26 Grignard Reagents

Grignard reagents are relatively easy to make from alkyl, aryl, and alkenyl under anhydrous conditions. That gives a lot of substrate scope, but they cannot be formed from substrates which would self-protonate or otherwise self-react.

Grignard's cannot be formed from substrates which have a β-leaving group, because of elimination to alkenes occurs. In fact, adding a small amount of 1,2-dibromoethane helps trigger Grignard formation reactions which are otherwise slow to start.

All the reactions considered here involve carbon electrophiles. Grignard's in these transformations react with these to give products with larger carbon frameworks, so this strategy is used to build up larger molecules; that strategy is valuable in organic synthesis. Biosynthesis of natural products is incompatible with anhydrous conditions so Nature uses condensations of enolates with to achieve carbon scaffold formations, and those reactions are covered much later in this series. Some students learning Grignard reagents for the first time come to appreciate creativity in design of organic synthesis; this book may be a first step in that direction.