Scheme 16.

Cycloclavine (26). Reagents and conditions: (a) EtOCHO, 93%; (b) LiAlH₄, Et₂O; (c) methacryloyl chloride 150, NaOH (aq), 79% (2 steps); (d) 152 (1 mol%), PhMe, reflux, 73%; (e) POCl₃, DMF, 91%; (f) (Boc)₂O, DMAP, MeCN, quant.; (g) NaBH₄, MeOH, 0 °C to room temperature, 92%; (h) Br₂, PPh₃, cyclohexane, 93%; (i) pyrrolinone 146, NaH, DMF, 0 °C to room temperature, 52%; (j) Pd(OAc)₂ (10 mol%), PPh₃ (60 mol%), Ag₂CO₃ (2 equiv.), NEt₃, PhMe, 110 °C, 74%; (k) LiAlH₄, THF, reflux, 56%