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 (1a) is reported. The key architectural framework in the natural product, 1-benzoxepine ring skeleton, was smoothly prepared from known salicylaldehyde 2g and phosphorane 3 via tandem S_N2/Wittig reaction. Pterulinic acid was prepared in 5 steps from 2g with overall yield of 25%. The versatility of tandem S_N2/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%).