Efficient entry to 1-benzoxepine ring skeleton via tandem SN2/Wittig reaction. Total synthesis of NADH: ubiquinone oxidoreductase (complex I) antagonist pterulinic acid

Concise synthesis of NADH: ubiquinone oxidoreductase (complex I) antagonist pterulinic acid () is reported. The key architectural framework in the natural product, 1-benzoxepine ring skeleton, was smoothly prepared from known salicylaldehyde and phosphorane via tandem SN2/Wittig reaction. Pterulinic acid was prepared in 5 steps from with overall yield of 25%. The versatility of tandem SN2/Wittig reaction was investigated. This tandem reaction tolerated various alkyl, ether, tertiaryamine and nitro substituted salicylaldehyde, and it gave the corresponding 1-benzoxepine ring skeleton in moderated yield (21–72%).