Catalytic, Asymmetric Synthesis of Cyanohydrin Ethyl Carbonates
Yuri N. Belokon, A. John Blacker, Lisa A. Clutterbuck and Michael North*
*Department of Chemistry, King's College London, Strand, London, WC2 R2LS,
UK, Email: michael.north
kcl.ac.uk
Y. N. Belokon, A. J. Blacker, L. A. Clutterbuck, M. North, Org. Lett., 2003, 5, 4505-4507.
DOI: 10.1021/ol035828f
Abstract
A bimetallic titanium complex [(salen)TiO]2 catalyzes the asymmetric addition of ethyl cyanoformate to aldehydes leading to cyanohydrin carbonates with high enantiomeric excesses.
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Details
The document discusses the catalytic, asymmetric synthesis of cyanohydrin ethyl carbonates using a bimetallic titanium complex [(salen)TiO]2. This complex, derived from (R,R)-cyclohexanediamine and 3,5-di-tert-butyl-salicylaldehyde, effectively catalyzes the addition of ethyl cyanoformate to aldehydes, producing cyanohydrin carbonates with high enantiomeric excesses. The study highlights the advantages of using ethyl cyanoformate over hazardous and expensive reagents like hydrogen cyanide and trimethylsilyl cyanide. The optimal conditions for the reaction were found to be 5 mol % of the catalyst at -40 °C, yielding products with up to 95% enantiomeric excess in significantly reduced reaction times. Various aldehydes, including aromatic and aliphatic types, were tested, showing high yields and enantiomeric excesses, particularly with electron-rich aromatic aldehydes. The methodology allows for the preparation of either enantiomer of the cyanohydrin carbonate, making it a versatile and efficient approach for synthesizing chiral cyanohydrins. The research was supported by the EPSRC and Avecia, Ltd., with further studies on the scope and mechanism of the reaction ongoing.
Key Words
cyanohydrins, carbonates, addition, enantioselective
ID: J54-Y2003-880
