Preparation of Regioselectively Protected Hydroquinones by Phosphorylation of p-Benzoquinones with Trialkyl Phosphites

The title reaction has been applied to 10 monosubstituted p-benzoquinones (Scheme 2, Table). The regioselectively of the O-phosphorylation is influenced by bulky substituents (t-butyl and trimethylsilyl) and, electronically, by the methoxy group. The regioselectivity, which is high in nonpolar media (benzene), is lower in polar solvents (CH₂Cl₂) and (CH₃CN). The synthetic potential of this transformation, exemplified by the preparation of compounds 29 (Scheme 3) and 32 (Scheme 4), is considerably extended by applying milder methods for the phosphate hydrolysis and by using the reagent couple P(OCH₃)₃/trimethylsilyl chloride, which gives clean access to p-hydroxyphenyl phosphates. p-Benzoquinones 4th and 4i with strong π-acceptor substituents react in a different way, giving phosphonates. The electronically induced regioselectivity of the O-phosphorylation is in according with the preferences expected for the attack by a nucleophilic phosphorylation agent.