Imines carbon-nitrogen bond formation

In addition to simply mediating the formation of carbon-nitrogen bonds, palladium catalysis can be used to construct these precursors in concert with cyclization. One example of this was demonstrated by Barluenga, where palladium catalysis is employed to form two separate bonds first the carbon-carbon bond via the arylation of the azaallylic anion of imine 19, followed by catalytic carbon-nitrogen bond formation (Scheme 6.38) [50]. 

Carbon-nitrogen bond formation is an important subject in the organic synthesis [301], and hydroamination is an atom-efficient process for the generation of amines and imines from olefins, allenes, and alkynes. Titanium-mediated hydroamination was among the most useful protocols thus far developed for this reaction. By using unsymmetrical olefins and alkynes, the addition of HNR2 can in principle lead to two isomeric products, where the isomeric ratio is usually dependent on the type of titanium catalyst used. 

Reductive Coupling. Formation of dicyclohexylamine (25) in hydrogenation of aniline probably involves addition of cyclohexylamine to an imine and subsequent hydrogenolysis of a carbon—nitrogen bond (11). 

The synthetic uses of hydrazones and oximes for carbon-bond formation differ little from those of imines as their anions represent enolate equivalents except for certain methods that have been developed for asymmetric induction. Conversely, the formal replacement of the carbon substituent of imines by a heteroatom (nitrogen for hydrazones and oxygen for imines) opens reaction pathways such as the Beckmann rearrangement of oximes and the Wolff-Kishner and Shapiro reductions of hydrazones that have no analogy in the chemistry of imines. 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

The photoelimination of carbon dioxide from esters and lactones is a process that has been the subject of detailed investigations. Discussion here is limited to nitrogen containing systems. 3,4-Diphenylsydnone (464), on irradiation in benzene, is converted via the nitrile imine 465 into 2,4,5-triphenyl-1,2,3-triazole (466)388 initial bond formation between N-2 and C-4 followed by loss of carbon dioxide to give the diazirine 467 is proposed to account for the formation of the nitrile imine. Nitrile imines generated in this way have been trapped with alkenes and alkynes to give pyrazoles389... 

Diazoesters 22 have an electronically unique a-carbon atom. (Scheme 9) They are commonly used for the formation of aziridines 23 from imines 24. The intermediate (25) resulting from the addition of a-diazoesters 22 to the latter (24) can undergo elimination of the proton at the a-position prior to extrusion of molecular nitrogen. This interrupted aza-Darzens reaction allows for the direct alkylation of diazoesters 22 via cleavage of a carbon-hydrogen bond. 

Simple carbon-carbon double bonds react slowly with azides and frequently take more than a week to react at 25 C. Increasing the reaction temperature is restricted by the thermal lability of most triazolines. In fact, some classes of triazolines decompose spontaneously at room temperature with the extrusion of nitrogen.189 The principal decomposition modes involve the formation of aziridines and imines and are outlined in Scheme 55. Usually, just a few of these modes operate in any particular system.190... 

The nitrile group in cyanopyridine can participate in intramolecular reactions. The presence in chalcone 118 of an ortho-hydroxyl substituent can lead to its addition to a carbon-nitrogen triple bond, with the formation of the 2/7-pyran-2-iminic moiety (compound 119) [126, 127] (Scheme 3.36). 

In a similar manner, imines 50 with various ancillary groups X, such as ethoxy-carbonyl, 2-pyridyl, or 2-thiazolyl, are also converted into lactams 51 in mod-erate-to-good yields (Eq. 24) [38]. The [2+2+1] lactam formation using a chiral substrate 52, ethylene, and CO quantitatively furnished the spiro lactam 53 (Eq. 25) [39]. The cycloaddition exclusively took place at the carbon-nitrogen double bond next to the oxazine oxygen atom, although 53 was obtained as a diastereomeric mixture. 

Dehydrogenations, which involve the elimination of hydrogen Ifom organic molecules, lead to compounds containing double bonds, multiple bonds, or aromatic rings. For practical reasons, only the formation of carbon-carbon double bonds, of carbon-nitrogen double bonds in cyclic amines, and of aromatic rings (both carbocyclic and heterocyclic) will be discussed in this chapter. The conversion of alcohols into aldehydes and ketones and of amines into imines and nitriles will be discussed in the chapter Oxidations (Chapter 3). 

The [3+2] cycloaddition of allylsilanes is applicable to imines and iminium salts [419, 484, 485], Highly substituted pyrrolidines can be synthesized with high diastereo and enantio control by reaction of homochiral crotylsilanes with carbon-nitrogen double bond generated in situ from acetals and methyl carbamate (Scheme 10.174) [419]. The cycloaddition to N-tosylaldimines of aromatic aldehydes proceeds with excellent 2,4-ds selectivity whereas the stereoselectivity with aliphatic aldimines is rather low [484]. With N-tosylaldimines, fhe formation of [2+2] adducts is not observed (vide infra). 

The mechanism of the alkylation of imines with electrophilic alkenes has been discussed by D Angelo and coworkers S who conclude that reaction occurs via an aza-ene reaction-like transition state 206 involving concerted proton transfer from the nitrogen and carbon-carbon bond formation (Scheme 206). ITiey further propose that the remarkable regiocontrol observed in these reactions originates from this crucial internal proton transfer which would not be possible in a conformation such as 207 of the less substituted enamine tautomer, since the N—H bond would be anti to the enamine double bond. However, although this seems probable, it is by no means proven. Inconsistencies in the argument and the evidence presented cast some doubt on the validity of these conclusions. For example ... 

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