[Kaladiscope]

Hello chemists,

Having one ketone and one aldehyde in the same molecule and using KCN, NaCN or TMSCN to generate the corresponding cyanohydrin...which entity would be more reactive, the ketone or the aldehyde? I assume that aldehydes are much more reactive than ketones...when we talk about nucleophilic addition...is that assumption right? or may I protect the ketone?

Thanks,

[orgopete]

Almost any reaction can be selective, sort of. If you are asking about doing this in the lab, I'd give it a try. Just limit the cyanide being used. Then it will become a question of isolation.

I don't necessarily see how protection would be better unless you come by the keto-aldehyde by a route that had one group protected or masked in some manner. Protect, isolate, make cyanohydrin, additional chemistry(?), deprotection doesn't necessarily look like an improvement in isolating your desired product.

[AlphaScent]

I would protect.  It is not difficult to deprotect the ketone with an acidic work-up.  Thats if you use a ketal.

[discodermolide]

I would protect.  It is not difficult to deprotect the ketone with an acidic work-up.  Thats if you use a ketal.

If you make a ketal the aldehyde will also form one!

[Kaladiscope]

I would just trust in the higher electrophilicity of aldehydes compare to ketones. Having both, with for example TMSCN, one could generate the correponding cyanohydrin and the protected alcohol with TMS...

[milo2112]

I would expect that lower temperatures would tend to decrease reactivity of the ketone. It seems to me that not only is the ketone derived cyano hydrin less stable (due to the sterics around the resulting tetrahedral carbon) but probably forms a bit slower than the aldehyde. I would try doing this at 0C, maybe -20C. Regardless, you should be able to separate them by chromatography. Although before that, I would run a 2D tlc to look for decomposition on silica (if that is your stationary phase) as cyanochydrins (or even the TMS protected derivatives) are not known for their stability.

Good luck