 0 1C with the catalyst (1.0 mol%) listed in Fig. 1
(Table 1). Diethyl 2,2-diallylmalonate (3a) afforded the corres-
ponding cyclic olefin (4a) in 91% yield with 1-TPPh as catalyst
(entry 1). However, the Grubbs second-generation catalyst
(1-Me) and 1-Ph, having simple Ph substituent in place of
TPPh, provided 4a in considerably lower yields, 60% and
57%, respectively (entries 2 and 3). The phosphine-free
catalyst 1-O-TPPh was not so effective as 1-TPPh possibly
due to low lability of intramolecular coordination of the
isopropoxy unit at such lower temperature (entry 4).11 The
efficacy of 1-TPPh as compared with 1-Me and 1-Ph was also
confirmed using various diolefins. In the reaction of malonate
esters (3b and 3c) affording six- (4b) and seven- (4c) membered
rings, 1-TPPh provided the products in much higher yields
(entries 5 and 8) than 1-Me (entries 6 and 9) and 1-Ph (entries 7
and 10). Furthermore, with 1-TPPh as the catalyst, diallyl
ether (3d) and 1,7-octadiene (3e) afforded the products
(4d and 4e) in 74% and 88% yields (entries 11 and 14),
respectively, while 1-Me (entries 12 and 15) and 1-Ph
(entries 13 and 16) were less efficient. In Table 1, selectivities
of the products (4) were high, and cross metathesis dimeriza-
tion/oligomerization did not substantially occur.
Hence, we tried to remove PCy3 from the catalyst systems
by adding CuCl as a phosphine scavenger12 (generating ill-
characterized CuCl-PCy3 complex),12b although it is known
that these catalysts tend to decompose more rapidly in the
presence of CuCl. The reaction of 3a was carried out with
1-TPPh as catalyst (1.0 mol%) in the presence of CuCl
(4.0 mol%) in THF at 0 1C under otherwise the same reaction
conditions as entry 1 in Table 1 (entry 1 in Table 3). Even
though the initial reaction rate in the reaction became much
higher, the yield (57% yield after 4 h) did not increase at all
during the following 24 h, indicating catalyst decomposition.
Thus, even 1-TPPh decomposed fairly fast when the PCy3 was
scavenged by CuCl. 1-Me decomposed much faster under the
same reaction conditions and 4a was obtained only in 10%
yield (entry 2).
Therefore, 1-TPPh* (Fig. 1) having eight methyl substitu-
ents on 1-TPPh was devised and synthesized by a similar
method.10 Unfortunately, good single crystals of 1-TPPh*
could not be obtained. However, the DFT optimized structure
(by B3LYP/LANL2DZ) clearly indicated that the intro-
duction of methyl moieties enhance the shielding effect for
the Ru coordination sphere (Fig. S5w).10 In the reaction of 3a
as a substrate, 1-TPPh* (entry 3) was a more efficient catalyst
than 1-TPPh (entry 4) to afford 4a in 91% yield,13 in 15 min at
10 1C, in the presence of CuCl (4.0 mol%) in THF. When the
catalyst loading was lowered to 0.04 mol%, the turnover
number (TON) reached 12 000 (entry 5). With more sterically
congested 3f, 1-TPPh* was a superior catalyst and provided 4f
in 90% yield in 15 min (entry 6), while 1-TPPh and 1-Me were
not effective giving 4f in 30% and 29% yields, respectively
(entries 7 and 8). These yields in entries 6 and 7 did not
increase at all even after 4 h, indicating both the catalysts
Table 1 Ring-closing metathesis of various diolefinsa
Entry Diolefin
Product
Catalyst
Time (h) Yield (%)b
1
2
3
4
1-TPPh
1-Me
1-Ph
17
91 (84)c
60
57
1-O-TPPh
48
5
6
7
1-TPPh
1-Me
1-Ph
8
6
99 (99)c
54
51
8
9
10
1-TPPh
1-Me
1-Ph
99 (72)c
38
29
Table 2 Effect of added PCy3 on the ring-closing metathesis of 3aa
11d
12d
13d
1-TPPh
1-Me
1-Ph
5
5
74
10
5
Entry
Added PCy3 (mol%)
Catalyst
Yield of 4a (%)b
1
2
3
4
0.10
0.10
0.20
0.20
1-TPPh
1-Me
1-TPPh
1-Me
94
38
39
31
14d
15d
16d
1-TPPh
1-Me
1-Ph
88
51
46
a
3a (0.25 mmol), catalyst (2.5 mmol, 1.0 mol%), added PCy3
(0.25 mmol: 0.10 mol% or 0.50 mmol, 0.20 mol%), in toluene
a
Diolefin (0.25 mmol), catalyst (2.5 mmol, 1.0 mol%), in toluene
b
b
(5.0 mL), at 0 1C for 17 h. Yield of the product based on the GC
internal standard technique.
(5.0 mL), at 0 1C. Yield of 4 based on the GC internal standard
technique. Isolated yield. In CH2Cl2 (5.0 mL) as the solvent.
c
d
c
9700 Chem. Commun., 2011, 47, 9699–9701
This journal is The Royal Society of Chemistry 2011

View Article Online
Table 3 The ring-closing metathesis of various diolefins in the
presence of CuCl in THFa
Notes and references
1 (a) S.-Y. Hau and S. Chang, in Handbook of Metathesis,
ed. R. H. Grubbs, Wiley VCH, Weinheim, 2003, vol. 2, pp. 5;
(b) R. H. Grubbs and T. M. Trink, in Ruthenium in Organic
Synthesis, ed. S.-I. Murahash, Wiley VCH, Weinheim, 2004,
pp. 153.
2 (a) M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett.,
1999, 1, 953; (b) T. M. Trnka and R. H. Grubbs, Acc. Chem. Res.,
2001, 34, 18; (c) P. Schwab, M. B. France, J. W. Ziller and
R. H. Grubbs, Angew. Chem., Int. Ed. Engl., 1995, 34, 2039;
(d) P. Schwab, R. H. Grubbs and J. W. Ziller, J. Am. Chem.
Soc., 1996, 118, 100.
3 (a) E. L. Dias, S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc.,
1997, 119, 3887; (b) M. S. Sanford, L. M. Henling, M. W. Day and
R. H. Grubbs, Angew. Chem., Int. Ed., 2000, 39, 3451;
(c) M. S. Sanford, M. Ulman and R. H. Grubbs, J. Am. Chem.
Soc., 2001, 123, 749; (d) M. S. Sanford, J. A. Love and
R. H. Grubbs, J. Am. Chem. Soc., 2001, 123, 6543;
(e) J. A. Love, M. S. Sanford, M. W. Day and R. H. Grubbs,
J. Am. Chem. Soc., 2003, 125, 10103.
4 (a) J. A. Love, J. P. Morgan, T. M. Trnka and R. H. Grubbs,
Angew. Chem., Int. Ed., 2002, 41, 4035; (b) M. S. Sanford and
J. A. Love, in Handbook of Metathesis, ed. R. H. Grubbs,
Wiley-VCH, Weinheim, 2003, vol. 1, pp. 129; (c) S. B. Garber,
J. S. Kingsbury, B. L. Gray and A. H. Hoveyda, J. Am. Chem.
Soc., 2000, 122, 8168; (d) H. Wakamatsu and S. Blechert, Angew.
Chem., Int. Ed., 2002, 41, 749; (e) H. Wakamatsu and S. Blechert,
Angew. Chem., Int. Ed., 2002, 41, 2403; (f) F. Boeda, H. Clavier
and S. P. Nolan, Chem. Commun., 2008, 2726; (g) A. Michrowska,
R. Bujok, A. Harutyunyan, V. Sashuk, G. Dolgonos and
K. Grrela, J. Am. Chem. Soc., 2004, 126, 9318.
Tempb Time Yield
Catalyst (1C)
Entry Diolefin
Product
(min) (%)c
1d
2d
3
3a
4a
1-TPPh
1-Me
0
0
240
240
15
15
60
57
10
1-TPPh* 10
1-TPPh 10
1-TPPh* RT
91 (84)e
63
49
4
5f
6
7
8
1-TPPh* RT
1-TPPh
1-Me
15
90 (80)e
30
29
9
3b
3c
4b
4c
1-TPPh*
1-TPPh
1-Me
1-TPPh*
1-TPPh
1-Me
0
0
10
10
(95)e
75
10
11
12
13
14
33
94 (88)e
87
30
15
16
17
1-TPPh* RT
1-TPPh
1-Me
2
99 (77)e
94
33
18
19
20
1-TPPh*
1-TPPh
1-Me
0
10
83 (81)e
79
42
a
5 (a) C. Samojlowicz, M. Bieniek and K. Grela, Chem. Rev., 2009,
109, 3708, and references cited therein; (b) K. M. Kuhn,
J.-B. Bourg, C. K. Chung, S. C. Virgil and R. H. Grubbs, J. Am.
Chem. Soc., 2009, 131, 5313; (c) L. Vieille-Petit, H. Clavier,
A. Linden, S. Blumentritt, S. P. Nolan and R. Dorta, Organo-
metallics, 2010, 29, 775; (d) M. Gatti, L. Vieille-Petit, X. Luan,
R. Mariz, E. Drinkel, A. Linden and R. Dorta, J. Am. Chem. Soc.,
2009, 131, 9498.
Diolefin (0.25 mmol), catalyst (2.5 mmol, 1.0 mol%), CuCl
(0.010 mmol, 4.0 mol%), THF (2.0 mL). RT = room temperature.
b
c
Yield of the product based on the GC internal standard technique.
e
THF (5.0 mL) was used. Isolated yield. 3a (2.5 mmol), 1-TPPh*
d
f
(0.10 mol, 0.040 mol%), CuCl (1.0 mmol, 0.40 mol%) in THF (0.4 mL)
at RT for 60 min.
6 (a) T. Fujihara, K. Semba, J. Terao and Y. Tsuji, Angew. Chem.,
Int. Ed., 2010, 49, 1472; (b) H. Ohta, M. Tokunaga, Y. Obora,
T. Iwai, T. Iwasawa, T. Fujihara and Y. Tsuji, Org. Lett., 2007,
9, 89; (c) O. Niyomura, M. Tokunaga, Y. Obora, T. Iwasawa and
Y. Tsuji, Angew. Chem., Int. Ed., 2003, 42, 1287.
7 (a) T. Fujihara, S. Yoshida, H. Ohta and Y. Tsuji, Angew. Chem.,
Int. Ed., 2008, 47, 8310; (b) T. Fujihara, S. Yoshida, J. Terao and
Y. Tsuji, Org. Lett., 2009, 11, 2121.
8 (a) T. Iwasawa, M. Tokunaga, Y. Obora and Y. Tsuji, J. Am.
Chem. Soc., 2004, 126, 6554; (b) H. Aoyama, M. Tokunaga,
J. Kiyosu, T. Iwasawa, Y. Obora and Y. Tsuji, J. Am. Chem.
Soc., 2005, 127, 10474.
decomposed within a few minutes under these reaction condi-
tions (Fig. S1w).10 1-TPPh* was also a better catalyst for 3b
and 3c as the substrates (entries 9 and 12) as compared with
1-TPPh (entries 10 and 13) and 1-Me (entries 11 and 14). In
the reaction of an allyl ether (3g) and a sulfonamide (3h), both
1-TPPh* (entries 15 and 18) and 1-TPPh (entries 16 and 19)
showed a higher catalytic activity than 1-Me (entries 17
and 20). It is noteworthy that in the presence of CuCl, THF
plays an important role. When the reaction of entry 3 in
Table 3 was carried out in toluene under otherwise identical
reaction conditions, the yield of 4a was reduced significantly to
44%.10 Upon addition of a small amount of THF (0.2 mL)
to toluene (1.8 mL) as solvent, the yield of 4a was recovered to
69%. Coordination of THF to stabilize the catalyst center
must be important.
9 (a) S. H. Hong, A. G. Wenzel, T. T. Salguero, M. W. Day and
R. H. Grubbs, J. Am. Chem. Soc., 2007, 129, 7961; (b) S. H. Hong,
M. W. Day and R. H. Grubbs, J. Am. Chem. Soc., 2004, 126, 7414.
10 See ESI for detailw.
11 T. Vorfalt, K.-J. Wannowius and H. Plenio, Angew. Chem., Int.
Ed., 2010, 49, 5533.
12 (a) E. L. Dias, S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc.,
1997, 119, 3887; (b) E. L. Dias and R. H. Grubbs, Organometallics,
1998, 17, 2758; (c) M. Ulman and R. H. Grubbs, J. Org. Chem.,
1999, 64, 7202.
13 When 1-TPPh* was used as a catalyst in entry 1 in Table 1 under
otherwise identical conditions, 4a was obtained in 91% yield after
24 h.
This work was supported by Grant-in-Aid for Scientific
Research on Innovative Areas (‘‘Organic synthesis based on
reaction integration’’ and ‘‘Molecular activation directed to-
ward straightforward synthesis’’) from MEXT, Japan.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 9699–9701 9701