# Catalytic Reductive C-H and C-C Silylation with Silyl Acetals

> **NIH NIH R15** · UNIVERSITY OF TEXAS ARLINGTON · 2020 · $448,991

## Abstract

Project Summary/Abstract
The long-term goal of this research is to develop highly efficient synthetic methods for preparation of high-
value synthetic building blocks and bioactive molecules and to advance our understanding of the associated
catalytic mechanisms. Organosilanes are stable, abundant, and virtually nontoxic, and they serve as
extremely important synthetic building blocks for preparation of a wide range of bioactive molecules.
Despite the advances on organosilane chemistry, much less success has been achieved on broadly
applicable regio-, stereo-, and chemoselective silylation of unactivated C–C and C–H bonds. The objective
of this proposal is to expand the dimension of organosilicon chemistry directed toward organic synthesis by
developing new synthetic methods for C–Si formation, based on understanding the underlying complex
organometallic mechanisms. The objective will be accomplished through development and application of
effective C–C and C–H silylation methodologies. This research program introduces three innovative
synthetic strategies: Specific Aim I: develop enantioselective redox neutral umpolung C–C silylation of
cyclopropanols; Specific Aim II: develop inverse polarity net oxidative C–C silylation of cyclopropanols;
Specific Aim III: develop a traceless, dual C–H silylation approach to modular synthesis of a large set of
chiral 3,3’-bis-silyl BINOLs and phosphorous ligands. Based on encouraging preliminary results and initial
mechanistic studies, the hypothesis for Aim I is that chiral ester or catalyst-controlled enantioselective C–
C activation directed by hydrosilyl acetals allows to install a silicon moiety on a hindered carbon regio- and
enantioselectively, leading to a silicon-bearing tetrasubstituted carbon center. The hypothesis for Aim II is
that an oxidative silylation of cyclopropanols can be achieved through formation of metallo homoenolate-
enol ether [(Z)-MHEE] intermediates that further undergoes subsequent silylation. The hypothesis for Aim
III is that a sequence of dual C–H silylation of BINOLs, followed by nucleophilic activation of the resulting
bis-dioxasilines with a variety of nucleophiles permit 3,3’-bis-silyl binaphthols with spontaneous removal of
the directing groups. The rationale is that completion will significantly improve our knowledge concerning
catalytic C–H and C–C silylation strategies and provide original approaches to structural motifs including
enantio-enriched cyclic silanes to access tertiary alcohols, metallo homoenolate-enol ether intermediates
leading to functionalized ketones, and chiral ligand scaffolds for asymmetric synthesis. These molecules
can be ultimately used for preparation of biomedically relevant targets. The expected outcome of this work
is to provide high-value synthetic building blocks, substructural units of biomedically relevant targets, and
silicon-containing bioactive molecules. The results will have an important positive impact because the
proposed research w...

## Key facts

- **NIH application ID:** 9881554
- **Project number:** 2R15GM116031-02
- **Recipient organization:** UNIVERSITY OF TEXAS ARLINGTON
- **Principal Investigator:** Junha Jeon
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,991
- **Award type:** 2
- **Project period:** 2016-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881554

## Citation

> US National Institutes of Health, RePORTER application 9881554, Catalytic Reductive C-H and C-C Silylation with Silyl Acetals (2R15GM116031-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/9881554. Licensed CC0.

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