Imine chemistry

A third early mechanism for enzymic processes involves the formation of imines between the amino group of a lysine residue on an enzyme and the carbonyl group of a substrate, followed by standard imine chemistry. The first example concerned the decarboxylation of acetoacetic acid (Hamilton and Westheimer, 1959). The mechanism was based on the non-enzymic physical organic chemistry of Kai Pedersen (Pedersen, 1934). He postulated that the catalysis by aniline of the decarboxylation of dimethylacetoacetic acid proceeds by a mechanism parallel to that shown in Scheme 7 for acetoacetic acid itself (Pedersen, 1938). 

One of the paradoxes of metal-imine chemistry is the observation that in many cases the imine is stabilised with respect to nucleophilic attack by water upon co-ordination, but is still prone to attack by amines. We saw in Chapter 4 how the hydrolysis of imines may be either promoted or inhibited by co-ordination to a metal, and we also saw a number of examples involving nucleophilic attack on an imine by a variety of other nucleophiles. A special case of such a nucleophilic attack involves another amine. The consequence is a transimination reaction, as indicated in Fig. 5-53. Presumably, intermediates of type 5.26 are involved. The procedure is of some synthetic use for the preparation of imine complexes (Fig. 5-54). 

Figure 10.4 Examples of covalent capture methods. (A) Covalent modification of native cysteines has been shown to modulate ion-channel activity and in the case of enzymes lead to allosteric inhibition. These findings can be important for structural-functional characterization or as starting points for drug discovery. (B) Reversible covalent capture using imine chemistry.

Fabris and coworkers have used the reversible imine chemistry for obtaining covalent molecular capsules 39 and 40 (Fig. 20).132 In one case, enantiopure... 

The concept of dynamic imine chemistry was further extended to the preparation of three nanosized cages 46-48 (Fig. 22) akin to nanocube 45... 

Covalent immobilization of cytophilic proteins by iCP can be also used to pattern cells on substrates. Cytophilic proteins can be printed in micropatterns on top of reactive SAMs using, for example, imine chemistry.109 Aldehyde-functionalized... 

The importance of the reagent on open dimers was also pointed out in the proposed mechanism of deprotonation by lithium amides and alkylation by organolithiums in carbonyl and imine chemistry (Figure 37). This... 

The reversible imine chemistry has been employed by Sessler and Katayev for the development of anion receptors for tetrahedral anions like S042- and HP042 [28, 29]. Thus, the dipyrrole 9 functionalized with aldehyde groups, and the... 

Fig. 9 DCL of macrocyclic anion receptors (12-16) obtained by reversible imine chemistry between the dialdehyde 9 and diamines 10, 11...

In the early 1960s, seminal work by Jencks and coworkers demonstrated that formation and hydrolysis of C=N bonds were proceeding via a carbinolamine intermediate, thus leading to a more general mechanism of addition reactions on carbonyl groups [17-19]. The dynamic nature of the reaction of imine formation can be exploited to drive the equilibrium either forward or backwards. Since the reaction involves the loss of a molecule of water, adding or removing water from the reaction mixture proved an efficient way to shift the equilibrium in either direction. The responsive behavior of imines to external stimuli makes the reversible reaction of imine formation perfectly suited for DCC experiments [20], Thermodynamically controlled reactions based on imine chemistry include (1) imine condensation/hydrolysis, (2) transiminations, and (3) imine-metathesis reactions... 

Another recent innovation regarding the use of imine chemistry in DCC relies on an original way to freeze the equilibrating mixture by Ugi reactions [27]. In other words, this consists in conjugating a reversible reaction of imine condensation with an irreversible Ugi reaction. The latter step therefore represents an alternative to the more widespread reduction of imines with borohydrides. Wessjohann and coworkers recently prepared a library of macrocyclic oligoimines by condensation... 

A number of comprehensive reviews of enamine and imine chemistry have appeared. Sections in other volumes of this series will concentrate explicitly on carbon-carbon bond forming reactions that use these species. They will be treated here mainly from the perspectives of methods for their formation and of their unique structural features. 

The synthesis arose from coordinated imine chemistry of the type described previously (16,17) and the discovery of the synthesis of a dioxa cylcam quadridentate on a metal center (25). 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Fig. 1, shown for the imine of crotonaldehyde). From the favored complex (shown on the left), the R group of the organolithium reagent is then transferred to the less-hindered face of the double bond of the unsaturated imine. These additions are the enantioselective evolution of Meyers s chiral oxazoline and chiral imine chemistry (Sect. 1.1). 

An interesting aspect of the imine chemistry is represented by the addition of ester enolates to an imine. In this case, the first formed P-amidoester can undergo addition-elimination to give the corresponding P-lactam (Scheme 1). This reaction, reported flrst in 1943 by Gilman and Speer using Reformasky reagents, has become one of the most important methods for the preparation of P-lactams. 

Baeza A, Pfaltz A. Iridium-catalyzed asymmetric hydrogenation of imines. Chemistry 2010 16(13) 4003-4009. 

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