Addition reactions nitrogen nucleophiles

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

Murahashi and co-workers (49) extensively studied the synthesis of nitrones such as 29 by a decarboxylative oxidation of proline derivatives (Scheme 12.12). However, these nitrones were primarily used in nucleophilic addition reactions rather than 1,3-dipolar cycloadditions. Others have synthesized cyclic nitrones 30 and 31 having a chiral center adjacent to the nitrogen atom (50,51). Saito and co-workers (51) applied nitrone 31 in reactions with fumaric and maleic acid... 

Diazines are considerably more reactive toward nucleophiles than pyridines and as the number of ring nitrogens increases the propensity for nucleophilic addition reactions increases still more. Many 1,2,4-triazines give addition products with various nucleophiles which are formally dihydrotriazines. 

Additions to l,3-dienes6 (12, 367-368 14, 249-250 15, 245). This reaction can be used to effect intramolecular cyclization of cyclic 1,3-dienes substituted by a suitable nitrogen nucleophile. Thus reaction of the amido diene 1 with lithium acetate catalyzed by Pd(OAc)2 (with benzoquinone as reoxidant) provides the ds-fused heterocycle cis-2, in which the acetoxy group is cis to the ring fusion, formed by an overall trans-1,4-oxyamidation of the diene system. Addition of a trace of LiCl improves the yield and results in an overall cis- 1,4-oxyamidation (equation I). Acetamides and carbamates can also be used in place of amides. 1,4-Chloroamidation can also be effected by use of 2 equiv. of LiCl. 

The nucleophilic addition reactions of enolates to imines and related compounds (the so-called Mannich-type reactions, equation 39) are important tools in organic synthesis and a variety of electrophiles have been used to obtain the resulting nitrogen-containing... 

The chemistry of amines is dominated by the nucleophilicity of the nitrogen atom. Amines form salts, participate in nucleophilic substitution reactions of alkyl halides and in nucleophilic addition reactions to carbonyl compounds. 

Oxazolidinone-Substituted Carbanions. Oxazolidinone-substituted organostannanes readily undergo transmetalation with alkyllithium reagents to the organolithium derivatives which then can undergo nucleophilic addition reactions. -Substituted oxazolidinones can act in this capacity as both a nitrogen source and source of chirality (eq 60). Although the a-stereoselection... 

In general, nucleophilic addition reactions of arene oxides with nonpolarizable oxygen and nitrogen nucleophiles are very slow. Thus both NH3 and NHj nucleophiles failed to add to benzene oxides under a range of conditions. Amine nucleophiles have, however, been found to react very slowly with benzene oxide. 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

The majority of cases (Table 1) involve activation of the diene by complexation to Pd(II) and Pt(II) centers. However, other metal-diene complexes have been examined including Ni(II), Ir(I), and Mn(I) complexes. Cationic or neutral complexes are used in the nucleophilic addition reactions. The most common nucleophiles employed are oxygen or nitrogen bases (hydroxide, alkoxides, carboxylates, amines) or stabilized carbon nucleophiles (malonate, j8-diketonates). The dienes employed include 1,5-cyc-looctadiene, norbomadiene, dicyclopentadiene, 4-vinylcyclohexene, 7-(alkylidene)nor-bornene and endo-4-vinylnorbornene. 

The mechanistic pattern of hydration and alcohol addition reactions of ketones and aldehydes is followed in reactions of carbonyl compounds with amines and related nitrogen nucleophiles. These reactions involve addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid catalyzed or base catalyzed. The rates of the reactions are determined by the energy and reactivity of the tetrahedral intermediates. With primary amines, C=N bond formation ultimately occurs. These reactions are reversible and the position of the overall equilibrium depends on the nitrogen substiments and the structure of the carbonyl compound. 

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

Intramolecular nucleophilic addition reactions of enamines to suitable electrophiles placed y to the enamine nitrogen atom afford quinolizine derivatives. Examples of this strategy (Schemes 50... 

The nitrogen atoms of the isocyanides ligands CNR in M2(CO)3(CNR)Cp2 ( M = Fe, Ru) has been proved to be very susceptible to alkylation reactions [12]. The cationic products contain the CN(R )R group invariably located in the bridging position. The carbyne character of these ligands has been evidenced from their p-C nucleophilic addition reactions of H" and CN" v/hich may form either bridging or terminal aminocarbene derivatives. The results of our studies, collected in Scheme 3, can be summarized as follows ... 

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