Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• . Under acidic conditions, these 1,2-dihydropyrazines can be converted to substituted Δ5-2-oxopiperazines providing a simple and efficient approach towards their preparation. Keywords: N-acylpyrazinium salts; 1,2-dihydropyrazines; Grignard reagents; Δ5-2-oxopiperazines; regioselective addition

• Δ5-2-oxopiperazines. Results and Discussion Our journey began by first reacting 2-methoxypyrazine with phenyl chloroformate to generate the N-acylpyrazinium salt 2 using DCM as the solvent. Next, phenylmagnesium bromide in THF was added at −41 °C. After stirring for 60 min, dihydropyrazine 3a was

• ) while the presence of an electron-withdrawing ester group generated 13 in a yield of 49%. With the substituted 1,2-dihydropyrazines in hand, we next wanted to demonstrate their usefulness for synthesizing substituted Δ5-2-oxopiperazines. Processes into this structural motif would be very useful due to