Unprecedented Reversal of Regioselectivity during Methanolysis and an Interception of Curtius Rearrangement. Issue 36 (27th September 2021)

• Record Type: Journal Article
• Authors: Mandal, Mihirbaran; Buevich, Alexei V.; Wang, Hongwu; Brunskill, Andrew; Orth, Peter; Caldwell, John P.; Liu, Xiaoxiang; Mazzola, Robert; Cumming, Jared; McKittrick, Brian; Zhu, Zhaoning; Stamford, Andrew
• Is Part Of: European journal of organic chemistry. Issue 36(2021)
• Page Start: 5073
• Page End: 5079
• Publication Date: 2021-09-27
• Subjects: Amine -- Curtius rearrangement -- Drug design -- Fluorine -- Regioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202101056
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: Unprecedented reversal in regioselectivity during methanolysis of anhydrides due to the change in substitution pattern of fluorine in the phenyl moiety, and the formation of nitrene intercepted intermediates during Curtius rearrangement of the acids were the major impediments for discovering bioactive molecules in beta amyloid cleaving enzyme‐1 (BACE1) program. Solutions to these synthetic challenges, and our investigation into this unexpected change in reactivity are discussed. Abstract : Subtle changes of substitution pattern of fluorine in the phenyl moiety resulted in unexpected reversal of regioselectivity of methanolysis and interception of Curtius rearrangement of quaternary acids to their corresponding amines.