# Synthetic Methods based on Biphilic Phosphorus Catalysts

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $447,189

## Abstract

PROJECT SUMMARY/ABSTRACT
Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to
treat human disease. This project has the long-term goal of developing a broad class of inexpensive
nonmetal catalysts that promote catalytic transformations via formal oxidation state cycling in qualitative
analogy to transition metal catalysis. Within this overarching goal, the primary focus of this proposal is
the design and application of phosphorus-based catalysts that function in the P(III)⇌P(V) redox couple.
While phosphines are well-established in catalysis as spectator ligands for transition metal catalysis and
as nucleophilic catalysts, this research describes innovative phosphorus-based catalysts of novel com-
position and structure that explore the structural and electronic conditions required to enable new catalyt-
ically-relevant reactivity via reversible P(III)⇌P(V) oxidation state cycling. The first major effort is the de-
velopment of new methods for activation of amides and stable oxoanions for direct functionalization via
P(III)⇌P(V) redox reactivity. The second major effort is the development of phosphine-catalyzed O-atom
transfer methods that result in reductive transformations of nitroarene compounds to furnish functional-
ized anilines through the formation of new carbon-nitrogen bonds. The third major effort involves the de-
velopment of P(III)⇌P(V)-catalyzed O-atom transfer methods that result in reductive N-functionalization
of nitroalkanes, including new phosphacyclic structures that express biphilic P(III)⇌P(V) redox reactivity.
The proposed research is expected to yield new practical catalytic methods for the construction of phar-
macologically-relevant small molecules that meet the challenges of sustainable synthesis, and an im-
proved fundamental understanding the interplay between structure and reactivity in the p-block that will
underpin future development of nonmetals for atom transfer, bond activation, and catalysis. Taken to-
gether, these outcomes will advance nonmetal-based redox catalysis as a powerful modality in pharma-
ceutical synthesis.

## Key facts

- **NIH application ID:** 10803827
- **Project number:** 2R01GM114547-11
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ALEXANDER T RADOSEVICH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $447,189
- **Award type:** 2
- **Project period:** 2015-03-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803827

## Citation

> US National Institutes of Health, RePORTER application 10803827, Synthetic Methods based on Biphilic Phosphorus Catalysts (2R01GM114547-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803827. Licensed CC0.

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