ortho‐Lithiation Reactions of O‐(3,n‐Dihalophenyl) N,N‐Diethylcarbamates: Synthesis of Dihalosalicylamides and 2,3,n‐Trihalophenol Derivatives

Feberero, Claudia; Velasco, Rocío; Sanz, Roberto

doi:10.1002/ejoc.201600933

Cited by 9 publications

(12 citation statements)

References 92 publications

(27 reference statements)

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“…We planned to take advantage of the Truce reaction [26], more recently developed and expanded by Alemán and García-Ruano [27,28], involving the use of arylsulfonylacetylenes as alkynylating reagents for organolithium and organomagnesium compounds. Alemán and García Ruano established that [17,18].…”

Section: Synthesis Of O-o-alkynylaryl Carbamatesmentioning

confidence: 99%

“…In our case, we decided to revisit the reported conditions to use the starting carbamate as the limiting reagent. After some experimentation, we observed that only slight excess of the alkynylsulfone was required as the electrophilic partner for the organolithium intermediate 1a-Li generated from the regioselective ortho-lithiation of O-3-fluorophenyl N,N-diethylcarbamate 1a [17,18]. Under these conditions, the O-2-alkynyl-3-fluorophenyl carbamate 2aa could be isolated in good yield, referred to as the starting carbamate 1a (Scheme 2B).…”

Section: Synthesis Of O-o-alkynylaryl Carbamatesmentioning

confidence: 99%

“…This approach supposed a straightforward entry to 4-halobenzo[b]furans, which could be subsequently transformed into 4-functionalized benzo[b]furan derivatives (Scheme 1A). More recently, we have expanded the scope of the regioselective lithiation of O-dihalophenyl-N,N-diethylcarbamates, which was found to be regioselective at the C-2 position due to the cooperative effect of the m-halide and the mighty carbamate-directed metalating group [18] (Scheme 1B).…”

Section: Introductionmentioning

confidence: 99%

“…Herein, we report a straightforward and transition metalfree synthesis of a wide variety of regioselectively halo-functionalized benzo[b]furans from readily available haloaryl carbamates, taking advantage of the powerful O-carbamate-directed metalation methodology pioneered by Prof. Snieckus [23][24][25]. [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

et al. 2022

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A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed metalation group, was crucial in providing access to O-2-alkynylaryl N,N-diethyl carbamates by a direct alkynylation of the o-lithiated carbamate, with arylsulfonylalkynes as electrophilic reagents. Cyclization of the generated o-alkynylaryl carbamates was successfully accomplished through a strategy involving in situ carbamate alkaline hydrolysis under conventional heating or microwave irradiation, coupled with a subsequent heterocyclization step delivering the desired benzo[b]furans. A wide variety of new halobenzo[b]furans has been synthesized and their utility has been demonstrated by their further transformation.

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Section: Synthesis Of O-o-alkynylaryl Carbamatesmentioning

confidence: 99%

Section: Synthesis Of O-o-alkynylaryl Carbamatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

et al. 2022

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“…To synthesize N‐(pyridine‐2‐yl)isopropyl‐, N‐(2‐(4,5‐dihydrooxazol‐2‐yl)phenyl)‐ and N‐(quinolin‐8‐yl)amides of mono‐4‐, 5‐, 6‐fluorosalicylic acids, the Cu‐mediated dimerization and oxidative hydroxylation of C−H bond of the corresponding benzamides was used . Difluorosalicylamides have been synthesized from O‐difluorophenyl‐N,N‐diethylcarbamates by o‐lithiation and tandem transnitrilation/S N Ar reaction sequence …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of 4‐Cycloaminopolyfluorosalicylic Acids

et al. 2019

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A series of novel 4-cycloamino-substituted polyfluorosalicylic acids, their esters and amides have been synthesized by the reactions of alkyl polyfluorosalicylates with morpholine, Nmethylpiperazine, pyrrolidine and proline. It was observed that esters of polyfluorosalicylic acids under prolonged heating with amines could undergo one pot nucleophilic substitution of fluorine and intramolecular acidic hydrolysis owing to catalysis by the neighboring hydroxyl group. According to ADME calculations, the synthesized compounds are suitable for drug-design. 4-(N-Methylpiperazinyl)-substituted polylfluorosalicylic acids were found to have good analgesic activity while 4morphonyl-containing analogs revealed moderate anti-inflammatory action. In addition, the presence of amine fragment in polyfluorosalicylates reduced acute toxicity comparing to nonsubstituted polyfluorosalicylic acids. The molecular docking of the most active compounds was carried out into the tyrosine site of cyclooxygenase-1.

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Dimethyl Malononitrile

Reich¹

2021

Encyclopedia of Reagents for Organic Synthesis

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ortho‐Lithiation Reactions of O‐(3,n‐Dihalophenyl) N,N‐Diethylcarbamates: Synthesis of Dihalosalicylamides and 2,3,n‐Trihalophenol Derivatives

Cited by 9 publications

References 92 publications

Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

Synthesis and Biological Activity of 4‐Cycloaminopolyfluorosalicylic Acids

Dimethyl Malononitrile

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