Cyanation of ketones

Cyanation of ketones, nitro compounds, or benzylic compounds... 

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

Scheme 5.34. Chiral base-catalyzed asymmetric cyanation of ketones.

Cyanation of carbonyl compounds has one of the richest histories of any transformation in the field of asymmetric catalysis, and intensive research efforts have continued unabated since the editorial deadline for the first edition of Comprehensive Asymmetric Catalysis in 1998. This chapter will summarize all efforts in this area from 1998 to date, highlighting the most important catalytic systems from a synthetic and/or mechanistic standpoint. Significant advances in both the cyanation of aldehydes (formation of secondary cyanohydrins Section 28.2.1) and the cyanation of ketones (formation of tertiary cyanohydrins Section 28.2.2) will be addressed [1,2]. 

Relatively few of the enzymatic methods applicable to the preparation of secondary cyanohydrins have been adapted successfully to the synthesis of optically pure tertiary cyanohydrins [1,3,4]. Similarly, progress in asymmetric hydro-cyanation of ketones with synthetic catalysts lagged far behind advances in aldehyde cyanation. This situation has changed fairly dramatically over the past... 

Rl a,p-unsat. or aliphatic, Rs = Me Scheme 2. Methodology for cyanation of ketones developed by Shibasaki and co-workers... 

Scheme 3. Cinchona alkaloid-based methodology for cyanation of ketones developed by Deng and Tian...

Additional experiments showed that the active species was a bimetallic complex [(salen)Ti(/i — 0)]2 (19), obtained by in situ addition of water to 18. When purified complex 19 was used in the catalysis, it was found to be far more active than 18, giving full conversions in only 5-60 min with 0.1 mol% of catalyst at room temperature. The enantiomeric excess was increased by lowering the temperature, but with erosion of the reactivity (Scheme 7.15). The cyanation of ketones was also possible with catalyst 19, with lower enantioselectivity and longer reaction times (48-96 h)." ... 

A silylene-bridged lanthanide complex was introduced by Luo et al. as a new entry of Lewis acid catalyst to cyanation of ketones (31). The complex was prepared from 9-fluorenylmethylphenylsilylene and LnClj by the action of butyUithiirm. In cyanosilylation of acetophenones, Pr complex (6) was found out to be one of the most active catalysts to afford TMS ether up to >99% yield (Scheme 13.13). PrCh itself failed to catalyze the reaction. The reactivity was dependent on the substituent on the aromatic ring. 

Scheme 13.13 Cyanation of ketones catalyzed by silylene-bridged Pr complex.

Deng has reported a range of asymmetric cyanations of ketones with ethyl cyanoformate using cinchona alkaloid derivatives 285-288 as catalysts (Figure 2.11) [181]. The catalysts themselves are the ligands that were uti-... 

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