Preparation of ortho-hydroxyalkylanilines as ortho-quinone methide imine precursors via an aminoborane complex

Abstract

A general process for ortho-specific hydroxyalkylation of secondary anilines has been developed. N-Methylanilinochlorophenylboranes react readily with aryl aldehydes, and with α,β-unsaturated or saturated aliphatic aldehydes to give the corresponding ortho-hydroxyalkylanilines in good yield. Thermolysis of the latter generated the corresponding ortho-quinone methide imine, which can participate in an electrocyclic or intramolecular [4 + 2] cycloaddition reaction to give various dihydro- and tetrahydroquinoline derivatives. Application of the method to the syntheses of 5-aza analogs of hexahydrocannabinol is demonstrated. Keywords: quinone methide imine, ortho-hydroxyalkylaniline, azacannabinoids.