Strecker-Type Reaction Using Ketones

Various fluorinated and nonfluorinated ketones were successfully employed in this MC Strecker reaction, and interestingly, the proper choice of the reaction conditions (catalyst and solvent) was crucial for the achievement of the process with very good results. Later, this research group developed a similar procedure using TMSOTf [63] or Nafion -H [64] as efficient catalysts of this reaction. 

Matsumoto, Kotsuki, Jenner, and cowoikers also reported the use of a wide scope of ketones in an MC Stredcer process using high pressure [65], and some scarce examples have beai also disclosed in other works mainly dedicated to aldehydes [66]. 

A plansible mechanism was envisioned by the anthors to explain the role of the catalyst in this process (Schane 10.27). 

The first step would be the in situ formation of the imine 71 between the ketone and the amine. Then, the catalyst would polarize the imine favoring the attack of the CN over the imine carbon and producing the TMS derivative 72, which would be later hydrolyzed with water to give the observed a-aminonitrile 70. 

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Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Although the Strecker reaction has been extensively studied with aldehydes using various kinds of catalysts and types of catalysis, the MC version nsing ketones has been less explored, maybe due to the less reactivity shown by these substrates, and only in 2007 it was reported the first efficient and extensively developed strategy using gallium triflate as catalyst (Scheme 10.25) [62]. 

Some imine-forming reactions are shown in Figure 14.30—all of these were part of longer synthetic sequences. Imines undergo many of the same types of addition reactions as aldehydes and ketones. A particularly useful example of this is their reaction with cyanide ion, the Strecker reaction (Figure 14.31). When a carbonyl compound is treated with ammonia and sodium or KCN, the ammonia adds to the carbonyl to give an unstable imine. This is attacked by cyanide to give the a-aminocyanide. Since the cyanide can be hydrolyzed to a carboxylic acid, this constitutes a simple amino acid synthesis. 

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