Innovative Tools for Chemical Synthesis: Cyclase-Inspired Catalysis, Shuttle Catalysis, and Tandem Catalysis

NIH RePORTER · NIH · R35 · $101,614 · view on reporter.nih.gov ↗

Abstract

Principle Investigator/Program Director (Last, first, middle): Dong, Vy, M   Project Summary/Abstract: The synthesis and implementation of organometallic reagents and intermediates has become a cornerstone in the formation of complex therapeutic agents. Thus, the development of novel methods for accessing these intermediates in a simple and efficient manner has become a large focus of the synthetic organic and organometallic community. Organozinc reagents have shown themselves to be a powerful tool in complex organic synthesis in areas such as carbonyl addition, cross coupling reactions (Negeshi coupling), and functionalization of alkenes and alkynes. As the need for these important nucleophiles becomes more apparent, chemists have sought out ways to make them by efficient and sustainable methods. Previous work by Knochel and Sato has shown that nickel and titanium catalysts can convert olefins to organozincs efficiently, however their work does not impose stereochemical selectivity. Our goal, described herein, is to expand on the use of titanium catalysis to generate organozincs in an enantiopure method using chiral titanium catalysts and simple, unbiased olefins as starting materials. Following the formation of these stereochemically active nucleophiles, we aim to couple them with carbon dioxide using chemistry similar to previous studies in the Dong research group. Utilizing simple and readily available starting materials as well as more structurally diverse catalysts and substrates to gain access to these species could improve access to organozinc intermediates as well as their use in the synthesis of complex final products.

Key facts

NIH application ID
10371806
Project number
3R35GM127071-04S1
Recipient
UNIVERSITY OF CALIFORNIA-IRVINE
Principal Investigator
Vy M Dong
Activity code
R35
Funding institute
NIH
Fiscal year
2021
Award amount
$101,614
Award type
3
Project period
2018-05-01 → 2023-04-30