# New Methods for the Synthesis of Carbocycles and Heterocycles

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $290,157

## Abstract

Project Summary
 The stereoselective construction of saturated heterocycles and carbocycles remains an important
challenge in organic synthesis, as many pharmaceutically relevant molecules and biologically active natural
products contain these subunits. Although the development of methods for the construction of heterocycles
and carbocycles has been of longstanding interest, a number of important targets are difficult to generate in a
stereoselective manner using existing transformations. In addition, many methods are not readily amenable
to the preparation of numerous analogs from a single precursor.
 The long-term goal of our research program is to develop new reactions for the construction of
enantiomerically enriched, biologically active molecules. The objectives of the research outlined in this
proposal, are to develop new alkene difunctionalization reactions for the construction of useful heterocycles
and carbocycles, to develop new catalysts for alkene difunctionalization reactions, and to gain insight into
factors that facilitate alkene heteropalladation and sp3C–N bond-forming reductive elimination. These
objectives will be achieved by pursuing two specific aims: (1) to prepare functionalized carbocycles via alkene
difunctionalization reactions between alkenes bearing pendant carbon-centered electrophiles and exogenous
nucleophiles; and (2) to prepare substituted heterocycles via alkene difunctionalization reactions that employ
nitrogen-centered electrophiles.
 The proposed studies are innovative because they will explore fundamentally new reactivity, such as the
use of allylic electrophiles, nitrogen-centered electrophiles, or chiral enamine nucleophiles in Pd-catalyzed
alkene difunctionalization reactions. Our experiments will result in new catalysts that facilitate challenging
anti-heteropalladation reactions of hindered alkenes, which have been implicated as key steps in other
synthetically useful transformations. These studies will also provide insight into factors that facilitate sp3C–N
bond-forming reductive elimination from Pd(II), which is a rare step in catalysis, but has the potential to be
broadly used as a key step in new reactions that lead to C–N bond formation. This knowledge will be of
significant utility in the future development of other new palladium-catalyzed transformations.
 The proposed research is significant because the new transformations developed during these studies will
provide access to important biologically active compounds that are difficult to generate with existing methods.
This will broaden the range of carbocyclic and heterocyclic building blocks available for use in medicinal
chemistry/drug development. In addition, these new transformations will also allow for facile generation of
analogs of interesting molecules, that differ in either their stereochemistry or in the nature of their
substituents, which can be used to optimize biological or pharmaceutical properties of lead compounds.

## Key facts

- **NIH application ID:** 10137262
- **Project number:** 5R01GM124030-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JOHN P WOLFE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $290,157
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137262

## Citation

> US National Institutes of Health, RePORTER application 10137262, New Methods for the Synthesis of Carbocycles and Heterocycles (5R01GM124030-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137262. Licensed CC0.

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