title: Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity.
abstract: 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 S═O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
authors: ‡Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 United States.
authors: Osvaldo
authors: O
authors: Gutierrez
authors: Dattatray
authors: D
authors: Metil
authors: Namrata
authors: N
authors: Dwivedi
authors: Nagaraju
authors: N
authors: Gudimalla
authors: E R R
authors: ER
authors: Chandrashekar
authors: Vilas H
authors: VH
authors: Dahanukar
authors: Apurba
authors: A
authors: Bhattacharya
authors: Rakeshwar
authors: R
authors: Bandichhor
authors: ‡Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 United States.
authors: Marisa C
authors: MC
authors: Kozlowski
mesh_terms: D000577:Amides / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008698:Mesylates / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry*; D000068900:Sitagliptin Phosphate; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000577:Amides; D008024:Ligands; D008698:Mesylates; D011719:Pyrazines; D014230:Triazoles; D005459:Fluorides; D000068900:Sitagliptin Phosphate