康 · 学术 | Reaction of the Day No. 1392
转自：康龙化成
Accessing Sulfonamides via FormalSO2 Insertion into C–N Bonds
MyojeongKim,1 Carys E. Obertone,1 Christopher B. Kelly,2,* Christopher A. Reiher,3,* Cristina Grosanu,4 James C. Robertson,5 and Mark D. Levin1,*
1 Departmentof Chemistry, University of Chicago, Chicago, Illinois 60637, United States;
2 Discovery Process Research, Johnson &Johnson Innovative Medicine, Spring House, Pennsylvania 19477, United States;
3 Parallel Medicinal Chemistry, Johnson& Johnson Innovative Medicine, Spring House, Pennsylvania 19477, UnitedStates;
4 High-Throughput Purification, Johnson& Johnson Innovative Medicine, Spring House, Pennsylvania 19477, UnitedStates;
5 In Silico Discovery, Johnson &Johnson Innovative Medicine, Spring House, Pennsylvania 19477, United States
—ChemRxiv, 2024, 10.26434/chemrxiv-2024-vj26z
Recommended by Rui Jin _ MC5
KEYWORDS: skeletal editing (反应类型), SO2 insertion (反应类型), Csp3–S, Csp2–S, S-N (成键类型), anomeric amide (催化剂), DABSO (原料), aliphatic amines (原料), anilines (原料), amides (原料), sulfonamides (产物), automation (其他)
ABSTRACT: MarkD. Levin et al. report a conceptually new strategy that enables net SO2-insertion into the C–N bond of primaryamines, enabling the direct synthesis of primary sulfonamides withoutpre-activation and effectively inverting the nitrogen’s properties (acidity,hydrogen bonding, etc.). The key to realizing this overall transformation isthe implementation of an anomeric amide as a dual-function reagent which bothserves to cleave the initial C–N bond and deliver a nitrogen atom to theproduct after SO2incorporation. The process tolerates awide array of functionalities and can be run in an automated fashion thusallowing libraries of amines to be viable progenitors to highly desirablesulfonamides.
Background and this work:(a)primary sulfonamides with therapeutic potential, (b) author’s goal and strategyfor underdeveloped direct SO2-insertion
Substrate scope for aliphatic amines,anilines and amides (selected examples)
Substrate scope: automated workflow
Proposedmechanism
