Peptide‐Catalyzed Desymmetrization of an Achiral Ferrocenyl Compound To Induce Planar Chirality

Abstract

Selective monohydrogenation of an achiral ferrocenebis(enal) was achieved with a resin‐supported peptide catalyst to afford an enantioenriched planar‐chiral product. It was also demonstrated that the reaction was followed by a kinetic resolution through cyclization of the product.

Asymmetric Catalysis Mediated by Synthetic Peptides, Version 2.0: Expansion of Scope and Mechanisms

“…This methodology was further expanded to address symmetrical, bis(enal)-containing ferrocene compounds, such as 3.12 (Figure 36b). 122 In this case, both monoreduced 3.13 and the product of intramolecular cyclization (3.14) were possible. The choice of an acidic additive proved essential to controlling the product ratio.…”

“…During their investigations into the kinetic resolution of metallocene 7.81 via transfer hydrogenation (Section 3.1), Kudo and coworkers also explored conjugate additions of nitromethane (Figure 141). 122 Using peptide 7.83, the same catalyst that was used to catalyze the transfer hydrogenation of 7.81, a high k rel was observed, providing the conjugate addition product (R p )-7.82 in >99:1 dr and 95% ee (Figure 141a). However, this catalyst proved ill-suited to catalyzing the related conjugate addition of nitromethane into [2.2] paracyclophane derivatives 7.84 (Figure 141b).…”

“…This orientation potentially facilitates secondary interactions between the iminium cation and the oxygen lone pairs of Hse­(Me), which may inhibit particular approach trajectories of the HEH reductant (Figure a). This methodology was further expanded to address symmetrical, bis­(enal)-containing ferrocene compounds, such as 3.12 (Figure b) . In this case, both monoreduced 3.13 and the product of intramolecular cyclization ( 3.14 ) were possible.…”

“…(a) Kinetic resolution of enal-containing ferrocene complexes with Pro-based peptide catalysts. (b) Desymmetrization of bis­(enal) containing ferrocene complexes. , …”

Organocatalytic enantioselective desymmetrisation

“…218 The process is based on their previous kinetic resolution of prochiral ferrocenyl enals; 219 it uses a solid-supported oligopeptide (14 amino acids) catalyst C-146 containing an N-terminal proline which is believed to form a reactive iminium adduct with the substrate (Scheme 121). 218 The process is based on their previous kinetic resolution of prochiral ferrocenyl enals; 219 it uses a solid-supported oligopeptide (14 amino acids) catalyst C-146 containing an N-terminal proline which is believed to form a reactive iminium adduct with the substrate (Scheme 121).…”