Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity. Academic Article uri icon


  • The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate SO, consistent with MsOH being crucial for high selectivity. The second is a novel C-HF interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.

published proceedings

  • Org Lett

author list (cited authors)

  • Gutierrez, O., Metil, D., Dwivedi, N., Gudimalla, N., Chandrashekar, E., Dahanukar, V. H., ... Kozlowski, M. C.

citation count

  • 18

complete list of authors

  • Gutierrez, Osvaldo||Metil, Dattatray||Dwivedi, Namrata||Gudimalla, Nagaraju||Chandrashekar, ERR||Dahanukar, Vilas H||Bhattacharya, Apurba||Bandichhor, Rakeshwar||Kozlowski, Marisa C

publication date

  • January 2015