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

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 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.

authors

• Gutierrez Santacruz, Osvaldo

published proceedings

• Org Lett

author list (cited authors)

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

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

publisher

• American Chemical Society (ACS)  Publisher

published in

• Organic Letters  Journal

keywords

• Amides
• Fluorides
• Hydrogen Bonding
• Ligands
• Mesylates
• Models, Molecular
• Molecular Structure
• Pyrazines
• Sitagliptin Phosphate
• Stereoisomerism
• Triazoles

PubMed Central ID

• 25799267

Digital Object Identifier (DOI)

• 10.1021/acs.orglett.5b00520

start page

• 1742

end page

• 1745

volume

• 17

issue

• 7