Table 2 Optimization of intramolecular hydroacylation conditionsa
hydroacylation of alkenes. The efficiency of the catalyst
originates from an innovative bifunctional ligand, which most
likely acts through reversible substrate binding thus facilitating
C–H activation, preventing decarbonylation and controlling
chemoselectivity. Future studies will address the mechanism
as well as further applications of bifunctional ligand L in
homogeneous catalysis.
This work was supported by the DFG, the International
Research Training Group ‘‘Catalysts and Catalytic Reactions
for Organic Synthesis’’ (IRTG 1038), the Fonds der
Chemischen Industrie, the Krupp Foundation (Alfried Krupp
Award for young university teachers to B.B.) and the
Humboldt Foundation (postdoctoral fellowship to N.R.V.).
We thank Umicore, BASF and Wacker for generous gifts of
chemicals.
Entry [Rh]/Ligand (1/1) (mol%) Conditions
Isolated yield (%)
1
2b
3
4
5
6
7
8
9
[Rh(PPh3)3Cl] (10)
[Rh(PPh3)3Cl] (10)
24 h, 150 1C 22
24 h, 150 1C o5
24 h, 150 1C 99
2 h, 150 1C
2 h, 150 1C
1 h, 150 1C
2 h, 150 1C
6 h, 150 1C
1 h, 150 1C
[Rh(COD)Cl]2/L (5)
[Rh(COD)Cl]2/L (5)
[Rh(COD)Cl]2/L (2.5)
[Rh(COD)2]BF4/L (5)
[Rh(COD)2]BF4/L (2.5)
[Rh(COD)2]BF4/L (0.5)
[Rh(COD)2]BF4/L0 (5)
95
46
96
84
67
42
Notes and references
a
Reaction conditions: 0.22 mmol of o-vinylbenzaldehyde, the rhodium
source and the ligand were heated in 200 mL of toluene in a closed
1 B. M. Trost, Acc. Chem. Res., 2002, 35, 695–705.
b
2 For reviews on hydroacylation reactions see: B. Bosnich, Acc.
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H. Suemune, Curr. Org. Chem., 2003, 7, 353–367; M. C. Willis,
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Schlenk vessel. 2-Amino-3-picoline/[Rh(PPh3)3Cl] = 4/1 in 200 mL of
toluene.
3 For general strategies on avoiding decarbonylation in hydro-
acylation reactions see: R. C. Larock, K. Oertle and
G. F. Potter, J. Am. Chem. Soc., 1980, 102, 190–197; K. P. Vora,
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M. Marchetti, A. N. Matukonis, J. D. Musselman and
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M. Tanaka, K. Tanaka, Y. Yamamoto, N. Imai-Ogata,
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5 C.-H. Jun, H. Lee and J.-B. Hong, J. Org. Chem., 1997, 62,
1200–1201; Y. J. Park, J.-W. Park and C.-H. Jun, Acc. Chem.
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2504–2507.
7 For other reversibly and covalent bound directing groups see:
T. E. Lightburn, M. T. Dombrowski and K. L. Tan, J. Am. Chem.
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Scheme 3 Intramolecular hydroacylation of o-vinylbenzaldehyde
derivatives (areaction time = 4 h).
With a highly active catalyst system in hand, (Table 2, entry
6), we investigated the scope of our protocol by diversifying
the backbone of o-vinylbenzaldehyde (see the ESIw for the
synthesis and characterization of the substrates) (Scheme 3).
The catalyst tolerates electron donating, neutral as well as
electron withdrawing substituents at the aromatic nucleus. A
wide range of functional groups including carboxylic esters,
halogens (chlorine and fluorine), nitro groups as well as a free
phenol function is compatible with the reaction conditions
and excellent yields are obtained. Conversely, employing
2-vinylpyridine-3-carbaldehyde did not show any reactivity,
and the starting material was recovered quantitatively: the
substrate may itself act as a competitive ligand for L at the
rhodium center thus preventing the turnover.
J. M. Caffyn, J. P. H. Charmant, L. C. Lewis-Alleyne, P. D. Long,
D. Polo-Ceron and S. Prashar, Chem. Commun., 2008, 990–992.
´
8 H. Sugimoto, Pure Appl. Chem., 1999, 71, 2031–2037.
9 D. Fairlie and B. Bosnich, Organometallics, 1988, 7, 936–945.
10 K. Kundu, J. McCullagh and A. T. Morehead, J. Am. Chem. Soc.,
2005, 127, 16042–16043.
In summary, we have developed a new catalyst system
that allows for both efficient inter- and intramolecular
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6635–6637 6637