Synthesis of the Nakanishi Ring-Locked Retinoid

Scheme 1

Reagents and conditions: (a) (i) NBS, ACHN, benzene, reflux, 2 h, and 34%; (ii) KOAc, TBAB, THF/H₂O, r.t., 4 days, and 17%; (b) NaH, (EtO)₂P(O)CH(CH₃)CN, THF, 0°C to r.t., and 20 h; (c) isomer separation by SiO₂ column chromatography, E 33%, and Z 17%; (d) K₂CO₃, MeOH, r.t., 1.5 h, and 99%; (e) TBSCl, imidazole, DMAP, CH₂Cl₂, r.t., 1 h, and 80%; (f) DIBAL-H, Et₂O, −78°C to 0°C, 2 h, and 96%.