Microwave-assisted synthesis of the Schِllkopf chiral auxiliaries: (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine

A practical and efficient methodology for the laboratory scale preparation of Schöllkopf’s bis-lactim ether chiral auxiliaries (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine has been developed. The key step is the preparation of the 2,5-diketopiperazine derivative by microwave-assisted heating in water. The protocol avoids reactions at low temperature and the use of high boiling solvents. Only inexpensive and readily available starting materials are required. The bis-lactim ethers were produced in high yields on a multigram scale.