Synthesis of Amino-1,4-benzoquinones and Their Use in Diels–Alder Approaches to the Aminonaphthoquinone Antibiotics

A new protocol for the synthesis of protected amino-1,4-benzoquinones by oxidation of the corresponding 2,5-dimethoxyaniline derivatives using PhI(OAc)2 or PhI(OCOCF3)2 in water containing 2.5% methanol is reported. The process represents an improvement over previously reported methods, both in terms of yield and number of steps, and in the range of nitrogen protecting groups that it tolerates. A number of novel aminobenzoquinones were prepared and subsequently used as dienophiles in Diels–Alder reactions to form building blocks for the synthesis of the aminonaphthoquinone antibiotics such as salinisporamycin.