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The selective preparation of diarylmethine stereogenic centers is a challenging endeavor in chemical synthesis, especially when there is little differentiation between the two aryl groups. As a result, the methods for the stereoselective synthesis of this motif are rather limited.1 Recent work by Carreira described the use of chiral dienes derived from [2.2.2]bicyclooctadiene as ligands in various asymmetric processes.2 More recently, Carreira has used the ligand 1 in the 1,4-addition of arylboronic acids to α,β-unsaturated carbonyls.
In one report, tert-butyl cinnamate was converted to (S)-tert-butyl 3-(4-methoxyphenyl)-3-phenylpropanoate in the presence of the Rh(I)-1 complex in excellent yield and selectivity (Scheme 1). Similarly, other 3,3-diaryl- and 3-aryl-3-heteroaryl-propanoates were prepared in good to excellent yields and with consistently high enantioselectivity (89-94% ee). Furthermore, from a single enantiomer of the ligand, access to both enantiomers of a product can be achieved simply by switching the aryl acceptor and donor. In this manner, (R)-tert-butyl 3-(4-methoxyphenyl)-3-phenylpropanoate was prepared from phenylboronic acid and tert-butyl 4-methoxycinnamate (Scheme 2).3
The preparation of chiral 3,3-diarylpropanals has recently been achieved by other researchers via an amine-catalyzed addition of aromatic nucleophiles to 3-substituted acrolein derivatives.4 Unfortunately, this method does not work well with electron poor aromatics. However, the Rh(I)-1-catalyzed conjugate addition offers a general route independent of the electronic nature of the aryl groups. The addition of 4-fluorophenylboronic acid to cinnamaldehyde provided the 1,4-adduct in 90% yield and 93% ee (Scheme 3). Again, other substrates maintained high enantioselectivity in the conjugate addition (89-93% ee).5
Sigma-Aldrich is pleased to offer both enantiomers of this effective ligand for your research purposes.
Product Information
| Product # |
Product Name/Description |
Structure |
Add to Cart |
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669490 |
(1R,4R,8R)-5-Benzyl-8-methoxy-1,8-dimethyl-2-(2′-methylpropyl)-bicyclo[2.2.2]octa-2,5-diene
≥98% |
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672254 |
(1S,4S,8S)-5-Benzyl-8-methoxy-1,8-dimethyl-2-(2′-methylpropyl)-bicyclo[2.2.2]octa-2,5-diene
≥98% |
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References:
(1) (a) Mauleón, P.; Carretero, J. C. Org. Lett. 2004, 6, 3195. (b) Bolshan, Y. et al. Org. Lett. 2004, 6, 111. (c) Duursma, A. et al. Org. Lett. 2003, 5, 3111. (d) Lautens, M.; Rovis, T. J. Org. Chem. 1997, 62, 5246.
(2) (a) Fischer, C. et al. J. Am. Chem. Soc. 2004, 126, 1628. (b) Defieber, C. et al. Org. Lett. 2004, 6, 3873.
(3) Paquin, J.-F. et al. Org. Lett. 2005, 7, 3821.
(4) Paras, N. A.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 7894.
(5) Paquin, J.-F. et al. J. Am. Chem. Soc. 2005, 127, 10850.
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