Iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides for synthesis of α-tertiary amines

A protocol for the synthesis of alpha-tertiary amines was developed by iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides. Nucleophilic 1,2-addition of organolithium reagents to carboxamides forms anionic tetrahedral carbinolamine (hemiaminal) intermediates, which are subsequently treated with bromotrimethylsilane (Me3SiBr) followed by organomagnesium (Grignard) reagents, organolithium reagents or tetrabutylammonium cyanide, affording alpha-tertiary amines. Employment of (trimethylsilyl)methylmagnesium bromide as the 2(nd) nucleophile allowed for aza-Peterson olefination of the resulting alpha-tertiary (trimethylsilyl)methylamines with acidic work-up, resulting in the formation of 1,1-diarylethylenes.

Automated summary

The synthesis of alpha-tertiary amines was achieved by iteratively adding carbon nucleophiles to N,N-dialkyl carboxamides, forming anionic tetrahedral carbinolamine intermediates. These intermediates were then treated with bromotrimethylsilane followed by organomagnesium or organolithium reagents to produce alpha-tertiary amines. The use of (trimethylsilyl)methylmagnesium bromide as the second nucleophile allowed for aza-Peterson olefination, resulting in the formation of 1,1-diarylethylenes after acidic work-up.