Issue 73, 2023

Diversifying chemical space of DNA-encoded libraries: synthesis of 2-oxa-1-azaspiro(bicyclo[3.2.0])heptanes on-DNA via visible light-mediated energy transfer catalysis

Abstract

Azaspiro[3.3]heptanes are valuable synthetic targets for drug discovery programs. The challenges associated with the preparation and diversification of this moiety as compared to other small, saturated rings have led to limited applications of compounds containing this spirocycle. In this regard, important advances in the field of synthetic photochemistry have exploited the biradical nature of the triplet excited state of 2-isoxazoline-3-carboxylates, engaging these species in intermolecular coupling reactions under visible light irradiation. As a continuation of our program preparing F(sp3)-rich, structurally complex molecules for DNA-encoded library technology (DELT) applications via photocatalysis, we disclose herein the incorporation of unique and densely functionalized 2-oxa-1-azabicyclo[3.2.0]heptanes via [2+2] cycloaddition energy transfer sensitization, providing access to an unexplored library of azaspiro compounds, many of which include additional synthetic handles important for further functionalization of the DNA-conjugated products and for library production.

Graphical abstract: Diversifying chemical space of DNA-encoded libraries: synthesis of 2-oxa-1-azaspiro(bicyclo[3.2.0])heptanes on-DNA via visible light-mediated energy transfer catalysis

Supplementary files

Article information

Article type
Communication
Submitted
15 Jul 2023
Accepted
15 Aug 2023
First published
23 Aug 2023

Chem. Commun., 2023,59, 10964-10967

Author version available

Diversifying chemical space of DNA-encoded libraries: synthesis of 2-oxa-1-azaspiro(bicyclo[3.2.0])heptanes on-DNA via visible light-mediated energy transfer catalysis

B. Matsuo, S. Kim, S. T. Shreiber, G. Levitre, L. Li, E. A. Crane, E. J. McClain, E. A. Voight and G. A. Molander, Chem. Commun., 2023, 59, 10964 DOI: 10.1039/D3CC03421F

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