Generation of secondary, tertiary, and quaternary centers by geminal disubstitution of carbonyl oxygens

Methods for replacing the carbonyl oxygen by two new substituents (C=O→CR(1)R(2)) are discussed in this Minireview, whereby R may be H, NR(2), alkyl, allyl, benzyl, vinyl, alkynyl, aryl, heteroaryl, or acyl groups. The most frequently used starting materials for geminal disubstitution with the formation of two C-C bonds (R(1),R(2)≠H, NR(2)) are amides and thioamides, which react with organometallic nucleophiles R-M (M=Li, MgX, CeX(2), TiX(3), ZrX(3)) to give tertiary sec- and tert-alkylamines. Quaternary centers can be built directly from ketones by treatment with Me(3)Al, MeTiCl(3), or Me(2)TiCl(2) (R(1)R(2)C=O→R(1)R(2)CMe(2)). The scope and limitations of the various methods and mechanistic models are briefly discussed. The remarkable variety and diversity of structures thus accessible are demonstrated by numerous examples.