Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

Inaba, Masanori; Sakai, Tatsuya; Shinada, Shun; Sugiishi, Tsuyuka; Nishina, Yuta; Shibata, Norio; Amii, Hideki

doi:10.3762/bjoc.14.12

Cited by 5 publications

(4 citation statements)

References 35 publications

(19 reference statements)

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“…As an application of the catalyst‐free transformation, we conducted the synthesis of trifluoromethylated phthalide 4 (Scheme ) . A mixture of 2‐cyanobenzaldehyde ( 1 h ) and Me 3 Si‐CF 3 ( 2 a ) in anhydrous NMP was stirred 50 °C for 3 h. After workup under acidic condition, 3‐(trifluoromethyl)‐1(3 H )‐isobenzofuranone ( 4 ) was obtained in 79% isolated yield (from aldehyde 1 h ).…”

Section: Methodsmentioning

confidence: 55%

Solvent‐Promoted Catalyst‐Free Nucleophilic Fluoroalkylation of Aldehydes

2019

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Fluoroalkyl silanes are useful building blocks for nucleophilic introduction of fluoroalkyl groups into organic molecules. In general, fluoroalkyl silanes per se are stable compounds, but they are amenable to reactions as fluoroalkyl anion equivalents in the presence of base such as fluoride ion. Usually, KF acts as a good catalyst for nucleophilic fluoroalkylation of carbonyl compounds. To avoid the use of hygroscopic fluoride salts, we have developed a convenient catalyst-free method for nucleophilic fluoroalkylation of aldehydes and ketones by the use of fluoroalkyl silanes. Trifluoromethyl(trimethyl)silane (Me 3 Si-CF 3 ), and other fluoroalkyl silanes (Me 3 Si-R f ) underwent solventpromoted nucleophilic addition to aldehydes smoothly to give fluoroalkylated alcohols in good yields. In the present reactions, the use of polar solvents such as DMSO, DMF or NMP is essential to the formation of 1,2-adducts.

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Section: Methodsmentioning

confidence: 55%

Solvent‐Promoted Catalyst‐Free Nucleophilic Fluoroalkylation of Aldehydes

2019

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“…The reaction proceeds via nucleophilic addition and subsequent intramolecular cyclization of B in high yields (Scheme 56). [51] …”

Section: Synthesis Of Phthalides and Imidatesmentioning

confidence: 99%

Multifaceted Behavior of 2‐Cyanobenzaldehyde and 2‐Acylbenzonitriles in the Synthesis of Isoindolinones, Phthalides and Related Heterocycles

2023

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2‐Cyanobenzaldehye (also called 2‐formylbenzonitrile) and related 2‐acylbenzonitriles belong to a class of bifunctional aromatic compounds that emerged as useful starting materials in developing efficient cascade‐type reactions leading to different heterocyclic compounds. The variety of sometimes unpredictable mechanisms that rise from these structurally simple starting materials renders this class of compounds unique to afford, through divergent cascade reactions, heterocycles like isoindolinones, phthalides (also known with the name of isobenzofuranones), imidates, and in less extent isoindolin‐1‐imine, six‐ and seven‐membered heterocycles, porphyrins, also in asymmetric way exploiting different organocatalytic activation modes. To give a picture, this chemistry can be associated to Goldberg variations which stem from a common motive in a pressing and surprising way. In this Review, emphasis is also given to the synthetic methods for the access to substituted 2‐cyanobenzaldehydes and 2‐acylbenzonitriles which allowed to enlarge the scope of the described cascade reactions.

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“…13 C NMR (100 MHz, CDCl 3 ):  = 186.7 (C-F, ddd, 2 J C,F = 30. 8,28.3,2.3 Hz),168.8,163.7,161.3,t,4 J C,F = 1.6 Hz), 134.6, 133.4 (C-F, t, 4 J C,F = 3.0 Hz), 133.3 (C-F, t, 4 J C,F = 3.2 Hz), 130.6 (C-F, t, 3 J C,F = 3.7 Hz), 126.6, 126.1, 126.0 (C-F, dd, 3 J C,F = 7.0, 3.2 Hz), 124.1 (C-F, d, 4 J C,F = 2.0 Hz ), 122.2, 122.0, 116.9 (C-F, t, 4 J C,F = 3.0 Hz), 116.7 (C-F, t, 4 J C,F = 3.0 Hz), 114.5 (C-F, dd, 1 J C,F = 265.2, 258.3 Hz), 77.2 (C-F, dd, 2 J C,F = 31.5, 26.3 Hz). 19…”

Section: Paper Synthesismentioning

confidence: 99%

“…7 Besides the radical methods developed, Amii and co-workers reported a one-pot two-step method to access 3-difluoroalkyl phthalides via nucleophilic addition with (difluoroalkyl)trimethylsilanes and subsequent intramolecular cyclization with several examples (Scheme 1b ). 8 Although great advances have been achieved, the development of simple and efficient methods for the construction of various 3-difluoroalkyl phthalides is still in great demand. Difluoroenoxysilanes have been demonstrated as multifunctional CF 2 -containing building blocks in synthetic chemistry that can be converted into diverse difluoroalkyled compounds over the past decade due to their facile preparation and good stability with the efforts of many organic chemists.…”

Section: Table 1 Optimization Of the Conditions For The Reaction Of Phthalaldehydic Acid With Difluoroenoxysilane mentioning

confidence: 99%

p-Toluenesulfonic Acid-Catalyzed Reaction of Phthalaldehydic Acids with Difluoroenoxysilanes: Access to 3-Difluoroalkyl Phthalides

Liu

Wang

et al. 2021

Synthesis

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A convenient approach for the synthesis of 3-difluoroalkyl phthalides has been developed from phthalaldehydic acids and difluoroenoxysilanes by using relatively inexpensive p-toluenesulfonic acid monohydrate (PTSA) as a catalyst. A series of 3-difluoroalkyl phthalides and cyclic difluoroalkyl ethers were obtained in up to 99% yield. The products obtained could be readily converted into difluoroalkyl phthalide derivatives by simple modifications.

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Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

Cited by 5 publications

References 35 publications

Solvent‐Promoted Catalyst‐Free Nucleophilic Fluoroalkylation of Aldehydes

Solvent‐Promoted Catalyst‐Free Nucleophilic Fluoroalkylation of Aldehydes

Multifaceted Behavior of 2‐Cyanobenzaldehyde and 2‐Acylbenzonitriles in the Synthesis of Isoindolinones, Phthalides and Related Heterocycles

p-Toluenesulfonic Acid-Catalyzed Reaction of Phthalaldehydic Acids with Difluoroenoxysilanes: Access to 3-Difluoroalkyl Phthalides

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