Synthesis of 4-Hydroxypipecolic Acid β-Lactam Analogues from Oxoazetidines

Significance

Two different stereocontrolled amino­cyclization routes from 3-azidoallenol-4-oxoazetidine-2-carbaldehyde 2 to new 4-hydroxypipecolic acid β-lactam analogues 6 and 8 are described. The route from 2 to 6 involves a key indium-mediated Barbier-type carbonyl-allenyl­ation reaction, followed by alcohol protection, reduction of azide to amine and finally aminocycli­zation. The route from 2 to 8 entails an organocatalytic (l-proline) aldol reaction followed by hydrogenation and aminocyclization. Enantio­pure compound 1 is reported.