Sunday, September 14, 2025 9/14/2025

Highly Selective Catalytic Reactions of Alkenes and Alkynes Relevant to Medicinal and Process Chemistry

Award Number: R35GM139545
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Highly Selective Catalytic Reactions of Alkenes and Alkynes Relevant to Medicinal and Process Chemistry - Project Summary/Abstract A recent critical analysis of biologically active molecules and reactions most often used for their preparation suggests that fraction of saturated carbons and presence of chiral centers correlate with success as a compound moves from discovery, through clinical trials to an approved drug. About a third of the compounds had at least one chiral center. In addition, practical aspects of manufacturing still need to be addressed to market a cost effective drug. Thus discovery of fundamentally new catalytic reactions, especially enantioselective ones, showing high turnover frequencies (i.e., substrate/ catalyst/unit time), that use readily available precursors, will have a significant impact on medicinal and process chemistry. Through an approach that relies heavily on mechanistic insights we strive to discover new enantioselective reactions of alkenes and alkynes. For example, use of low-valent chiral (L*)cobalt complexes has enabled heterodimerization between a broad range of 1,3-dienes, and, ethylene and alkyl acrylates, which are feedstock materials. The products of these reactions are synthetically valuable chiral 1,4-skipped dienes (produced in >90% yield and ee) which can be turned into pharmaceutically relevant classes of compounds. Examples cited include anti-microbial and anti-tumor and antifungal agents, GABA analogs, and metalloproteinase inhibitors. On-going mechanistic studies strongly suggest the intermediacy of a cationic {[P~P)Co(L)]+}X– species in these exceptionally selective C-C bond-forming reactions that proceed under ambient conditions. Most remarkably, we recently (2018/2019) found that the chiral cationic Co(I) complexes with custom-designed ligands catalyze enantioselective [2+2]-additions of alkynes and vinyl-X derivatives, opening, arguably, the best route to enantiopure 3-substituted cyclobutenes, potential precursors other valuable compounds. In sharp contrast to 1,3-dienes, 1,3-enynes form, initially, vinylcyclobutenes and then, in a tandem fashion, highly functionalized cyclobutanes with an all-carbon quaternary centers. Such reactions are highly efficient and uncommon. Preliminary results also indicate that chiral cationic Co(I)-complexes catalyze at least 4 other types of reactions (hydroboration, hydroacylation and hydrosilylation of prochiral 1,3-dienes, and, cyclizaion/HV of 1,6- enynes). We plan to explore how many of the combinations of reactions can be run in tandem, in attempts to exploit the full potential of the new cobalt chemistry in organic syntheis. Historically some of the reactions we work on had been carried out using precious metals. We expect, when fully devloped, cobalt (which is 100 to 200 time cheaper than Rh for example), will be able to catalyze some of these basic reactions. The interdisciplinary nature of the work proposed here provides outstanding opportunities to train future scientists at every level of their education.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $383,960 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	002	5	8/13/2025	NON-COMPETING CONTINUATION	$38,396
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	5	12/12/2024	NON-COMPETING CONTINUATION	$345,564
2025	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	4	11/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,960

Issue Date FY: 2024 ( Subtotal = $383,960 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	4	5/20/2024	NON-COMPETING CONTINUATION	$38,396
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	4	12/7/2023	NON-COMPETING CONTINUATION	$345,564
														Subtotal = $383,960

Issue Date FY: 2023 ( Subtotal = $383,960 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	3	12/14/2022	NON-COMPETING CONTINUATION	$345,564
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	3	4/5/2023	NON-COMPETING CONTINUATION	$38,396
														Subtotal = $383,960

Issue Date FY: 2022 ( Subtotal = $463,633 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	002	2	6/30/2022	NON-COMPETING CONTINUATION	$38,396
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	2	5/24/2022	SUPPLEMENT FOR EXPANSION	$79,673
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	2	12/30/2021	NON-COMPETING CONTINUATION	$345,564
														Subtotal = $463,633

Issue Date FY: 2021 ( Subtotal = $453,506 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	1	12/21/2020	NEW	$453,506
														Subtotal = $453,506

Grand Total All Awards = $2,069,019

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Highly Selective Catalytic Reactions of Alkenes and Alkynes Relevant to Medicinal and Process Chemistry

Award Number: R35GM139545

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer