Radical arylation of phenols, phenyl ethers, and furans.
Radical arylations of para-substituted phenols and phenyl ethers proceeded with good regioselectivity at the ortho position with respect to the hydroxy or alkoxy group. The reactions were conducted with arenediazonium salts as the aryl radical source, titanium(III) chloride as the reductant, and diluted hydrochloric acid as the solvent. Substituted biaryls were obtained from hydroxy- and alkoxy-substituted benzylamines, phenethylamines, and aromatic amino acids. The methodology described offers a fast, efficient, and cost-effective new access to diversely functionalized biphenyl alcohols and ethers. Free phenolic hydroxy groups, aromatic and aliphatic amines, as well as amino acid substructures, are well tolerated. Two examples for the applicability of the methodology are the partial synthesis of a beta-secretase inhibitor and the synthesis of a calcium-channel modulator.
Wetzel
Alexander
A
Department für Chemie und Biochemie, Organische Chemie 1, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Pratsch
Gerald
G
Kolb
Roman
R
Heinrich
Markus R
MR
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D003979:Diazonium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry*; D006851:Hydrochloric Acid / Q000737:chemistry; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry*; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D003979:Diazonium Compounds; D005609:Free Radicals; D005663:Furans; D010636:Phenols; D010647:Phenyl Ethers; D012997:Solvents; D053829:Amyloid Precursor Protein Secretases; D006851:Hydrochloric Acid