Asymmetric Total Synthesis and Absolute Configuration Reassignment of Indole Alkaloid (+)-Alsmaphorazine D

The first asymmetric total synthesis of (+)-alsmaphorazine D has been achieved through a traceless chirality transfer strategy, which also enabled absolute configuration reassignment of the natural product. Key steps of this efficient approach entail a catalytic oxidative cyclization [To a solution of indoline ester 8 (5.82 g, 10 mmol) in AcOH (100 mL) were added CAN (550 mg, 1 mmol) and NaOAc (1.64 g, 20 mmol). The reaction vessel was exposed to air through a CaCl2 tube. The resulting mixture was stirred at 110 degrees C for 12 h before it was concentrated in vacuo. The residue was diluted with H2O, neutralized with NaHCO3 (sat. aq.) and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V: V=4: 1) afforded d-lactamindole 7 (4.34 g, 75%) as a white amorphous solid], a diastereoselective oxidative cyclic aminal formation [To a stirred solution of mono-ester 13 (5.20 g, 10 mmol, dr=1: 1) in acetone (100 mL) at 0 degrees C was added NaHCO3 (100 mL, sat. aq.). The resulting mixture was stirred for 0.5 h before it was added oxone (12.28 g, 20 mmol) slowly. The reaction mixture was stirred at 0 degrees C for an additional 2 h before it was diluted with H2O. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V: V=3: 1) afforded pyrroloindole 6' (1.61 g, 71%) as a white amorphous solid] and an intramolecular radical cyclization [To a stirred solution of ent-5 (250 mg, 0.47 mmol) in benzene (5 mL) at 80 degrees C were added n-Bu3SnH (152 mu L, 0.56 mmol) and AIBN (5 mu L, 0.047 mmol). The resulting mixture was stirred for 0.5 h before it was concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V: V=1: 1) afforded C(16)-epi-ent-4 (213 mg, 72%) as a colorless oil.].