Stereoselective nucleophilic substitution of 6-(tert-butyldimethylsilyloxy)-3,6-dihydro-2H-pyran-3-yl acetate: application to the synthesis of a NK1 receptor antagonist

Reaction of chiral cis- and trans-6-(tert-butyldimethylsilyloxy)-3,6-dihydro-2H-pyran-3-yl acetates with various nucleophiles (allyltrimethylsilane, bistrimethylsilylacetylene, benzyl alcohol, benzyl carbamate etc.) in the presence of a Lewis acid gave the corresponding 2,3-unsaturated pyran derivatives in good to excellent yield with trans selectivity. Application to the synthesis of NK1 antagonist is also described.

Graphical abstractThe reactions of 1b or 5b with various nucleophiles were investigated. Application to the synthesis of 12, a key intermediate for a NK1 antagonist, is also described.Download full-size image