# Catalytic Methods for Organic Synthesis

> **NIH NIH R35** · RUTGERS THE STATE UNIV OF NJ NEWARK · 2022 · $378,644

## Abstract

PROJECT SUMMARY
 Transition-metal-catalyzed cross-coupling reactions are among the most important methods for the
synthesis of pharmaceuticals and enable facile preparation of molecules essential for synthetic chemistry,
medicinal chemistry and pharmaceutical purposes. Further advancement in the field of cross-coupling is
closely tied to (1) the development of new cross-coupling precursors, and (2) the design of new highly active
catalysts that allow rapid access to important pharmaceutically relevant structural motifs.
 Accordingly, the purpose of this work is two-fold: (1) to develop a valuable new reaction manifold of
carboxylic acids that permits ready access to metal electrophiles from ubiquitous carboxylic acids, and (2) to
develop new classes of well-defined metal catalysts based on NHC ligands (NHC = N-heterocyclic carbene).
 Work in this laboratory over the last four years has introduced new methods for the direct cross-
coupling of amide bonds in a range of generic transition-metal catalyzed cross-couplings using Pd, Rh and Ni
catalysis. These methods permit direct engagement of one of the most fundamental bonds in chemistry,
namely, the amide linkage, in cross-coupling reactions of high value. Furthermore, research in this laboratory
has demonstrated metal-NHC catalysts as highly reactive catalysts in activating traditionally inert acyl bonds.
Importantly, this permits conceptualization of a cross-coupling concept between amides and esters.
 Broadly speaking, the goal of our research for the next five years is to develop new methods that allow
direct engagement of ubiquitous carboxylic acids in cross-coupling reactions of high synthetic value. In this
reactivity manifold, the ubiquitous carboxylic acid moiety serves as an equivalent of aryl halide or pseudohalide
by exploiting the oxidative addition/decarbonylation pathway. Although carboxylic acids are among the most
important motifs in organic synthesis, biologically active compounds and pharmaceuticals, their cross-coupling
with a concomitant loss of carbon dioxide is inherently limited by the use of expensive oxidants, harsh
conditions and specific substitution patterns. This prohibits generality stemming from the rational control of
elementary steps in the catalytic cycle.
 As a second general goal of our research, we aim to develop new, rationally-designed metal-catalysts
based on NHC ligands for cross-coupling reactions. Our studies will outline the synthesis and generation of
highly active, electron-rich, sterically-hindered and flexible catalysts that promote a broad range of important
cross-couplings by controlling elementary steps of the catalytic cycle by ligand design. The studies will involve
cross-couplings that are currently beyond the scope of current methods as well as C–C, C–N and C–X cross-
coupling reactions that are routinely employed in the most important pharmaceutical transformations.
 The new catalytic methods and catalysts targeted by our research program wil...

## Key facts

- **NIH application ID:** 10437845
- **Project number:** 5R35GM133326-04
- **Recipient organization:** RUTGERS THE STATE UNIV OF NJ NEWARK
- **Principal Investigator:** Michal Szostak
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,644
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437845

## Citation

> US National Institutes of Health, RePORTER application 10437845, Catalytic Methods for Organic Synthesis (5R35GM133326-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437845. Licensed CC0.

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