Asymmetric Synthesis of 1-Substituted 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazines

The reactions of 1-(2-haloethyl)pyrrole-2-carbaldehyde with (S)-1-phenylglycinol or (S)-valinol produced the fused tricyclic oxazolidines as single diastereomers, from which 1,2-disubstituted 1,2,3,4-tetrahydropyrrole[1,2-a]pyrazines were obtained by addition of organometallic reagents. The diastereoselectivity was dependent on the nature of both the chiral auxiliary and the organometallic reagent. The best diastereoselectivity (d.r. up to 98:2) was obtained using Grignard reagents on the oxazolidine derived from (S)-phenylglycinol. (+)-1-Methyl- and (+)-1-ethyl-1,2,3,4-tetrahydropyrrole[1,2-a]pyrazines were obtained by reductive removal of the N2-substituent.