Catalytic asymmetric synthesis of 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines as useful building blocks for SAR-studies

Lennart Brewitz, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The first protocol for the asymmetric synthesis of 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines which function as fluorinated surrogates for α-isopropylbenzylamines in SAR-studies is presented herein. Crucial for the successful synthesis was the application of a recently developed direct catalytic asymmetric Mannich-type reaction of fluorinated amide for the key bond-forming step. The utility of this versatile protocol was demonstrated by the synthesis of fluorinated analogues of a T-type selective Ca2+ channel blocker and a prolylcarboxypeptidase inhibitor. The predominant conformation of their fluorinated analogues was investigated by X-ray crystallography and NMR spectroscopy which revealed a strong influence of a fluorine mediated gauche effect.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Fluorine Chemistry
Volume194
DOIs
Publication statusPublished - 2017 Feb 1
Externally publishedYes

Keywords

  • Chiral 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines
  • Cooperative catalysis
  • Fluorinated α-isopropylbenzylamines
  • Fluorine gauche effect
  • Structure-activity relationship
  • Trifluoromethyl

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Chemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Catalytic asymmetric synthesis of 2,3,3,3-tetrafluoro-2-methyl-1-arylpropan-1-amines as useful building blocks for SAR-studies'. Together they form a unique fingerprint.

Cite this