Scheme 1. Synthesis of enantiopure A-ring variants of 1. i) NiCl2 (10 mol%), BPhen (10 mol%), Mn (3 equiv.), 25 (1.2 equiv.), NMP. ii) Zn (2.9 equiv.), I2 (0.1 equiv.), 25 (1.3 equiv.), DMF; add iodoindole, Pd2dba3 (2 mol%), SPhos (4 mol%). iii) HCl in MeOH. iv) HCl in EtOAc. v) SOCl2, MeOH. vi) 4 Å MS, CH2Cl2; TFA; isolate trans-diastereomer. vii) Ti(Oi-Pr)4, TFAA, TFA, 70 °C; MeOH, NaOH (aq); isolate trans-diastereomer. viii) Amberlyst hydroxide, THF/MeOH/H2O, 16 h; AcOH (aq).
