Synthetic Studies towards Maoecrystal V

Abstract

The investigation of an intramolecular Diels-Alder reaction, en route to a projected total synthesis of maoecrystal V, is described.

Figure 1

Maoecrystal V (1).

Figure 2

Transition structures for the Diels-Alder reaction.

Scheme 1

A proposed route to maoecrystal V.

Scheme 2

Synthesis of intermediate 2. Reagents and conditions: (a) Pd(OAc)₂, 2-di-t-butylphosphino-2′-methylbiphenyl, K₃PO_4,, THF, 80 °C, 12 h, 91%; (b) TMSCHN₂, Hunig’s base, CH₃CN/MeOH = 9:1, 6 h, 100%; (c) Bu₃SnCH₂OMOM, BuLi, THF, −78 °C to −40 °C, 30 min, 0.5% HCl work-up, 75%; (d) HCl/MeOH, 50 °C, 75%; (e) PivCl, Py, DCM, 12 h, 96%; (f) NaBH₄, CeCl₃, MeOH, 0 °C, 2 h, 93%; (g) MOMCl, Hunig’s base, DCM, 12 h, 95%; (h) DIBAL-H, −78 °C, DCM, 30 min, 95%; (i) KH, 18-crown-6, ICH₂SnBu₃, 0 °C, THF, 6 h, 90%; (j) n-BuLi, −78 °C to −20 °C, THF, 6 h, 88%.

Scheme 3

Intramolecular Diels-Alder reaction of 15c. Reagents and conditions: (a) Li, NH₃(l), t-BuOH/THF, −78 °C, 20 min, −33 °C, 40 min; (b) 1 N HCl, 0 °C, THF/MeOH (10/1), 8 h, 2 steps, 78%; (c) acid chloride, Py, DCM, 0 °C. 15a : 70%, 15b : 75%, 15c : 72%; (d) TBSOTf, TEA, DCM, 0 °C, 15 h, 81%; (e) 180 °C, sealed tube, toluene, 12 h; (f) TBAF, 0 °C, THF, 2 steps, 48%.