N-Fluorobenzenesulfonimide (NFSI)
N-Fluorobenzenesulfonimide serves as a gentle electrophilic fluorinating agent and is also capable of acting as a potent oxidant to facilitate reductive elimination processes involving transition metals.
Recent Literature
Organic selenium-based catalysis provides an efficient methodology for the synthesis of 3-amino allylic alcohols, achieving remarkable regio- and stereoselectivity when conducted in the presence of a base. In contrast, the absence of a base leads to the formation of α,β-unsaturated aldehydes in high yields. Notably, the presence of a hydroxyl group is essential for the direct amination process to occur.
Z. Deng, J. Wei, L. Liao, H. Huang, X. Zhao, Org. Lett., 2015, 17, 1834-1837.
https://doi.org/10.1021/acs.orglett.5b00213
A highly diastereoselective Pd-catalyzed carbonyl allylation reaction of aldehydes and isatins, employing simple acyclic olefins as allylating agents, involves two key steps: a Pd-catalyzed oxidative allylic C-H borylation followed by a phosphoric acid-accelerated allylboration of carbonyls. In this process, N-fluorobenzenesulfonimide serves as a crucial oxidant.
Z.-L. Tao, X.-H. Li, Z.-Y. Han, L.-Z. Gong, J. Am. Chem. Soc., 2015, 137, 4054-4057.
https://doi.org/10.1021/jacs.5b00507
Cu(acac)2 facilitates an innovative N-demethylation process of N-methyl amides when combined with N-fluorobenzenesulfonimide acting as an oxidant. This reaction pathway proceeds through the formation of carbinolamines as transient intermediates, which, due to their intrinsic instability, spontaneously degrade into N-demethylated amides and formaldehyde.
X. Yi, S. Lei, W. Liu, F. Che, C. Yu, X. Liu, Z. Wang, X. Zhou, Y. Zhang, Org. Lett., 2020, 22, 4583-4587.
https://doi.org/10.1021/acs.orglett.0c00863
The synergistic application of silyl radical-mediated halogen-atom abstraction and benzophenone photosensitization facilitates the fluorination of alkyl bromides. In this process, a preference for halogen-atom abstraction over Si-F bond formation is observed when employing an electrophilic fluorinating reagent characterized by a weak N-F bond.
G. H. Lovett, S. Chen, X.-S. Xue, K. N. Houk, D. W. C. MacMillan, J. Am. Chem. Soc., 2019, 141, 20031-20036.
https://doi.org/10.1021/jacs.9b11434
A Cu-catalyzed C-H fluorination reaction, utilizing N-fluorobenzenesulfonimide (NFSI) as the fluorinating agent, enables the subsequent substitution of the generated fluoride with various nucleophiles. This strategy facilitates a site-selective conversion of benzylic C-H bonds into a range of functional groups.
A. Vasilopoulos, D. L. Golden, J. A. Buss, S. S. Stahl, Org. Lett., 2020, 22, 5746-5748.
https://doi.org/10.1021/acs.orglett.0c02238
Planar chiral [2.2]paracyclophane-derived isothiourea catalysts mediate a highly efficient enantioselective fluorination of carboxylic acids, yielding a diverse array of optically active α-fluoroesters in high yields and with exceptional enantioselectivity.
S. Yuan, C. Liao, W.-H. Zheng, Org. Lett., 2021, 23, 4142-4146.
https://doi.org/10.1021/acs.orglett.1c01046
A catalytic asymmetric coupling reaction between aryl alkyl ketenes and commercially available N-fluorobenzenesulfonimide (NFSI), in the presence of C6F5ONa, leads to the formation of tertiary α-fluoroesters. Mechanistic investigations indicate that the inclusion of an external nucleophile, specifically C6F5ONa, is essential for catalyst turnover by liberating the catalyst from an N-acylated intermediate.
S. Y. Lee, S. Neufeind, G. C. Fu, J. Am. Chem. Soc., 2014, 136, 8899-8902.
https://doi.org/10.1021/ja5044209
Functionalized aryl or heteroaryl magnesium reagents, generated from the respective bromides or iodides via halogen-magnesium exchange or direct magnesium insertion in the presence of lithium chloride, undergo a smooth reaction with N-fluorobenzenesulfonimide, yielding the corresponding aromatic fluorides in satisfactory amounts.
S. Yamada, P. Knochel, Synthesis, 2010, 2490-2494.
https://doi.org/10.1055/s-0029-1218816
The coupling of esters with geminal bis(boron) compounds, accomplished without the use of transition metals, yields an α,α-bis(enolate) equivalent. This intermediate can be readily captured by electrophiles such as alkyl halides and fluorinating agents, offering an efficient and convergent synthetic approach for the preparation of α,α-difunctionalized ketones.
C. E. Iacono, T. C. Stephens, T. S. Rajan, G. Pattison, J. Am. Chem. Soc., 2018, 140, 2036-2040.
https://doi.org/10.1021/jacs.7b12941
The coupling of esters with geminal bis(boron) compounds, accomplished without the use of transition metals, yields an α,α-bis(enolate) equivalent. This intermediate can be readily captured by electrophiles such as alkyl halides and fluorinating agents, offering an efficient and convergent synthetic approach for the preparation of α,α-difunctionalized ketones.
C. E. Iacono, T. C. Stephens, T. S. Rajan, G. Pattison, J. Am. Chem. Soc., 2018, 140, 2036-2040.
https://doi.org/10.1021/jacs.7b12941
A vanadium-catalyzed reaction that couples allenylic alcohols with electrophilic halide reagents yields α-halo-α',β'-unsaturated ketones. This methodology is versatile, allowing the use of fluorine, chlorine, and bromine electrophiles. The resulting products serve as valuable intermediates, enabling the introduction of nitrogen, oxygen, sulfur, and iodine nucleophiles at the α-position relative to the ketone through substitution chemistry.
B. M. Trost, J. S. Tracy, T. Yusoontorn, Org. Lett., 2019, 21, 1207-1211.
https://doi.org/10.1021/acs.orglett.9b00195
The isothiourea-catalyzed fluorination of alkynyl-substituted acetic acids enables the synthesis of a diverse array of optically active tertiary α-alkyl fluorides with remarkable enantioselectivity, achieving up to 97% enantiomeric excess (ee). Notably, this protocol can be readily scaled up to the Gram level while maintaining its high enantioselectivity, making it a practical and efficient approach for accessing these valuable fluorinated compounds.
S. Yuan, W.-H. Zheng, J. Org. Chem., 2022, 87, 713-720.
https://doi.org/10.1021/acs.joc.1c02710
By employing a carefully selected combination of an N-heterocyclic carbene (NHC) precatalyst, an appropriate base, and a fluorine-containing reagent, the fluorination of alkynals was achieved efficiently, leading to the formation of a diverse array of α-fluoroallenoates with remarkable chemoselectivity. These α-fluorinated allenoates serve as highly valuable synthetic intermediates, enabling the synthesis of various other fluorine-containing molecular scaffolds.
X. Wang, Z. Wu, J. Wang, Org. Lett., 2016, 18, 576-579.
https://doi.org/10.1021/acs.orglett.5b03615
An organocatalytic approach utilizing a synergistic combination of L-proline and salicylic acid facilitates the highly stereoselective construction of α,α-difluoro-γ,γ-disubstituted butenals. This reaction system demonstrates a broad substrate compatibility and, in the majority of instances, delivers exceptional E-stereoselectivity.
S. Arimitsu, M. Nakasone, J. Org. Chem., 2016, 81, 6707-6713.
https://doi.org/10.1021/acs.joc.6b01334
The application of organic selenium catalysis offers an efficient pathway for the synthesis of 3-amino allylic alcohols, characterized by remarkable regio- and stereoselectivity, when conducted in the presence of a base. Conversely, in the absence of bases, the reaction predominantly yields α,β-unsaturated aldehydes with excellent efficiency. Notably, the presence of the hydroxy group is essential for the direct amination process to proceed effectively.
Z. Deng, J. Wei, L. Liao, H. Huang, X. Zhao, Org. Lett., 2015, 17, 1834-1837.
https://doi.org/10.1021/acs.orglett.5b00213
A straightforward and gentle iron-catalyzed 1,2-azidoamidation of 1,3-dienes exhibits exceptional functional group tolerance, yielding versatile precursors for 1,2-diamine derivatives with high site-, regio-, and stereoselectivity. The proposed mechanism involves a single electron transfer, followed by radical addition and C-N bond formation in a relay fashion.
Z.-Y. Dai, I. A. Guzei, J. M. Schomaker, Org. Lett., 2024, 26, 269-273.
https://doi.org/10.1021/acs.orglett.3c03947
The copper-catalyzed ring-opening of arylcyclopropanes in the presence of N-fluorobenzenesulfonimide and (2,2′-bipyridine)Zn(CF3)2 affords γ-trifluoromethylated amines in good yields at room temperature.
H. Zhang, H. Xiao, F. Jiang, Y. Fang, L. Zhu, C. Li, Org. Lett., 2021, 23, 2268-2272.
https://doi.org/10.1021/acs.orglett.1c00390
The use of N-fluorobenzenesulfonimide (NFSI) as an oxidant enables a metal-free oxidative trideuteromethylthiolation of alkenes with CD3SSO3Na as a readily available reagent. An aminotrideuteromethylthiolation could be easily achieved in the presence of a cobalt catalyst.
W. Wang, L. Zhao, H. Wu, Y. He, G. Wu, Org. Lett., 2023, 25, 7078-7082.
https://doi.org/10.1021/acs.orglett.3c02329
The use of N-fluorobenzenesulfonimide (NFSI) as an oxidant enables a metal-free oxidative trideuteromethylthiolation of alkenes with CD3SSO3Na as a readily available reagent. An aminotrideuteromethylthiolation could be easily achieved in the presence of a cobalt catalyst.
W. Wang, L. Zhao, H. Wu, Y. He, G. Wu, Org. Lett., 2023, 25, 7078-7082.
https://doi.org/10.1021/acs.orglett.3c02329
The outcome of a regioselective palladium-catalyzed diamination reaction of unactivated alkenes is influenced by the steric hindrance of the ligand employed. This process can yield either amino-functionalized piperidines or pyrrolidines. Specifically, when a less sterically encumbered quinox ligand is used, the reaction proceeds via 6-endo diamination, resulting in the formation of 3-aminopiperidines. Conversely, the use of a bulky pyox ligand favors 5-exo diamination, leading to the production of amino-substituted pyrrolidines.
X. Liu, C. Hou, Y. Peng, P. Chen, G. Liu, Org. Lett., 2020, 22, 9371-9375.
https://doi.org/10.1021/acs.orglett.0c03634
A recently developed selenium-catalyzed method facilitates the direct, intramolecular amination of C(sp²)-H bonds in ortho-vinyl anilines and vinylated aminopyridines. This approach employs N-fluorobenzenesulfonimide as the terminal oxidant, enabling the efficient synthesis of a wide array of diversely functionalized indoles and azaindoles. A critical aspect of this protocol is the significant carbophilicity of selenium electrophiles, which plays a pivotal role in the catalytic activation of alkenes.
S. Ortgies, A. Breder, Org. Lett., 2015, 17, 2748-2751.
https://doi.org/10.1021/acs.orglett.5b01156
The incorporation of N-fluorobenzenesulfonimide (NFSI) facilitates an efficient, straightforward, and metal-free fluorination process for 2H-indazoles in an aqueous environment under ambient air conditions. This reaction offers direct access to a diverse range of fluorinated indazole derivatives with excellent functional group tolerance and good yields. Experimental findings indicate that the reaction proceeds via a radical-based mechanism.
P. Ghosh, A. Hajra, J. Org. Chem., 2021, 86, 10883-10888.
https://doi.org/10.1021/acs.joc.1c01253
The use of the commercially available N-fluorobenzenesulfonimide (NFSI) as an amination reagent enables a copper-catalyzed aminative aza-annulation of enynyl azide to provide amino-substituted nicotinate derivatives in a single step in good yield.
C. R. Reddy, S. K. Prajapti, R. Ranjan, Org. Lett., 2018, 20, 3128-3131.
https://doi.org/10.1021/acs.orglett.8b01228
An effective organoselenium-catalyzed aza-Wacker reaction has been developed for olefinic hydrazones and oximes, leading to the formation of isoquinolinium imides and isoquinoline N-oxides. This transformation proceeds through a direct intramolecular C-H amination pathway.
H. Li, L. Liao, X. Zhao, Synlett, 2019, 30, 1688-1692.
https://doi.org/10.1055/s-0039-1690103
Quoted
from:https://www.organic-chemistry.org/chemicals/oxidations/n-fluorobenzenesulfonimide-nfsi.shtm