Chiral Phosphoric Acids: Versatile Organocatalysts with Expanding Applications

Introduction

We are proud to offer a suite of BINOL-derived chiral phosphoric acids in our collection of products for asymmetric catalysis. This well established class of chiral Brønsted acid catalysts has been applied to an ever-increasing number of useful transformations.

Figure 1. BINOL-derived Chiral Phosphoric Acids

Advantages

• Alternative to metal catalysts and chiral auxiliaries
• Both enantiomers of catalyst are available
• Relatively low catalyst loading (often 1-5 mol %)
• High selectivity at non-cryogenic reaction temperatures (-30 to 23 °C)

Representative Applications

Reductive Amination
One of the earliest demonstrations of chiral phosphoric acid catalysis is the metal-free reduction of imines with an organic reductant (Hantzsch ester) to give enantioenriched amines.¹

Figure 2. Reductive Amination

Allylation
The enantioselective allylation of aldehydes can be accomplished under very mild conditions at non-cryogenic temperature (-30 °C).²

Figure 3. Allylation

Friedel-Crafts Alkylation
Functionalized indoles^3,4 and pyrroles⁵ can be accessed in enantioenriched form by asymmetric alkylation.

Figure 4. Friedel-Crafts Alkylation

References

1. Rueping M, Sugiono E, Azap C, Theissmann T, Bolte M. 2005. Enantioselective Brønsted Acid Catalyzed Transfer Hydrogenation:? Organocatalytic Reduction of Imines. Org. Lett.. 7(17):3781-3783. https://doi.org/10.1021/ol0515964

2. Hoffmann S, Seayad AM, List B. 2005. A Powerful Brønsted Acid Catalyst for the Organocatalytic Asymmetric Transfer Hydrogenation of Imines. Angew. Chem. Int. Ed.. 44(45):7424-7427. https://doi.org/10.1002/anie.200503062

3. Storer RI, Carrera DE, Ni Y, MacMillan DWC. 2006. Enantioselective Organocatalytic Reductive Amination. J. Am. Chem. Soc.. 128(1):84-86. https://doi.org/10.1021/ja057222n

4. Jain P, Antilla JC. 2010. Chiral Brønsted Acid-Catalyzed Allylboration of Aldehydes. J. Am. Chem. Soc.. 132(34):11884-11886. https://doi.org/10.1021/ja104956s

5. Terada M, Sorimachi K. 2007. Enantioselective Friedel?Crafts Reaction of Electron-Rich Alkenes Catalyzed by Chiral Brønsted Acid. J. Am. Chem. Soc.. 129(2):292-293. https://doi.org/10.1021/ja0678166

6. Itoh J, Fuchibe K, Akiyama T. 2008. Chiral Phosphoric Acid Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with Nitroalkenes: Cooperative Effect of 3 Å Molecular Sieves. Angew. Chem. Int. Ed.. 47(21):4016-4018. https://doi.org/10.1002/anie.200800770

7. He Y, Lin M, Li Z, Liang X, Li G, Antilla JC. 2011. Direct Synthesis of Chiral 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazines via a Catalytic Asymmetric Intramolecular Aza-Friedel?Crafts Reaction. Org. Lett.. 13(17):4490-4493. https://doi.org/10.1021/ol2018328