Nucleophilic groups ketone functionalization

Ley and Middleton synthesized ketone-functionalized lactam complexes 260 (Scheme 2.64) by sonication of vinylaziridines 259 with Fe2(CO)9 in benzene. These complexes were easily converted into the corresponding (3-lactams 261 by stereoselective addition of nucleophiles such as NaBH4 or trialkylaluminium to the carbonyl group followed by decomplexation with Me3NO [96]. 

Peptidyl fluoromethyl ketones are widely used as fairly potent inhibitors for a variety of proteases, including serine, cysteine, and aspartyl proteases. Unlike other halomethyl ketones (Section 15.1.3), fluoromethyl ketones are reversible transition-state mimics. The electron-withdrawing fluorine(s) next to the carbonyl group enhances the electrophilicity of the a-fluoroalkyl ketone functionality, thereby making the carbonyl more susceptible to nucleophilic attack. a-Fluoroalkyl ketones are good mimics of peptide bonds due to the small size of the fluorine and the stability of C F bonds. There are three general classes of peptidyl fluoromethyl ketones fluoromethyl ketones (irreversible inhibitors of cysteine proteases), difluoromethyl ketones (reversible inhibitors of both serine and aspartyl proteases), and trifluoromethyl/perfluoroalkyl ketones, which typically exist in hydrated forms and are excellent inhibitors of both serine and cysteine proteasesJ1 ... 

Thus we find some functional groups are more likely to react as nucleophiles while some functional groups are more likely to react as electrophiles, e.g., amines, alcohols and ethers are more likely to react as nucleophiles, because they have strong nucleophilic centres and weak electrophilic centres. Alkyl halides are more likely to react as electrophiles because they have strong electrophilic centres and weak nucleophilic centres. Aldehydes and ketones can react as nucleophiles or electrophiles because in both electrophilic and nucleophilic centres are strong. 

First we note that it is necessary to form a carbon-carbon bond because the starting material has only two carbons and the target has seven. Because the starting material is an alkyne, we can probably use an acetylide anion as the nucleophile to form the carbon-carbon bond (see Section 10.8). How can a ketone functional group be introduced Section 11.6 described the hydration of an alkyne to produce a ketone. Our retrosynthetic analysis then becomes ... 

Because monosaccharides contain alcohol functional groups and aldehyde (or ketone) functional groups, the reactions of monosaccharides are an extension of what you have already learned about the reactions of alcohols, aldehydes, and ketones. For example, an aldehyde group in a monosaccharide can be oxidized or reduced and can react with nucleophiles to formimines, hemiacetals, and acetals. When you read the sections that deal with the reactions of monosaccharides, you will find cross-references to the sections in which the same reactivity for simple organic compounds is discussed. As you study, refer back to these sections they will make learning about carbohydrates a lot easier and will give you a good review of some chemistry that you have already learned about. 

Remember that not all nucleophiles will successfully undergo Michael additions—you must bear this in mind when making a 1,3-disconnection of this type. Most reliable are those based on nitrogen, sulfur, and oxygen (Chapter 22). Our second example is an amine structurally similar to the deadly nightshade drug, atropine, which has the ability to calm involuntary muscle movements. There is a 1,3-relationship between the amine and ketone functional groups, and 1,3-disconnection takes us back to piperidine and an unsaturated ketone. 

Activation of the functionalized support is most often achieved with glutaraldehyde, which introduces a carbonyl residue that subsequently reacts with nucleophilic groups on the enzyme. The activation of the functional material and the biding of the enzyme result in the formation of a Schiff base. The optimum pH for these reactions is a compromise between the preferred acidic catalytic conditions, the of the nucleophilic groups (in such a way that the unpro-tonated form is desirable) and the stability of the enzyme at different pH values. The reversibility of Schiff base formation is suppressed by the addition of sodium cyanotrihydroborate, a weak reducing agent, which does not reduce aldehydes or ketones at neutral pH but readily reduces the imine form to the... 

Since oxidation and reduction reactions can provide many organic compounds with reactive functional groups such as aldehydes, ketones, enones, amines, alcohol, allylic alcohols, and so on, further transformations can easily be added to give a domino process. Depending upon the position of the oxidation or reduction reaction in the domino process, this chapter is divided into three classes first, the domino reaction is initiated by an oxidation or reduction reaction second, the domino reaction has the oxidation or reduction step in the middle and third, the domino reaction is terminated by an oxidation or reduction reaction. Most of the oxidation and reduction reactions come under the category of anionic domino process, as they provide nucleophilic or electrophihc functionalities and only very few oxidation and reduction reactions proceed with cationic domino process. 

These versatile reactions, commonly referred to as Stille and Suzuki couplings, respectively, are performed with organostannanes or organoboranes as nucleophiles and are tolerant to most functional groups. Ketones are obtained if carbon monoxide is present in the Stille reaction. This gives the possibility to label an aromatic methyl ketone in two different positions by the use of either [ C] carbon monoxide or [ C] methyl iodide, as shown in O Fig. 41.22 (Andersson et al. 1995 Andersson and Langstrom 1995a, b). 

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