Two-Step Synthesis of Difluoromethyl-Substituted 2,3-Dihydrobenzoheteroles

Fujita, Takeshi; Sanada, Shohei; Chiba, Yosuke; Sugiyama, Kazuki; Ichikawa, Junji

doi:10.1021/ol5001582

Cited by 38 publications

(16 citation statements)

References 53 publications

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“…Notably, even without any precious metal catalyst present, exclusive γ-selective substitution (>99/1) was observed without any detectable formation of the α-substitution product. In contrast, for other allylic electrophiles such behavior in the absence of transition metal catalysts is difficult to control 63 .…”

Section: Resultsmentioning

confidence: 99%

3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

Spannenberg

et al. 2021

Nat Commun

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The selective synthesis of fluorinated organic molecules continues to be of major importance for the development of bioactive compounds (agrochemicals and pharmaceuticals) as well as unique materials. Among the established synthetic toolbox for incorporation of fluorine-containing units, efficient and general reagents for introducing -CF2- groups have been largely neglected. Here, we present the synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) as stable, and scalable gem-difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles. DFPAs smoothly react with N-, O-, S-, Se-, and C-nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogues of existing pharmaceuticals.

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Section: Resultsmentioning

confidence: 99%

3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

Spannenberg

et al. 2021

Nat Commun

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“…Ichikawa and co-workers (2014) used a radical approach for the synthesis of 3-(difluoromethyl)-DHBs from 2-bromophenols in 2 steps: (1) -selective allylic substitution of 3-bromo-3,3-difluoropropene and (2) intramolecular radical cyclization of the resulting 1-bromo-2-(3,3-difluoroallyloxy)benzenes by AIBN/Bu 3 SnH. 117 The reaction tolerated Cl-, Me-, and MeO-substituents on the benzene ring giving the corresponding 3-(difluoromethyl)-DHBs in good yields.…”

Section: Scheme 45 Carbolithiation-cyclization-electrophilic Substitumentioning

confidence: 99%

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

Laurita

D’Orsi²,

Chiummiento³

et al. 2020

Synthesis

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This review gives an overview on recent developments in methods for the construction of compounds with the 2,3-dihydrobenzofuran core in the period 2012 to 2019. Interest in 2,3-dihydrobenzofurans is constantly increasing. The methods are divided into intermolecular and intramolecular approaches. Intermolecular approaches are subdivided according to the parent intermediate for the key reaction, while intermolecular approaches are subdivided according by which bond is formed in the key reaction. The transformation of benzofurans to dihydrobenzofurans and other miscellaneous methods are also discussed. Approaches useful for the synthesis of natural products are emphasized.1 Introduction2 Intermolecular Approaches2.1 o-Quinone Methides and o-Quinones2.2 p-Quinone Methides and p-Quinones2.3 Nitrogen-Containing Phenols and Quinones2.4 o-Hydroxyphenylcarbonyl Derivatives and Phenols2.5 Miscellaneous3 Intramolecular Approaches3.1 O–C2 Bond Forming3.2 C2–C3 Bond Forming3.3 C3–Aryl Bond Forming3.4 O–Aryl Bond Forming4 From BF to DHB5 Rearrangements and Aromatizations

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“…12 (G) Ichikawa and co-workers found conditions for a selective γ-attack (S N 2′) of 3,3,3-bromodifluoro-1-propene by 1,2-bromoheteroarenes to give 3,3-difluoroallylic compounds which could undergo an intramolecular radical cyclisation to gain access to 3-difluoromethylated dihydrobenzoheteroles. 13…”

Section: Brmentioning

confidence: 99%

3,3,3-Bromodifluoro-1-propene: The Mild Introduction of CF2

Mears

2014

Synlett

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Paul Mears graduated with a first class honours degree in Applied Chemistry from the University of Leeds, UK in 2010. He subsequently moved to the University of Manchester, UK to pursue graduate studies under the supervision of Prof. Jim Thomas. His work is focused on natural product total synthesis, specifically of the bryostatin macrolides, as well as routes towards difluorinated analogues of these and related compounds.

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Two-Step Synthesis of Difluoromethyl-Substituted 2,3-Dihydrobenzoheteroles

Cited by 38 publications

References 53 publications

3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

3,3,3-Bromodifluoro-1-propene: The Mild Introduction of CF2

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