The first total syntheses of lorneic acids C and D and improved synthetic routes to lorneic acids A and J

We report the first total syntheses of lorneic acids C and D, each in 4 steps, from commercially-available 2-bromo-5-methyl benzaldehyde in 61 % and 36 % overall yields, respectively. A key feature of the syntheses includes a Suzuki cross-coupling to introduce the carboxylic sidearms in the natural products. Additionally, our group previously reported the construction of lorneic acids A and J, in 7 steps, with 23 % overall yields that included a lengthy 3-step sequence of reactions for the 1-carbon homologation of the allylic alcohols. Herein, we report second-generation synthetic routes towards lorneic acids A and J, each in 5 steps with 50 % and 46 % overall yields. In this case, a palladium-catalyzed carboxylation of allylic alcohol intermediates with formic acid secured the carboxylic acid sidearms. The new and improved routes shorten the total syntheses by 2 steps and double the yields of both natural products.