# Development of Regioselective Alkene Dicarbofunctionalization Reactions

> **NIH NIH R35** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $371,643

## Abstract

Project Summary/Abstract
Catalytic dicarbofunctionalization of unactivated alkenes offers a powerful method to create two carbon-carbon
bonds simultaneously. Achievement of this objective offers to construct the cores of many biologically important
molecules rapidly, concisely and cost-effectively. Our long-term goal is to devise and create such reactions by
intercepting alkylmetal intermediates, generated in situ after the addition of organic halides to alkenes, with
carbon nucleophiles. The development of these processes with simple unactivated alkenes has been shown to
be exceptionally challenging, however, because of two key issues; slow migratory insertion of alkenes leading
to the formation of cross-coupling products, and faster -H elimination from alkylmetal intermediates than
transmetalation leading to the formation of Heck products. In the proposed research, we will implement three
strategies to difunctionalize unactivated alkenes regioselectively with organic halides and organometallic
reagents. First, we will introduce a strategy of Synergistic Bimetallic Cationic Catalysis, where cationic Ni(II)
catalysts are generated in situ to address the key issues identified above. This process will enable us to perform
regioselective ,-difunctionalization of unactivated alkenes located at the ,-position of carbonyl compounds.
In our second strategy, we introduce the concept of Metallacycle Contraction Process, a reaction that harnesses
the potential of alkylmetal intermediates to undergo -H elimination to contract a six-membered metallacycle to
a five-membered metallacycle, and difunctionalizes unactivated alkenes at the unusual 1,3-position rather than
the usual 1,2-position of alkenes. This unprecedented reaction allows us to create two new carbon-carbon bonds
at the - and -positions of carbonyl compounds containing ,-alkenes. Third, our ultimate goal is to develop
novel catalysts to modulate migratory insertion and -H elimination processes, and enable difunctionalization to
proceed with simple alkenes without requiring a coordinating group. We present different catalytic conditions,
which enable dicarbofunctionalization of alkenes lacking a coordinating group. The catalytic alkene
dicarbofunctionalization reactions proposed and for which we have strong preliminary results are unique
transformations that cannot be achieved with using other methodology.

## Key facts

- **NIH application ID:** 9999602
- **Project number:** 5R35GM133438-02
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Ramesh Giri
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,643
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999602

## Citation

> US National Institutes of Health, RePORTER application 9999602, Development of Regioselective Alkene Dicarbofunctionalization Reactions (5R35GM133438-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999602. Licensed CC0.

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