Nucleophilic Addition to Carbon-Heteroatom Multiple Bonds

14 NUCLEOPHILIC ADDITION TO CARBON-HETEROATOM MULTIPLE BONDS 

In this section, we will focus primarily on nucleophilic additions to carbonyl groups. The carbonyl substrate may be an aldehyde or ketone, as well as various carboxylic acid derivatives such acid halides and esters. Among the variety of nucleophiles that can participate in these reactions are hydride, hydroxide, alkoxide, and a variety of carbon-based nucleophiles. For carbonyl substrates, attack by a nucleophile typically results in an opening up of the C-O ar-bond, leading to a tetrahedral intermediate, as shown below for the addition of cyanide to a ketone in the presence of water. 

The anionic alkoxide intermediate picks up a proton from water to generate the cyanohydrin product  

A similar reaction may also be accomplished under nonaqueous conditions with trimethylsilyl cyanide. Though exceedingly unstable by themselves, trimethylsilyl cations in complexed form may be profitably viewed as fat protons and are excellent Lewis acids  

The interaction between the carbonyl compound and the catalyst, trimethylsilyl triflate, may be envisioned as an A-D sequence, as shown below  

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L. Miginiac, Nucleophilic Addition to Carbon-Heteroatom Multiple Bonds O, S, N, P, in Handbook of Grignard Reagents (G. S. Silverman, P. E. Rakita, Eds.), Marcel Dekker Inc., New York, 1996, 361-372. 

Nucleophilic Addition to Carbon-Heteroatom Multiple Bonds O, S, N, P... 

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