A regioselective Ru-catalyzed alkene-alkyne coupling

Article abstract of DOI:10.1021/ol0059504

(matrix presented) The reaction of silylalkynes and terminal alkenes proceeds with complete control of regioselectivity by the silyl substituent to give geometrically defined vinylsilanes. Since terminal alkynes normally give mixtures, protodesilylation o

Full text of DOI:10.1021/ol0059504

ORGANIC
LETTERS
2000
Vol. 2, No. 12
1761-1764
A Regioselective Ru-Catalyzed
Alkene−Alkyne Coupling
Barry M. Trost,* Michelle Machacek, and Matthew J. Schnaderbeck
Department of Chemistry, Stanford UniVersity, Stanford, California 94305-5080
bmtrost@leland.stanford.edu
Received April 13, 2000
ABSTRACT
The reaction of silylalkynes and terminal alkenes proceeds with complete control of regioselectivity by the silyl substituent to give geometrically
defined vinylsilanes. Since terminal alkynes normally give mixtures, protodesilylation of these adducts then constitutes a regioselective addition
of terminal alkynes to terminal alkenes.
Simple addition reactions are attractive because they repre-
sent atom-economical processes1 that quickly build molecular
complexity.2 The intermolecular cross-coupling of an alkene
and alkyne (a type of Alder ene reaction) as shown in eq 1
chemoselectivity and stereoselectivity, in terms of alkene
geometry of the product, are excellent, regioselectivity
remains an issue. Consideration of the proposed mechanism
reveals the origin of the regioselectivity problems. The
orientation of the terminal alkene is not a factor, since only
one will lead to a productive intermediate. On the other hand,
the alkyne can and will coordinate and undergo cyclization
in either orientation. In essence, the competition between
interactions of the substituents on the carbons forming the
new C-C bond of the ruthenacycle and the substituents on
requires metal catalysis if the alkyne does not bear a strong
electron-withdrawing group,3 and even in the latter cases,
Lewis acids are typically employed.4 The ability to utilize a
Ru complex as shown in Scheme 1 expands the scope
considerably to even unactivated systems, provides unusual
selectivities, and allows the reaction to proceed under rather
mild conditions.3 A major consideration of the synthetic
utility of any new reaction deals with selectivity. While
(5) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer-
Verlag: Berlin, 1983.
(6) Greene, T. W.; Wutz, P. G. M. ProtectiVe Groups in Organic
Synthesis; Wiley: New York, 1999; pp 68-86.
(7) Fleming, I.; Dunoques, J.; Smithers, R. H. Org. React. 1989, 37, 57.
(8) For a related study in cobalt catalyzed reactions, see: Earl, R. A.;
Vollhardt, K. P. C. J. Am. Chem. Soc. 1983, 105, 6991. Also see: Baxter,
J. B.; Knox, G. R.; Pauson, P. L.; Spicer, M. O. Organometallics 1999, 18,
197, 215.
(9) Albers, M. O.; Robinson, D. J.; Shaver, A.; Singleton, E. Organo-
metallics 1986, 5, 2199. Ashworth, T. V.; Singleton, E.; Hough, J. J. J.
Chem. Soc., Dalton Trans. 1977, 1089. Bennett, M. A.; Wilkenson, G.
Chem. Ind. (London) 1959, 1516.
(10) All new compounds have been satisfactorily characterized spectrally,
and elemental compositions have been confirmed by combustion analysis
and/or high-resolution mass spectrometry.
(1) Trost, B. M. Science 1991, 254, 1471. Trost, B. M. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 259.
(2) Wender, P. A.; Miller, B. L. Org. Synth.: Theory Appl. 1993, 2, 27.
Bertz, S. H.; Sommer, T. J. Org. Synth.: Theory Appl. 1993, 2, 67.
(3) Trost, B. M.; Indolese, A. F.; Mu¨ller, T. J. J.; Treptow, B. J. Am.
Chem. Soc. 1995, 117, 615.
(4) Cf. Dauben, W. G.; Brookhart, T. J. Am. Chem. Soc. 1981, 103, 237.
Snider, B. B. ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 1-28.
(11) Gill, T. P.; Mann, K. R. Organometallics 1982, 1, 485.
(12) Trost, B. M.; Toste, F. D. Tetrahedron Lett. 1999, 40, 7739. Trost,
B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 9728.
10.1021/ol0059504 CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/20/2000

Scheme 1. Mechanistic Proposal for Ru-Catalyzed Alkene-Alkyne Addition
the alkyne and the ruthenium would then dictate the
fall to nearly 1:1 or even reverse as in the case of the
propargyl alcohol 1 with 1-octene (2) as shown in eq 2.
A silyl substituent has proven to be an effective regio-
chemical control element for both steric and electronic
reasons in a number of reactions.5 In the present instance, it
is difficult to conjecture in which direction the selectivity
regioselectivity. The latter can be repulsive, if they simply
derive from nonbonded steric interactions, or attractive, if a
substituent could possibly coordinate to ruthenium. To
illustrate, while the branched to linear ratios for the reactions
of terminal alkynes typically range from 4:1 to 5:1, it can
Table 1. Cross-Coupling of Silylalkynes and Alkenes Catalyzed by CpRu(COD)Cl (5)a
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Org. Lett., Vol. 2, No. 12, 2000

-
Table 2. Cross-Coupling of Silylalkynes and Alkenes Catalyzed by CpRu(NCCH3)3+PF6 (20)a
might change. If, in Scheme 1, R2 ) a silyl group, steric
would disfavor I; however, such interactions between the
interactions between the silicon substituent and the alkene
silicon substituent and the ruthenium center could disfavor
II. Despite this ambiguity, the attractiveness of the silicon
group, because of its ease of introduction onto the terminal
alkyne, the ease by which vinylsilanes can undergo protode-
silylation,5,6 and perhaps most significantly, the utility of
vinylsilanes for further elaboration,5,7 led us to explore its
protential.8
Initial studies as outlined in Table 1 were quite promising.
For example, the silyl version of the propargyl alcohol 1
(i.e., 6) reacts with 1-octene, utilizing the ruthenium complex
59 as catalyst to form a single product 710 that corresponds
to the branched product 3 after protodesilylation (Table 1,
Org. Lett., Vol. 2, No. 12, 2000
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entry1). Gratifyingly, in each and every case, only one regio-
and geometric isomer was obtained. Disappointingly, the
conversions were unacceptably low, as revealed by the fact
that the yields of product based upon recovered starting
material are actually quite good. Since increasing reaction
times normally did not improve the yields, the source of the
problem appeared to be a limitation on the catalyst turnover
number. Indeed, doubling the catalyst did double the isolated
yield but led to no increased turnover number.
For example, 3-butyn-1-ol gave a 1:1 ratio of branched and
linear product with safrole (13). Only 26, which would form
the branched adduct after protodesilylation, is generated with
the silyl substrate. These results indicate that 33 rather than
34 is the product-determining intermediate. If steric factors
alone dictated the regioselectivity, these observations require
that the steric hindrance afforded to the C-C bond forming
reaction to generate 34 would be worth at least 2.5 kcal/mol
in the transition state. On the other hand, it is possible that
an electronic effect may also be involved. The simplest
notion invokes the silicon stabilizing the forming C-Ru
bond. However, another aspect should be considered. In the
electrocyclic process leading to the ruthenacycle, the ability
of silicon to stabilize a positive charge â to itself may induce
a polarization of the alkyne-ruthenium cationic π-complex
and thus subsequent nucleophilic attack by the alkene as
depicted in 32 which then generates the observed product.
Further work to verify the mechanistic scheme is clearly
In a search for a way to increase our turnover number,
we examined a second generation ruthenium catalyst 2011
whose higher intrinsic activity in other reactions under study12
suggested its exploration. Its higher reactivity presumably
stems from the absence of chloride as a “ligand”. Whereas
methanol is an unsatisfactory solvent for complex 20, acetone
proved to be excellent. Indeed, subjecting a 1:1 ratio of
alkyne and alkene to 10 mol % of 20 in acetone at room
temperature allowed reaction to go to completion within 2
h in most cases. Comparison of entries 1-5 of both tables
reveals the efficacy of the second generation catalyst. Only
in the case of the propargyl alcohol was the yield modest;
however, the reaction still did proceed nearly to completion
in 2 h. Increasing the bulk of the silyl group from TMS to
TES (Table 2, entries 5 and 6) has no discernible effect. On
the other hand, increasing it to diphenylmethylsilyl (Table
2, entries 7 and 8) led to some recovered starting material
in the 2 h reaction time frame. The excellent chemoselectivity
as illustrated by the compatibility with alcohols, esters,
amides, ketones, and internal alkenes is noteworthy consider-
ing the high reactivity of this cationic complex. It is
interesting to note that the vicinal diol undergoes simulta-
neous acetonide formation (Table 2, entry 9) and suggests
the effectiveness of this complex as a catalyst for such
ketalizations.
needed before any definitive conclusions can be drawn. The
ability to effect ipso substitution of the silyl group with
electrophiles with complete control of regio- and geometric
selectivity5 imparts special significance to this highly selec-
tive synthesis of vinylsilanes.
Acknowledgment. We thank the National Science Foun-
dation and the National Institutes of Health for the generous
support of our programs. Mass spectra were provided by the
Mass Spectrometry Regional Center of the University of
California-San Francisco supported by the NIH Division of
Research Resources.
Supporting Information Available: Experimental details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The dramatic influence on regioselectivity of the silyl
group is particularly noteworthy with alkynes 1, 11, 25, and
27. The parent alkynes related to these substrates have a
strong tendency to increase the amount of the linear products.
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Org. Lett., Vol. 2, No. 12, 2000