Carreira DOLEFIN Ligands

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

we are pleased to offer both enantiomers of this effective ligand for your research purposes.

References

1. Mauleón P, Carretero JC. 2004. Rhodium-Catalyzed Enantioselective Conjugate Addition of Organoboronic Acids to ?,?-Unsaturated Sulfones. Org. Lett.. 6(18):3195-3198. https://doi.org/10.1021/ol048690p

2. Bolshan Y, Chen C, Chilenski JR, Gosselin F, Mathre DJ, O'Shea PD, Roy A, Tillyer RD. 2004. Nucleophilic Displacement at Benzhydryl Centers:? Asymmetric Synthesis of 1,1-Diarylalkyl Derivatives. Org. Lett.. 6(1):111-114. https://doi.org/10.1021/ol0361655

3. Duursma A, Hoen R, Schuppan J, Hulst R, Minnaard AJ, Feringa BL. 2003. First Examples of Improved Catalytic Asymmetric C?C Bond Formation Using the Monodentate Ligand Combination Approach. Org. Lett.. 5(17):3111-3113. https://doi.org/10.1021/ol035106o

4. Lautens M, Rovis T. 1997. General Strategy toward the Tetrahydronaphthalene Skeleton. An Expedient Total Synthesis of Sertraline. J. Org. Chem.. 62(16):5246-5247. https://doi.org/10.1021/jo971115x

5. 2004. Readily Available [2.2.2]-Bicyclooctadienes as New Chiral Ligands for Ir(I):  Catalytic, Kinetic Resolution of Allyl Carbonates. J. Am. Chem. Soc.. 126(6):1628-1629. https://doi.org/10.1021/ja0390707

6. Defieber C, Paquin J, Serna S, Carreira EM. 2004. Chiral [2.2.2] Dienes as Ligands for Rh(I) in Conjugate Additions of Boronic Acids to a Wide Range of Acceptors. Org. Lett.. 6(21):3873-3876. https://doi.org/10.1021/ol048240x

7. Paquin J, Stephenson CRJ, Defieber C, Carreira EM. 2005. Catalytic Asymmetric Synthesis with Rh?Diene Complexes:? 1,4-Addition of Arylboronic Acids to Unsaturated Esters. Org. Lett.. 7(17):3821-3824. https://doi.org/10.1021/ol051533l

8. Paras NA, MacMillan DWC. 2002. The Enantioselective Organocatalytic 1,4-Addition of Electron-Rich Benzenes to ?,?-Unsaturated Aldehydes. J. Am. Chem. Soc.. 124(27):7894-7895. https://doi.org/10.1021/ja025981p

9. 2005. Asymmetric Synthesis of 3,3-Diarylpropanals with Chiral Diene?Rhodium Catalysts. J. Am. Chem. Soc.. 127(31):10850-10851. https://doi.org/10.1021/ja053270w