Chiral Oxazaborolidines

Chiral oxazaborolidines and its cation are a special Lewis acid catalyst discovered in the 1980s. The typical reaction catalyzed by the reagent is a variety of Lewis acid-catalyzed organic chemical reactions such as asymmetric reduction of ketone carbonyl, asymmetric reduction of quinone imine, imine, and stereoselective Diels-Alder reaction. It is foreseeable that chiral oxazaborolidines will play an increasingly important role in asymmetric synthesis.

Applications

Chiral oxazaborolidine is an important catalyst for asymmetric interfacial formation. It can catalyze important organic chemical reactions such as asymmetric reduction of ketone, meso-imine and imine, catalytic stereoselective Diels-Alder reaction and asymmetric Mukaiyama reaction in high yield and high stereoselectivity.

• Catalytic reduction of ketones: The researchers have studied the asymmetric reduction of chiral oxazaborolidines to ketone. It was found that when the amount of amino alcohol was 10 mol% of the reduced ketone, the ee value of the product was lower than the ee value of the product when the amount of amino alcohol was 100 mol%. If the steric hindrance near the amino group increases, the asymmetric induction effect is better.

Figure 1. Catalytic reduction of ketones

• Catalytic asymmetric reduction of mesocyclic imides: Mesocyclic imides such as cis-3,4-disubstituted imides is a useful class of compounds in the field of asymmetric synthesis. One of the carboxyl groups of the stereoselective reduction can give a compound having two adjacent chiral centers. This compound is a chiral cleavage commonly used in the synthesis of many natural products. Therefore, the asymmetric reduction of mesocycloimide has attracted the attention of many chemists. Conventional reduction methods are enzymatic and catalytic hydrogenation. The asymmetric reduction of mesocycloheximide with borane as a reducing agent and oxazole borane as a chiral catalyst was reported for the first time. The reaction yield is high and the asymmetric reduction effect is better.

Figure 2. Mesocyclic imides

• Catalytic stereoselective Diels-Alder reaction: The stereoselective Diels-Alder reaction is a very important reaction in organic synthesis. It is widely used in the synthesis of Daran, non-Daran active compounds and drug molecules, and therefore has received much attention. Researchers conducted a study on the asymmetric Diels-Alder reaction catalyzed by chiral oxazaborolidines. For example, a new class oxazaborolidines cation catalysts can catalyze the Diels-Alder reaction of cyclopentadiene with α, β-ethyl acrylate in a yield of up to 98%. 

Figure 3. A new class oxazaborolidines cation catalysts

• Asymmetric reduction of catalytic imine: Chiral amines are commonly used synthons and resolving agents in organic synthesis and are widely used in the synthesis of drug molecules and biologically active compounds. One of the methods for synthesizing chiral amines is the asymmetric reduction of imines. The Chiral oxazaborolidines can be used to catalyze the asymmetric reduction of imines, especially when catalyzing the asymmetric catalysis of N-H imines.

Figure 4. Asymmetric Reduction of N-H Imine Mixtures

• Catalyze other types of reactions: Oxazole borane and cation oxazolidine borane belong to Lewis acid. For many Lewis acid-catalyzed organic chemical reactions, they both show good asymmetric catalysis. For example, catalytic asymmetric Mukaiyama condensation reaction, catalytic imine Symmetrical hydrocyanation, catalyzed asymmetric acylation of aldehydes and ketones, catalyzed synthesis of chiral β-lactones, etc.

References

1. Hirao, A; Itsuno, S; Nakahama, S; Yamazaki, N. J. Chem Soc.(1981). Chem. Commun. 12,315.
2. Payette, J. N; Yamamoto, H.(2007). J. Am. Chem. Soc. 14,9536.
3. Wang, J; Liu, H; Dua, D. M.(2009). Tetrahedron: Asymmetry. 20,605.