ORGANIC
LETTERS
2011
Vol. 13, No. 21
5824–5826
Palladium-Catalyzed 1,4-Addition of
Diarylphosphines to r,β-Unsaturated
Aldehydes
Yun-Rong Chen and Wei-Liang Duan*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Received September 7, 2011
ABSTRACT
A highly stereoselective asymmetric 1,4-addition of diarylphosphines to R,β-unsaturated aldehydes catalyzed by a bis(phosphine) pincerÀPd
complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 98% ee) under mild conditions. The
application of the current method to the synthesis of enantiopure bisphosphine and its pincerÀPd complex has also been demonstrated.
Enantioselective conjugate addition is one of the most
important processes in asymmetric catalysis.1 It comprises
the reactions of various electron-deficient alkenes with
nucleophiles to furnish valuable optically active com-
pounds. In this process, R,β-unsaturated aldehydes have
been frequently used as electrophilic components to react
with various carbon,1bÀd nitrogen,1g sulfur,1h and oxygen1i
nucleophiles, because of the versatility of their carbonyl
group for further functionalization. On the other hand, the
asymmetric addition of phosphorus nucleophiles to R,
β-unsaturated aldehydes have been scarcely investigated,2,3
although the obtained phosphorus adducts can be very
useful precursors for the preparation of chiral phosphine
ligands for asymmetric catalysis.4 Recently, Melchiorre
and Cordova independently reported the first asymmetric
conjugate addition of diphenylphosphine to R,β-unsatu-
rated aldehydes in the presence of proline-derived organo-
catalysts with excellent enantioselectivities and yields.5 Aside
from these two examples, no other catalytic methods were
reported in the above reaction. Recently, we successfully
(1) For reviews on asymmetric 1,4-addition, see: (a) Catalytic
ꢀ
Asymmetric Conjugate Reactions; Cordova, A., Eds.; Wiley-VCH: Weinheim,
2010. For reviews on metal-catalyzed asymmetric 1,4-addition, see: (b)
Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (c) Miyaura, N.
€
Synlett 2009, 2039. (d) Christoffers, J.; Koripelly, G.; Rosiak, A.; Rossle,
M. Synthesis 2007, 1279. For reviews on organocatalytic asymmetric
1,4-addition, see:(e) Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701. (f)
Vicario, J. L.; Badıa, D.; Carrillo, L. Synthesis 2007, 2065. (g) Enders,
D.; Wang, C.; Liebich, J. X. Chem.;Eur. J. 2009, 15, 11058. (h) Enders,
(4) For reviews on catalytic asymmetric synthesis of chiral phos-
phanes, see: (a) Glueck, D. S. Chem.;Eur. J. 2008, 14, 7108. (b) Glueck,
D. S. Synlett 2007, 2627. (c) Harvey, J. S.; Gouverneur, V. Chem.
Commun. 2010, 7477. For leading examples, see:(d) Kovacik, I.; Wicht,
D. K.; Grewal, N. S.; Glueck, D. S.; Incarvito, C. D.; Guzei, I. A.;
Rheingold, A. L. Organometallics 2000, 19, 950. (e) Scriban, C.;Kovacik,
I.; Glueck, D. S. Organometallics 2005, 24, 4871. (f) Bartoli, G.; Bosco,
M.; Carlone, A.; Locatelli., M.; Mazzanti, A.; Sambri, L.; Melchiorre, P.
Chem. Commun. 2007, 722. (g) Sadow, A. D.; Haller, I.; Fadini, L.; Togni,
A. J. Am. Chem. Soc. 2004, 126, 14704. (h) Sadow, A. D.; Togni, A. J. Am.
Chem. Soc. 2005, 127, 17012. (i) Nielsen, M.; Jacobsen, C. B.; Jorgensen,
K. A. Angew. Chem., Int. Ed. 2011, 50, 3211.
(5) (a) Carlone, A.; Bartoli, G.; Bosco, M.; Sambri, L.; Melchiorre, P.
Angew. Chem., Int. Ed. 2007, 46, 4504. (b) Ibrahem, I.; Rios, R.; Vesely,
J.; Hammar, P.; Eriksson, L.; Himo, F.; Cordova, A. Angew. Chem., Int.
Ed. 2007, 46, 4507. (c) Ibrahem, I.; Hammar, P.; Vesely, J.; Rios, R.;
Eriksson, L.; Cordova, A. Adv. Synth. Catal. 2008, 350, 1875.
€
D.; Luttgen, K.; Narine, A. A. Synthesis 2007, 959. (i) Nising, C. F.;
€
Brase, S. Chem. Soc. Rev. 2008, 37, 1218.
(2) For a review of 1,4-addition reaction of phosphorus nucleophiles
to electron-deficient olefins, see: Enders, D.; Saint-Dizier, A.; Lannou,
M,-I.; Lenzen, A. Eur. J. Org. Chem. 2006, 29.
(3) For catalytic asymmetric 1,4-addition of substitited phosphines
or phosphine oxides to R,β-unsaturated carbonyl compounds, see: (a)
Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. J. Am. Chem. Soc. 2010,
132, 5562. (b) Zhao, D.; Mao, L.; Wang, Y.; Yang, D.; Zhang, Q.; Wang,
R. Org. Lett. 2010, 12, 1880. (c) Zhao, D.; Mao, L.; Yang, D.; Wang, R.
J. Org. Chem. 2010, 75, 6756. (d) Wen, S.; Li, L.; Wu, H.; Yu, F.; Liang,
X.; Ye, J. Chem. Commun. 2010, 4806. (e) Huang, Y.; Pullarkat, S. A.; Li,
L.; Leung, P.-H. Chem. Commun. 2010, 6950. (f) Russo, A.; Lattanzi, A.
Eur. J. Org. Chem. 2010, 6736. (g) Yang, M.-J.; Liu, Y.-J.; Gong, J.-F.;
Song, M.-P. Organometallics 2011, 30, 3793. (h) Du, D.; Duan, W.-L.
Chem. Commun. 2011, 47, 11101.
r
10.1021/ol2024339
Published on Web 10/06/2011
2011 American Chemical Society