Allylic alcohols as substrate for ruthenium-catalyzed C-C coupling allylation reactions: Preliminary communication

Article abstract of DOI:10.1002/hlca.200790030

Allylic alcohols, rather than halides, acetates, or carbonates can be used directly in the Friedel-Crafts-type coupling with various phenols. The use of a Ru^IV, rather than a Ru^II, precursor promotes the formation of one H per cycle

Full text of DOI:10.1002/hlca.200790030

Helvetica Chimica Acta – Vol. 90 (2007)
271
Allylic Alcohols as Substrate for Ruthenium-Catalyzed CÀC Coupling
Allylation Reactions
Preliminary Communication
by Ignacio Fernµndez Nieves, Dani›le Schott, Stefan Gruber, and Paul S. Pregosin*
Laboratory of Inorganic Chemistry, ETH Hçnggerberg HCI, Wolfgang-Pauli-Strasse 10,
CH-8093 Zürich
Allylic alcohols, rather than halides, acetates, or carbonates can be used directly in the Friedel–
Crafts-type coupling with various phenols. The use of a RuIV, rather than a RuII, precursor promotes
the formation of one H+ per cycle so that a large excess of acid is never present in the reaction mixture.
Consequently, the leaving group in the oxidative addition reaction is H2O, thereby avoiding the produc-
tion of an unnecessary by-product.
An increasing variety of metal-mediated catalytic transformations involving allyl
compounds have been developed, and these tools are rapidly becoming indispensable
in organic synthesis [1–5]. Generally, p- or s-allyl species are regarded as important
intermediates in these various transformations [6][7]. Typically, allyl sources such as
halides, acetates, or carbonates have been employed since the allyl moiety often
requires a ꢀleaving groupꢁ to be effective; however, the direct activation of an allyl alco-
hol is both economically and environmentally more desirable, in that the leaving group
is not wasted.
One finds only a modest number of reports in which an allyl alcohol is employed as
substrate [8–13], and Akita and co-workers [8] have summarized several mechanistic
possibilities for the use of an alcohol, e.g., either an oxidative addition reaction or a
dehydration pathway. The former is not favored because the OH group is thought to
be a poor leaving group. The latter mechanism works under acidic conditions; however,
this often requires excess acid and/or severe reaction conditions [8].
We have recently shown [14] that [Ru(Cp*)(MeCN)2)(h3-PhCH=CHCH2)](PF6)2
((Cp*=1,2,3,4,5-pentamethylcyclopenta-1,3-dien-1-yl); 1) facilitates Friedel–Crafts
type aromatic allylation reactions of phenols and related arene compounds under rel-
atively mild conditions, using allyl carbonate substrates. There is now a modest litera-
ture involving metal-catalyzed Friedel–Crafts reactions [15], but little involving ruthe-
nium [16]. We report here an extension of this chemistry and show that the dicationic
catalyst precursor 1, which contains RuIV rather than RuII, affords the CÀC coupling
products starting from a selection of alcohols, as indicated in Scheme 1. The Table
gives a list of the substrates and products tested. The reactions were, in many cases,
fairly rapid (often complete conversion in less than 20 min) and regioselective in that
the attack occurred at the least-substituted allyl C-atom, and proceeded to completion
under relatively mild conditions in MeCN solution. Several of the tested alcohols
ꢂ 2007 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 90 (2007)
Scheme 1
reacted relatively slowly, e.g., allyl alcohol; nevertheless, this reaction proceeded satis-
factorily.
We suggest that the relative ease with which an allyl alcohol can be employed as
substrate for this reaction derives from a mechanism which allows for the controlled
release of one proton (see Scheme 2). Starting from the RuIV catalyst, the reaction pro-
ceeds via a) reductive attack of (for example) the phenol nucleophile to afford a RuII
olefin complex such as 2, followed by b) loss of H+ to reform the aromatic moiety with
concomitant dissociation of the product, thus opening a coordination position at RuII,
c) olefin coordination of the allylic alcohol and O-protonation1) to afford 3, and then d)
oxidative addition with loss of H2O (as the leaving group) to reform the RuIV catalyst.
The proton is generated during the reduction of RuIV to RuII, and then ꢀconsumedꢁ as
H2O. Consequently, the use of the higher-oxidation-state complex as the starting precur-
sor facilitates the controlled release of the proton, thereby avoiding a large excess of
acid at any time.
In addition to the results given in the Table, we also prepared and carried out the
coupling reactions of several para-substituted 1,3-diphenylallyl alcohols (=a-(2-aryl-
ethenyl)benzenemethanols) 4 with 2,6-dimethylphenol as nucleophile, with the aim
of understanding which electronic factors favor this transformation. In contrast to
the catalytic data in the Table, these reactions were performed on a preparative scale
by using 1equiv. each of the reagents and 3 mol-% of catalyst. The products were iso-
lated, purified, and fully characterized by 2D-NMR and mass spectroscopy. The yields
of the products isolated from the reactions of 4b–d were 72, 81, and 89%, respectively.
Compounds 4b and 4c were purified by chromatography; however, this procedure was
not necessary for 4d. For further details, see the Exper. Part.
We found that the reactions of 4b–d afforded a mixture of the two expected iso-
meric products in the ratios 1.38 :1, 1.15 :1, and 2.30 :1, respectively. The major product
results from attack of the phenol at the allyl terminus proximate to the 4-methylphenyl
moiety (and not, e.g., the allyl terminus close to the 4-ClÀC6H4 or 4-NO2ÀC6H4 group).
Presumably, the favored product is that in which the newly formed Ru–olefin bond
1
)
The sequence in which complexation/protonation occurs is not defined.

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Table. Selected Ru-Catalyzed CÀC Bond-Formation Reactions, by Using Alcohol Precursors. In MeCN at
353 K, with 1 as catalysta).
Allylic substrate
Phenol derivative
Time [min]
Productsb)
phenol
6-bromonaphthalen-2-ol
4
8
100 (10 :6 :84)
94
phenol
4-methylphenol
6-bromonaphthalen-2-ol
18
9
6
100 (13 :6 :81)
100 (0 :15 :85)
96
phenol
10
100 (6 :2 :92)
6-bromonaphthalen-2-ol
192
phenol
00 (8 :4 :88)
11
6-bromonaphthalen-2-ol
190
phenol
6-bromonaphthalen-2-ol
800 (13 h)
310
ca. 60
ca. 60
6-bromonaphthalen-2-ol
125
100
a) Conditions: 0.07 mmol of allylic substrate, 0.21mmol of the corresponding phenol derivative, and 0.002
mmol of catalyst (3 mol-%) in 0.5 ml of solvent at room temperature. b) Conversion in %; o/m/p ratio in
parentheses, as determined by 1H-NMR spectroscopy.
derives from the most-electron-donating aryl moiety, i.e., complex 5 is slightly favored
relative to 6. One might have expected the preferred attack of the phenol nucleophile
to take place at the electron-poorer terminal allyl carbon; however this is not the case.

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Scheme 2
Interestingly, for X=MeO in 4, we did not observe the formation of product. This is
consistent with the observations that the substrate alcohols 7 and 8, react only very
slowly2) with 6-bromonaphthalen-2-ol to afford the CÀC coupling products, even
after 24 h at 353 K in MeCN.
This relative lack of reactivity most likely arises from the formation of an h6-arene complex which is
2
)
stable, and observable, under these conditions, due to the strongly electron-donating MeO group.

Helvetica Chimica Acta – Vol. 90 (2007)
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Concluding, the selection of a [RuIV(allyl)] catalyst precursor, rather than a more
readily available RuII species, permits the use of the economically and environmentally
more favorable alcohol (rather than a carbonate or acetate) substrate in the CÀC cou-
pling reaction described.
Experimental Part
2,6-Dimethyl-4-[(2E)-1-(4-methylphenyl)-3-(4-nitrophenyl)prop-2-enyl]phenol and 2,6-Dimethyl-4-
[(2E)-3-(4-methylphenyl)-1-(4-nitrophenyl)prop-2-enyl]phenol. To a soln. of (2E)-1-(4-methylphenyl)-
3-(4-nitrophenyl)prop-2-en-1-ol (4d; 71.6 mg, 0.266 mmol) in MeCN (2 ml) was added
[Ru(Cp*)(MeCN)2
(h3-PhCH=CHCH2)](PF6)2 (1; 6.0 mg, 0.008 mmol; 3 mol-%) and 2,6-dimethylphe-
G
nol (32.5 mg, 0.266 mmol). The resulting brown suspension was stirred at 353 K overnight. Filtration
through silica gel and subsequent washing of the silica gel with AcOEt removed the Ru-catalyst. The
mixed solvent was then evaporated to afford the crude product as a yellow powder. This material was
washed with hexane and dried i.v.: 148 mg (89%) of the product as a mixture of isomers (for 4b and
4c, it was necessary to chromatograph the crude product to obtain a pure material). 1H- and 13C-
NMR: a selection of assignments is given in the Figure. MS: 373 (M+), 358 ([MÀMe]+), 251
([MÀC6H4NO2]+), 236 ([MÀMeÀC6H4NO2]+). Anal. for C24H23NO3 :C 77.19, H 6.21, N 3.75; found:
C 76.52, H 6.18, N 3.83.
Figure. Selection of 1H- and 13C-NMR assignments for 2,6-dimethyl-4-[(2E)-1-(4-methylphenyl)-3-(4-
nitrophenyl)prop-2-enyl]phenol and 2,6-dimethyl-4-[(2E)-3-(4-methylphenyl)-1-(4-nitrophenyl)prop-2-
enyl]phenol
REFERENCES
[1] B. M. Trost, M. L. Crawley, Chem. Rev. 2003, 103, 2921; B. M. Trost, D. L. van Vranken, Chem. Rev.
1996, 96, 395.
[2] M. Johannsen, K. A. Jorgensen, Chem. Rev. 1998, 98, 1689.
[3] O. Reiser, Angew. Chem. 1993, 105, 576.
[4] C. Hubert, J. L. Renaud, B. Demerseman, C. Fischmeister, C. Bruneau, J. Mol. Catal. A 2005, 237,
161; M. D. Mbaye, B. Demerseman, J. L. Renaud, L. Toupet, C. Bruneau, Adv. Synth. Catal. 2004,
346, 835.
[5] V. Cadierno, S. E. Garcia-Garrido, J. Gimeno, N. Nebra, Chem. Commun. 2005, 4086; D. A. Evans,
K. R. Campos, J. S. Tedrow, F. E. Michael, M. R. Gange, J. Am. Chem. Soc. 2000, 122, 7905.
[6] P. S. Pregosin, R. Salzmann, Coord. Chem. Rev. 1996, 155, 35.
[7] M. Kollmar, G. Helmchen, Organometallics 2002, 21, 4771.
[8] C. Dubs, T. Yamamoto, A. Inagaki, M. Akita, Chem. Commun. 2006, 1962.

276
Helvetica Chimica Acta – Vol. 90 (2007)
[9] F. Ozawa, T. Ishiyama, S. Yamamoto, S. Kawaguchi, H. Murakami, M. Yoshifuji, Organometallics
2004, 23, 1698; F. Ozawa, H. Okamoto, S. Kawagishi, S. Yamamoto, T. Minami, M. Yoshifuji, J.
Am. Chem. Soc. 2002, 124, 10968.
[10] H. Saburi, S. Tanaka, M. Kitamura, Angew. Chem., Int. Ed. 2005, 44, 1730.
[11] C. Garcꢃa-Yebra, J. P. Janssen, F. Rominger, G. Helmchen, Organometallics 2004, 23, 5459.
[12] R. Takeuchi, M. Kashio, J. Am. Chem. Soc. 1998, 120, 8647.
[13] H. Bricout, J. F. Carpentier, A. Mortreux, J. Mol. Catal. A 1998, 136, 243; H. Bricout, J. F. Carpen-
tier, A. Mortreux, Tetrahedron 1998, 54, 1073.
[14] I. Fernꢄndez, R. Hermatschweiler, F. Breher, P. S. Pregosin, L. F. Veiros, M. J. Calhorda, Angew.
Chem., Int. Ed. 2006, 45, 6386.
[15] A. Corma, H. Garcia, Adv. Synth. Catal. 2006, 348, 1391; D. O. Jang, K. S. Moon, D. H. Cho, J. G.
Kim, Tetrahedron Lett. 2006, 47, 6063; P. Kuhn, D. Semeril, C. Jeunesse, D. Matt, P. J. Lutz, R.
Louis, M. Neuburger, Dalton Trans. 2006, 3647; M. Soueldan, J. Collin, R. Gil, Tetrahedron Lett.
2006, 47, 5467; R. Nishio, S. Wessely, M. Sugiura, S. Kobayashi, J. Combin. Chem. 2006, 8, 459;
M. Rueping, B. J. Nachtsheim, W. Leawsuwan, Adv. Synth. Catal. 2006, 348, 1033; V. D. Sarca, K.
K. Laali, Green Chem. 2006, 8, 615; Z. P. Li, D. S. Bohle, C. J. Li, Proc. Natl. Acad. Sci. U.S.A.
2006, 103, 8928.
[16] A. Fürstner, D. Vogtlꢅnder, W. Schrader, D. Giebel, M. T. Reetz, Org. Lett. 2001, 3, 417; Y. Nishi-
bayashi, M. Yamanashi, Y. Takagi, M. Hidai, Chem Commun. 1997, 859.
Received October 23, 2006