Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers

• Published in: Angewandte Chemie International Edition Vol. 57; no. 20; pp. 5853 - 5857
• Main Authors: Feng, Guang‐Shou, Chen, Mu‐Wang, Shi, Lei, Zhou, Yong‐Gui
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.05.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: 1,3-diamines; Chemistry; Chemistry, Multidisciplinary; cyclic ureas; Hydrogenation; Isomerization; Optical activity; Palladium; Physical Sciences; Pyrimidines; Science & Technology; tautomerization; Tautomers; Thiourea; Thiourea derivatives; Ureas; ACID; ENANTIOSELECTIVE SYNTHESIS; cyclic ureas; IMINES; BIGINELLI REACTION; 1,3-diamines; PYRIDINIUM SALTS; MULTIPLE STEREOGENIC CENTERS; HETEROAROMATIC-COMPOUNDS; CATALYZED ASYMMETRIC HYDROGENATION; tautomerization; palladium; pyrimidines; DERIVATIVES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201801485

A facile access to optically active cyclic ureas was developed through palladium‐catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin‐2(1H)‐one, acid‐catalyzed isomerization of enamine–imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity. Introducing asymmetry: An enantioselective palladium‐catalyzed hydrogenation of pyrimidines containing a tautomeric hydroxy group is described. This methodology provides a convenient route to chiral cyclic ureas with up to 99 % ee. The cyclic chiral ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity.