Imines addition reactions

Finally a general approach to synthesize A -pyrrolines must be mentioned. This is tl acid-catalyzed (NH4CI or catalytic amounts of HBr) and thermally (150°C) induced tea rangement of cyclopropyl imines. These educts may be obtained from commercial cyan> acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1-silyloxy-l-vinylcyclopropancs (p. 7 83) but since it is acid-catalyzed it occurs at much lower temperatures. A -Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

The metal coordination complexes of both sahcylaldehyde phenyhiydrazone (91) and sahcylaldoxime provide antioxidant (92) protection and uv stabihty to polyolefins (see Antioxidants). In addition, the imines resulting from the reaction of sahcylaldehyde and aromatic amines, eg, p- am in oph en o1 or a-naphthylamine, can be used at very low levels as heat stabiLizers (qv) in polyolefins (93). 

Acyl isocyanates (13,X = O, S) have been shown to react as heterodienes ia most cycloadduct formations. Notable examples iaclude autodimerization and the addition to imines (46,47). Unlike aromatic isocyanates, it is not possible to predict the reaction pathway nor the stmcture of the products which may arise from a given approach or set of reaction conditions. 

Catalytic enantioselective addition to imines, in particular, aza-Diels-Alder reaction 99CRV1069. 

Imine formation and enamine formation appear different because one leads to a product with a C=N bond and the other leads to a product with a C=C bond. Actually, though, the reactions are quite similar. Both are typical examples of nucleophilic addition reactions in which water is eliminated from the initially formed tetrahedral intermediate and a new C=Nu bond is formed. 

Each of the following substances can be prepared by a nucleophilic addition reaction between an aldehyde or ketone and a nucleophile. Identify the reactants from which each was prepared. If the substance is an acetal, identify the carbonyl compound and the alcohol if it is an imine, identify the carbonyl compound and the amine and so forth. 

Reductive amination takes place by the pathway shown in Figure 24.4. An imine intermediate is first formed by a nucleophilic addition reaction (Section 19.8), and the C=N bond of the imine is then reduced. 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

Since alkenes are relatively impotent precursors to aziridines, especially with regard to stereoselective reactions, substantially greater advances have been made in this field by means of the addition reactions between imines and a range of car-bene equivalents. 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

An analogous cyclization to eventually form five-membered rings has also been observed for l-metalla-l,3,5-hexatrienes with an additional heteroatom within the chain, such as in the complexes 157. These are obtained by Michael additions of imines to alkynylcarbene complexes in good to excellent yields (reaction type F in Scheme 4), and their configurations were determined to be Z (>91%) in all cases. Upon warming in THF solution, complexes 157 underwent cyclization with reductive elimination to furnish 2Ff-pyrroles 158 in up to 97% yield (Scheme 34). With two cyclopropyl substituents at the terminus in... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

The addition of terminal acetylenes to imines is an important reaction because of the importance of these products as building blocks. Conventionally, the addition reaction shown in Scheme 5.2 is performed with stoichiometric amounts of butyllithium in a step that is, separate from the subsequent nucleophilic addition reaction (see (b)). Carreira has recently developed a procedure that utilizes an iridium catalyst to effect the addition reaction to a wide range of aldimines and ketimines (see (a)). ... 

Table 1.2 gives a representative sampling of eqnilibrinm constants for additions to varions types of carbonyl compounds. Notice that there are nnmerons gaps in the table. This means that mnch remains to be done in the stndy of carbonyl addition reactions. In trying to devise schemes for predicting the eqnilibrinm constants for snch reactions, the scarcity of experimental data is a serions handicap. There are many fewer equilibrium constants for additions to imines, and even fewer cases where... 

Derivatization of the optically active aldehydes to imines has been used for determination of their enantiomeric excess. Chi et al.3 have examined a series of chiral primary amines as a derivatizing agent in determination of the enantiomeric purity of the a-substituted 8-keto-aldehydes obtained from catalysed Michael additions. The imine proton signals were well resolved even if the reaction was not completed. The best results were obtained when chiral amines with —OMe or —COOMe groups were used [2], The differences in chemical shifts of diastereo-meric imine proton were ca. 0.02-0.08 ppm depending on amine. This method has been also used for identification of isomers of self-aldol condensation of hydrocinnamaldehyde. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Other examples of ZnR2-initiated radical additions to C=N bond-containing compounds can be found in a recent review by Miyabe et al 7 Overall, radical additions to imines and related derivatives may be considered as a valuable alternative to nucleophilic additions, particularly for the introduction of secondary and tertiary alkyl groups. In general, organozinc-mediated radical reactions are a new and significant direction with great potential.382,385... 

Phosphorous acid has also been of use for additions to imines. Originally investigated by Moedritzer and Irani,241 who developed a Mannich-type procedure for the preparation of phosphorus-centered species, the approach was found later to be useful for both primary and secondary amines in reaction with formaldehyde and phosphorous acid. The approach was later used for the preparation of a cationic exchange resin using a polymer substrate.242... 

A variety of reaction conditions have been employed for Pudovik-type additions to imines, including the use of additional tertiary amines,323 324 sodium hydride,325 and sodium ethoxide,326/327 as well as monobasic trivalent phosphorus-containing acids.319/328-340... 

These authors also found that the addition of excess MgO during the in situ preparation of allyltantalum species improved reaction outcomes, even allowing for the first example of allylation of imines derived from aliphatic amines and aliphatic aldehydes (prepared in situ at room temperature in the presence of molecular sieves) (Equation (18)). The selective addition to imines permitted three-component reactions. 

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