Tandem catalysis: The sequential mediation of olefin metathesis, hydrogenation, and hydrogen transfer with single-component Ru complexes

Full text of DOI:10.1021/ja016431e

11312
J. Am. Chem. Soc. 2001, 123, 11312-11313
Tandem Catalysis: The Sequential Mediation of
Olefin Metathesis, Hydrogenation, and Hydrogen
Transfer with Single-Component Ru Complexes
Table 1. Tandem RCM-Hydrogenation Reactions Catalyzed by 1
or 2a
Janis Louie, Christopher W. Bielawski, and
Robert H. Grubbs*
Arnold and Mabel Beckman Laboratories of Chemical
Synthesis, DiVision of Chemistry and Chemical Engineering
California Institute of Technology,
Pasadena, California 91125
ReceiVed June 15, 2001
ReVised Manuscript ReceiVed September 26, 2001
Organometallic catalysts are traditionally designed and opti-
1
mized to mediate a single reaction. However, the increasing
demand for expedient and efficient synthetic processes requires
the development of organometallic reagents that are capable of
catalyzing multiple, mechanistically distinct reactions directly or
3 2 2
by simple modification. While the Ru complex (PCy ) Cl Rud
2
3
CHPh (1) has found extensive use in olefin metathesis, it was
also recently shown to be an effective precatalyst for mediating
radical additions4 and hydrogenation reactions.5 We recently
demonstrated all three reactions could be performed in tandem
6
to afford well-defined block copolymers. Herein, we report that
complex 1, or its more active derivative 2, is also useful in
7
mediating a variety of other catalytic hydrogenation reactions that
include regiospecific ketone and olefin reductions, transfer
hydrogenations of ketones, and dehydrogenative oxidations of
alcohols. In addition, we demonstrate a variety of “one-pot”
tandem metathesis-hydrogenation procedures for the rapid
construction of small molecules, including (R)-(-)-Muscone.
a
Reactions conditions: 3-5 mol % catalyst 1 or 2, 40 °C
Figure 1. First and second generation ruthenium alkylidenes.
(metathesis) and 70 °C (hydrogenation), 0.1 M substrate in ClCH CH Cl.
2 2
b
Determined by GC. c Isolated yield based on starting substrate.
Reaction was performed under dilute conditions (see Supporting
d
Addition of H
afforded the hydride complex RuHCl(H
2
(1 atm, 25 °C) to complex 1 quantitatively
Information). e Hydrogenation was conducted at 100 °C.
8
2
)(PCy
hydrogenation catalyst.5 The same Ru hydride complex was
observed upon the introduction of H following a ring-closing
3 2
) , an effective
,6
9
catalysis protocol. Upon the conclusion of the metathesis reaction
2
metathesis (RCM) or cross-metathesis (CM) reaction. Thus, as
shown in Tables 1 and 2, excellent yields of various saturated
products were obtained by using a convenient, “one-pot” tandem
(performed at 40 °C), the reaction vessel was simply pressured
with hydrogen and then heated to 70 °C. The order of olefin
reactivity appeared to follow the general trend cis > trans >
conjugated > trisubstituted, and permitted the regioselective
hydrogenation of substrate 19 (Table 1, entry 4). In some cases
(
1) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals;
Wiley: New York, 1988.
2) Schwab, P. E.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
18, 100.
(Table 1, entries 2 and 8), higher pressures were employed to
(
1
achieve acceptable reaction rates under the relatively dilute
conditions necessary for the olefin metathesis reaction. Impor-
tantly, the Ru catalyst tolerated a wide range of functional groups
without any noticeable loss in activity. In addition, the catalyst
did not facilitate the hydrodehalogenation of aryl halides (Table
(
3) For reviews on olefin metathesis see: (a) Schuster, M.; Blechert, S.
Angew. Chem., Int. Ed. Engl. 1997, 20377. (b) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413.
(
4) Simal, F.; Demonceau, A.; Noels, A. F. Angew. Chem., Int. Ed. Engl.
1
999, 38, 538.
5) (a) McLain, S. J.; McCord, E. F.; Arthur, S. D.; Hauptman, A. E.;
(
2, entry 4), which is a common drawback of many hydrogenation
Feldman, J.; Nugent, W. A.; Johnson, L. K.; Mecking, S.; Brookhart, M. Proc.
Am. Chem. Soc.; DiV. Polym. Mater. Sci. Eng. 1997, 76, 246. (b) Watson, M.
D.; Wagener, K. B. Macromolecules 2000, 33, 3196. (c) For an example with
a related bimetallic Ru complex, see: Dias, E. L.; Grubbs, R. H. Organo-
metallics 1998, 17, 2758.
procedures. Overall, this “one pot”, tandem Ru-catalyzed me-
tathesis-hydrogenation approach is much more convenient than
standard procedures where Pd/C or Rh hydrogenation catalysts
1
0
(
6) Bielawski, C. W.; Louie, J.; Grubbs, R. H. J. Am. Chem. Soc. 2000,
are used after the olefin metathesis product has been isolated.
1
22, 12872.
Noyori has developed powerful diamine-coordinated Ru com-
plexes for the regioselective hydrogenation of ketones in the
presence of olefins.11 Similarly, we found that complexes 1 or 2
(
7) (a) Scholl, M.; Ding, S.; Lee C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
9
1
53. (b) Bielawski, C. W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2000, 34,
234.
(8) (a) Wilhelm, T. E.; Belderrain, T. R.; Brown, S. N.; Grubbs, R. H.
Organometallics 1997, 18, 33867. (b) Oliv a´ n, M.; Caulton, K. G. Inorg. Chem.
999, 38, 566. (c) For an excellent mechanistic analysis of this reaction, see:
Drouin, S. D.; Yap, G. P. A.; Fogg, D. E. Inorg. Chem. 2000, 39, 5412.
(9) Under relatively low pressures of H
ClCH CH Cl) appeared to be critical for successful hydrogenation as only
isomerization was observed in aromatic solvents.
2 2 2
, chlorinated solvents (CH Cl or
1
2
2
1
0.1021/ja016431e CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/17/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 45, 2001 11313
Table 2. Tandem CM-Hydrogenation Reactions Catalyzed by 1
(e.g., ketones), remains a useful protocol for reducing ketones
a
or 2
(
and olefins) and oxidizing alcohols. We found that omplexes 1
15-17
and 2 were also effective transfer hydrogenation precatalysts.
As shown in eq 1, following the RCM of ketone 12, simply adding
2 3
excess base (e.g., K CO
or NaOH)18 and 2-propanol selectively
afforded the unsaturated alcohol 43 in 56% overall yield from
a
12. Similarly, transfer dehydrogenation of the allyl alcohol 44
Reaction conditions: 3 mol % catalyst 1 or 2, 40 °C (metathesis)
(obtained via CM of 3-buten-2-ol and 5-acetoxy-1-hexene) with
and 70 °C (hydrogenation, 100 psi H
2 2 2
), 0.1 M substrate in ClCH CH Cl.
b
Determined by GC. c Isolated yield based on starting substrate.
3-pentanone and NaOH afforded R,â-unsaturated ketone 35 in
77% yield over the two steps (eq 2).
were also excellent catalysts for regiospecific ketone reductions
upon the addition of ethylenediamine. Thus, as shown in Scheme
As shown in Scheme 2, the tandem catalytic reactions
12
developed above were combined for a “one-pot” synthesis of (R)-
1
9
1
, the “one-pot” tandem metathesis-hydrogenation procedure was
(-)-Muscone, a natural product with a desirable fragrance.
Following RCM of the readily available diene 45,19 the addition
of 3-pentanone and NaOH initiated the (Ru catalyzed) transfer
dehydrogenation of the resulting alcohol (46) and afforded the
extended to include regiospecific ketone reductions. Following
the CM of styrene with methyl vinyl ketone, the addition of
2
ethylenediamine (1.1 equiv/Ru), NaOH (5 equiv/Ru), and H (1
atm, balloon) quantitatively afforded the corresponding allyl
alcohol 41 after 12 h (25 °C). No trace of olefin saturation was
observed. Alternatively, reduction of both the olefin and the ketone
was obtained by applying these conditions after the tandem CM-
hydrogenation procedure described above to afford the secondary
alcohol 42 in moderate yield (30%).13
macrocyclic ketone 47. Finally, the addition of H
(-)-Muscone in 56% overall yield from 45.
2
gave (R)-
Scheme 2. A “One-Pot”/Three (Ru catalyzed)-Step Synthesis
of (R)-(-)-Muscone
Scheme 1. Tandem Ru-Catalyzed Reactionsa
a
See Table 2 for the synthesis of 37. Method A: H
N(CH NH (1.1 equiv/Ru), NaOH (5 equiv/Ru),
(1 atm), 25 °C, 12 h.
2
(100 psi), 70 °C,
1
0 h. Method B: H
i-PrOH, H
2
2
)
2
2
2
Acknowledgment. The support of the National Institute of Health
(NIH) is acknowledged. J.L. is grateful to the NIH for a postdoctoral
fellowship. C.B. is grateful to the ACS Division of Organic Chemistry
Transfer hydrogenation,14 where H
from a “hydrogen donor” (e.g., alcohols) to a “hydrogen acceptor”
is effectively transferred
2
(sponsored by Rohm and Haas) and the National Science Foundation for
(
10) (a) F u¨ rstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska, B. J. Org.
fellowship support.
Chem. 2000, 65, 7990. (b) Creighton, C. J.; Reitz, A. B. Org. Lett. 2001, 3,
8
93. (c) Wallace, D. J.; Goodman, J. M.; Kennedy, D. J.; Davies, A. J.;
Supporting Information Available: Full experimental procedures
and characterization data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
Cowden, C. J.; Ashwood, M. S.; Cottrell, I. F.; Dolling, U.-H.; Reider, P. J.
Org. Lett. 2001, 3, 671.
(
11) (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1
995, 117, 10417. (b) Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.;
Noyori, R. J. Org. Chem. 1996, 61, 4872. (c) Ohkuma, T.; Koizumi, M.;
Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa,
T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529. (d) Noyori,
R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
JA016431E
(15) Transfer hydrogenation conditions: 5 mol % of Ru catalyst, NaOH
or K CO (5 equiv/Ru), iPrOH or 3-pentanone as solvent, 80 °C.
2 3
(
12) Under H
ethylenediamine (en) quantitatively afforded RuHCl(en)(PCy
3
IMes)(PCy ) ( P
2
(1 atm), complex 1, NaOH (5 equiv), and 1.1 equiv of
(16) For example, with 1 as catalyst and NaOH as base, cyclohexanone
was converted to cyclohexanol in under 1 h. Similar results were obtained
with complex 2.
3
1
3 2
) ( P NMR:
31
δ 52.5 ppm). Similarly, complex 2 afforded RuHCl(en)(H
2
NMR: δ 52.4 ppm). The structures of both complexes were verified through
independent synthesis: Louie, J.; Bielawski, C. W.; Grubbs, R. H. Unpublished
results.
(17) The catalytically active species is currently under investigation. For
additional mechanistic details, see ref 14.
(18) Elevated reaction rates were observed with NaOH, compare (cyclo-
(
13) Once the diamine Ru complex was formed, higher pressures of
hydrogen (100 psi) did not facilitate olefin reduction.
14) (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97. (b)
Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045.
2 3
hexanone to cyclohexanol, 50% conversion): K CO , 24 h; NaOH, <1 h.
(19) A similar multistep procedure has been reported recently, see: Kamat,
V. P.; Hagiwara, H.; Katsumi, T.; Hoshi, T.; Suzuki, T.; Ando. M. Tetrahedon
2000, 56, 4397.
(