Immonium ions, reactions with enamines

The formation of oxygen-containing heterocyclic compounds is also a consequence of the Maillard reaction. Amines and amino acids have a catalytic effect upon the formation of 2-furaldehyde (5), 5-(hydroxy-methyl)-2-furaldehyde (11),2-(2-hydroxyacetyl)furan (44),2 and 4-hy-droxy-5-methyl-3(2//)-furanone (111) (see Ref. 214). This catalytic effect can be observed with several other non-nitrogenous products, including maltol. The amino acid or amine catalysis has been attributed to the transient formation of enamines or immonium ions, or the 1,2-2,3 eno-lization of carbohydrates. Of interest is the detection of A -(2-furoyl-... 

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. 

On the basis of distribution of products obtained in these reactions with the change of solvents, temperature and molar ratio of reactants, a mechanism has been suggested for the anomalous annulation which does not involve an initial attack of the tetrasub-stituted isomer of the enamine (equation 16)51. Alkylation of the more stable cis isomer of the enamine (80) with methyl vinyl ketone (MVK) would afford zwitterion 81 (attack by the other side of the enamine leads to strong steric interactions in the transition state). Reaction of the thermodynamically less favorable trans isomer 83 gives rise to zwitterions 84 and 89 (both without axial-axial interactions), and ion 84 is sterically able to undergo intramolecular proton shift to afford enamine 85. Zwitterionic intermediates 81 and 89 can be stabilized by conversion to dihydropyrans 82 and 90, or protonated to immonium ions. The pair 81-82 will lead to enamine 85, while the pair 89-90 will afford enamine 91. Then, cyclization of 85 or 91 will afford the enone expected from the normal enamine version of the Robinson annulation. 

Interpretation of these studies, as well as those involving reaction with methyl acrylate and acrylonitrile as electrophiles, are complicated by the possibility that these reactions are reversible. Conversely, reaction with molecular bromine is considerably faster than regioisomerization, an observation that has been used to prepare separate samples of 2-bromo-6-methyl- and 2-bromo-2-methyl-cyclohexanone. Thus, in the reaction of a nearly one to one mixture of the less and more substituted enamines derived from methylcyclohexanone with 0.5 equiv. of bromine, only the less substituted isomer is converted to the intermediate immonium ion, which precipitates from ether solution at -50 C (Scheme 8). Separation, and then addition of more bromine to the filtrate, then effected reaction of the more substituted isomer. 

Reactions of enamines with activated olefins can give several possible products (Scheme 3). The exact composition of the adducts formed depends critically on the substrates employed and the reaction conditions utilized. An initial zwitterionic adduct (3.1) is believed to be the first intermediate formed. Intermediate 3.1 is usually unstable under the reaction conditions and undergoes one of four possible transformations. Cyclization of 3.1 can occur in two ways. Intramolecular closure can occur by addition of the acceptor-stabilizing substituent (Y) to the carbon of the immonium ion to provide 3.2... 

Evidence for the intermediacy of the enamine (138) and the immonium ion (140) derives from the condensation reaction in which potassium cyanide replaced sodium cyanoborohydride the immonium ion (140) was thus trapped by reaction with nucleophilic cyanide ion, with formation of 21-cyanotetrahydroalstonine (141a) and 21-cyanoakuammigine (141b). Both cyano-compounds suffered slow reduction to the parent alkaloid by sodium borohydride, and were re-converted (by silver acetate) into the precursor immonium ions (140), which could be rapidly reduced (NaBH4) to the alkaloids. Scheme 17 illustrates some, but not by any means all, of the numerous interconversions involved in these biomimetic experiments. 

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