Thursday, December 18, 2025 12/18/2025

Mild Strategies in the Direct Generation of Carbocation Intermediates from C(sp3)–H Bonds

Award Number: R35GM147021
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: 07/05/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Mild Strategies in the Direct Generation of Carbocation Intermediates from C(sp3)–H Bonds - Project Summary/Abstract The broad goal of the proposed research is to develop highly enabling and rapid chemical technologies for the synthesis of life-altering drug compounds. Our focus is in the area of C–H functionalization, a synthetic strategy that is well-established to expedite the discovery of bioactive small molecules. Since its conception, the majority of Csp3–H functionalization methods rely on open-shell mechanistic pathways via alkyl radicals or metal alkyl intermediates. To continue the advancement of C–H modification technologies, there is a critical need for new mechanistic designs. We hypothesize that polar (two- electron) mechanisms can be accessed in a C–H functionalization context to offer orthogonal reactivity to the current state-of-the-art methods. To this end, our central hypothesis is to design reaction platforms that can access carbocation intermediates directly from a Csp3–H bond. The design will bypass the need for pre-installed functional groups that are usually required to generate carbocations, thus streamlining the direct modification of late-stage drug leads and resulting in the rapid synthesis of compound libraries for high-throughput drug development. The innovative approach to convert Csp3–H bonds into highly reactive carbocations is via a stepwise dismantling process: first hydrogen atom abstraction at the desired bond followed by a radical-polar crossover, or oxidation of a carbon radical to its cationic equivalent. With the design of the mechanism executed with a photocatalytic platform, we envision the reaction to be mild and capable of engaging a broad scope. The five-year goal is to utilize the proposed strategy to target benzylic, aliphatic and a-halo C–H bonds and utilize the resulting carbocations to facilitate high value bond formations with abundant nucleophilic partners. The proposal is significant in that we will be investigating an underexplored reaction space that is ripe with new synthetic opportunities that have the potential to offer modularity in approach, simplicity of reagents, and complexity of products.


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 = $822,263 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	008	5	7/31/2025	NON-COMPETING CONTINUATION	$399,291
2025	2025	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	005	3	6/20/2025	NON-COMPETING CONTINUATION	$399,291
2025	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	3	6/12/2025	NON-COMPETING CONTINUATION	-$363,983
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	006	4	6/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$98,046
2025	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	003	2	6/20/2025	NON-COMPETING CONTINUATION	-$1
2025	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	004	2	6/20/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	005	3	6/20/2025	NON-COMPETING CONTINUATION	-$1
2025	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	001	3	6/16/2025	SUPPLEMENT FOR EXPANSION	-$9,172
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	007	4	6/25/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	002	4	6/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$396,837
2025	2023	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	003	2	6/20/2025	NON-COMPETING CONTINUATION	-$77,637
2025	2023	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	004	2	6/20/2025	SUPPLEMENT FOR EXPANSION	-$20,408
														Subtotal = $822,263

Issue Date FY: 2024 ( Subtotal = $373,156 )
2024	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	3	5/6/2024	NON-COMPETING CONTINUATION	$363,984
2024	2024	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	001	3	5/7/2024	SUPPLEMENT FOR EXPANSION	$9,172
														Subtotal = $373,156

Issue Date FY: 2023 ( Subtotal = $462,739 )
2023	2023	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	001	2	5/26/2023	SUPPLEMENT FOR EXPANSION	$96,320
2023	2023	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	2	5/22/2023	NON-COMPETING CONTINUATION	$366,419
														Subtotal = $462,739

Issue Date FY: 2022 ( Subtotal = $341,864 )
2022	2022	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	1	7/5/2022	NEW	$341,864
														Subtotal = $341,864

Grand Total All Awards = $2,000,022

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mild Strategies in the Direct Generation of Carbocation Intermediates from C(sp3)–H Bonds

Award Number: R35GM147021

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: 07/05/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer