2,5 -Diethoxy-3,6-dihydropyrazine alkylation

The earliest report on such lactim ether formation was from Sammes [72JCS(P1)2494], who converted piperazine-2,5-dione to 2,5-diethoxy-3,6-dihydropyrazine (173) with an excess of triethyloxonium fluoroborate. Subsequently, Rajappa and Advani (73T1299) converted proline-based piperazine-2,5-diones into the corresponding monolactim ethers. The starting material was a piperazinedione in which one of the amino acid units was the secondary amino acid proline, and the other a primary amino acid. This naturally led to the regiospecific formation of a monolactim ether (169) (on O-alkylation) from the secondary amide, whereas the tertiary amide remained intact. This was later extended to piperazine-2,5-diones in which the secondary amino acid was sarcosine [74JCS(P 1)2122], leading to the monolactim ethers (170). 

Diethoxypyrazine (87) gave the unisolated dihydro adduct (88), and thence racmic-2-butyl-3,6-diethoxy-2,5-dihydropyrazine (89) (BuLi, Et2NCH2CH2NEt2, THF, -70°C, 3 h then pH 7 buffer 75%) this underwent normal Schollkopf lithiation/alkylation at the 5-position but the product and derived amino acid were naturally both racemic.539... 

---