Carbon-nitrogen bond forming reactions ketones

Reactions of this type are mostly performed with internal nucleophiles attached to the carbon atom adjacent to the iminium nitrogen, thus leading to tropane-like azabicyclic systems. Both allyl- and propargylsilanes, activated and unactivated alkenes, and ketones have been successfully used as nucleophiles. The products 1 and 2 are also obtained via two consecutive C —C bond-forming reactions in a single operation. 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

The N2 hgand bound to a metal atom may also be susceptible to attack by electrophilic reagents other than acids. In fact, reactions of coordinated N2 or its protonated derivatives have been extensively studied with a range of organic compounds including alkyl and acyl halides, carboxyhc anhydrides, aldehydes, ketones, and activated aryl or vinyl halides to directly form the carbon-nitrogen bonds. 

A compound with a carbon-nitrogen double bond, formed by the reaction of a ketone or aldehyde with a primary amine. A substituted imine is often called a Schiff base. (p. 850)... 

Hydrogen cyanide adds to the carbon-nitrogen double bonds present in various aldehyde and ketone derivatives, like those in imines, hydrazones, oximes, and Schiff bases. In each instance, a new carbon-carbon linkage is formed. Thus, the reaction of dry hydrogen cyanide with an imine... 

Topics that have formed the subjects of reviews this year include contemporary issues in electron transport research, dynamics of bimolecular photoelectron transfer reactions, photophysical properties of functionalised fullerene derivatives, carbon-carbon bond formation via radical ions, photoinduced electron transfer processes in ketone, aldehyde, and ester synthesis, photochemical reactions between arenenitriles and benzylic donors, photo-oxidation of conjugated dienes, photoredox reactions of aromatic nitro compounds, electron transfer-mediated photochemistry of some unsaturated nitrogen-containing compounds, reactions of 02( Ag), carbon dioxide activation by aza-macrocyclic complexes, and photochromism of chalcone derivatives. ... 

Overall, the addition of a nitrogen nucleophile to an aldehyde or a ketone is a nucleophilic addition-elimination reaction nucleophilic addition of an amine to form an unstable tetrahedral intermediate, followed by elimination of water. The tetrahedral intermediates are unstable because the newly formed sp carbon is bonded to an oxygen and to a nitrogen—another electronegative atom. Water is eliminated, and loss of a proton from the resulting protonated imine forms a stable imine. 

A valuable feature of the enamine reaction is that it is regioselective. In the alkylation of an unsymmetrical ketone, the product of reaction at the /ess-substituted a-carbon atom is formed in greater amount, in contrast to direct base-mediated alkylation of unsymmetrical ketones, which usually gives a mixture of products. For example, reaction of the pyrrolidine enamine of 2-methylcyclohexanone with iodomethane gives 2,6-dimethylcyclohexanone almost exclusively. This selectivity derives from the fact that the enamine from an unsymmetrical ketone consists mainly of the more-reactive isomer in which the double bond is directed toward the less-substituted carbon atom. In the more-substituted enamine, there is decreased interaction between the nitrogen lone pair and the -ir-system of the double bond because of steric interference between the a-substituent (the methyl group in Scheme 1.33) and the a-methylene group of the amine. 

In addition to tin and silicon, carbon-nitrogen double bonds as hydrazones, oximes, and nitrones can be treated with ozone to form carbonyl compounds (eq 53)7 While the transformation can be accomplished on several types of substrates, ketone-derived starting materials (e.g., ketoximes) perform better in the reaction, as the aldehyde-derived starting materials have the potential for overoxidation to the corresponding carboxylic acid product. 

Because the polarity of carbon-hydrogen bond is very small and exhibits very low acidity, very strong bases are required for such reactions. However, C-H bonds adjacent to substituents such as carbonyl or cyano groups are stabiUzed by resonance/induction and are more acidic. Nitrogen bases have been used effectively in these reactions to minimize the nucleophihc addition that can compete with proton removal when an organometallic compound such as n-butyllithium is used as the base. For example, methyl ketones react with Hthium diisopropylamide (LDA) to form the enolate ion (Eq. (3.4)), and even more sterically hindered amides have been used. The enolate anion is a strong base and a good nucleophile ... 

An SB contains a carbon-nitrogen double bond formed from the reaction of an amino group and an aldehyde or ketone with the elimination of water. This process is reversible and can effect the hydrolysis of imine to amine and aldehyde/ketone (Figure 1.25). 

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