Projects per year
Azetidines are important motifs in medicinal chemistry, but there are a limited number of methods for their synthesis. Herein, we present a new method for their modular construction by exploiting the high ring strain associated with azabicyclo[1.1.0]butane. Generation of azabicyclo[1.1.0]butyl lithium followed by its trapping with a boronic ester gives an intermediate boronate complex which, upon N-protonation with acetic acid, undergoes 1,2-migration with cleavage of the central C-N bond to relieve ring strain. The methodology is applicable to primary, secondary, tertiary, aryl, and alkenyl boronic esters and occurs with complete stereospecificity. The homologated azetidinyl boronic esters can be further functionalized through reaction of the N-H azetidine, and through transformation of the boronic ester. The methodology was applied to a short, stereoselective synthesis of the azetidine-containing pharmaceutical, cobimetinib.
FingerprintDive into the research topics of 'Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines'. Together they form a unique fingerprint.
- 2 Finished
Changing the Synthesis Landscape with Boron at the Helm: from Chiral Organometallics to Assembly Line Synthesis
14/05/12 → 13/01/18
The development of strain-release-driven transformations: 1,2-metallate and semipinacol rearrangement reactionsAuthor: Gregson, C. H. U., 28 Sep 2021
Supervisor: Aggarwal, V. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)File