Sunday, August 17, 2025 8/17/2025

Unlocking Access to Cyclopropanones as Divergent Reactive Intermediates in Synthesis

Award Number: R35GM142965
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: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Unlocking Access to Cyclopropanones as Divergent Reactive Intermediates in Synthesis - ABSTRACT Strained cyclic compounds are often used as key intermediates in the synthesis of bio-active drugs and natural products through strain-releasing reactions such as ring-expansion and ring-opening processes. While small ring ketones such as cyclobutanones have found widespread applicability in these transformations, the analogous use of cyclopropanone derivatives as substrates has seriously lagged behind, as these compounds have long been considered unsustainable synthetic intermediates due to their extreme strain and kinetic instability. This work proposes the use of 1-sulfonylcyclopropanols as a general class of stable cyclopropanone surrogates in organic synthesis, unlocking access to myriad previously inaccessible synthetic disconnections via strain-releasing reactions. These include (1) rearrangements initiated by the addition of nucleophiles, (2) transition metal-catalyzed C–C activation and deconstruction strategies, and (3) application of cyclopropanone derivatives as 1,1-cyclopropyl linchpins. We have already developed an efficient enantioselective route to these compounds and have obtained significant preliminary data in each of these types of reactions, leading to a variety of chiral synthons difficult to access by other methods. Both the electronic and steric nature of the sulfonyl moiety in these surrogates, which is acting here as a base-labile protecting group and conferring crystallinity to these compounds, is found to have a crucial impact on their rate of equilibration to cyclopropanone, highlighting their tunable reactivity and the potential for their widespread applicability as synthetic intermediates. During the funding period and using the mechanistic knowledge acquired, this technology leading to enantioenriched 1-sulfonylcyclopropanols will be extended to the formation of 1- sulfonylcyclopropylamine and hydrazines as modular precursors of chiral cyclopropanimines and hydrazones, respectively, and will allow novel access to chiral amine-containing scaffolds as well as strained chiral carbene equivalents. We firmly believe that the stability, ease of synthesis and modular character of these reagents will serve as a general solution to harvest the untapped versatility of cyclopropanones and its analogues as highly reactive building blocks in synthesis. Thus, this work will significantly expand the scope of disconnections available to chemists in the realm of strained ring activation and functionalization, evolving these severely strained derivatives from chemical curiosities to versatile synthetic intermediates, greatly contributing to streamline the production of biologically relevant organic molecules.


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 = $357,509 )
2025	2025	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Biomedical Research and Research Training	000	5	7/25/2025	NON-COMPETING CONTINUATION	$357,509
														Subtotal = $357,509

Issue Date FY: 2024 ( Subtotal = $359,554 )
2024	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Biomedical Research and Research Training	000	4	5/14/2024	NON-COMPETING CONTINUATION	$359,554
														Subtotal = $359,554

Issue Date FY: 2023 ( Subtotal = $361,413 )
2023	2023	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Biomedical Research and Research Training	000	3	5/15/2023	NON-COMPETING CONTINUATION	$361,413
														Subtotal = $361,413

Issue Date FY: 2022 ( Subtotal = $363,102 )
2022	2022	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Biomedical Research and Research Training	000	2	5/9/2022	NON-COMPETING CONTINUATION	$363,102
														Subtotal = $363,102

Issue Date FY: 2021 ( Subtotal = $360,324 )
2021	2021	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Biomedical Research and Research Training	000	1	7/15/2021	NEW	$360,324
														Subtotal = $360,324

Grand Total All Awards = $1,801,902

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Unlocking Access to Cyclopropanones as Divergent Reactive Intermediates in Synthesis

Award Number: R35GM142965

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: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer