Nitrogen nudeophiles

In these reactions, the nitrogen nudeophile is typically an amide, carbamate, or a sulfonamide. Because of the low nudeophiUdty of such nitrogen functions, no intermolecular 1,4-addition involving C-N bond formation is known. In aU cases reported, the carbon-nitrogen coupling takes place in an intramolecular aminopalladation. 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

The addition of methanol or hydrazoic acid to ethenylidenecydopentadiene 3 demonstrates that 3 behaves like an acceptor-substituted allene (Scheme 7.27) [226, 227]. More examples of nudeophilic additions to alkyl-substituted derivatives of 3 were reported by Hafner [228]. Photoelectron spectroscopy of the spirocyclic compound 165b, easily accessible from azide 164b, shows that the lone-pair orbital n(N) of the 2H-azirine nitrogen atom interacts strongly with the Jt1-orbital of the cyclo-pentadiene ring [227]. 

One of the important challenges in modern synthetic and pharmaceutical chemistry is to design and develop efficient, clean, and fast routes to obtain architectural molecules from simple starting materials [102, 103]. The ewdo-selective cydoisome-rization (Scheme 4.13a) of terminal alkynes tethered to alcohols, nitrogen, and sulfur nudeophiles is one of the interesting transformations widely utilized in effident syntheses of antiviral nucleosides [104, 105], polycyclic ethers [106], and oligosac-... 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

Of course a nitrile is not a carbonyl. But nitrile and carbonyl chemistries are similar, and an examination of nitrile reactions naturally belongs in this section. Like carhonyl compounds, nitriles are both electrophiles and nucleophiles. As in carhonyl compounds, a polar resonance form contributes to the structure of nitriles (Fig. 18.44). Consequently, the triple bond is polarized and the carhon acts as a Lewis add. One might antidpate that nudeophiles would add to nitriles, and that idea is correct. These similarities mean that many of the reactions of carhonyl groups are also possible for nitriles, and the mechanisms are generally dosely related. Students sometimes have trouble with the nitrile reactions, however, so it is important not to dismiss them with only a cursory look. For some reason, the analogy between the carbon—oxygen double bond and the carbon—nitrogen triple bond is not always easy to keep in mind. 

Reetz and co-workers " first used metal-free carbon, nitrogen, or sulfur nudeophiles as initiators for the controlled anionic polymerization of nBA. It was thought that repladng the metal counterion in the polymerization would reduce the problem assodated with aggregation and improve the control over the polymerization. Tetrabutylammonium salts of malo-nate derivatives provided poly(n-butyl acrylate) (PnBA) of rdativdy narrow MWD at room temperature (Scheme 14). Many metal-free initiators for the polymerization of alkyl (meth) acrylates using a variety of anions and cations have been reported (Scheme 15) 208,220-224... 

Garrett, C.E. and Fu, G.C. (1998) Nudeophilic catalysis with Jt-bound nitrogen heterocydes synthesis of the first ruthenium catalysts and comparison of the reactivity and the enantioselectivity of ruthenium and iron complexes. J. Am. Chem. Soc., 120, 7479-7483. 

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