[kriggy]

I read that grignards are pretty strong bases with pka in range of 45-50. How is that i get an addition to a aldehyde or ketone when most of the ketones and aldehydes have acidic hydrogens at their α carbons, therefore decomposing the grignard reagent?

It feels like pretty stupid question but it hit me this morning and cant figure it out. I mean everone is happy when one writes grignard with aceton in exams but given my argument you would need several equivalents of grignard reagent and I think thats not the case how its done in a lab.

[Dan]

Hint: Kinetics vs thermodynamics

[kriggy]

Im not sure if I follow. Kinecics means that the product is created faster and thermodynamics that its more stable. But acidobasic reactions are the fastest reactions known so thats confusing. Or does it mean that the addition to cabonyl is faster than the acidobasic reaction?

[Dan]

does it mean that the addition to cabonyl is faster than the acidobasic reaction?

Yes, generally, but it depends on the steric environment of the Grignard and of the electrophile. This is why you can use a Grignard to alkylate enolisable carbonyls despite the sizeable pKa difference. Deprotonation is thermodynamically very favourable, but nuclephilic reactivity is faster if the nucleophile and carbonyl are not crowded.

[kriggy]

Ah thanks. I thought that the deprotonation would be kineticaly favourable and the addition thermodynamicaly.