Synthesis of the tricyclic dihydrofuran moiety of azadirachtin: efficient transformation of the Claisen rearrangement intermediate into a functionalized tricyclic dihydrofuran core

The Azadirachtin Story

“… Studies towards C8C14 bond formation with achiral decalin surrogate 235 103. Reagents and conditions: a) EDCI, DMAP, CH 2 Cl 2 , RT, 2 h, 72 %; b) KHMDS, TMS‐CI, Et 3 N, toluene, −78 °C to 70 °C, 12 h, 87 %.…”

“… Murai's approach to C8C14 bond formation 103. Reagents and conditions: a) EDCI, DMAP, CH 2 Cl 2 , RT, 72 %; b) SiMe 2 Cl 2 , Et 3 N, toluene, LiHMDS, −78 °C to 70 °C, 87 %, (4:1) 240 : 241 .…”

“…This was achieved in a high‐yielding four‐step sequence ( 237 → 242 , Scheme ). Model studies were also employed to examine the installation of the sterically congested C13C14 epoxide in 5 103. Standard manipulations permitted the transformation of exo olefin 242 to a suitable epoxidation precursor 243 .…”

“… Tether removal and model epoxidation studies 103. Reagents and conditions: a) CH 2 N 2 , Et 2 O, 0 °C; b) DIBAL‐H, CH 2 Cl 2 , −78 °C, 99 % over 2 steps; c) imidazole, PPh 3 , I 2 , benzene, RT, 93 %; d) NaBH 4 , DMSO, 100 °C, 87 %; e) m CPBA, NaHCO 3 , CH 2 Cl 2 , RT, 90 %; f) BF 3 ⋅Et 2 O, CH 2 Cl 2 , −55 °C, 7 h, 78 %; g) KHMDS, HMPA, THF, −55 °C, then NBS, 71 %; h) LiBr, Li 2 CO 3 , DMF, 125 °C, 99 %; i) NaBH 4 , CeCl 3 ⋅7 H 2 O, MeOH, 0 °C, 78 %; j) [VO(acac) 2 ], TBHP, CH 2 Cl 2 , RT, 99 %.…”

Die Azadirachtin‐Story

“… Studien zur C8‐C14‐Bindungsbildung mit einem achiralen Decalinmodell 235 103. Reagentien und Reaktionsbedingungen: a) EDCI, DMAP, CH 2 Cl 2 , RT, 2 h, 72 %; b) KHMDS, TMS‐CI, Et 3 N, Toluol, −78 °C bis 70 °C, 12 h, 87 %.…”