Immonium ions, cycloaddition

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. 

Maximally unsaturated azepines feature during the period under review. Cyclisation of the P,y-unsaturated aldehyde (1) by treatment with trifluoroacetic acid, followed by treatment with base (DABCO or DMAP) affords 2//-azepine <95AG(E)I469>. The compound itself is difficult to isolate but it is remarkably stable in solution, no trace of the thermodynamically favoured 3/f-azepine being observed after 48h at room temperature. In addition, the bicyclic adduct (2) is formed, probably arising from [2 + 4] cycloaddition of isobutene formed in situ and the intermediate immonium ion (3). 

This cycloreversion reaction has been utilized to generate 34 and study its reactions with olefins in a FTICR spectrometer43. 34 has been found to react with various olefins essentially along two competing channels H atom abstraction leading to the immonium ion m/z 44 (Scheme 36) and regioselective cycloaddition-cycloreversion. The latter reaction opens up a new possible access to ionized primary enamines in the gas phase. 

Since the initial report in 1962 by Merten and Muller of the cycloaddition of an -acyl imine with a conjugated diene,a number of examples of this type of reaction have appeared. In general, IV-acyl im> ines are highly reactive, unstable species which are rarely isolated, but rather are generated in situ from stable precursors. Depending upon the method of formation of the particular dienophile and the reaction conditions, a neutral A -acyl imine or a protonated (or Lewis acid complexed) IV-acyl immonium ion may be involved in the Diels-Alder reaction. 

As a rule, cycloadditions with acyclic -acyl imino dienophiles are useful synthetic reactions which demonstrate excellent regio- and stereo-selectivity. A commonly used source of IV-acyl immonium dienophiles are bis-urethanes such as (13) (equation S), which upon treatment with a Lewis acid and a diene afford Diels-Alder adducts. In this case, (13) reacts with boron trifluoride etherate to afford immonium ion (14) which adds to diene (15), yielding tetrahydfopyridine (16). ... 

In another recent study, Giieco et al. have found that C-acyl immonium ions formed in situ under aqueous conditions undergo [4 + 2] cycloadditions as shown in equation (14). This group has utilized similar methodology for other immonium Diels-Alder reactions (see Sections 4.2.2.4 and 4.2.2.8). 

The acid-catalyzed or Lewis acid-catalyzed (TiCU, BF3-OEt2 -78 C) in situ generation of A -alkyl-aiylimmonium ions in the presence of electron-rich or neutral alkenes has been shown to provide [4 + 2] cycloadducts (IV-methyltetrahydroquinolines) in excellent yields (Scheme 27). More recent efforts have demonstrated that immonium ions derived from the cmidensation of aryl amines and aldehydes in the presence of cyclopentadiene participate as effective 4 ir components of [4 + 2] cycloadditions and complement their demonstrated 2 ir participation in related [4 + 2 ] cycloaddition reactions (Scheme 27). Additional examples of the participation of cationic azadienes in [4 + 2] cycloaddition reactions... 

Another convenient synthesis of cyclobutanones employs cycloadditions of keten-immonium ions. These have previously been generated by the rather expensive method of dechlorination of an a-chloro-enamine with silver fluoroborate, but a new procedure which uses zinc chloride instead is reported to give high yields (Scheme 26). Even ethylene was found to react with the complex (319) at room temperature and atmospheric pressure. ... 

Water has been shown to be the polar solvent of choice for the intramolecular Diels-Alder cycloaddition of immonium ions, e.g. (77), to produce the single tricyclic amine (78) (Scheme 28). The activation free energy and transmission coefficient for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene in water have been calculated using molecular-dynamics and reaction-flux simulations. Water has been shown to enhance significantly the Ni +- and Co -catalysed Diels-Alder reaction between 3-phenyl-l-(2-pyridyl)prop-2-en-l-ones and... 

Azomethine ylides are organic 1,3-dipoles possessing a carbanion next to an im-monium ion [ 12]. Cycloadditions to dipolarophiles provide access to pyrrolidine derivatives, useful intermediates in organic synthesis with stereo- and regiochem-ical control. Azomethine ylides can be readily produced upon decarboxylation of immonium salts derived from the condensation of a-amino acids with aldehydes or ketones. When they are added to C60, a fulleropyrrolidine monoadduct is formed in which a pyrrolidine ring is fused to the junction between two six-memberedrings of afullerene [13-15].Very importantly,functionalized aldehydes lead to the formation of 2-substituted fulleropyrrolidines, whereas reaction with AT-substituted glycines leads to AT-substituted fulleropyrrolidines (Scheme 1). 

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