Willis et al.
aldehyde and alkene functional groups has generally been
unsuccessful as a strategy to prepare larger ring systems,
although the use of diene-9 and cyclopropane-containing10
substrates has allowed access to several enlarged ring structures.
Intermolecular reactions are more challenging, with the use of
high temperatures and/or pressures of CO or ethene often being
needed to limit decarbonylation.11 The synthetic utility of many
systems is also limited, with aromatic aldehydes and simple
unfunctionalized alkenes being the most commonly employed
substrates. An exception to this is the method developed by
Brookhart, who has reported the combination of a range of alkyl
and aryl aldehydes with electron-rich vinyl silanes using Co(I)
complexes at ambient temperatures.12 Jun has been able to utilize
alkyl and aryl aldehydes in combination with simple alkenes
using catalytic Rh(I) and catalytic 2-amino-picoline at elevated
temperatures (generally >100 °C).13 The Jun methodology
involves the in situ generation of aldimine intermediates, and
it is proposed that chelation-stabilization of the subsequently
formed iminoacyl-rhodium species is responsible for the success
of these systems.
that could employ both alkene and alkyne substrates, tolerate a
variety of functional groups, operate under mild reaction
conditions, and employ low catalyst loadings.19
Results and Discussion
Despite the high temperatures needed in the Jun chemistry,
the ability to employ a range of aldehydes in HA reactions,
together with encouraging studies from Suggs,20 Suemune,21 and
Bendorf,22 suggested that chelation stabilization of rhodium-
acyls offered the possibility of developing a more broadly
applicable HA system. Our goals were to define a range of
aldehydes bearing coordinating substituents that would form
stable chelated intermediates and still allow the HA reaction to
proceed under mild conditions (Scheme 2). Importantly, for the
process to be synthetically useful, we reasoned that the
coordinating group must offer the possibility of further func-
tionalization or derivatization after the HA event. For similar
reasons we wished to employ functionalized alkenes with the
hope of producing more valuable products and settled on the
use of enones, with synthetically useful 1,4-dicarbonyl com-
pounds the target.23 The transformation could then be considered
as a Rh(I)-catalyzed Stetter reaction.24
Alkyne hydroacylation has been less studied,14 although Fu
has shown that Rh-catalyzed intramolecular alkyne HA can be
used to prepare cyclopentenones via the trans-addition of acyl-
rhodium species to alkynes.15 Desymmetrization methods have
been used to allow the enantioselective synthesis of similar
products.16 More recently, Tanaka has employed 5- and
6-alkynals to access R-alklylidene-cyclopentanones and cyclo-
hexanones.17 Jun has also demonstrated that his aldimine
methods can be used to effect intermolecular alkyne HA.18
The focus of the present research was the development of
synthetically useful intermolecular hydroacylation methodology
SCHEME 2
We elected to evaluate aldehyde substrates in addition
reactions with methyl acrylate (Table 1). With the possible
synthetic utility in mind we first evaluated aldehydes bearing
ether substituents as the coordinating group. The reaction
between methyl acrylate and â-benzyloxypropanal, employing
Wilkinson’s complex as the catalyst, resulted in decarbonylation
(entry 1).23 Switching the catalyst to the cationic complex [Rh-
(dppe)]ClO4, used extensively in intramolecular systems,5
resulted in no reaction, attributed to catalyst deactivation due
to the electron-rich aryl group of the benzyl ether (entry 2).
Using a methyl ether resulted in a small amount of the desired
product, but decarbonylation was by far the major pathway
(entry 3). However, the use of the corresponding methyl sulfide
delivered 36% of the HA adduct together with a side-product
originating from Tischenko-like processes (entry 4).25 Employ-
ing dichloroethane (DCE) as solvent and increasing the reaction
temperature to 60 °C achieved a 96% conversion to product
(7) For examples of enantioselective cyclisations, see; (a) Bosnich, B.
Acc. Chem. Res. 1998, 31, 667 and references therein. (b) Ducray, P.;
Rousseau, B.; Mioskowski, C. J. Org. Chem. 1999, 64, 3800. (c) Tanaka,
M.; Imai, M.; Fujio, M.; Sakamoto, E.; Takahashi, M.; Eto-Kato, Y.; Wu,
X. M.; Funakoshi, K.; Sakai, K.; Suemune, H. J. Org. Chem. 2000, 65,
5806 and references therein. (d) Kundu, K.; McCullagh, J. V.; Morehead,
A. T., Jr. J. Am. Chem. Soc. 2005, 127, 16042.
(8) Campbell, R. E., Jr.; Miller, R. G. J. Organomet. Chem. 1980, 186,
C27. See also ref 6a.
(9) Sato, Y.; Oonishi, Y.; Mori, M. Angew. Chem., Int. Ed. 2002, 41,
1218.
(10) Aloise, A. D.; Layton, M. E.; Shair, M. D. J. Am. Chem. Soc. 2000,
122, 12610.
(11) For Rh-based systems used in combination with CO or ethylene
atmospheres, see: (a) Schwartz, J.; Cannon, J. B. J. Am. Chem. Soc. 1974,
96, 4721. (b) Vora, K. P.; Lochow, C. F.; Miller, R. G. J. Organomet.
Chem. 1980, 192, 257. (c) Isnard, P.; Denise, B.; Sneeden, R. P. A.; Cognio,
J. M.; Dural, P. J. Organomet. Chem. 1982, 240, 285. (d) Vora, K. P. Synth.
Commun. 1983, 13, 99. (e) Marder, T. B.; Roe, D. C.; Milstein, D.
Organometallics 1988, 7, 1451. For Ru based systems, see; (f) Kondo, T.;
Tsuji, Y.; Watanabe, Y. Tetrahedron Lett. 1987, 28, 6229. (g) Kondo, T.;
Akazome, M.; Tsuji, Y.; Watanabe, Y. J. Org. Chem. 1990, 55, 1286. (h)
Kondo, T.; Hiraishi, N.; Morisaki, Y.; Wada, K.; Watanabe, Y.; Mitsudo,
T.-A. Organometallics 1998, 17, 2131.
(19) (a) Willis, M. C.; McNally, J. S.; Beswick, P. J. Angew. Chem.,
Int. Ed. 2004, 43, 340. (b) Willis, M. C.; Randell-Sly, H. E.; Woodward,
R. L.; Currie, G. S. Org. Lett. 2005, 7, 2249.
(20) (a) Suggs, J. W. J. Am. Chem. Soc. 1978, 100, 640. (b) Suggs, J.
W. J. Am. Chem. Soc. 1979, 101, 489.
(12) (a) Lenges, C. P.; Brookhart, M. J. Am. Chem. Soc. 1997, 119, 3165.
(b) Lenges, C. P.; White, P. S.; Brookhart, M. J. Am. Chem. Soc. 1998,
120, 6965. Also see ref 11a.
(13) (a) Jun, C.-H.; Lee, D.-Y.; Lee, H.; Hong, J.-B. Angew. Chem., Int.
Ed. 2000, 39, 3070. (b) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur.
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and references therein.
(14) (a) Tsuda, T.; Kiyoi, T.; Saegusa, T. J. Org. Chem. 1990, 55, 2554.
(b) Kokubo, K.; Matsumasa, K.; Nishinaka, Y.; Miura, M.; Nomura, M.
Bull. Chem. Soc. Jpn. 1999, 72, 303.
(15) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 11492.
(16) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 10296.
(17) Takeishi, K.; Sugishima, K.; Sasaki, K.; Tanaka, K. Chem. Eur. J.
2004, 10, 5681.
(18) Jun, C.-H.; Lee, H.; Hong, J.-B.; Kwon, B.-I. Angew. Chem., Int.
Ed. 2002, 41, 2146.
(21) (a) Tanaka, M.; Imai, M.; Yamamoto, Y.; Tanaka, K.; Shimowatari,
M.; Nagumo, S.; Kawahara, N.; Suemune, H. Org. Lett. 2003, 5, 1365. (b)
Imai, M.; Tanaka, M.; Tanaka, K.; Yamamoto, Y.; Imai-Ogata, N.;
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(22) Bendorf, H. D.; Colella, C. M.; Dixon, E. C.; Marchetti, M.;
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(23) Willis, M. C.; Sapmaz, S. Chem. Commun. 2001, 2558.
(24) Stetter, H.; Kuhlmann, H. Org. React. 1991, 40, 407.
(25) For the isolation of similar Tischenko products, see: (a) Bergens,
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