Controlling the Substitution Pattern of Hexasubstituted Naphthalenes by Aryne/Siloxyfuran Diels–Alder Additions: Regio‐ and Stereocontrolled Synthesis of Arizonin C1 Analogs

Abstract

3,4‐Dimethoxybenz‐1‐yne and 2‐siloxylated furans without or with a bromine atom at C‐3 undergo Diels–Alder reactions with orientational selectivity. Hydrolysis furnished a bromine‐free or a bromine‐containing naphthalene, respectively. Bromination of the former provided a regioisomer of the latter. Either of the two compounds was processed to give a variety of unnatural naphthoquinonopyrano‐γ‐lactones. This occurred by a succession of (1) Heck coupling, (2) asymmetric dihydroxylation, (3) oxa‐Pictet–Spengler cyclization, and (4) oxidation. The fifteen monomeric naphthoquinonopyrano‐γ‐lactone structures that we prepared resemble the natural product (–)‐arizonin C1 or its C‐5 epimer. Accordingly, they represent hexasubstituted naphthalenes likewise. The sixteenth naphthoquinonopyrano‐γ‐lactone that we synthesized is a kind of dimer. Its moieties are bridged differently than those in naturally occurring naphthoquinonopyrano‐γ‐lactone dimers.