Synthesis of novel 2,5-substituted p-aminophenols and 2,5-substituted p-quinones in a one-pot reaction between α-alkoxyvinyl(ethoxy)carbene complexes, amines and alkynes

Abstract

The synthesis of novel p-aminophenols 19a-o and p-quinones 21a-i was carried out by an aminolysis reaction/[3 + 2+1] cycloaddition cascade process of α-alkoxyvinyl (ethoxy) Fischer carbene complexes of group 6 metals (M = Cr, Mo, W), primary and secondary amines and terminal alkynes. The multicomponent reaction of carbenes 1a-c with morpholine (6a) and piperidine (6c), respectively, and terminal alkynes 17a-d only afforded the 4-aminophenols 19a-o in moderated yields. The products bore the terminal alkyne substituent at the ortho position of the hydroxyl group. These one-pot reactions showed highly regio- and chemoselectivity, favoring the benzannulation products. When carbene complexes 1a-c were reacted with primary amines 10a-c and alkynes 17a-c under the same conditions, the cascade process led to the formation of p-quinones 21a-21i, in moderate yields. The regiochemistry of the compounds was established by NOE experiments, and the structures of morpholinocarbene 7a, p-aminophenols 19b, 19d and p-quinone 21b were confirmed by single-crystal X-ray diffraction.