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

Abstract

The direct electrophilic α-cyanation of β-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.

Highly Enantioselective α‐Cyanation with 4‐Acetylphenyl Cyanate

“…There are methodologies for their synthesis, such as nucleophilic substitution or addition with anionic cyanides, affording cyanohydrins and aliphatic nitriles, respectively. Recently, we disclosed a new protocol to synthesize α‐nitriles from active hydrogen substitution with cyano‐hyperiodinate as the electrophile . Following closely, Waser and co‐workers reported the first asymmetric version with moderate enantioselectivity with cinchona alkaloid organocatalysts .…”

“…We knew that the racemic reaction could be catalyzed by Lewis acids . Together with the knowledge of the good solubility and mild reactivity of cyanate, we chose phenylcyanate as the cyano source to develop the asymmetric version with a transition‐metal complex as the catalyst.…”

Cyclische hypervalente Iodreagentien für Atomtransferreaktionen – jenseits der Trifluormethylierung

“…Chen und Mitarbeiter beschrieben 2015 die erste Cyanierung von cyclischen Ketoestern in hoher Ausbeute durch das Cyanbenziodoxolon 16 (Schema ) . Danach berichteten Waser und Mitarbeiter über die Verwendung des Cinchona‐Alkaloids 182 als Katalysator zur enantioselektiven Cyanierung mit bis zu 48 % ee .…”

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

“…The benziodoxole-based five-membered iodine heterocycles represent a particularly important class of hypervalent iodine(III) reagents. Substituted benziodoxoles 1 ( Scheme 1 ) are commonly employed as efficient electrophilic atom-transfer reagents useful for conversion of various organic substrates to the corresponding products of azidation [ 7 – 11 ], amination [ 12 – 13 ], cyanation [ 14 – 17 ], alkynylation [ 18 – 20 ], or chlorination [ 21 – 22 ]. Recently, Zhang and co-workers reported the preparation of several bicyclic benziodoxoles 3 starting from 2-iodoisophthalic acid ( 2 , Scheme 1 ).…”