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Asymmetric Conjugate Addition

By: William Sommer, Aldrich ChemFiles 2008, 8.6, 11.

Aldrich ChemFiles 2008, 8.6, 11.

In the past 5 years, chiral diene ligands have surfaced for a variety of asymmetric transformations. Hayashi1 and Carreira2 pioneered this field by synthesizing chiral diene ligands that formed stable complexes with metals and exerted high catalytic activity as well as high enantioselectivity. Carreira and co-workers reported the asymmetric synthesis of 3,3-diarylpropanals using a chiral bicyclo[2.2.2]octadiene as a ligand with a rhodium complex.3 This new synthesis provides access to important building blocks that are otherwise not readily available. The reaction offers a general synthesis of a wide variety of diaryl propanals. This rhodium catalyzed conjugate addition of aryl boronic acids is both chemo- and regio-selective wherein conjugate addition is favored over 1,2-addition. In a typical reaction, 3.3 mol% of the ligand and 3 mol% of the rhodium complex in a mixture of methanol and water is required. Good yields and selectivity were reported with both electron rich and electron poor boronic acids and various cinamaldehydes (Scheme 1).

Scheme 1.(672254)

Following on the work of Carreira and Hayashi, Feng et al. developed a new type of diene ligand based on a nonbridged bicyclo[3.3.0]octadiene framework.4 The two cis-fused cyclopentadiene rings generate a wedge structure providing a chiral environment giving excellent enantiocontrol in the reaction when coordinated to the metal. The activity of the ligand was evaluated in the asymmetric arylation of N-tosylarylimines with aryl boronic acids. Using 3 mol% of [RhCl(C2H4)2]2 and 3.3 mol% of the ligand, a variety of aryl boronic acids and N-tosylarylimines were screened. It is important to note that the reactants screened had diverse steric and electronic properties and showed little influence on the yield and enantioselectivity of the reaction (Scheme 2).

Scheme 2.

To expand the scope of this new ligand, Feng et al. investigated the asymmetric 1,4-addition of aryl boronic acids to α,β-unsaturated carbonyl compounds.5 Using 2.5 mol% of [RhCl(C2H4)2]2 and 5.5 mol% of the ligand, a variety of sterically hindered, electron donating and electron withdrawing substituted aryl boronic acids were screened (Scheme 3). The nature of the substituant on the aryl boronic acid had no influence on the yield and the enantioselectivity.

Scheme 3.

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  1. Hayashi, T. et al. J. Am. Chem. Soc. 2003, 125, 11508.
  2. Fischer, C. et al. J. Am. Chem. Soc. 2004, 126, 1628.
  3. Paquin, J. -F. et al. J. Am. Chem. Soc. 2005, 127, 10850.
  4. Wang, Z., -Q. Et al. J. Am. Chem. Soc. 2007, 129, 5336.
  5. Feng, C. -G. Et al. Chem. Asian. J. 2008, ASAP

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