Organocatalytic aldol approach for the protecting group-free asymmetric synthesis of (7R′)-parabenzlactone, (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, (+)-isostegane and allied lignans

A short and efficient catalytic asymmetric protection-free synthesis of dibenzylbutyrolactone lignans, such as (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, and their 7-hydroxylignans - (7R)-parabenzlactone, (7R)-hydroxyyatein, (7R)-hydroxybursehernin, and (7R)-hydroxy pluviatolide, respectively, is described. The syntheses of (+)-isostegane and the formal synthesis of (-)-podophyllotoxin and bicubebins are also described. Organocatalytic aldol-reduction-lactonization and Pd/C-catalyzed hydrogenative debromination are two-pot sequential reactions for the enantioselective synthesis of hydroxybutyrolactone 13b with excellent diastereo-and enantioselectivity (dr 33:1 and >99% ee). The protecting group-free chemoselective alpha-alkylation of 13b directly led to 7-hydroxydibenzylbutyrolactone lignans, followed by hydrogenative dehydroxylation, which led to their (deoxy) dibenzylbutyrolactone lignans, and the syntheses were completed in three to five steps from 6-bromopiperonal.

Automated summary

In this study, a short and efficient catalytic asymmetric synthesis of dibenzylbutyrolactone lignans was described. Various compounds, including (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, and their 7-hydroxylignans, were successfully synthesized. The method involved organocatalytic aldol-reduction-lactonization and Pd/C-catalyzed hydrogenative debromination reactions, which allowed for a streamlined synthesis with high selectivity.