N-Heterocyclic Carbene Boronic Esters (NHC-BE) for the Formation of Electron-Withdrawing Benzoin Products

The benzoin reaction has been widely investigated in the field of organocatalysis. This reaction was originally discovered by Wöhler and Liebig in 1832 using cyanide as a catalyst.¹ In recent years, numerous research groups have focused on developing enantioselective routes to form benzoin products using N-Heterocyclic Carbene (NHC) catalysts in the presence of an appropriate base.²

In 2009 Zeitler, Connon and colleagues reported the most efficient conditions for the enantioselective benzoin reaction to date using catalytic amount of pentafluorophenyl-substituted NHC (4 mol %) and Rb₂CO₃ in THF (1.1M) at 0 ^oC to room temperature.³ However, to date, the enantioselective benzoin reaction has not been extensively studied with electron-withdrawing substituted aryl-aldehydes. Herein, we wish to demonstrate our new concept for enantioselective benzoin reaction catalyzed by NHC (6 mol%) in the presence of Rb₂CO₃ (4 mol%), MS, and boronic acid (7.2 mol%) in dry THF (1.1M) at 20 ^oC.⁴ These new conditions afforded highly enantioselective benzoin reactions for electron-withdrawing substrates (F, Cl, Br, I, CN, CO₂Me, CF₃ and NO₂) in the range of 86-97 %ee with good yields.

Figure 1. Enantioselective benzoin reaction catalyzed by NHC-BE

References

1. Wöhler, F.; Liebig, J. Ann. Der. Pharm. 1832, 3, 249-287.
2. Flanigan, D. M.; Michailidis, F-R.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307-9387.
3. Baragwanath, L.; Rose, C. A.; Zeitler, K.; Connon, S. J. J. Org. Chem. 2009, 74, 9214-9217.
4. Neel, A. J.; Milo, A.; Sigman, M. S.; Toste, F. D. J. Am. Chem. Soc. 2016, 138, 3863-3875.