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Direct Transformation of N‑Protected α,β-Unsaturated γ‑Amino Amides into γ‑Lactams through a Base-Mediated Molecular Rearrangement

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journal contribution
posted on 11.11.2019, 14:39 by Mothukuri Ganesh Kumar, Kuruva Veeresh, Sachin A. Nalawade, Raj V. Nithun, Hosahudya N. Gopi
Here, we are reporting a single-step transformation of N-protected α,β-unsaturated γ-amino amides into 5,5-disubstituted γ-lactams through a base-mediated new molecular rearrangement. In contrast to the known N- to C­(O) cyclization of saturated γ-amino acids into corresponding γ-lactams, the new rearrangement involves the cyclization between N-terminal Cγ- to C-terminal amide N. The cyclization process was initiated by the migration of double bond from α,β → β,γ position. The enamine–imine tautomerization of the new β,γ-double bond and subsequent 5-exo-trig cyclization of terminal amide leads to the formation of N-protected 5,5-disubstituted γ-lactam. The structures of various γ-lactams obtained from the rearrangement were studied in single crystals. Overall, the results reported here demonstrate the facile and single-step transformation of N-protected α,β-unsaturated γ-amino amides into γ-lactams and provided an excellent opportunity to construct small-molecule peptidomimetics.

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