Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 4573–4578 |
Number of pages | 6 |
Journal | Journal of the American Chemical Society |
Volume | 141 |
Issue number | 11 |
Early online date | 5 Mar 2019 |
DOIs | |
Publication status | Published - 20 Mar 2019 |
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Dive 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.Projects
- 2 Finished
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FRESCO: Efficient, Flexible Synthesis of Molecules with Tailored Shapes: from Photoswitchable Helices to anti-Cancer Compounds
Aggarwal, V. K. (Principal Investigator)
1/10/15 → 31/03/21
Project: Research
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Changing the Synthesis Landscape with Boron at the Helm: from Chiral Organometallics to Assembly Line Synthesis
Aggarwal, V. K. (Principal Investigator)
14/05/12 → 13/01/18
Project: Research
Student theses
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The development of strain-release-driven transformations: 1,2-metallate and semipinacol rearrangement reactions
Gregson, C. H. U. (Author), Aggarwal, V. (Supervisor), 28 Sept 2021Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)
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Profiles
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Professor Varinder K Aggarwal
- School of Chemistry - Alfred Capper Pass Chair of Chemistry
Person: Academic