Di-tert-butyl Ethynylimidodicarbonate as a General Synthon for the β‑Aminoethylation of Organic Electrophiles: Application to the Formal Synthesis of Pyrrolidinoindoline Alkaloids (±)-CPC‑1 and (±)-Alline

• Published in: Journal of organic chemistry Vol. 85; no. 13; pp. 8447 - 8461
• Main Authors: Beveridge, Ramsay E, Hu, Yiwei, Gregoire, Bruce, Batey, Robert A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02-07-2020
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c00781

The reagent di-tert-butyl ethynylimidodicarbonate is demonstrated as a β-aminoethyl anion synthetic equivalent. It can be used to install ethyleneamine groups by exploiting its terminal alkyne reactivity with common organic electrophiles. Reactions exemplified with this terminal ynimide reagent include additions to imines, aldehydes, ketones, pyridinium salts, Michael acceptors, epoxides, and Pd-catalyzed Sonogashira couplings. Subsequent regioselective [3 + 2] cycloadditions of the alkynyl-imides (ynimides) generate N,N-di-Boc imide-functionalized triazole and isoxazole heterocycles. Reduction of the ynimides with Pd-catalyzed hydrogenation generates ethyleneimides with easily removable N,N-di-Boc-carbamate protecting groups, allowing for a flexible ynimide-based approach to ethyleneamine installation. The utility of this two-step aminoethylation strategy was demonstrated in the short formal syntheses of pyrrolidinoindoline alkaloids (±)-CPC-1 and (±)-alline. Analogously, the reagent (N,N,N′)-tri-Boc 2-ethynylhydrazine serves as a β-hydrazinoethyl anion synthetic equivalent.