Enantioselective Synthesis of Ferrocene‐Fused Planar‐Chiral Cyclic Phosphonic Acid Derivatives

Planar‐chiral ferrocene‐fused cyclic phosphonic acid half‐ester ( S )‐ 1a was prepared in an enantiomerically pure form by the enantioselective transformation. The synthesis started from Kagan's chiral ferrocenyl acetal (–)‐ 2a and resulted in ferrocene derivative ( S )‐ 6a substituted by a 2‐hydroethyl substituent at the 1‐position and by a (EtO) 2 P(O)‐ group at the 2‐position. The chiral acetal substituent in (–)‐ 2a is a powerful chiral directing group, and thus planar‐chiral ( S )‐ 6a was isolated in >99% ee. The base‐promoted intramolecular transesterification/cyclization of ( S )‐ 6 and following selective hydrolysis of the exocyclic ethoxy moiety afforded ( S )‐ 1a in an enantiomerically pure form. The ( η 5 ‐C 5 Me 5 )Fe and ( η 5 ‐C 5 Ph 5 )Fe analogues, ( S )‐ 1b and ( S )‐ 1c , were prepared by the similar strategy, but the use of the exocyclic benzyl ester and the palladium‐catalyzed benzyl‐selective hydrogenolysis is essential to complete the synthesis of ( S )‐ 1b /( S )‐ 1c . Brønsted acidic ( S )‐ 1a‐c were examined as chiral organocatalysts in the direct Mannich reaction between N ‐boc‐imine 10 and acetylacetone showing good catalytic activity and modest enantioselectivity.