Titanium Salalen Catalyzed Enantioselective Benzylic Hydroxylation

Area of Science:

• Organometallic Chemistry
• Catalysis
• Organic Synthesis

Background:

• The Berkessel-Katsuki catalyst, a titanium complex with a cis-1,2-diaminocyclohexane (cis-DACH) derived Berkessel-salalen ligand, is known for efficient asymmetric epoxidation.
• Asymmetric catalytic hydroxylation of benzylic C-H bonds remains a challenge in synthetic chemistry.

Purpose of the Study:

• To investigate the potential of the Berkessel-Katsuki catalyst for asymmetric benzylic C-H hydroxylation.
• To develop an optimized catalyst for enhanced enantioselective hydroxylation and epoxidation reactions.

Main Methods:

• Mechanism-based ligand optimization of the Berkessel-salalen ligand.
• Asymmetric epoxidation of terminal olefins using hydrogen peroxide.
• Asymmetric hydroxylation of benzylic C-H bonds using hydrogen peroxide.

Main Results:

• The developed nitro-salalen Ti-catalyst exhibits the highest efficiency reported for asymmetric catalytic benzylic hydroxylation, achieving up to 98% enantiomeric excess (ee).
• Overoxidation to ketone byproducts was minimal.
• The novel catalyst also demonstrated enhanced epoxidation efficiency, converting 1-decene to its epoxide in 90% yield with 94% ee at a low catalyst loading (0.1 mol-%).

Conclusions:

• The novel nitro-salalen Ti-catalyst is highly effective for both asymmetric benzylic C-H hydroxylation and olefin epoxidation.
• This catalyst represents a significant advancement in enantioselective catalysis, offering broad applicability in organic synthesis.