New reactivity from (PCy3)2Cl2Ru=CHPh: A mild catalyst for Kharasch additions

Full text of DOI:10.1021/jo982349z

344
J . Org. Chem. 1999, 64, 344-345
chemistry led to the discovery that 1 is an efficient and mild
New Rea ctivity fr om (P Cy3)2Cl2Ru dCHP h :
A Mild Ca ta lyst for Kh a r a sch Ad d ition s
catalyst for the Kharasch addition of CHCl3 across olefins.7
J ohn A. Tallarico, Lisa M. Malnick, and
Marc L. Snapper*
Eugene F. Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02167-3860
Received December 1, 1998
The availability of new olefin metathesis catalysts1 has
led to the emergence of several new, important methods for
small molecule synthesis.2 The widely used Grubbs’ ruthe-
nium catalyst3 1, for example, has played a pivotal role in
the development of synthetically useful transformations,
such as ring-closing, ring-opening, and cross metatheses.4
Within the context of these recent advancements, we wish
to report some unexpected reactivity from this popular olefin
metathesis catalyst (1).5
During an investigation of novel, metathesis-active ru-
thenium complexes,6 we isolated a product derived not from
olefin metathesis (eq 1) but from a metal-catalyzed addition
of CHCl3 across an alkene (eq 2). An investigation of this
In contrast to AIBN- or peroxide-promoted addition of
halocarbons to alkenes, transition-metal complexes have
demonstrated higher chemo- and regioselectivity for similar
transformations.8 Ruthenium, in particular, has played a
prominent role in Kharasch chemistry with Cl2Ru(PPh3)3
(2)9 displaying some of the highest efficiency and versatility
for halocarbon activation and addition to alkenes.10 Accord-
ingly, we compared the reactivity of ruthenium carbene 1
with other known Kharasch addition catalysts.
The ability of complex 1 to catalyze the Kharasch addition
of CHCl3 across various olefins is contrasted to catalyst 2
in Table 1. While higher temperatures (>120 °C) and
prolonged reaction times (>8 h) have usually been required
in previously reported Kharasch additions, exposure of
styrene to chloroform (10 equiv) in the presence of alkylidene
1 (2.5 mol %) for only 2 h at 65 °C resulted in a quantitative
yield of addition product 4 (entry 1). The same reaction
conditions with Cl2Ru(PPh3)3 (2) provided <5% of 4. Not
surprisingly, 1-octene (5) underwent an olefin metathesis,
as well as a Kharasch addition of CHCl3 (entry 2). These
results indicate that, in CHCl3, readily metathesizable
olefins, such as unhindered alkenes, are susceptible to both
reaction pathways.
With this in mind, less metathesis-active substrates were
subjected to conditions that facilitate Kharasch additions (5-
7.5 mol % 1, 10 equiv of CHCl3, 65 °C)11 and were compared
to results obtained with catalyst 2. In all cases, alkylidene
1 provided significantly greater reactivity than catalyst 2
(entries 1-7). For instance, as illustrated in entry 3, in the
presence of catalyst 1, CHCl3 adds across methyl acrylate
(7) in 84% yield, whereas with catalyst 2, less than 5% of 8
is observed. As seen in entries 4-6, complex 1 catalyzes the
intermolecular addition of CHCl3 to 1,1-disubstituted sub-
strates. While these additions were slower than with mono-
substituted olefins, they proceeded in synthetically useful
yields. To the best of our knowledge, this intermolecular
addition of CHCl3 to these types of olefins have not been
previously reported; this is presumably due to substrate
polymerization under the typically harsh reaction conditions.
Entry 7 indicates that the ruthenium-catalyzed addition
could not be extended to a 1,2-disubstituted substrate, even
under forcing conditions.
(1) (a) Couturier, J .-L.; Paillet, C.; Leconte, M.; Basset, J .-M.; Weiss, K.
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Feldman, J .; Calabrese, J . C. Tetrahedron 1995, 117, 8992-8998. (c)
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2056. (b) Fu¨rstner, A. Top. Catal. 1997, 4, 285-299. (c) Armstrong, S. K. J .
Chem. Soc., Perkins Trans. 1 1998, 371-387. (d) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413-4450. For specific examples, see: (e) Snapper,
M. L.; Tallarico, J . A.; Randall, M. L. J . Am. Chem. Soc. 1997, 119, 1478-
1479. (f) Harrity, J . P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda,
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36, 257-259. (i) Fu¨rstner, A.; Langemann, K. J . Am. Chem. Soc. 1997, 119,
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C. Angew. Chem., Int. Ed. Engl. 1997, 36, 166-168. (k) Meng, D.; Su, D.-
S.; Balog, A.; Bertinato, P.; Sorenson, E. J .; Danishefsky, S. J .; Zheng, Y.-
H.; Chou, T.-C.; He, L.; Horwitz, S. J . Am. Chem. Soc. 1997, 119, 2733-
2714. (l) Kim, S.-H.; Figueroa, I.; Fuchs, P. L. Tetrahedron Lett. 1997, 38,
2601-2604. (m) Winkler, J . D.; Stelmach, J . E.; Axten, J . Tetrahedron Lett.
1996, 36, 4317-4318. (n) Barret, A. G. M.; Baugh, S. P. D.; Gibson, V. C.;
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(3) Fluka’s 1998 “Reagent of the Year”.
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5427. (b) Martin, S. F.; Wagman, A. S. Tetrahedron Lett. 1995, 36, 1169-
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(d) Randall, M. L.; Tallarico, J . A.; Snapper, M. L. J . Am. Chem. Soc. 1995,
117, 9610-9611. (e) Schneider, M. F.; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1996, 35, 411-412. (f) Crowe, W. E.; Zhang, Z. J . J . Am. Chem. Soc.
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Chem.sEur. J . 1997, 3, 441-446. Also see ref 2.
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1997, 119, 7157-7158.
Several experiments were performed to examine the
nature of the species responsible for the Kharasch addition
chemistry. Both tricyclohexylphosphine and tricyclohexyl-
phosphine oxide were treated with styrene (10 equiv) and
CHCl3 (100 equiv) and heated (65 °C) under inert atmo-
(7) (a) Kharasch, M. S.; J ensen, E. V.; Urry, W. H. Science 1945, 102,
128. (b) Kharasch, M. S.; J ensen, E. V.; Urry, W. H. J . Am. Chem. Soc.
1945, 67, 1864-1865. (c) Kharasch, M. S.; J ensen, E. V.; Urry, W. H. Ibid.
1946, 68, 154-155. (d) Kharasch, M. S.; J ensen, E. V.; Urry, W. H. Ibid.
1945, 67, 1626. (e) Kharasch, M. S.; J ensen, E. V.; Urry, W. H. Ibid. 1947,
69, 1100-1105. (f) Kharasch, M. S.; Reinmuth, O.; Urry, W. H. Ibid. 1947,
69, 1105-1110. For reviews of transition metal-promoted radical addition
reactions, see: (g) Minisci, F. Acc. Chem. Res. 1975, 8, 165-171. (h) Iqbal,
J .; Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519-564.
(9) For an early example of an intermolecular Kharasch addition
catalyzed by Ru, see: Matsumoto, H.; Nakano, T.; Nagai, Y. Tetrahedron
Lett. 1973, 51, 5147-5150.
(8) For copper-promoted reactions, see: Asscher, M.; Vofsi, D. J . Chem.
Soc. 1963, 3921-3927. For molybdenum-promoted reactions, see: Davis,
R.; Groves, I. F. J . Chem. Soc., Dalton Trans. 1 1987, 1515-1520. For iron-
promoted reactions, see: Elzinga, J .; Hogeeven, H. J . Org. Chem. 1980,
45, 3957-3969. For palladium-promoted reactions, see: Tsuji, J .; Sato, K.;
Nagashima, H. Chem. Lett. 1981, 1169-1170.
(10) (a) Lee, G. M.; Parvez, M.; Weinreb, S. M. Tetrahedron 1988, 44,
4671-4678. (b) Grigg, R.; Devlin, J .; Ramasubbu, A.; Scott, R. M.; Stevenson,
P. J . Chem. Soc., Perkin Trans. 1 1985, 1515-1520. (c) Lee, G. M.; Weinreb,
S. M. J . Org. Chem. 1990, 55, 1281-1285 and references therein.
(11) The use of as little as 3 equiv of chloroform results in similar
reactivity with slightly lower yields.
10.1021/jo982349z CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/05/1999

Communications
J . Org. Chem., Vol. 64, No. 2, 1999 345
Ta ble 1. Kh a r a sch Ad d ition s w ith Com p lexes 1 a n d 2
Experiments to probe further the catalytic role of ruthe-
nium were also conducted. For example, one possibility is
that a minor impurity in complex 1 affects the observed
reactivity. Along these lines, intermediates in the synthesis
of alkylidene 1 were tested for Kharasch activity. Complexes
(Ph3P)2Cl2RuCHPh and Cl2Ru(PPh3)3 (2) with and without
additional trialkylphosphines showed little activity (<5%
conversion).
Detailed studies of ruthenium complex 2 suggest that
halocarbon addition occurs through a radical-based pathway
within the coordination sphere of the metal.14 If this mech-
anism holds true for carbene 1, radical scavengers should
selectively influence intermediates in the catalytic cycle of
the Kharasch addition. Along these lines, the addition of
either 2,6-di-tert-butyl-4-methylphenol (BHT) or galvinoxyl
to alkylidene 1 were found to severely limit the formation
of the expected Kharasch product (3 f 4) without signifi-
cantly affecting metathesis activity (17 f 18, eq 3).15
Whereas the specific structures and events in the catalytic
cycle are unclear for complex 1, these results support the
ruthenium-mediated, radical nature of the reaction.
a
Catalyst 1 ) Cl2Ru(PCy3)2CHPh; catalyst 2 ) Cl2Ru(PPh3)3.
In light of these observations and with the interest of
developing new synthetic opportunities for metatheses, this
divergence in reactivity is noteworthy. Numerous examples
of the RCM of macrocycles and trisubstituted olefins, as well
as the ROMP of sterically demanding or low-strain mono-
mers, have appeared recently in the literature,16 very often
requiring more forceful reaction conditions. It is of impor-
tance to note that with alkylidene 1 the higher temperatures
and the use of chlorinated hydrocarbon solvents, such as
chloroform, could lead to anomalous metathesis results from
competing Kharasch chemistry.
In summary, Grubbs’ ruthenium benzylidene complex 1
catalyzes the chemo- and regioselective addition of chloro-
form across mono- and 1,1-disubstituted olefins. In compari-
son to previously described ruthenium-based Kharasch
catalysts, the mild conditions under which complex 1 affects
the addition of CHCl3 are particularly noteworthy. The
factors defining this reactivity and applications to other
known Kharasch-type reactions are currently under inves-
tigation.
2.5 mol % of catalyst. c 7.5 mol % of catalyst. 5.0 mol % of
b
d
catalyst. e Plus mainly 7-tetradecene.
sphere (Ar). These conditions resulted only in recovered
starting material, indicating that the phosphine alone is not
responsible for the observed reactivity. In fact, excess
phosphine has an inhibitory affect on the Kharasch reactiv-
ity of 1. The addition of 10 mol % of PCy3 with 5.0 mol % of
1 leads to <5% of 4, even after 18 h of heating (65 °C).12
This finding suggests that, like olefin metathesis, catalyst
activation through phosphine dissociation may play a role
in the Kharasch chemistry.13 Catalyst 1 was also subjected
to typical reaction conditions with styrene as substrate under
an O2 atmosphere, and as before, no Kharasch addition
products (i.e., <2%) were observed. These data imply that
oxidative modification of ruthenium does not facilitate the
addition chemistry.
(12) The reaction was complete within 2 h in the absence of excess
phosphine.
Ack n ow led gm en t. We are grateful to the National
Science Foundation and DuPont for generous support of
this research. In addition, M.L.S. acknowledges the Alfred
P. Sloan Foundation, the Camille and Henry Dreyfus
Foundation, Glaxo-Wellcome, and Eli Lilly for support of
our program.
(13) (a) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J . Am. Chem. Soc. 1997,
119, 3887-3897. (b) Aagaard, O. M.; Meier, R. J .; Buda, F. J . Am. Chem.
Soc. 1998, 120, 7174-7182.
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1985, 280, 397-406. (b) Matsumoto, H.; Nikaido, T.; Nagai, Y. Tetrahedron
Lett. 1975, 11, 899-902. (c) Matsumoto, H.; Nikaido, T.; Nagai, Y. J . Org.
Chem. 1978, 43, 1734-1736. Also see ref 10.
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115, 9856-9857.
(16) (a) Miller, S. J .; Blackwell, H. E.; Grubbs, R. H. J . Am. Chem. Soc.
1996, 118, 9606-9614. (b) Maier, M. E.; Langenbacher, D.; Rebien, F.
Liebigs Ann. 1995, 1843-1848. (c) Lynn, D. M.; Kanaoka, S.; Grubbs, R.
H. J . Am. Chem. Soc. 1996, 118, 784-790.
Su p p or tin g In for m a tion Ava ila ble: Experimental details for
the syntheses and characterizations of compounds 6-14 (9 pages).
J O982349Z