Nitrogen nucleophiles reactions

Thus, this chapter focuses on the most investigated classes of metal-catalyzed coupling reactions—namely, reactions of aromatic and aliphatic electrophiles with main group carbon or nitrogen nucleophiles, reactions of aromatic halides with olefins, including enanti-oselective versions of these reactions, and direct coupling processes. The mechanisms of these reactions are presented with reference to the chapters on the stoichiometric steps of these catalytic processes. 

Most syntheses of nitrogen heterocycles involve substitution and/or condensation reactions of nitrogen nucleophiles with difunctional halides or carbonyl compounds. Common nitrogen reagents are ... 

Regioselectivity becomes important, if unsymmetric difunctional nitrogen components are used. In such cases two different reactions of the nitrogen nucleophile with the open-chain educt may be possible, one of which must be faster than the other. Hydrazone formation, for example, occurs more readily than hydrazinoLysis of an ester. In the second example, on the other hand, the amide is formed very rapidly from the acyl chloride, and only one cyclization product is observed. 

Chemical Properties The formation of salts with acids is the most characteristic reaction of amines. Since the amines are soluble in organic solvents and the salts are usually not soluble, acidic products can be conveniendy separated by the reaction with an amine, the unshared electron pair on the amine nitrogen acting as proton acceptor. Amines are good nucleophiles reactions of amines at the nitrogen atom have as a first step the formation of a bond with the unshared electron pair of nitrogen, eg, reactions with acid anhydrides, haUdes, and esters, with carbon dioxide or carbon disulfide, and with isocyanic or isothiocyanic acid derivatives. 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Kinetic data on acetate displacement from C-3 using a number of sulfur and nitrogen nucleophiles in aqueous solution at near neutral pH demonstrate that the reaction proceeds by an 5 1 mechanism (B-72MI51004). The intermediate in this reaction is depicted as a dipolar allylic carbonium ion (9) with significant charge delocalization. Of particular significance in this regard is the observation that the free carboxylate at C-4 is required since... 

Diazetidines applications, 7, 483 electrophilic reaction, 7, 460 nitrogen inversion, 7, 10 nucleophilic reactions, 7, 462 photochemical reactions, 7, 456-457 reductive cleavage, 7, 465 spectroscopy, 7, 451-454 structure, 7, 451... 

Reaction at position 4 of perfluotopyndme thus occurs readily with nitrogen nucleophiles, as exemplified by its reactions with sodium azide and with hydroxyl-amme [75, 76] (equation 39)... 

Phosphorus nucleophiles have received little attention compared with nitrogen nucleophiles in reactions with fluonnated systems Yields with phosphorus nucleophiles are sometimes low, but interesting materials are obtained [80, 81] (equations 42 and 43). 

Reactions at the carbon-nitrogen double bond of iminium salts are analogous to nucleophilic reactions at the carbonyl group of aldehydes and ketones. This is why free enamines do not react with nucleophilic reagents, whereas their salts can undergo such reactions. 

Amines can be prepared by means of Sn2 reactions involving alkyl halides and nitrogen nucleophiles. 

In addition to their reactions with amines, Zincke salts also combine with other nitrogen nucleophiles, providing various A -substituted pyridine derivatives. Pyridine A -oxides result from the reaction with hydroxylamine, as exemplified for the conversion of Zincke salt 38 to the A -oxide 39 Reactions of Zincke salts with hydrazine, meanwhile, lead... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Unusual orientation has been reported for amination with halomines and with NCI3 in the presence of AICI3. For example, toluene gave predominately meta amination. It has been suggested that initial attack in this case is by Cl and that a nitrogen nucleophile (whose structure is not known but is represented here as NHJ for simplicity) adds to the resulting arenium ion, so that the initial reaction is addition to a carbon-carbon double bond followed by elimination of HCl ... 

---