Molecular Editing by Nitrogen Insertion

Introduction

NINSERT constitutes a program to embark on selective and mild nitrogen insertions, both within and beyond carbonyl chemistry. Reagent development, catalyst design, and synergistic effects will be evaluated to provide a platform for late-stage skeletal editing, an area that has been recently brought to the forefront of organic chemistry.

Focus on Heterocycles

With a primary emphasis on heterocyclic motifs, commonly encountered in natural products and drug candidates, NINSERT offers a powerful tool to streamline future syntheses of nitrogen-containing compounds. Notably, approximately 59% of all small-molecule drugs feature nitrogen heterocycles, underscoring the profound impact this program will have on pharmaceutical research.

Tailoring Compound Profiles

Adjusting physicochemical properties by late-stage nitrogen insertion will enable medicinal chemists to tailor the overall compound profile on its way to candidate nomination and ultimately clinical studies.

Asymmetric Methods

Furthermore, asymmetric methods, as elucidated in this proposal, will give rise to molecular complexity within the 3D chemical space. Guided by the principles of strain-release and molecular recognition, we will utilize our expertise on asymmetric ring expansion and atom insertion reactions to deliver highly selective methods applicable to both academic and industrial research.

Historical Context

Despite the pioneering work of Beckmann and Schmidt over a century ago, nitrogen insertions have remained significantly constrained over the years, largely due to their substrate limitations, harsh reaction conditions, and unselective outcomes.

Conclusion

The progression to selective and widely applicable nitrogen insertions has been long overdue and marks a major driving force behind the development of NINSERT.