Diastereoselective Synthesis of Chiral Tertiary Methyl Ethers

Significance

An auxiliary-based synthesis of chiral tertiary methyl ethers 3 through addition of titanium enolates to dialkyl ketals is reported. The products, obtained in good yields and moderate selectivities, are densely functionalized and constitute an important class of chiral synthons. The motif is difficult to obtain through aldol condensation owing to the low reactivity of ketones; however, examples can be found utilizing chiral auxiliaries (P. C. Bulman Page and co-workers J. Org. Chem. 2000, 65, 6027) or chiral catalysts (M. Shibasaki and co-workers J. Am. Chem. Soc. 2006, 128, 7164). Reductive aldol reactions have also been applied (O. Riant and co-workers Angew. Chem. Int. Ed. 2006, 45, 1292).