Reaction with Iminium Ions

Flouk has also considered the alkylation reactions of pyrroles and indoles using the same class of catalyst. The report addresses the fact that while catalyst 12 provides high ees in the alkylation of pyrroles (Scheme 15), the same is not true of indoles and catalyst 21 is required instead (Scheme 16). A thorough examination of the accessible transition states for the reaction of iminium ion 184 with pyrrole and with indole led to the conclusion that the two reactions occur through different transition states. Pyrrole adopts a closed transition state reminiscent of that of the Diels-Alder reaction whereas indole adopts an open transition state (Fig. 19) [233]. 

Recently, a new type of reaction - that is, aerobic oxidative cyanation of tertiary amines - was discovered. In this reaction, oxidation with molecular oxygen in place of peroxides, in addition to direct carbon-carbon bond formation by trapping of the iminium ion intermediates with a carbon nucleophile under oxidative conditions, is accomplished simultaneously. The ruthenium-catalyzed oxidation of tertiary amines with molecular oxygen (1 atom) in the presence of sodium cyanide gives the corresponding a-aminonitriles (Eq. 3.74) [132], which are useful for synthesis of a-amino acids and 1,2-diamines. 

In the laboratory of S.F. Martin, the vinylogous Mannich reaction (VMR) of a 2-silyloxyfuran with a regioselectively generated iminium ion was utilized as the key step in the enantioselective construction of (+)-croomine. " The carboxylic acid moiety of the starting material was converted to the acid chloride which spontaneously underwent decarbonylation to give the corresponding iminium ion. Reaction of this iminium ion with the 2-silyloxyfuran afforded the desired threo butenolide isomer as the major product. 

Brandange, S., and Lindblom, L. The enzyme "aldehyde oxidase" is an iminium oxidase. Reaction with nicotine -iminium ion. 

This methodology was employed for the synthesis of the reported structure of the alkaloid jamtine (02OL715, 02JOC929). The key sulfoxide intermediate 307 was heated with CSA to produce several tricyclic products (98% yield) as a mixture (5 2 1 1) of diastereomers in which 308 predominated (Scheme 57). The stereochemistry of 308 was secured by X-ray crystallographic analysis and is consistent with a Nazarov-type conrotatory 47i-electrocyclization followed by attack of the nucleophilically disposed aromatic ring from the least hindered side of the intermediate iminium ion. Reaction of a-ethylthio amide 308 with NaH effected an intramolecular alkylation to provide tetracycle 309. 

Various aromatic aldehydes react with active methylene compounds in the presence of piperidine to give the corresponding dipiperidines (18), which are in equilibrium with the iminium ion (16) under the reaction conditions (Scheme 8). In addition, the primary reaction products (17) of iminium ions (16) with the active methylene compound (11) can also be isolated. In the reaction of V,iV-dimethylbarbituric acid and citronellal using catalytic amounts of ethylenediammonium diacetate, the 3-hydroxy-1,3-dicarbonyl has been identified by NMR spectroscopy. ... 

Borohydride trapping was also used to demonstrate the presence of an iminium ion in the pathway involved in pyrrole biosynthesis from two molecules of A-amino-levulinic acid [123]. This reaction, shown in Scheme 23, involves iminium ion formation with 1 mole of substrate, eneamine formation by deprotonation, and then... 

Recent advances have been made in the enantioselective cycloaddition of nitrones and alkenes. By using a chiral auxiliary attached to the nitrone or the alkene, moderate to good levels of asymmetric induction have been reported. A number of metal complexes with chiral ligands catalyse the cycloaddition reaction of nitrones, particularly for dipolarophiles containing two carbonyl groups for biden-tate co-ordination to the metal. An alternative approach, using a,p-unsaturated aldehydes and chiral secondary amines has been successful (3.138). The endo product is the major stereoisomer in these cycloaddition reactions and the catalysis is thought to proceed via the reactive intermediate iminium ion 210, with addition of the nitrone to the face of the alkene opposite the benzyl substituent. 

Ni(COD)2/dppf catalyses the cyclisation of N-benzoyl aminals in the presence of a stoichiometric Lewis acid, forming isoindolinones in 43-76% yields. The reaction may occur via an iminium-ion intermediate formed by reaction of iV-benzoyl aminals with Lewis acid. Reaction of the iminium-ion intermediate with electron-rich Ni(0) leads to cyclisation products (Scheme 14.60). ... 

In a series of papers, Kucklander has provided additional evidence for the Nenitzescu-Allen mechanism, in particular theD->-E- F- G transformation [18-20]. Eor example, isolated carbinolamine 35 gives byproducts 36-38 in addition to indole 39 (Scheme 7, equation 1) [18]. The formation of 36 presumably involves reaction of iminium ion 40 with acetate and rearrangement of 41 to 36 as shown (Scheme 7, eqnation 2) [20], Kucklander and Hiihnermann found that benzoquinone reacts with p-arylaminocrotonates in propionic acid to afford 6-hydroxyindoles 42 (10%-30%) (equation 3), along with the byproducts 5-acyloxy-4-hydroxyindoles (20%-35%) and arylaminobenzofurans (10%-15%) [21]. 

The overall cyclocondensation of iminium ions proceeds with the regio-and stereoselectivity expected for a true Diels-Alder process. The formation of a single diastereomer in the reaction of ( , )-2,4-hexadiene with iminium ion 1 is consistent with a concerted [2+4] cycloaddition rather than an ionic, stepwise process ... 

Grieco et al. have also reported the use of C-acyl iminium ions as heterodienophiles in the aqueous Diels-Alder reaction with cyclopentadiene [8]. This work details the cyclocondensation of C-acyl A-alkyl iminium ions 18 and C-acyl A-unsubstituted iminium ions 19 with cyclopentadiene in water ... 

We identified an efficient DDQ-mediated CDC reaction between IV-phenyl THIQ and nitromethane that provides access to a number of rare chiral vicinal diamines [via 27d, Scheme 11.22). ° In the course of this work we observed NMR spectroscopic evidence for the long-supposed iminium ion and noted the precipitation of a solid in the reaction mixture which when isolated and then dissolved led to the reaction product. Subsequent focus on this solid using elemental analysis led to its suggested identity being 26c, where an iminium ion paired with the anion of the DDQ reaction product (the dihydroquinone) and this salt precipitated with another molecule of the protonated dihydroquinone (DDQHa). The solid was successfully... 

The dye is initially linked to a ballasted thiazoUdine, which reacts with silver to form a silver iminium complex. The alkaline hydrolysis of that complex yields an alkali-mobile dye. Concomitantiy the silver ion is immobilized by reaction with the ballasted aminoethane thiol formed by cleavage of the thiazolidine ring. 

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