Alkynes as synthetic equivalents to stabilized wittig reagents: Intra- and intermolecular carbonyl olefinations catalyzed by Ag(I), BF3, and HBF4

Article abstract of DOI:10.1021/ol050838x

(Chemical Equation Presented) The first use of cationic silver (AgSbF ₄) as a catalyst for intra- and intermolecular alkyne - carbonyl coupling to form conjugated enones is described, and a comparison to corresponding Bronsted acid (HBF₄

Full text of DOI:10.1021/ol050838x

ORGANIC
LETTERS
2005
Vol. 7, No. 12
2493-2495
Alkynes as Synthetic Equivalents to
Stabilized Wittig Reagents: Intra- and
Intermolecular Carbonyl Olefinations
Catalyzed by Ag(I), BF3, and HBF4
Jong Uk Rhee and Michael J. Krische*
Department of Chemistry and Biochemistry, UniVersity of Texas at Austin,
Austin, Texas 78712
mkrische@mail.utexas.edu
Received April 16, 2005
ABSTRACT
The first use of cationic silver (AgSbF4) as a catalyst for intra- and intermolecular alkyne−carbonyl coupling to form conjugated enones is
described, and a comparison to corresponding Brønsted acid (HBF4) and Lewis acid (BF3) catalyst systems is made. Notably, intermolecular
coupling proceeds stereoselectively to afford the corresponding trisubstituted enones as single geometrical isomers. This transformation
represents a completely atom economical alternative to the use of stabilized Wittig reagents in carbonyl olefination and may be viewed as a
formal alkyne−carbonyl metathesis.
Despite tremendous advances in transition metal-catalyzed
alkene-alkene, alkene-alkyne, and alkyne-alkyne metath-
esis,1 related metal-catalyzed metatheses of carbonyl partners
are far less developed.2,3 The most broadly utilized method
for carbonyl olefination is the Wittig reaction. However,
many commonly employed variants of the Wittig reaction
suffer due to the stoichiometric production of triphenylphos-
phine oxide. In view of this deficiency, we were inspired by
reports of Brønsted and Lewis acid-catalyzed cyclizations
of acetylenic ketones to afford conjugated enones: a formal
alkyne-carbonyl metathesis.4-6 In this account, we report
the first late transition metal catalyst for formal alkyne-
(3) For selected examples of intramolecular alkylidene-mediated alkene-
carbonyl metathesis, see: (a) Fu, G. C.; Grubbs, R. H. J. Am. Chem. Soc.
1993, 115, 3800. (b) Stille, J. R.; Grubbs, R. H. J. Am. Chem. Soc. 1986,
108, 3800. (c) Nicalaou, K. C.; Posteema, M. H. D.; Claiborne, C. F. J.
Am. Chem. Soc. 1996, 118, 1565.
(4) For examples of the catalytic cyclization of acetylenic ketones, see:
(a) Harding, C. E.; Hanack, M. Tetrahedron Lett. 1971, 12, 1253. (b) Balf,
R. J.; Rao, B.; Weiler, L. Can. J. Chem. 1971, 49, 3135. (c) Hanack, M.;
Harding, C. E.; Derocque, J. Chem. Ber. 1972, 105, 421. (d) Lange, G. L.;
Hall, T.-W. J. Org. Chem. 1974, 39, 3819. (e) Harding, C. E.; Stanford, G.
R. J. Org. Chem. 1989, 54, 3054. (f) Harding, C. E.; King, S. L. J. Org.
Chem. 1992, 57, 883. (g) Sisko, J.; Balog, A.; Curran, D. P. J. Org. Chem.
1992, 57, 4341. (h) Grunwell, J. R.; Wempe, M. F.; Mitchell, J.; Grunwell,
J. R. Tetrahedron Lett. 1993, 34, 7163. (i) Balog, A.; Curran, D. P. J. Org.
Chem. 1995, 60, 337. (j) Balog, A.; Geib, S. J.; Curran, D. P. J. Org. Chem.
1995, 60, 345. (k) Wempe, M. F.; Grunwell, J. R. J. Org. Chem. 1995, 60,
2714. (l) Wempe, M. F.; Grunwell, J. R. Tetrahedron Lett. 2000, 41, 6709.
(1) For selected reviews, see: (a) Grubbs, R. H. Tetrahedron 2004, 60,
7117. (b) Diver, S. T.; Giessert, A. J. Chem. ReV. 2004, 104, 1317. (c)
Deiters, A.; Martin, S. F. Chem. ReV. 2004, 104, 2199. (d) Connon, S. J.;
Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900. (e) Schrock, R. R.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592. (f) Hoveyda, A.
H.; Schrock, R. R. Chem. Eur. J. 2001, 7, 945. (g) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18. (h) Furstner, A. Angew. Chem., Int.
Ed. 2000, 39, 3012. (i) Schrock, R. R. Tetrahedron 1999, 55, 8141.
(2) For selected reviews encompassing carbonyl olefinations that are
postulated to occur through the intermediacy of metal carbene complexes,
see: (a) Nenajdenko, V. G.; Korotchenko, V. N.; Shastin, A. V.; Balenkova,
E. S. Russ. Chem. Bull., Int. Ed. 2004, 53, 1034. (b) Kuhn, F. E.; Santos,
A. M. Mini-ReV. Org. Chem. 2004, 1, 55. (c) Breit, B. Angew. Chem., Int.
Ed. 1998, 37, 453. (d) Ephritikhine, M. Chem. Commun. 1998, 2549. (e)
McMurry, J. E. Chem. ReV. 1989, 89, 1513.
10.1021/ol050838x CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/11/2005

Scheme 1a
a Left: Alkyne-carbonyl metathesis via alkyne or aldehyde complexation-initiated oxete formation. Right: 13C NMR spectroscopic
analysis of an equimolar mixture of 1-phenyl propyne and isobutyraldehyde reveals a substantial upfield shift of the alkyne carbon signals
upon addition of AgSbF6, while signals corresponding to isobutyraldehyde exhibit negligible change.
carbonyl metathesis. Specifically, upon exposure to cationic
Ag(I) salts, alkynes and aldehydes undergo intra- and
intermolecular alkyne-carbonyl coupling to provide trisub-
stituted enones. Notably, in the case of intermolecular
coupling, complete levels of regio- and stereocontrol are
observed. Additionally, as part of a broad effort to develop
the use of alkynes as atom economical alternatives to Wittig-
type reagents, comparisons are made with related Brønsted
acid (HBF4)- and Lewis acid (BF3‚OEt2)-catalyzed processes.
Brønsted and Lewis acid-catalyzed couplings of acetylenic
carbonyl compounds are likely initiated through activation
of the carbonyl partner by complexation of oxygen non-
bonding electrons. While transannular ring closures of this
type are unlikely to proceed through the intermediacy of anti-
Bredt oxetes,4k,l simple nontransannular cyclizations may
involve a mechanism involving stepwise oxete formation
followed by cycloreversion to provide the conjugated enone.
Such a mechanism is consistent with isotopic labeling studies
on the acid-catalyzed rearrangement of 6-octyn-2-one in the
presence of H218O, which occurs without 18O-incorporation.4f
The independent preparation of oxetes, typically under
photochemical conditions, and their authenticated cyclo-
reversion lends additional support to this mechanism.7
An alternative catalytic mechanism potentially promoted
through the use of a “carbophillic” Lewis acid involves
alkyne complexation-initiated oxete formation (Scheme 1,
right). Predicated on the basis of the well-established ability
of silver(I) salts to form strong π-complexes with alkene and
alkyne partners,8,9 the intramolecular silver(I)-catalyzed me-
tathesis of acetylenic aldehyde 3a was explored. Gratifyingly,
exposure of 3a to substoichiometric quantities of AgSbF6
(10 mol %) in dichloroethane at ambient temperature led to
a nearly quantitative isolated yield of the trisubstituted enone
3b. Withstanding changes in temperature, these conditions
proved to be applicable across a diverse set of acetylenic
aldehydes 1a-9a, enabling formation of both five- and six-
membered ring products. Additionally, as demonstrated by
the cyclization of 10a, acetylenic ketones in the form of 1,3-
diones also participate in the reaction. In each case, Lewis
(BF3‚OEt2)- and Brønsted acid (HBF4)-catalyzed reactions
also were explored. For certain substrates, the silver(I)
catalyst is more effective (5a, 6a, 7a, 9a, 10a), while in other
cases (1a, 2a) use of the Lewis or Brønsted acid catalyst is
preferred (Table 1).
Intermolecular carbonyl metathesis of aliphatic and aro-
matic aldehydes (300 mol %) with 1-phenyl-1-propyne (100
mol %) affords enones 11b-14b. Complete regioselection
is observed. Additionally, the trisubstituted alkenes appear
as single geometrical isomers. Under a range of related
conditions, terminal alkynes such as phenylacetylene provide
dramatically reduced yields of the analogous 1,2-disusbituted
enone products (Table 2).
Addition of AgSbF6 to an equimolar solution of 1-phenyl-
1-propyne and isobutyraldehyde results in significant upfield
(5) Intermolecular alkyne-aldehyde metathesis has been achieved using
stoichiometric Lewis acid promoters: (a) Viswanathan, G. S.; Li, C.-J.
Tetrahedron Lett. 2002, 43, 1613. (b) Hayashi, A.; Yamaguchi, M.; Hirama,
M. Synlett 1995, 195.
(6) A single example of catalytic intermolecular alkyne-aldehyde
metathesis has been described. This Yb(OTf)3-catalyzed process enables
the formation of chalcones from aromatic alkynes: Curini, M.; Epifano,
F.; Maltese, F.; Rosati, O. Synlett 2003, 552.
(7) For the isolation and cycloreversion of oxetes, see: (a) Friedrich, L.
E.; Lam, P. Y.-S. J. Org. Chem. 1981, 46, 306. (b) Martino, P. C.; Shevlin,
P. B. J. Am. Chem. Soc. 1980, 102, 5429. (c) Friedrich, L. E.; Bower, J. D.
J. Am. Chem. Soc. 1973, 95, 6869. (d) Friedrich, L. E.; Schuster, G. B. J.
Am. Chem. Soc. 1971, 93, 4602. (e) Middleton, W. J. J. Org. Chem. 1965,
30, 1307.
(8) For reviews encompassing Ag(I)-alkene complexes, see: (a) Bennett,
M. A. Chem. ReV. 1962, 62, 611. (b) Quinn, H. W.; Tsai, J. H. AdV. Inorg.
Radiochem. 1969, 12, 217. (c) Beverwijk, C. D. M.; Van der Kerk, G. J.
M.; Leusink, A. J.; Noltes, J. G. Organomet. Chem. ReV. 1970, 75, 215.
(d) Herberhold, M. In Metal-π-Complexes; Elsevier: Amsterdam, 1972;
Vol. 2, pp 232-256.
(9) For selected examples of Ag(I)-alkyne complexes characterized by
single-crystal X-ray diffraction analysis, see: (a) Ferrara, J. D.; Djebli, A.;
Tessier-Youngs, C.; Youngs, W. J. J. Am. Chem. Soc. 1988, 110, 647. (b)
Gleiter, R.; Karcher, M.; Kratz, D.; Ziegler, M. L.; Nuber, B. Chem. Ber.
1990, 123, 1461. (c) Meier, H.; Dai, Y. Tetrahedron Lett. 1993, 34, 5277.
(d) Nishinaga, T.; Kawamura, T.; Komatsu, K. Chem. Commun. 1998, 2263.
(e) Schulte, P.; Behrens, U. J. Organomet. Chem. 1998, 563, 235. (f) Chi,
K.-M.; Lin, C.-T.; Peng, S.-M.; Lee, G.-H. Organometallics 1996, 15, 2660.
2494
Org. Lett., Vol. 7, No. 12, 2005

Table 1. Intramolecular Alkyne-Carbonyl Coupling Catalyzed
by Ag(I)SbF6, HBF4, and BF3‚OEt2
Table 2. Intermolecular Alkyne-Carbonyl Coupling Catalyzed
by Ag(I)SbF6, HBF4, and BF3‚OEt2
a
a
a See Supporting Information for detailed experimental procedures.
Brønsted acids that may catalyze enone formation, the
olefination proceeds readily in the presence of homogeneous
and heterogeneous bases such as i-Pr2NEt, 2,6-di-tert-
butylpyridine, and K2CO3 (Scheme 1, left).
In summary, AgSbF6 catalyzes intra- and intermolecular
alkyne-carbonyl coupling to form conjugated enones. A
comparison to corresponding Brønsted acid (HBF4) and
Lewis acid (BF3) catalyst systems reveals that the AgSbF6-
catalyzed process is moderately more efficient in certain
cases. Notably, intermolecular coupling proceeds stereose-
lectively to afford the corresponding trisubstituted enones
as single geometrical isomers. This transformation represents
a completely atom economical alternative to the use of
stabilized Wittig reagents in carbonyl olefination and may
be viewed as a formal alkyne-carbonyl metathesis. Future
studies will focus on the development of improved second-
generation catalyst systems.
Acknowledgment. Acknowledgment is made to the
Research Corporation Cottrell Scholar Award (CS0927), the
Alfred P. Sloan Foundation, the Camille and Henry Dreyfus
Foundation, the Robert A. Welch Foundation, Eli Lilly, and
Merck for partial support of this research.
a See Supporting Information for detailed experimental procedures.
shifts of the alkyne signals in the 13C NMR spectra. The
aldehyde chemical shifts remain essentially unchanged.
While these data suggest alkyne-initiated oxete formation, a
Curtin-Hammett scenario in which coupling occurs through
the intermediacy of small quantities of silver-aldehyde
complex cannot be discounted. While it is possible that
AgSbF6 may react with residual moisture to produce
Supporting Information Available: Spectral data for all
new compounds (1H NMR, 13C NMR, IR, HRMS). This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL050838X
Org. Lett., Vol. 7, No. 12, 2005
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