Formylation of Electron-Rich Aromatic Rings Mediated by Dichloromethyl Methyl Ether and TiCl4: Scope and Limitations

Ramos-Tomillero, Iván; Paradís-Bas, Marta; Moreira, Ibério de P. R.; Bofill, Josep María; Nicolás, Ernesto; Alberício, Fernando

doi:10.3390/molecules20045409

Cited by 22 publications

(20 citation statements)

References 36 publications

(39 reference statements)

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“…Although there is a wide range of approaches available for the introduction of an aromatic formyl group, the formylation of pinocembrin proceeded slowly due to deactivation of the A-ring via the electron-withdrawing effect of the C-4 carbonyl group. Standard procedures such as Reimer–Tiemann, Duff, Gattermann, Vilsmeier, and triethyl orthoformate/AlCl 3 formylations afforded low yields.…”

Section: Results and Discussionmentioning

confidence: 99%

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography

Zaki

Nanayakkara²,

Hetta

et al. 2016

J. Nat. Prod.

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Two new flavonoids, rac-6-formyl-5,7-dihydroxyflavanone (1) and 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (2), together with five known derivatives, rac-8-formyl-5,7-dihydroxyflavanone (3), 4',6'-dihydroxy-2'-methoxy-3'-methyldihydrochalcone (4), rac-7-hydroxy-5-methoxy-6-methylflavanone (5), 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone (6), and 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7), were isolated from the leaves of Eugenia rigida. The individual (S)- and (R)-enantiomers of 1 and 3, together with the corresponding formylated flavones 8 (6-formyl-5,7-dihydroxyflavone) and 9 (8-formyl-5,7-dihydroxyflavone), as well as 2',4',6'-trihydroxychalcone (10), 3'-formyl-2',4',6'-trihydroxychalcone (11), and the corresponding 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7) and 2',4',6'-trihydroxydihydrochalcone (12), were synthesized. The structures of the isolated and synthetic compounds were established via NMR, HRESIMS, and electronic circular dichroism data. In addition, the structures of 3, 5, and 8 were confirmed by single-crystal X-ray diffraction crystallography. The isolated and synthetic flavonoids were evaluated for their antimicrobial and cytotoxic activities against a panel of microorganisms and solid tumor cell lines.

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Section: Results and Discussionmentioning

confidence: 99%

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography

Zaki

Nanayakkara²,

Hetta

et al. 2016

J. Nat. Prod.

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“…Compounds 3j – l were envisaged as precursors for three naturally occurring 8-prenylcoumarins. The required salicyl aldehydes 1j , 1m , , 1k , and 1l were synthesized from commercially available 2,4,5-trimethoxybenzaldehyde ( 4 ) and 3,4,5-trimethoxyphenol ( 5 ) by following or adapting literature procedures (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Prenylcoumarins in One or Two Steps by a Microwave-Promoted Tandem Claisen Rearrangement/Wittig Olefination/Cyclization Sequence

Schultze

Schmidt

2018

J. Org. Chem.

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The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated salicylaldehydes and the stabilized ylide [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was found to have a limited scope. The sequence suffers from a difficult and sometimes low-yielding synthesis of the precursors and from a competing deprenylation upon microwave irradiation. This side reaction occurs in particular with electron rich arenes with two or more alkoxy groups at adjacent positions, a prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both limitations of this one-step sequence were overcome by a two-step synthesis consisting of a microwave-promoted tandem allyl ether Claisen rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2-methyl-2-butene. The cross metathesis step proceeds with a high selectivity and yields exclusively the desired prenyl, rather than the alternative crotyl substituent. Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.

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“…We next examined the coupling reaction of 1 a with 3,5‐dimethyl phenol ( 2 h ) and 3,5‐dimethoxy phenol ( 2 i ; Scheme ). In each case, the coupling reaction proceeded to give the coupling product in good yield, along with a regioisomeric mixture of para and ortho coupling products ( 3 ah / 3 ah ′=42:58; 3 ai / 3 ai ′=45:55) . In Kürti's procedure, the coupling reaction of 1 a with 2 h and 2 i only gave the corresponding coupling products with bond formation at the ortho position of these phenols …”

Section: Methodsmentioning

confidence: 99%

Efficient Coupling Reaction of Quinone Monoacetal with Phenols Leading to Phenol Biaryls

et al. 2016

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A simple and efficient synthesis of phenol biaryls by the cross‐couplings of quinone monoacetals (QMAs) and phenols is reported. The Brønsted acid catalytic system in 1,1,1,3,3,3‐hexafluoro‐2‐propanol was found to be particularly efficient for this transformation. This reaction can be extended to the synthesis of various phenol biaryls, including sterically hindered biaryls, with yields ranging from 58 to 90 % under mild reaction conditions and in a highly regiospecific manner.

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Formylation of Electron-Rich Aromatic Rings Mediated by Dichloromethyl Methyl Ether and TiCl4: Scope and Limitations

Cited by 22 publications

References 36 publications

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography

Prenylcoumarins in One or Two Steps by a Microwave-Promoted Tandem Claisen Rearrangement/Wittig Olefination/Cyclization Sequence

Efficient Coupling Reaction of Quinone Monoacetal with Phenols Leading to Phenol Biaryls

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