Nucleophilic addition of amine

Nucleophilic addition of amines to aide hydes and ketones (Sections 17 10... 

Nucleophilic addition of amines to aldehydes and ketones (Sections 17.10, 17.11) Primary amines undergo nucleophilic addition to the carbonyl group of aldehydes and ketones to form carbinol-amines. These carbinolamines dehydrate under the conditions of their formation to give A/-substituted imines. Secondary amines yield enamines. 

As mentioned in the introduction, l-heterobut-l-en-3-ynes, RXCH=CHC=CH (X = RN, O, S R = organic radical), are the nearest and most important diacetylene derivatives readily formed by nucleophilic addition of amines, alcohols, and thiols to diacetylene. In many heterocyclization reactions (especially those leading to fundamental heterocycles) l-heterobut-l-en-3-ynes behave as diacetylene synthetic equivalents, but unlike diacetylene, they are nonhazardous. Therefore, the syntheses of heterocycles therefrom are often more attractive in preparative aspect. 

Nucleophilic Addition of Amines Imine and Enamine Formation... 

Carbinolamine (Section 19.8) A molecule that contains the R2C(OH)NH2 functional group. Carbinolamines are produced as intermediates during the nucleophilic addition of amines to carbonyl compounds. 

Abbott and coworkers229 found that nucleophilic addition of amines to a, p-unsaturated sulfoxide gave asymmetrically induced adducts. For example, treatment of (R)-(—)-cis-propenyl p-tolyl sulfoxide 184 with piperidine in methanol gave a quantitative mixture of the diastereomeric adduct 185. Reduction of this mixture gave (Rs)-(Sc)-2-piperidinopropyl p-tolyl sulfide 186 in 74% optical yield, suggesting that the amines attack from the opposite side of the bulky aryl group at the transition state, as shown above (Figure 6). 

The nucleophilic addition of amines to cyclic 2,3-allenamides 565 leads to ( )-3-amino-2-enamides 566 [260]. 

Nucleophilic additions of amines to acceptor-substituted dienes were examined as early as 1950. Frankel and coworkers98 found that the reaction of 2,4-pentadienenitrile with various secondary amines proceeded regioselectively to furnish the 1,6-addition products (equation 29). In some cases, these could converted into the 2,4-diamino-substituted pen-tanenitriles by isomerization and 1,4-addition of a second molecule of amine. Analogous results were reported by other groups17,99 100 and extended to hydrazine as nucleophile101 and to vinylcyclobutenones48 and dienoates102-104 as Michael acceptors. 

Another pyrrole cyclization involves nucleophilic addition of amines to electrophilic 1,3-dienes, e.g. 2,3-diphenylsulfonyl-1,3-butadiene and 2-acetyl-3-phenylsulfonyl-1,3-butadiene (88TL3041, 9ism). 

Coordinated a-amino amides can be formed by the nucleophilic addition of amines to coordinated a-amino esters (see Chapter 7.4). This reaction forms the basis of attempts to use suitable metal coordination to promote peptide synthesis. Again, studies have been carried out using coordination of several metals and an interesting early example is amide formation on an amino acid imine complex of magnesium (equation 75).355 However, cobalt(III) complexes, because of their high kinetic stability, have received most serious investigation. These studies have been closely associated with those previously described for the hydrolysis of esters, amides and peptides. Whereas hydrolysis is observed when reactions are carried out in water, reactions in dimethyl-formamide or dimethyl sulfoxide result in peptide bond formation. These comparative results are illustrated in Scheme 91.356-358 The key intermediate (126) has also been reacted with dipeptide... 

Investigation of the stereochemistry of the nucleophilic addition of amines to 1,3-dienylsulfone revealed that the Z/E ratios of the resulting allylic sulfones varied with amines, solvents, temperature, and concentrations. The predominant formation of (Z)- (g) isomer was rationalized by a syn-eiiecV, which could be mainly regarded as a result of the njo —> rt interactions.184... 

Nucleophilic addition of amine nucleophiles formation of imines and enamines... 

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