Imine reactions

This area of research has only recently attracted the attention of synthetic organic chemists, but there has been a flurry of impressive activity in the area. Simple (i. e., unstabilized) carbenes suffer from many of the problems of nitrenes (vide infra) and most reported synthetically useful procedures use carbenoids the majority of recent reports have focussed upon reactions between a-diazoesters and imines in the presence of a range of catalysts. In one of the earliest reports of enantioselective carbene-imine reactions, for instance, Jacobsen and Finney reported that ethyl diazoacetate reacts with N-arylaldimines in the presence of cop-per(i) hexafluorophosphate with mediocre stereoselectivity to give N-arylaziridine carboxylates. Though the diastereoselectivities of the reaction were often acceptable (usually >10 1, in favor of the cis isomers) the observed enantioselectivity was low (no more than 44% ee Scheme 4.27) [33],... 

The mechanism of the classic ketene-imine reaction to form /J-lactams [17,18] is thought to involve perpendicular attack of the imine nitrogen on the ketene carbonyl carbon from the side of the sterically smaller of the two groups, followed by conrotatory closure of the zwitterionic intermediate (Eq. 6). This... 

An interesting [1,3]-Si shift from nitrogen to nitrogen has been observed in the Staudinger imination reaction of AT-ferf-butyl-iV-trimethylsilyl-P,P-di-methyl phosphinous amide 32 with trimethylsilylazide [137]. The steric bulk provided by the tert-hutjl group seems to determine the direction of the silyl shift (Scheme 32). 

Aldehydes and ketones can react with primary and secondary amines to form Schiff bases, a dehydration reaction yielding an imine (Reaction 45). However, Schiff base formation is a relatively labile, reversible interaction that is readily cleaved in aqueous solution by hydrolysis. The formation of Schiff bases is enhanced at alkaline pH values, but they are still not stable enough to use for crosslinking applications unless they are reduced by reductive amination (see below). 

This effect has recently been explained by considering that under the action of microwave irradiation the route involving direct reaction between the acyl chloride and the imine competes efficiently with the ketone-imine reaction pathway, a situation highlighted by theoretical calculations [113]. In the other words and according to our assumptions, it can be stated that the transition state leading to the trans isomer therefore seems to be more polar than that leading to the cis compound. 

Several reviews of P-lactam chemistry have appeared including a general survey with 407 references <99MI335>. Other reviews include discussions of thioester enolate-imine reactions , enantio- and diastereo-selective routes to azetidinones <99MI221>, the use of diazoketones in diastereoselective synthesis <99MI43>, and solid-phase and combinatorial syntheses of p-lactams <99MI955>. 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

Metal/Ligand Imine Reaction time (h) Amine Yield [%) e.e. (%) (config.)... 

Theoretical studies of the ester enolate-imine reaction <98MI1826>, the effects of solvation on barriers of reaction <99JPC8628>, interactions of P-lactams in aqueous solution <99MI1401> and their ammonolysis and aminolysis <99JOC3281,99MI1045> are available. 

It is of some interest to speculate briefly oonocming the nature of the peracid-imine reaction. It xb quite possible that this reaction is analogous to the epoxidation of olefins with peracids and involves a similar oydks transition state (X). An equally attractive if less obvious possibility is that the imine reaction proceeds through addition of the peracid to the azomethine followed by internal nucleophilic displace ment of the basic nitrogen atom on the peroxide bond. This reaction... 

Numerous dinucleating macrocyclic and macrobicyclic ligands have been synthesized, in particular by the versatile amine + carbonyl — imine reaction they form dinuclear metal complexes as well as cascade complexes with bridging groups [2.58-2.63, 3.24-3.27, 4.1-4.4], for instance in dicobalt complexes that are oxygen carriers [3.26]. 

The diazoacetonitrile-imine reaction may be considered complimentary to azide addition to cinnamonitriles because in the latter case only triazoline thermolysis products result.284 The reversed order of reactivity of the diazoacetonitrile to that of diazomethane implies an electrophilic attack on the imine and is explained in terms of a LUMOdi MC lonit[ile-HOMOin,int controlled interaction. Thus electron-rich enamines, which do not react with diazoalkanes, may be expected to react with electron-poor diazo compounds. 

Recently, they have synthesized enantiomerically pure 1,3-thiazolidine-derived spiro-(3-lactams [111] (Scheme 37) using Staudinger ketene-imine reaction starting from optically active lV-boc-1,3- thiazolidine-2-carboxylic acid derivatives and imines, thus confirming the generality of the earlier reported 1,3-thiazolidine-derived spiro-(3-lactams. 

Different metal complexes have shown the ability to catalyze these imination reactions, such as rhodium, copper, and iron.22 In 2005, Bolm found that the disilver(I) complex described in Section 6.2.2 catalyzes the imination of sulfides and sulfoxides... 

Reactions were studied under the pseudo first-order condition of [substrate] much greater than [initial dihydroflavin]. Under these conditions, the reactions are characterized by a burst in the production of Flox followed by a much slower rate of Flox formation until completion of reaction. The initial burst is provided by the competition between parallel pseudo first-order Reactions a and b of Scheme 3. These convert dihydroflavin and carbonyl compound to an equilibrium mixture of carbinolamine and imine (Reaction a), and to Flox and alcohol (Reaction b), respectively. The slower production of Flox, following the initial burst, occurs by the conversion of carbinolamine back to reduced flavin and substrate and, more importantly, by the disproportionation of product Flox with carbinolamine (Reaction c followed by d). Reactions c and d constitute an autocatalysis by oxidized flavin of the conversion of carbinolamine back to starting dihydroflavin and substrate. In the course of these studies, the contribution of acid-base catalysis to the reactions of Scheme 3 were determined. The significant feature to be pointed out here is that carbinolamine does not undergo an elimination reaction to yield Flox and lactic acid (Equation 25). The carbinolamine (N(5)-covalent adduct) is formed in a... 

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