Rational Design of New Dihydrobenzooxophosphole-Based Lewis Base Organocatalysts
Bo Qu1, Lalith P Samankumara1, Anjan Saha1
1Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA.
Summary
New organocatalysts efficiently perform stereoselective conjugate reductions of carbon-carbon double bonds using trichlorosilane. Computational studies reveal a key hydrogen bond interaction enhances catalyst reactivity.
Area of Science:
- Organic Chemistry
- Catalysis
- Computational Chemistry
Background:
- Organocatalysts are crucial for sustainable chemical synthesis.
- Stereoselective reductions are vital for creating complex molecules.
- Dihydrobenzooxophosphole scaffolds offer unique catalytic properties.
Purpose of the Study:
- To design and synthesize novel dihydrobenzooxophosphole-based Lewis base organocatalysts.
- To evaluate their efficacy in trichlorosilane-mediated stereoselective conjugate reductions.
- To elucidate the mechanism of catalysis using DFT calculations.
Main Methods:
- Synthesis of dihydrobenzooxophosphole derivatives.
- Stereoselective conjugate reduction reactions using trichlorosilane.
- Density Functional Theory (DFT) calculations for transition state analysis.
Main Results:
- Successful synthesis of a series of new organocatalysts.
- Demonstration of high efficiency in stereoselective conjugate reductions.
- Identification of a significant hydrogen bond interaction stabilizing the transition state.
Conclusions:
- The developed organocatalysts are effective for stereoselective conjugate reductions.
- The amide linker's hydrogen bond plays a critical role in catalyst reactivity.
- This work provides insights into the design of advanced Lewis base organocatalysts.
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