Deconstructive diversification of cyclic amines

Jose B. Roque, Yusuke Kuroda, Lucas T. Göttemann and Richmond Sarpong ()
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Jose B. Roque: University of California
Yusuke Kuroda: University of California
Lucas T. Göttemann: University of California
Richmond Sarpong: University of California

Nature, 2018, vol. 564, issue 7735, 244-248

Abstract: Abstract Deconstructive functionalization involves carbon–carbon (C–C) bond cleavage followed by bond construction on one or more of the constituent carbons. For example, ozonolysis1 and olefin metathesis2,3 have allowed each carbon in C=C double bonds to be viewed as a functional group. Despite the substantial advances in deconstructive functionalization involving the scission of C=C double bonds, there are very few methods that achieve C(sp3)–C(sp3) single-bond cleavage and functionalization, especially in relatively unstrained cyclic systems. Here we report a deconstructive strategy to transform saturated nitrogen heterocycles such as piperidines and pyrrolidines, which are important moieties in bioactive molecules, into halogen-containing acyclic amine derivatives through sequential C(sp3)–N and C(sp3)–C(sp3) single-bond cleavage followed by C(sp3)–halogen bond formation. The resulting acyclic haloamines are versatile intermediates that can be transformed into various structural motifs through substitution reactions. In this way we achieve the skeletal remodelling of cyclic amines, an example of scaffold hopping. We demonstrate this deconstructive strategy by the late-stage diversification of proline-containing peptides.

Keywords: Cyclic Amines; Scaffold Hopping; Deconstructive Strategy; Single Bond Cleavage; Proline-containing Peptides (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0700-3

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