Tandem cross-metathesis/hydrogenation/cyclization reactions by using compatible catalysts

Article abstract of DOI:10.1021/ol027347m

(Matrix presented) A one-pot tandem cross-metathesis/hydrogenation/cyclization procedure was achieved at room temperature, under 1 atm of hydrogen, in the presence of a ruthenium catalyst and PtO₂ showing the compatibility of the two catalysts. This tandem reaction allows the synthesis of substituted lactones and lactols from acrylic acid and acrolein, respectively, in the presence of unsaturated alcohols.

Full text of DOI:10.1021/ol027347m

ORGANIC
LETTERS
2003
Vol. 5, No. 4
459-462
Tandem Cross-Metathesis/
Hydrogenation/Cyclization Reactions by
Using Compatible Catalysts
Janine Cossy,* Fre´de´ric Bargiggia, and Samir BouzBouz
Laboratoire de Chimie Organique associe´ au CNRS, ESPCI, 10 rue Vauquelin,
75231 Paris Cedex 05, France
janine.cossy@espci.fr
Received November 25, 2002
ABSTRACT
A one-pot tandem cross-metathesis/hydrogenation/cyclization procedure was achieved at room temperature, under 1 atm of hydrogen, in the
presence of a ruthenium catalyst and PtO showing the compatibility of the two catalysts. This tandem reaction allows the synthesis of
2
substituted lactones and lactols from acrylic acid and acrolein, respectively, in the presence of unsaturated alcohols.
One of the challenging goals of synthetic chemistry is the
development of new reactions and strategies that allow for
Scheme 1
the facile conversion of simple compounds into complex
molecules. In this regard, the use of homogeneous transition-
metal catalysts has been successful.1 Organometallic catalysts
are traditionally designed and optimized to mediate a single
reaction. The increasing demand for efficient synthetic
processes requires the development of organometallic re-
agents that are capable of catalyzing multiple reactions or
are compatible with other catalysts to perform sequential
reactions. For example, the second generation ruthenium
Grubbs' catalyst is able to catalyze a tandem ring-closing
metathesis (RCM)/hydrogenation reaction under a hydrogen
atmosphere.2 However, the in situ alignment of several
distinct catalytic processes, which is quite common in
enzyme-catalyzed reaction sequences,3 is still at an early
stage in homogeneous transition-metal catalysis.4
In a recent paper, we have described a one-pot tandem
cross-metathesis/hydrogenation process and shown the com-
5
patibility of ruthenium catalyst I5,6 (Scheme 1) with PtO2
under 1 atm of hydrogen, which produced linear γ-silylated
(1) Tsuji, J. Transition Metal Reagent and Catalyst; Wiley & Sons:
Susex, UK, 2000. (b) Beller, M.; Bolm, C. Transition Metals for Organic
Synthesis; Wiley-VCH: Weinheim, Germany, 1998.
(2) Louie, J.; Bielawski, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2001,
123, 11312-11313. (b) Børsting, P.; Nielsen, P. J. Chem. Soc., Chem.
Commun. 2002, 2140-2141.
functionalized compounds.7 Herein, we would like to report
a three-step one-pot synthesis of cyclic compounds such as
10.1021/ol027347m CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/30/2003

Scheme 2
Table 1. Lactones from Secondary Unsaturated Alcohols
The first step was accomplished by using ruthenium
catalyst I, and the second step, which involved a hydrogena-
tion, was achieved in the presence of PtO2. The cyclization
took place in situ after the formation of the ω-hydroxy acids
or ω-hydroxy aldehydes. As expected, ruthenium catalyst I
was tolerant of all the reaction conditions and effective for
the first reaction. Thus, lactones and lactols were prepared
from readily available chemicals in a three-step one-pot
reaction.
Treatment of allylic or homoallylic alcohols (1.0 equiv)
with acrylic acid (3.0 equiv) in CH2Cl2 at room temperature
in the presence of ruthenium catalyst I (0.05 equiv) and PtO2
Table 2. Lactols from Secondary Unsaturated Alcohols
a Isolated yields. b Not detected by GC/MS.
substituted lactones and lactols. We choose to synthesize
substituted lactones and lactols since most of the synthetic
methods to access these compounds require several steps.8
Scheme 1 shows the synthetic pathway to these products
from allylic and homoallylic alcohols.
(3) Schoevaart, R.; van Rantwijk F.; Sheldon R. A. J. Org. Chem. 2000,
65, 6940-6943. (b) Zimmermann, F. T.; Schneider, A.; Scho¨rken, U.;
Sprenger, G. A.; Fessner, W.-D. Tetrahedron: Asymmetry 1999, 10, 1643-
1646. (c) Gijsen, H. J. M.; Wong, C.-H. J. Am. Chem. Soc. 1995, 117,
2947-2948
(4) Son, S. U.; Park, K. H.; Chung, Y. K. J. Am. Chem. Soc. 2002, 124,
6838-6839. (b) Drouin, S. D.; Zamanian, F.; Fogg, D. E. Organometallics
2001, 26, 5495-5497. (c) Evans, A.; Robinson, J. E. J. Am. Chem. Soc.
2001, 123, 4609-4610. (d) Jeong, N.; Seo, S. D.; Shin, J. Y. J. Am. Chem.
Soc. 2000, 122, 10220-10221. (e) Barnhart, R. W.; Bazan, G. C.; Mourey
T. J. Am. Chem. Soc. 1998, 120, 1082-1083. (f) Takayoshi, A.; Sasai, H.;
Aoe, K.-I.; Okamura, K.; Date, T.; Shibazaki, M. Angew. Chem., Int. Ed.
Engl. 1996, 35, 104-106.
(5) Purchased from Aldrich.
(6) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2000, 122, 8168-8179.
(7) Cossy, J.; Bargiggia, F.; BouzBouz, S. Tetrahedron Lett. 2002, 43,
6715-6717.
(8) For example, see: (a) Paddon-Jones, G. C.; Moore, C. J.; Brecknell,
D. J.; Ko¨nig, W. A.; Kitching, W. Tetrahedron Lett. 1997, 38, 3479-3482.
(b) Kula, J.; Sikora, M.; Sadowska, H.; Piwowarski, J. Tetrahedron 1996,
52, 11321-11324. (c) Bloch, R.; Gilbert, L. J. Org. Chem. 1987, 52, 4603-
4605. (d) Ortun˜o, R. M.; Merce, R.; Font, J. Tetrahedron 1987, 43, 4497-
4506. (e) Bravo, P.; Resnatl, G.; Vlanl, F.; Arnone, A. Tetrahedron 1987,
43, 4635-4647.
a Isolated yields. b Not detected by GC/MS.
460
Org. Lett., Vol. 5, No. 4, 2003

Table 3. Lactones from Tertiary Unsaturated Alcohols
Table 4. Lactols from Tertiary Unsaturated Alcohols
a Isolated yields. b Not detected by GC/MS. c Detected by GC/MS.
case of allylic alcohol 5, lactone 17 was isolated in 10%
yield. This low yield is probably due to the fact that the
benzyl ether functionality is sensitive to the hydrogenation
conditions. The results are summarized in Table 1.
It is worth noting that ruthenium catalyst I as well as PtO2
do not catalyze the esterification of acids, ruling out an
esterification/ring-closing metathesis/hydrogenation sequence
(Scheme 2).
a Isolated yields. b Not detected by GC/MS. c Detected by GC/MS.
Substituted lactols are useful intermediates in synthesis
as they are synthetic equivalents of ω-hydroxyaldehydes. By
using a three-step one-pot reaction, five-membered and six-
membered ring lactols were obtained from secondary allylic
and homoallylic alcohols, respectively, when treated with
acrolein (3 equiv) in the presence of ruthenium catalyst I
(0.05 equiv) and PtO2 (0.05 equiv) under 1 atm of hydrogen
at room temperature. Under these conditions, lactols were
isolated in good yields (45-70%). During this process small
amounts of the saturated alcohols 2′ and 6′ were formed
(yields <15%). The results are reported in Table 2.
Spirocyclic lactones and lactols can be synthesized in a
three-step one-pot reaction from unsaturated tertiary alcohols
from acrylic acid and acrolein, respectively. Spirocyclic
(0.05 equiv) under 1 atm of hydrogen9 led to the formation
of five-membered and six-membered ring lactones, respec-
tively, in yields between 45 and 70%. The saturated alcohols
were not detected by GC/MS. It is worth noting that in the
(9) Typical procedure for tandem cross-metathesis/hydrogenation reac-
tion: In a 10 mL round-bottom flask, a solution of R,â-unsaturated carbonyl
compound (3 equiv, 1.2 mmol) and allylic or homoallylic alcohol (1 equiv,
0.4 mmol) in CH2Cl2 (0.2 M, 2.5 mL) was degassed under vacuum and
purged with H2, and then catalyst I and PtO2 were introduced. The reaction
mixture was degassed again under vacuum and then vigorously stirred under
1 atm of hydrogen. After 15 h at room temperature, the solvent was
evaporated and the residue was purified by flash chromatography to produce
the corresponding lactol or lactone.
Org. Lett., Vol. 5, No. 4, 2003
461

lactones were obtained in good yields (yield >40%) except
when allylic alcohols 11 and 12 were used. In that case,
lactone 27 was not detected (yield < 5%) and the saturated
alcohol 11′ was isolated in 71% yield. Using the homoallylic
alcohol 12 allowed lactone 28 to be isolated in 35% yield
and the saturated alcohol 12′ in 35% yield. For these two
latter alcohols 11 and 12, the yield in lactones was not as
high as that for alcohols 7-10 and the saturated alcohols
11′ and 12′ were formed in modest to high yields.
Scheme 3
The same phenomena were observed in the three-step one-
pot lactolization reaction, as spirocyclic lactols were obtained
in high yields from tertiary alcohols 9 and 10 and in low
yields from the tertiary alcohols 11 and 12 (Tables 3 and 4).
To verify if the cross-metathesis reaction could take place
with the sterically hindered tertiary alcohols 11 and 12, these
two alcohols were treated with acrylic acid just in the
presence of catalyst I at room temperature in CH2Cl2. Under
these conditions the cross-metathesis product 33, which could
be obtained from 11, was not detected (<5%). In contrast,
the cross-metathesis compound 34 was obtained in good yield
(>90%) and with high stereoselectivity (E/Z < 20/1) from
alcohol 12 (Scheme 3). These results imply that when a
sterically hindered allylic alcohol is treated with I and PtO2
at room temperature, under 1 atm of hydrogen, the hydro-
genation is faster than the cross-metathesis reaction.
step one-pot reaction for the construction of substituted
lactones and lactols.
This tandem reaction is performed under very mild
conditions (room temperature, 1 atm of hydrogen), and
purification of the intermediate can be avoided. The sequence
is general and useful for synthetic objectives, which will be
reported in due course.
Supporting Information Available: Detailed experi-
mental procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, we have shown the usefulness of the
combination of ruthenium catalyst I and PtO2 in a three-
OL027347M
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Org. Lett., Vol. 5, No. 4, 2003