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

The reactions of 1-(2-haloethyl)pyrrole-2-carbaldehydes with (1S)-1-phenylglycinol or (1S)-valinol gave the corresponding 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 (dr <= 98:2) was obtained by using Grignard reagents with the oxazolidine derived from (1S)-phenylglycinol. (+)-1-Methyl- and (+)-1-ethyl-1,2,3,4-tetrahydropyrrole[1,2-a]pyrazines were obtained by reductive removal of the N2-substituent.