The fluorine atom has several unique properties: an atomic radius close to that of hydrogen atoms, the highest electronegativity of all elements and a strong C-F bond. For this reason, there are many reports of significant improvements in the activity and physical properties of functional molecules (pharmaceuticals, agrochemicals, liquid crystal materials, electronic materials, etc.) when fluorine atoms are introduced into them.¹⁾ Although many excellent fluorinating reagents and reagents for introducing fluorine-containing functional groups have been developed,^2,3) there is still a need to develop more powerful fluorinating agents and trifluoromethylating agents.

TCI offers an electrophilic trifluoromethylating agent, Umemoto Reagent IV (Product No. T4082) and an electrophilic fluorinating agent, NFBB (Product No. F1345), developed by Umemoto et al.

Electrophilic Trifluoromethylating Agent: Umemoto Reagent IV

Umemoto Reagent IV (Product No. T4082) is a reagent designed to introduce a trifluoromethyl group into various compounds.⁴⁾ Umemoto Reagent IV exhibits higher reactivity than conventional trifluoromethylating agents such as Umemoto Reagent I and II due to the electronic effects of two trifluoromethoxy groups.⁵⁾ In addition, Umemoto Reagent IV is a stable solid, easy to handle in the atmosphere and has low hygroscopicity.³⁾

Product

T4082

Umemoto Reagent IV

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Advantages

• Higher reactivity than Umemoto Reagent I and Umemoto Reagent II
• Enables trifluoromethylation of active methylene compounds and electron-rich aromatic rings
• Stable solid that is easy to handle in the atmosphere

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Applications

Trifluoromethylation of active methylene compounds using Umemoto Reagent IV ⁴⁾

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Trifluoromethylation of nitrogen-containing electron-rich aromatic rings using Umemoto Reagent IV ⁴⁾

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Trifluoromethylation of hydroxyamines using Umemoto Reagent IV ⁴⁾

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Electrophilic Fluorinating Agent: NFBB

NFBB (Product No. F1345) is a fluorinating agent sterically protected by a bulky tert-butyl group and designed to suppress degradation by strong bases.⁵⁾ Conventional fluorinating agents such as NFSI (Product No. F0335)⁶⁾ and F-TEDA-BF₄ (Product No. F0358)⁷⁾ are known to be degraded by organolithium species, but NFBB is not subject to such degradation. The sulfonimide anion generated in the reaction system acts as a deprotonating agent so that the amount of base (cesium carbonate) required to fluorinate active methylene compounds can be reduced to a catalytic amount. NFBB is a stable and easy-to-handle liquid and can be used to synthesize compounds known as pharmaceutical intermediates.

Product

F1345

N-(tert-Butyl)-N-fluoro-2-methylpropane-2-sulfonamide (= NFBB)

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Advantages

• Fluorinating agent designed to suppress degradation by strong bases
• Reduces the amount of base to a catalytic amount as it also acts as a deprotonating agent
• Allows fluorination of aryl lithium and alkenyl lithium in good yields
• Stable liquid, easy to handle

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Applications

Fluorination of aryl lithium using NFBB ⁵⁾

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Fluorination of alkenyl lithium using NFBB ⁵⁾

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Fluorination of active methylene compounds using NFBB ⁵⁾

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Related Products

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Related Product Category Page

TCI also offers a variety of other fluorination reaction reagents. For more information, please see the product category pages below.

• Fluorination Reagents [Synthetic Reagents]

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Product Brochures

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References

• 1) Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design
  • N. A. Meanwell, J. Med. Chem. 2018, 61, 5822.
• 2) Recent Advances in Trifluoromethylation Reactions with Electrophilic Trifluoromethylating Reagents
  • S. Barata-Vallejo, B. Lantaño, A. Postigo, Chem. Eur. J. 2014, 20, 16806.
• 3) Introduction of Fluorine and Fluorine-Containing Functional Groups
  • T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214.
• 4) Synthesis and applications of S-(trifluoromethyl)-2,8-bis(trifluoromethoxy) dibenzothiophenium triflate (Umemoto reagent IV)
  • S. R. Mudshinge, G. B. Hammond, T. Umemoto, J. Fluor. Chem. 2022, 261–262, 110015.
• 5) Self-Sustaining Fluorination of Active Methylene Compounds and High-Yielding Fluorination of Highly Basic Aryl and Alkenyl Lithium Species with a Sterically Hindered N-Fluorosulfonamide Reagent
  • Y. Yang, G. B. Hammond, T. Umemoto, Angew. Chem. Int. Ed. 2022, 61, e202211688.
• 6) N-Fluorobenzenesulfonimide
  • V. Bizet, Synlett 2012, 23, 2719.
• 7) Selectfluor: Mechanistic Insight and Applications
  • P. T. Nyffeler, S. G. Durón, M. D. Burkart, S. P. Vincent, C. Wong, Angew. Chem. Int. Ed. 2004, 44, 192.

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