Fig. 3: Optimization of reaction conditions.
Unless otherwise stated,the yields were determined by 1H NMR with 1,3,5-trimethoxybenzene as the internal standard. a Optimization of the Diels–Alder reaction. [a] After 12 h, the same equiv. maleic anhydride was added. [b] Scale up to 100 g, isolated yield with 6% (molar ratio) maleic anhydride. b Optimization of decarboxylative hydroxylation. [a] d.r. > 95:5, 30 g scale. [b] Isolated yield on 1 g scale using a circulating flow system. c Optimization of the SmI2/H2O/amine-mediated fragmentation. [a] HMPA (10 eq). [b] Et3N (24 eq)/H2O (24 eq). The yield in the bracket is an isolated yield. [c] Et3N (36 eq)/H2O (36 eq). [d] pyrrolidine (60 eq)/H2O (60 eq). [e] SmI2 (3 eq), 55 °C, without purification followed by reduction using LiAlH4. The yield is isolated yields for the two steps on decagram scale. d Selectivity of nucleophilic addition. The aldehyde functional group is highlighted in red. N.D. not determined, MTBE methyl tert-butyl ether.
