Enantioselective Synthesis of Cyclopropanes That Contain Fluorinated Tertiary Stereogenic Carbon Centers: A Chiral α‐Fluoro Carbanion Strategy

Shen, Xiao; Zhang, Wei; Zhang, Lei; Luo, Tao; Wan, Xiaolong; Gu, Yu‐Cheng; Hu, Jinbo

doi:10.1002/ange.201202451

Cited by 28 publications

(6 citation statements)

References 48 publications

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“…Firstly, we developed an efficient synthesis of ( R )‐ N ‐ tert ‐butyldimethylsilyl‐ S ‐fluoromethyl‐ S ‐phenylsulfoximine ( 1 ). ( R )‐ N ‐tosyl‐ S ‐fluoromethyl‐ S ‐phenylsulfoximine ( 3 ) was readily prepared according to reported procedures 10b. The tosyl group of 3 was readily removed in aqueous H 2 SO 4 (18.4 m) , thus affording ( R )‐S‐fluoromethyl‐S‐phenylsulfoximine ( 4 ) in 97 % yield.…”

Section: Methodsmentioning

confidence: 99%

Stereoselective Nucleophilic Fluoromethylation of Aryl Ketones: Dynamic Kinetic Resolution of Chiral α‐Fluoro Carbanions

Shen

Miao

et al. 2013

Angewandte Chemie

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Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-tohandle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral a-fluoro carbanions.Scheme 8. Synthesis of optically enriched monofluoromethyl alcohols through reductive desulfoximination of 6. Typical procedure: under N 2 atmosphere, the newly prepared Al/Hg (405 mg of Al) was added to the solution of 6 (d.r. 99:1, 0.5 mmol) in THF/water (5 mL:5 mL) at room temperature in several portions and stirred overnight. Substrates 6 were diastereomerically pure except for 6a. The yield refers to the yield of isolated product and the yield in parentheses was determined by 19 F NMR spectroscopy.Scheme 9. Synthesis of natural-product analogues.

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Section: Methodsmentioning

confidence: 99%

Stereoselective Nucleophilic Fluoromethylation of Aryl Ketones: Dynamic Kinetic Resolution of Chiral α‐Fluoro Carbanions

Shen

Miao

et al. 2013

Angewandte Chemie

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“…[53] Thus, the authors turned their attention to the charge-neutral sulfoximine-based CH 2 F reagent 3 h, originally developed by Hu and co-workers. [54] Reduction of the reagent requires strong reducing power (E red = À 2.02 V) because of its low electrophilicity. However, the authors developed a highly reducing organic photocatalyst, BDN (1,4-bis(diphenylamino)naphthalene) (E* ox = À 1.99 V).…”

Section: Use Of Ch 2 Fà Sulfoximine Reagentmentioning

confidence: 99%

“…In 2019, Koike and Akita reported that use of 3 e was unsuitable for photocatalytic monofluoromethylation because the 1e‐reduction generates a mixture of CH 2 F and aryl radicals (Scheme a) . Thus, the authors turned their attention to the charge‐neutral sulfoximine‐based CH 2 F reagent 3 h , originally developed by Hu and co‐workers . Reduction of the reagent requires strong reducing power ( E red =−2.02 V) because of its low electrophilicity.…”

Section: Strategies For Reductive Generation Of Fluoromethyl Radicalsmentioning

confidence: 99%

Frontiers in Radical Fluoromethylation by Visible‐Light Organic Photocatalysis

Koike

2020

Asian J Org Chem

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Fluoromethyl groups, including tri‐, di‐, and mono‐fluoromethyl (CF3, CF2H, and CH2F, respectively) groups, are important structural motifs in medicinal chemistry. Radical fluoromethylation has attracted significant interest for the late‐stage functionalization of complex bioactive molecules. Recently, light energy has been used for radical reactions in synthesis of various valuable products. Strategies using organic photocatalysts (OPCs) are beneficial for synthetic radical chemistry and various aspects of “sustainable development goals (SDGs)”. Particularly, over the past several years, considerable progress has been made in the field of photoinduced radical fluoromethylation by OPCs. In this minireview, the concepts of representative reaction systems for fluoromethyl radical generation will be discussed.

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“…Fluoromethylation has recently been investigated, offering a single attachment point for the target substrate . However, fluoromethylene group transfer − formally offers two connection points, giving access to monofluorinated 3-membered rings . Along this line, we have recently reported on fluoromethylene transfer from S -monofluoromethyl- S -phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate ( 2a ) (Figure ) via ylide intermediate as an alternative to freon (CHFX 2 ) chemistry to access monofluorinated cyclopropane , and epoxide derivatives.…”

Section: Introductionmentioning

confidence: 99%

Optimized Monofluoromethylsulfonium Reagents for Fluoromethylene-Transfer Chemistry

et al. 2021

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An investigation of the properties and reactivity of fluoromethylsulfonium salts resulted in the redesign of the reagents for fluoromethylene transfer chemistry. The model reaction, fluorocyclopropanation of nitrostyrene, turned out to be a suitable platform for the discovery of more streamlined fluoromethylene transfer reagents. The incorporation of halides on one aryl ring increased the reactivity, and 2,4-dimethyl substitution on the other aryl ring provided a balance between the reactivity/crystallinity of the reagent as well as the atom economy. The utility of new reagents was demonstrated by the development of an efficient fluorocyclopropanation protocol to access a range of monofluorinated cyclopropane derivatives.

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Enantioselective Synthesis of Cyclopropanes That Contain Fluorinated Tertiary Stereogenic Carbon Centers: A Chiral α‐Fluoro Carbanion Strategy

Abstract: Keywords: asymmetric synthesis · chiral fluoroalkylation reagent · cyclopropanation · fluorine · sulfoximine Scheme 4. Preparation of cyclopropanes 6 a and 6 b, which contain fluorinated quaternary stereogenic carbon centers.Scheme 5. Synthetic applications of product 4 h.

Cited by 28 publications

References 48 publications

Stereoselective Nucleophilic Fluoromethylation of Aryl Ketones: Dynamic Kinetic Resolution of Chiral α‐Fluoro Carbanions

Stereoselective Nucleophilic Fluoromethylation of Aryl Ketones: Dynamic Kinetic Resolution of Chiral α‐Fluoro Carbanions

Frontiers in Radical Fluoromethylation by Visible‐Light Organic Photocatalysis

Optimized Monofluoromethylsulfonium Reagents for Fluoromethylene-Transfer Chemistry

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