Selective TES-ether deprotection followed by selective ester hydrolysis in the synthesis of (-)-CP2-Disarazole C1

Alcohols as TES and TBS  ethers: P. Wipf’s group had protected 3 alcohol groups in (-)-CP₂-Disarazole C_1.  Two were protected as TBS (tert butyldimethylsilyl) ethers and one was protected as TES (triethylsilyl) ether.  The TES ether was deprotected selectively keeping the two TBS ethers intact.

Installation: TESOTf, 2,6-lutidine, CH₂Cl₂, 0 °C, 93% yield

Survived: OsO₄/NMO, NaIO₄, NaBH₄, KHMDS

Removal: PPTS, MeOH, 0 °C, 63% yield

Reference: Organic Letters, 2011, 13, 4088-4091

Lactone as methyl ester:  A lactone was masked as a methyl ester. Another ester linkage was present in the molecule as it was dimer.  The simpler methyl ester was deprotected selectively in the presence of a substituted isopropyl ester.  Activation of the resulting acid with MNBA (2-methy-6-nitrobenzoic acid), DMAP, and triethylamine in toluene resulted in lactonization. 

Installation: commercially available starting material (serine methyl ester hydrochloride)

Survived: DDQ, Dess-Martin, KHMDS, PPTS

Removal: Ba(OH)₂, THF/H₂O followed by activation/lactonization: overall 55% yield in 2 steps.

Reference: Organic Letters, 2011, 13, 4088-4091

Interestingly, the preparation of one intermediate started with an ethyl ester, but it got transformed into a methyl ester during the deprotection of a TMS protecting acetylinic group (K₂CO₃, MeOH).