# Nickel-Catalyzed Enantioconvergent Cross-Couplings of Racemic Silyl Electrophiles

> **NIH NIH F32** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $65,310

## Abstract

Project Summary
The past decade has seen substantial progress in the enantioselective transition metal
catalyzed cross couplings of alkyl halides with various organonucleophiles to form new
C-C bonds. More importantly, earth abundant metals have been realized to be excellent
catalysts for these processes compared to their precious metal counterparts. With the
use of metals such as Ni, Cu and Fe, current mechanistic data has pointed to single
electron pathways as important processes that provide new opportunities towards
asymmetric catalysis. For example, recent studies from the Fu group have provided
convincing evidence that radical intermediates are formed during Ni-catalyzed cross-
couplings between alkyl halides and organometallic partners. This in turn has allowed an
enantioconvergent approach using racemic starting materials and chiral catalysts to
construct carbon-centered stereogenic centers. This proposal expands on this concept
to discover and develop a novel enantioconvergent Ni-catalyzed cross-coupling between
halosilanes and boronic acids to control silicon-centered stereogenic centers. The first
specific aim will encompass two aspects. Initially the focus will be the discovery and
development of this methodology using rapid assay using chiral GC analysis will be
conducted to ascertain % conversion, % yield, and % ee. The second aspect will deal
with applications towards known silicon incorporated biologically active compounds will
then highlight this approach. Specifically, the first enantioselective total synthesis of a
silicon analog of combretastatin A-4, a novel tumor cell growth inhibitor, will be achieved.
The second specific aim will focus on systematic mechanistic studies will be performed
to elucidate if this novel methodology is mechanistically related to previous
enantioconvergent systems or has a unique operative pathway. Kinetic studies in
combination with EPR, UV-vis and mass spectrometry will be invaluable tools for the
success in this endeavor.

## Key facts

- **NIH application ID:** 9927488
- **Project number:** 5F32GM133109-02
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Robynne Kiley Neff
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927488

## Citation

> US National Institutes of Health, RePORTER application 9927488, Nickel-Catalyzed Enantioconvergent Cross-Couplings of Racemic Silyl Electrophiles (5F32GM133109-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9927488. Licensed CC0.

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