Stereoselective Synthesis of 1,1',2,2'-Tetrasubstituted Ferrocenes by Double Lithiation of a 1,1'-Disubstituted Ferrocenyl Pyrroloimidazolone

Abstract

This thesis explores the synthesis of 1,1'-ferrocenyl pyrroloimidazolone for the double diastereoselective lithiation-electrophile quench to yield 1,1',2,2'-tetrasubstituted ferrocenyl compounds. The synthesis followed known literature procedures affording 1,1'-ferrocenyl bisacylazide that then underwent Curtius rearrangement followed by condensation with excess L-proline to yield the desired bishydantoin product. One-pot hydrozirconation/hydrosilylation reaction of the bishydantoin was performed affording the desired chiral pyrroloimidazolone auxiliary. Optimization of the lithiationsubstitution procedure with different amounts of t-BuLi followed by quenching with chlorotrimethylsilane (TMSCl) determined that 4 equivalents of base was necessary to yield predominantly 1,1',2,2'-tetrasubstituted ferrocenyl compounds. Other electrophiles were used to expand the scope of the reaction. The stereochemistry of the tetrasubstituted products was elucidated from X-ray crystallography of the stannane adduct, as well as transmetalation, elimination, and deuteration experiments. It was revealed that the tetrasubstituted products have R-planar (Rp) chirality and the reaction proceeded with high diastereoselectivity (>95:5 dr).