Outer-Sphere Control for Divergent Multicatalysis with Common Catalytic Moieties.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Simultaneous reactions offer efficiency but often face challenges in controlling selectivity.
• Orthogonal catalysts with shared motifs present an opportunity for complex one-pot transformations.
• Chiral scaffolds play a crucial role in directing stereochemical outcomes in catalysis.

Purpose of the Study:

• To demonstrate the feasibility of one-pot, simultaneous reactions using multiple orthogonal catalysts.
• To explore the use of chiral phosphoric acids (CPA) and peptide-based catalysts in complex synthetic sequences.
• To investigate how appended chiral scaffolds influence catalyst selectivity through outer-sphere interactions.

Main Methods:

• Employing BINOL-derived chiral phosphoric acids (CPA) and phosphothreonine (pThr)-embedded peptides for double reductions of bisquinolines.
• Utilizing π-methylhistidine (Pmh)-containing peptides to catalyze enantio- and chemoselective acylations and phosphorylations.
• Designing systems where common catalytic moieties achieve distinct selectivities based on their chiral environments.

Main Results:

• Successful execution of two distinct one-pot, simultaneous reaction cascades.
• Demonstrated matching of CPA and pThr-peptides for sequential steps in bisquinoline reductions.
• Achieved high enantio- and chemoselectivity in acylations and phosphorylations using Pmh-peptides.
• Showcased that chiral scaffolds modulate selectivity of common reactive groups via outer-sphere interactions.

Conclusions:

• One-pot, simultaneous reactions are achievable with multiple orthogonal catalysts sharing catalytic motifs.
• Peptide-based catalysts, functionalized with specific chiral scaffolds, offer precise control over complex transformations.
• This strategy provides a powerful platform for efficient and selective synthesis of diverse molecules.