Asymmetric Synthesis of PlanarChiral 2-Monosubstituted Diferrocenyl Ketones

Abstract

A highly efficient and rapid entry to planar chiral 2monosubstituted diferrocenyl ketones is reported. Key step is the highly diastereoselective ortho-metalation of diferrocenyl ketone-SAMP-hydrazone, followed by trapping with various electrophiles. The subsequent racemisation-free cleavage of the chiral auxiliary affords the title diferrocenyl ketones 4a-g with one exception in good to very good overall yields and all with high enantiomeric excesses (ee = 97-99%).

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

“…155 The asymmetric formation of the carbon-heteroatom (Si, P, S) bonds was also possible via ortho-lithiation in the enantioselective synthesis of planarly chiral 1,1′-bisbenzoylferrocene and diferrocenyl ketone derivatives (Schemes 10 and 11). [125][126][127] …”

“…The racemization-free cleavage of the resulting hydrazones 72 afforded the corresponding ketones in good to very good overall yields (21-97%, depending on the cleavage method) and high enantiomeric excesses (97-99%). 126 The monosubstituted diferrocenyl ketones 72 (E ) SMe, PPh 2 /BH 3 , C(OH)Ph 2 ) have been subjected to ortho-metalation and reactions with electrophiles MeI, (i-PrS) 2 , (MeS) 2 , Me 3 SiCl. The reactions gave chiral disubstituted bisferrocenes in low to moderate yields (20-54%) and excellent stereoselectivities (97% to >99% ee, >96% de), however with poor regioselectivities in several cases.…”

“…The same diastereoselective ortho -metalation of diferrocenyl ketone SAMP-hydrazone 71 was applied to the preparation of planar chiral 2-monosubstituted diferrocenyl ketones (yields 88−99%, de ≥ 96%, Scheme ). The racemization-free cleavage of the resulting hydrazones 72 afforded the corresponding ketones in good to very good overall yields (21−97%, depending on the cleavage method) and high enantiomeric excesses (97−99%) . The monosubstituted diferrocenyl ketones 72 (E = SMe, PPh 2 /BH 3 , C(OH)Ph 2 ) have been subjected to ortho -metalation and reactions with electrophiles MeI, ( i -PrS) 2 , (MeS) 2 , Me 3 SiCl.…”

Comparison of Diastereoselective ortho-Metalations and C–H ­Activations of Chiral Ferrocenes

“…The method was also extended to 1,1´-disubstituted ferrocene ketones, 58 and diferrocene ketones. [59][60] Scheme 7 ortho-Lithiation of hydrazone derivatives.…”

Chiral Auxiliaries - Principles and Recent Applications

“…High yields and stereose-Scheme 37 Asymmetric Mannich reaction. 96 For all reported electrophiles the alkylation step proceeds with 96% de. This sequence provides ready access to a novel class of planar chiral ferrocenyl ligands containing a diferrocenyl ketone backbone.…”