Preparation of Optically Active α-Amino[3]ferrocenophanes-Building Blocks for Chelate Ligands in Asymmetric Catalysis

摘要

Treatment of 1,1'-diacetylferrocene (4) with dimethylamine and TiCl_4 yielded the unsaturated dimethylamino-substituted [3]ferrocenophane product 5. Its catalytic hydrogenation gave the corresponding saturated [3]ferroenophane system 6 (trans/cis ≈ 7:1). The rac-[3]ferrocenophane amine 6 was partially resolved (to ca. 80% ee) by means of L- or D-O,O'-dibenzoyltartrate salt formation. Treatment of 4 with the pure (R)- of (S)-methyl(1-phenylethy) amine (8)/TiCl_4 gave the corresponding optically active unsaturated [3]ferrocenophane amines (R)-(+)-9 and (S)-(-)-9, respectively. Their catalytic hydrogenation again proceeded trans-selectively, giving the corresponding saturated diastereomeric [3]ferrocenophane amines (1R,3R,5R)-10a and (1S,3S,5R)-10b [starting from (R)-9], their enantiomers ent-10a and ent-10b were obtained from (S)-9, but with a poor asymmetric induction (10a/10b < 2:1). Quaternization of 6 (CH_3I) followed by amine exchange using (R)- or (S)-methyl(1-phenylethyl)-amine (8), respectively, proceeded with overall retention. Subsequent chromatographic separation gave the pure diastereoisomers (1R,3R,5R)-10a and (1S,3S,5R)-10b [from (R)-8, ent-10a and ent-10b from (S)-8] in > 60% yield. Subsequently, the benzylic (1-phenylethy) auxiliary was removed from the nitrogen atom by catalytic hydrogenolysis to yield the enantiomerically pure (> 98%) ([3]ferrocenophanyl)-methylamines (1R,3R)-11 and (1S,3S)-11, respectively, which were converted into the corresponding dimethylamino-substituted [3]ferrocenophanes (1R,3R)-6 and (1S,3S)-6. Each enantiomer from the following enantiomeric pairs was isolated in its pure form and characterized by X-ray diffraction: (R)-9/(S)-9; (1R,3R,5R)-10a/(1S,3S,5S)-10a; (1R,3R,5S)-10b/(1S,3S,5R)-10b; (1R,3R)-11/(1S,3S)-11.