C O M M U N I C A T I O N S
Table 2. Ruthenium-Catalyzed Cross-Coupling of Tertiary
Propargyl Alcohols with ω-Cyanoalkynes
(13, not observed), is either not formed or exists in rapid equilibrium
with its prefered congener 11a.
In summary, we have developed an unprecedented, atom-
economical14 ruthenium-catalyzed alkyne-alkyne cross coupling
between cyanoalkynes and propargyl alcohols. It provides an
interesting example of the uniqueness of the cyano group in the
context of coordination to metal fragments, while delivering highly
functionalized, stereodefined dienylketones. Moreover, this reaction
can be considered as a chemoselective, atom-economical surrogate
for the aldol condensation (eq 3) as the products are formally
derived from a vinylaldehyde 13 and an unsubstituted methyl ketone
14; that the thermodynamically less stable, (Z)-double bond isomer
is selectively produced only further emphasizes the unusual
character of this process, as such a direct reaction is not feasible
with the currently available aldol technology.15 Importantly, since
quantitative isomerization to the (E)-counterpart can be easily
achieved, stereoselective access to both isomers at will is gained.
Acknowledgment. We thank the National Science Foundation
for their generous support of our programs. N.M. is grateful to the
Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT) for the awarding of
a Postdoctoral fellowship. We thank Johnson-Matthey for a
generous gift of ruthenium complexes.
a All reactions carried out at room temperature (4-8 h) with 3 equiv
of 9 and 1 equiv of 1. b Yields refer to pure, isolated products. Yields
between brackets are based on recovered, unreacted propargyl alcohol.
For details on the amounts of dimer 3 isolated, see the Supporting
Information.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds. This material is available
also appears to be broad, allowing the presence of free carbonyl groups
and acetals (Table 1, entries 8-10). Importantly, the length of the nitrile
tether can also be varied to considerable extent (9a-9c), indicating
that there is some flexibility in the coordination mode of the cyano-
partner to the metal center.13
Furthermore, in all obtained products the R,ꢀ-unsaturated moiety
is exclusively Z-configured (to the limit of detection by NMR), an
observation with important implications in mechanistic terms (vide
infra). On the other hand, smooth and quantitative (Z)- to (E)-
isomerization can be brought about by brief exposure of the products
to catalytic PhSSPh in refluxing THF, thus providing easy access
to both double-bond stereoisomers at will (eq 2).
References
(1) See: (a) Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem.sEur. J. 2002, 8,
36–44.
(2) For selected reviews: (a) Guillena, G.; Najera, C.; Ramon, D. J. Tetrahedron:
Asymmetry 2007, 18, 2249–2293. (b) List, B. Tetrahedron 2002, 58, 5573–
5590.
(3) (a) Jang, H.-Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653–661. (b)
Montgomery, J. Acc. Chem. Res. 2000, 33, 467–473.
(4) (a) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem. ReV. 2001, 101,
2067–2096. (b) Trost, B. M.; Krische, M. J. Synlett 1998, 1–16.
(5) (a) Vollhardt, K. P. C. Acc. Chem. Res. 1977, 10, 1–8. (b) Lautens, M.;
Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49–92. (c) Saito, S.; Yamamoto,
Y. Chem. ReV. 2000, 100, 2901–2915.
(6) For instance, the extensive body of work done on the [2+2+2] cyclotri-
merization of alkynes shows that, in general, regioselectivity can only be
reliably achieved when two of the alkyne partners are tethered. See: (a)
Maitlis, P. M. Acc. Chem. Res. 1976, 9, 93–9, and ref 3 For an example of
in situ-tethering, see: (b) Yamamoto, Y.; Ishii, J.; Nishiyama, H.; Itoh, K.
J. Am. Chem. Soc. 2005, 127, 9625–9631.
(7) (a) Trost, B. M.; Rudd, M. T. J. Am. Chem. Soc. 2001, 123, 8862–8863.
(8) For other examples of alkyne dimerization processes, see: (a) Le Paih, J.;
Derien, S.; Demerseman, B.; Bruneau, C.; Dixneuf, P. H.; Toupet, L.;
Dazinger, G.; Kirchner, K. Chem.sEur. J. 2005, 11, 1312–1324. (b) Le
Paih, J.; Monnier, F.; Derien, S.; Dixneuf, P. H.; Clot, E.; Eisenstein, O.
J. Am. Chem. Soc. 2003, 125, 11964–11975. (c) Le Paih, J.; Derien, S.;
Bruneau, C.; Demerseman, B.; Toupet, L.; Dixneuf, P. H. Angew. Chem.,
Int. Ed. 2001, 40, 2912–2915. (d) Le Paih, J.; Derien, S.; Dixneuf, P. H.
Chem. Commun. 1999, 1437–1438.
Our working mechanistic rationale for this catalytic, atom-
economical process is depicted in Scheme 2.7-9 Of the two possible
nonsymmetric ruthenacyclopentadienes that can be formed, the 2,5-
disubstituted isomer 11a is likely to be favored because of the
possibility of chelation by the cyano substituent. The alternative
isomer 11b, which would lead to an aldehyde cross-coupled product
(9) For further development of cycloisomerizations based on the same principle,
see: (a) Trost, B. M.; Rudd, M. T. J. Am. Chem. Soc. 2005, 127, 4763–
4776. (b) Trost, B. M.; Rudd, M. T.; Costa, M. G.; Lee, P. I.; Pomerantz,
A. E. Org. Lett. 2004, 6, 4235–4238. (c) Trost, B. M.; Rudd, M. T. J. Am.
Chem. Soc. 2003, 125, 11516–11517. (d) Trost, B. M.; Rudd, M. T. J. Am.
Chem. Soc. 2002, 124, 4178–4179.
Scheme 2. Mechanistic Proposal for the Cross-Coupling Reaction
(10) Slow addition of the propargyl alcohol component via syringe pump techniques
or similar attempts at minimizing the effective concentration of the propargyl alcohol
in solution did not provide significant improvement either.
(11) Other acid additives tested include trifluoroacetic acid, CeCl3, and
DABCO · 2HPF6.
(13) No dimerization of the cyanoalkyne was observed.
(14) Trost, B. M. Science 1991, 254, 1471–1477.
(15) For a surrogate to such a reaction, see: Nakamura, S.; Hayakawa, T.; Nishi,
T.; Watanabe, Y.; Toru, T. Tetrahedron 2001, 6703–6711.
JA8077686
9
J. AM. CHEM. SOC. VOL. 131, NO. 2, 2009 421