Selective TBS-ether deprotection in presence of TBDPS-ether in the synthesis of protectin-D1

Alcohols as TBS and TBDPS  ethers: Y. Kobayashi’s group had 2 alcohol groups in protectin-D1. One (primary) was protected as TBS (tert butyldimethylsilyl) ether and the other one (secondary)  was protected as TBDPS (tert butyldiphenyl) ether.  The TBS ether was deprotected selectively keeping the TBDPS ether intact.

Installation: not shown – but fairly simple substrates.  Standard methods would have sufficed.

Survived: H₂/Pd(Lindlar), Py.SO₃/NaClO₂/CH₂N₂

Removal: PPTS, CH₂Cl₂/EtOH, 94% yield

Reference: Tetrahedron Letters, 2011, 13, 3001-3004

There is one very interesting selective hydrogentation step towards the end of the synthesis.  In Scheme 5, intermediate 27 has two acetylinic bonds – one has two alkyl chains attached to it, while the other has a TMS group and an alkene attached to it.  Hydrogenation using Pd/BaSO₄ in ethyl acetate selectively reduced the alkyne with the two alkyl chains to the cis alkene, keeping the other acetylenic bond intact to give intermediate 28. 

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).