Nitrogen nucleophiles processes

The replacement of reactive aromatic fluonne by nitrogen nucleophiles is a well-known process for the preparation of aromatic amines The aromatic fluonne IS activated by the presence of electron-withdrawing substituents on the aromatic ring, especially in ortho and para positions [57 38, 39] (equations 25-27)... 

One of the most well used methods for the synthesis of aziridines involves a two (or sometimes more) step process in which an epoxide is opened by a nitrogen nucleophile. The resulting P-amino alcohol (e.g. 79) is then converted to an aziridine via a number of different processes. This method is generally not broadly applicable when a variety of different groups on the nitrogen of the aziridine are desired. A useful method to convert an epoxide to a number of different /V-sulfonyl aziridines (e.g. 80) has been reported <06S425>. Simple addition of a sulfonamide to an epoxide provides high yields of 79 which is readily closed to form the aziridine. 

In general, the reaction of unsaturated 5(4//)-oxazolones 497 with nitrogen nucleophiles effects ring opening to give the corresponding unsaturated acylamino amides 498 (Scheme 7.158). Depending on the nucleophile, for example, amines, hydrazines, oximes, and so on, the products obtained can be cyclized and this process allows the synthesis of a wide variety of new heterocyclic compounds. 

A number of important chemical and biochemical processes are initiated by addition of a nitrogen nucleophile to a carbonyl group.86 These processes have been the subject of extensive study, and we shall not attempt to do more than outline the main features. 

But due to the importance of nitrogen functional groups, the addition reactions of selenium electrophiles to alkenes using nitrogen nucleophiles represent another synthetically relevant process. Nitriles have been used as versatile... 

The intermolecular addition of nitrogen nucleophiles has been shown to lead to interesting products, with remarkable control based on the reaction conditions (Scheme 10). Carbonylation of the organo-Pd intermediate can also be efficient, leading to /3-amino esters. Unfortunately, these processes require stoichiometric Pd no reoxidation scheme has been developed. 

In addition to the most important 1,2-difunctionalization assisted or catalyzed by palladium(II) complexes, a catalytic 1,1-arylamination process of alkenes, applied to the construction of nitrogen heterocycles from 4-pentenylamides, was realized29,30. The mechanism involves the formation of arylpalladium chloride from alkyl(aryl)stannanes, the addition to the alkene, the isomerization of the adduct to the more stable benzylic palladium complex, and the displacement of palladium by an internal nitrogen nucleophile. In the presence of a substituent, mixtures of diastereomers were generally obtained. 

This section focuses on those reactions of nitrogen nucleophiles with rr-allylpalladium complexes which proceed by stereoselective C-N bond formation. For the sake of brevity, the rr-allyl-palladium complexes involved as reactive intermediates in catalytic processes arc omitted in the diagrams and tables. If not explicitly mentioned otherwise, the depicted structures represent racemic mixtures. 

Due to the important role of nitrogen functional groups, the addition reactions of an electrophilic selenium reagent and a nitrogen nucleophile to a carbon-carbon double bond represent a synthetically relevant process with potential practical applications. Among the reactions of this type which have been described already, perhaps the most important contribution is represented by the Ritter-type amide synthesis described by Toshimitsu and Uemura [48a, 48b]. The addition of a phenylselenyl and of an acylamino group to a mono or a 1,2-disubstituted olefin was accomplished by treating the olefin with PhSeCl in acetonitrile and water in the presence of trifluoromethanesulfonic acid. 

Although this process seems straightforward, polyalkylation of the nitrogen nucleophile limits its usefulness. Any amine formed by nucleophilic substitution still has a nonbonded electron pair, making it a nucleophile as well. It will react with remaining alkyl halide to form a more substituted amine. Because of this, a mixture of 1°, 2°, and 3° amines often results. Only the final quaternary ammonium salt, with four alkyl groups on N, cannot react further, and so the reaction stops. 

---