Lewis Acid-Catalyzed Asymmetric Selenocyanation of ß-Ketoesters with N-Selenocyanatosaccharin.

The first electrophilic asymmetric selenocyanation has been achieved in the presence of Ni(OTf)2 and (R,R)-DBFOX/Ph using N-selenocyanatosaccharin as the new selenocyanation reagent. Thus, a series of α-selenocyanato-ß-keto esters were synthesized with high yields (up to 99%) and good ee values (up to 92% ee). The readily preparation of the reagent and high enantioselectivity make this methodology much practical for the synthesis of chiral selenocyanates.

Organocatalyzed Asymmetric α-Thiocyanation of Oxindoles: Synthesis of Chiral Tertiary 3-Thiocyanatoxindoles.

An enantioselective thiocyanation of oxindoles has been developed for the first time using a bifunctional cinchona-derived organo-catalyst and N-thiocyanatophthalimide as the electrophilic thiocyanation source in the presence of 2-naphthol as the additive. Various enantioenriched 3,3'-disubstituted oxindoles with SCN-containing quaternary carbon stereocenters were synthesized under mild conditions in high yields (up to 99%) and good enantioselectivities (up to 6:94 er).

Enantioselective Organocatalyzed Direct α-Thiocyanation of Cyclic ß-Ketoesters by N-Thiocyanatophthalimide.

A new electrophilic thiocyanation reagent, N-thiocyanatophthalimide, was synthesized and applied to the first example of catalytic asymmetric electrophilic α-thiocyanation of various cyclic ß-ketoesters by the bifunctional cinchona alkaloid catalysis. Thus, a variety of chiral α-thiocyanato ß-ketoesters with a quaternary carbon center have been achieved in excellent yields (up to 99%) and high enantioselectivities (up to 94% ee) in a convenient manner.

N-Thiocyanatosaccharin: A "Sweet" Electrophilic Thiocyanation Reagent and the Synthetic Applications.

N-Thiocyanatosaccharin (R1) was readily prepared from the sweet additive Saccharin in two steps with a 71% overall yield. By applying this new reagent to diverse nucleophiles such as benzothiophenes, indoles, oxindoles, aromatic amines, phenols, ß-keto carbonyl compounds, and aromatic ketones, a novel electrophilic thiocyanation reaction was achieved with high yields (up to 99%). The potential recycling of Saccharin, the wide scope of substrates, and the mild reaction conditions made this protocol much more practical.

Enantioselective electrophilic cyanation of ß-keto amides catalysed by a cinchona organocatalyst.

An operationally simple protocol for the enantioselective electrophilic α-cyanation of ß-keto amides catalyzed by cinchona-derived catalysts has been demonstrated. The resulting products could be obtained with good to high enantioselectivities (up to 88% ee) and with excellent yields (up to 94%) by employing the mild active 4-acetylphenyl cyanate as the cationic cyano source in the catalytic asymmetric α-cyanation reaction.

Catalytic Asymmetric Electrophilic Cyanation of 3-Substituted Oxindoles.

The first example of catalytic asymmetric electrophilic cyanation of 3-substituted oxindoles has been achieved using readily accessible 4-acetylphenyl cyanate as the cyano source. Thus, a series of all-carbon quaternary center 3-aryl-3-cyano oxindoles were prepared using a zinc complex of a chiral pincer ligand as the catalyst in high yields (up to 95%) and excellent enantioselectivities (up to >99% ee) in the presence of 4 Å MS and 2,6-lutidine in THF at 0 °C.

Highly Enantioselective α-Cyanation with 4-Acetylphenyl Cyanate.

A highly effective asymmetric version of α-cyanation of ß-keto esters and amides was developed with a Lewis-acid catalyst. Thus, by using 10 mol % of a tridentate bisoxazoline-zinc(II) complex as the catalyst, a series of chiral nitriles containing a quaternary carbon center were obtained in excellent enantioselectivities (up to 97 % enantiomeric excess) and up to 95 % yield in the presence of 4 Šmolar sieve at room temperature. For the first time, mild and active 4-acetylphenyl cyanate was used instead of cyano-hyperiodinate as the cationic cyano source for catalytic asymmetric α-cyanation.

The direct electrophilic cyanation of ß-keto esters and amides with cyano benziodoxole.

The direct electrophilic α-cyanation of ß-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.