C-Nucleophiles

Figu re 9.4 Chiral ligands other than phosphoramidites that have been used in Ir-catalyzed allylic substitutions. 

In this chapter, we have seen many different kinds of nucleophiles that can attack ketones and aldehydes. We started with hydrogen nueleophiles. Then we moved on to oxygen nucleophiles and sulfur nucleophiles. In the previous section, we covered nitrogen nucleophiles. In this section we will discuss carbon nucleophiles. We will see three types of carbon nucleophiles. 

Our first carbon nucleophile is the Grignard reagent. You may have been exposed to this reagent in the first semester. If you weren t, here is a quick overview  

Alkyl halides will react with magnesium in the following way  

Essentially, an atom of magnesium inserts itself in between the C—Cl bond (this reaction works with other halides as well, such as Br or I). This magnesium atom has a significant electronic effect on the carbon atom to which it is attached. To see the effect, consider the alkyl halide (before Mg entered the picture)  

The carbon atom (connected to the halogen) is poor in electron density, or 8+, because of the inductive effects of the halogen. But after magnesium is inserted between C and Cl, the story changes very drastically  

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In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

Monomeric thiazyl halides can be stabilized by coordination to transition metals and a large number of such complexes are known (Section 7.5). In addition, NSX monomers undergo several types of reactions that can be classified as follows (a) reactions involving the n-system of the N=S bond (b) reactions at the nitrogen centre (c) nucleophilic substitution reactions (d) halide abstraction, and (e) halide addition. Examples of each type of behaviour are illustrated below. 

Synthesis, properties, and applications of nonsymmetric triazinones 99MI26. Transformations of 1,2,4-triazines by the action of C-nucleophiles 98ZOR327. 1,2,4-Triazine A -oxides and their annelated derivatives 98UK707. 

The reaction of 1,2,4-triazine 4-oxides 55 with thiophenols proceeds in the same manner, resulting in the corresponding 5-arylmercapto-1,2,4-triazines 80 in high yields. Thiophenols in this case react as S-nucleophiles, in spite of the relative phenols—the C-nucleophiles (01RCB1068). 

A different type of denitrocyclization reaction reported by Krohnke et al. involving C-nucleophiles is represented by treatment of some A-(2,4,6-trini-trobenzyl)pyridinium salts, e.g. 168, with sodium hydroxide providing high... 

A novel route to 2-fluoropyridines involved the base-induced decomposition of substituted N-fluoropyridinium salts. Abstraction of the 2-H produces a singlet carbene (11) that removes F from a counterion. This is in contrast to the reaction with C nucleophiles, which are fluorinated, and is attributed to the high stability of C—F compared to O—F and N—F (89JOC1726). 

Two principle approaches from thiopyrylium salts to thiopyrans accompanied by C-substitution have been found, e.g., the one-step additions of C-nucleophiles or the two-step procedures involving primary conversions of the salts to nucleophilic intermediates followed by attacks with appropriate electrophiles. 

Synthesis of Complex Molecules by Ring-opening of Epoxides with C-Nucleophiles 289... 

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