82780-52-7

Upstream product

• 82780-48-1 N,N-Dimethyl-2-methoxy-6-methylbenzamide 
• 7291-34-1 2-methoxy-N,N-dimethylbenzamide 
• 6346-05-0 3-benzyloxy-4-methoxybenzaldehyde 
• 66947-61-3 5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-ol 
• 74-88-4 methyl iodide 
• 144192-07-4 2-methoxy-6-((trimethylsilyl)methyl)benzoyl chloride 
• 6520-83-8 ethyl 2-methoxy-6-methylbenzoate 
• 82780-50-5 1-(3-benzyloxy-4-methoxyphenyl)-2-(2-N,N-dimethylamido-3-methoxyphenyl)ethanol 
• 2161-90-2 1-methoxy-1,3-cyclohexadiene 
• 146518-50-5 ethyl 5-(3-benzyloxy-4-methoxyphenyl)-5-tetrahydropyranyloxy-2-pentynoate 

Downstream Products

• 55555-33-4 phyllodulcin 

Relevant academic research and scientific papers

Reaction of Benzocyclobutenoxides with Aldehydes: Synthesis of Peshawarine and Other 3,4-Dihydroisocoumarins

Deprotonation of benzocyclobutenols 6 in presence of aromatic aldehydes affords benzopyranols 7 in high yield.In the key step of this process, an o-tolualdehyde anion generated by the known ring-opening of benzocyclobutenoxides adds to the aldehyde to give 7 which is easily oxidized to 3-substituted 3,4-dihydroisocoumarins 8 including intermediates in some natural product syntheses.For example, reaction of 6-methoxybenzocyclobutenol (1) with LTMP and p-anisaldehyde gave in 96percent yield to benzopyranol 16, which subsequently was converted to (+/-)-hydrangenol (17).Similar treatment of 1 with LDA and isovanillin benzyl ether afforded the benzopyranol 19 (87percent yield) which already has been converted to (+/-)-phyllodulcin (21).Finally, reaction of 5,6-(methylenedioxy)benzocyclobutenol (10) with LTMP and the aldehyde 26 (from treatment of hydrastinine with ClCO2Me) followed by methanolysis produced the acetal 28 in 96percent yield.The overall yield was 65percent for the five-step synthesis of the alkaloid (+/-)-peshawawine (24) from 10 and 26.Extension of the process to aliphatic aldehydes was illustrated by the preparation of 32 from benzocyclobutenol and isobutyraldehyde in 69percent overall yield after oxidation with PCC.

o-Toluate carbanions: Facile synthesis of hydrangenol and phyllodulcin

The carbanion generated from the ester 1c on the reaction with appropriate aromatic aldehydes gives the title compounds which are naturally occuring dihydroisocoumarins of pharmacological interest.

SYNTHETIC APPROACH TO OPTICALLY ACTIVE 3-ARYL-3,4-DIHYDROISOCOUMARINS

Some optically active 3-aryl-3,4-dihydroisocoumarins have been obtained by enantioselective reduction of the corresponding aryl 2-carboxybenzyl ketones with the CBS catalyst.The ketones were obtained by the condensation of the o-toluate carbanion with ald

Ortho-Lithiated Tertiary Benzamides. Chain Extension via o-Toluamide Anion and General Synthesis of Isocoumarins Including Hydrangenol and Phyllodulcin

Lithiation of N,N-diethyl-2-methylbenzamide (2a) followed by condensation with aromatic aldehydes and basic hydrolysis leads to 3-aryl-3,4-dihydroisocoumarins 4 in modest overall yields.Adoption of this methodology to N,N-dimethyl-2-methyl-6-methoxybenzamide (7b) provides isocoumarins 9a and 9b which by selective demethylation procedures yields hydrangenol (10a) and phyllodulcin (10c), naturally occurring isocoumarins of pharmacological interest.A one-pot, abbreviated procedure for the preparation of both 9a and 9b starting with N,N-Dimethyl-2-methoxybenzamide (6c) is also described.

DIRECTED METALATION OF TERTIARY BENZAMIDES. SHORT SYNTHESES OF HYDRANGENOL AND PHYLLODULCIN

Brief syntheses of isocumarin natural products hydragenol(2) and phyllodulcin(3) via ortho-lithiated benzamide intermediates are described.