Rhodium‐Catalyzed Addition of Aryl Boronic Acids to 2,2‐Disubstituted Malononitriles

• Published in: Angewandte Chemie International Edition Vol. 56; no. 24; pp. 6999 - 7002
• Main Authors: Malapit, Christian A., Caldwell, Donald R., Luvaga, Irungu K., Reeves, Jonathan T., Volchkov, Ivan, Gonnella, Nina C., Han, Zhengxu S., Busacca, Carl A., Howell, Amy R., Senanayake, Chris H.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.06.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Acids; Aromatic compounds; boronic acids; Catalysis; Chemistry; Chemistry, Multidisciplinary; Collapse; homogeneous catalysis; Imines; Physical Sciences; Rhodium; Science & Technology; sulfinimines; β-ketonitriles; sulfinimines; beta-ketonitriles; ARYLBORON COMPOUNDS; IMINES; DIMETHYLMALONONITRILE; KETONES; TRANSNITRILATION; ALPHA-CYANO; homogeneous catalysis; NITRILE; TERT-BUTANESULFINAMIDE; CONDENSATION; boronic acids; rhodium; β-ketonitriles
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201703471

β‐Ketonitriles bearing a quaternary carbon at the 2‐position were prepared through Rh‐catalyzed addition of aryl boronic acids to 2,2‐disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro‐Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β‐ketonitriles. The products could be further derivatized to valuable chiral α,α‐disubstituted‐β‐aminonitriles through addition reactions to the corresponding N‐tert‐butanesulfinyl imines. All about that base: In the presence of a Rh catalyst, aryl boronic acids add to 2,2‐disubstituted malononitriles to give β‐ketonitriles. A change of base from Cs2CO3, which was employed in a previous transnitrilation reaction, to a proton sponge prevents retro‐Thorpe fragmentation of the intermediate β‐iminonitrile. The utility of the β‐ketonitriles was demonstrated by highly diastereoselective additions to the corresponding N‐tert‐butanesulfinyl imines.