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Monotrifluoroacetoxyborane-amines: chemoselective reagents for challenging reductive aminations
P Veeraraghavan Ramachandran1, Shivani Choudhary1
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana, 47907, USA. chandran@purdue.edu.
Chemical Communications (Cambridge, England)
|October 5, 2022
Summary
Trifluoroacetoxyborane-amines (TFAB-amines) are novel reagents for reductive amination. TFAB-triethylamine shows superior selectivity and mildness compared to existing methods for synthesizing amines from aldehydes and ketones.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Reductive amination is a crucial transformation for synthesizing amines.
- Existing reagents like sodium cyanoborohydride and sodium triacetoxyborohydride have limitations in selectivity and substrate scope.
- Borane-amine complexes are versatile precursors in organic synthesis.
Purpose of the Study:
- To introduce trifluoroacetoxyborane-amines (TFAB-amines) as novel chemoselective reagents for direct reductive amination.
- To evaluate the performance of TFAB-triethylamine (TFAB-NEt3) against established reductive amination reagents.
- To elucidate the reaction mechanism involving TFAB-amines.
Main Methods:
- Monoacetoxylation of borane-amines to yield TFAB-amines.
- Application of TFAB-amines in the direct reductive amination of various aldehydes and ketones.
- Comparative studies with sodium cyanoborohydride (NaBH3CN) and sodium triacetoxyborohydride (Na(AcO)3BH).
- Mechanistic investigations including dehydroacetoxylation to polyaminoborane.
Main Results:
- Exclusive monoacetoxylation of borane-amines to TFAB-amines was achieved.
- TFAB-NEt3 demonstrated high chemoselectivity and mild reaction conditions for reductive amination.
- Superior performance of TFAB-NEt3 was observed compared to NaBH3CN and Na(AcO)3BH, particularly with challenging substrates and at elevated temperatures.
- A reaction mechanism involving polyaminoborane intermediates was proposed.
Conclusions:
- TFAB-amines represent a new class of effective reagents for direct reductive amination.
- TFAB-NEt3 offers a milder and more selective alternative to conventional reagents for amine synthesis.
- The mechanistic insights provide a foundation for further development of borane-based amination strategies.
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