Reissert chemistry

Reissert chemistry has been employed for polymeric attachment of the isoquinoline heterocycle. Reissert compound (227) reacted with poly(vinylbenzyl chloride) (192) yielding the substitution product (228) in quantitative yield (Scheme 110) (76MI11111). Alkaline hydrolysis of (228) afforded the fully aromatized, polymer-bound isoquinoline derivative (229), again in quantitative yield. In a variation of this reaction (76MI11112), the Reissert... 

Several classes of carbon nucleophiles have been successfully used in these systems, reflecting the utility of Reissert chemistry for derivatizing azines via carbon-carbon bond formation. Apart from cyanide anion, other classes of carbon nucleophiles have been explored. For instance, addition of indole (51) to A-acyla-zinium salts proceeds selectively at the a-position (Scheme 9). Pyrrole, quinolines and isoquinolines all behave similarly [73-76]. A related reaction, yielding adduct 70 (Scheme 12b) has also been described. In this case, azine activation is promoted by Vilsmeier reagents (generated by reaction of amides with POCI3) [77]. p-Dicarbonyls are reactive inputs in this chemistry, and dialkyl malonates 53... 

Scheme 13 Activated alkenes and related species as nucleophiles in Reissert chemistry...

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

Apart from isolated reports summarized in Scheme 47, the chemistry of the fully conjugated ring systems has not been especially developed since CHEC-II(1996). In 1999, Monnier et al. reported the 1,3-dipolar cycloaddition of Reissert compound 160 with acrylates. Addition of triethylamine traps hydrofluoroboric acid and increases the proportion of milnchnone imine 160B the reaction therefore predominantly yields 1,3-adduct 161 which rearranges to 162 (Scheme 47) <1996BSB777, 1999EJ0297>. 

The chemistry of Reissert compounds has been the subject of numerous general reviews (3-10). In 1973 Popp gave a summary on the use of Reissert compounds in the synthesis of isoquinoline alkaloids and related compounds (7). We now wish to summarize new results that have appeared from 1973 to the end of 1985 for the application of Reissert compounds in the synthesis of isoquinoline as well as indole alkaloids. 

The Chemistry of Reissert Compounds F. D. Popp, Bull. Soc. Chim. Belg., 1981, 90, 609-613. 

There are also reviews on the biological activity of certain phthalazines (59MI21203) and on Reissert compounds from phthalazines (80H(14)1033). The chemistry of benzo[c]cinnolines has also been covered (79AHC(24)l5l). 

Developments in the chemistry ol furans (1952-1963), 7, 377 of Reissert compounds (1968-1978), 24, 187 Dewar Heterocycles and Related Compounds, 31, 169... 

Standard heterocyclic syntheses tend to have a name associated with them and it is simply not worth while learning these names. Few chemists use any but the most famous of them we will mention the Knorr pyrrole synthesis, the Hantzsch pyridine synthesis, and the Fischer and Reissert indole syntheses. We did not mention that the synthesis of furans from 1,4-dicarbonyl compounds is known as the Feist-Benary synthesis, and there are many more like this. If you are really interested in these other names we suggest you consult a specialist book on heterocyclic chemistry. 

Popp, F.D. 1968. Reissert compounds. Advances in Heterocyclic Chemistry, 9 1-25. 

Abstract The chapter reviews the classic Reissert reaction, the keystone of a broad family of multicomponent reactions involving azines, electrophilic reagents and nucleophiles to yield A,a-disubstituted dihydroazine adducts. The first sections deal with the standard nucleophilic attack upon activated azines, including asymmetric transformations. Section 5 focuses on the generation of dipolar intermediates by azine activation, and on their subsequent transformation chiefly in cycloadditions. Lastly, Sect. 6 is primarily devoted to a special branch of this chemistry involving isocyanides. It also covers the reactivity of dihydroazines and reviews the mechanistic proposals for related reactions. 

In a different approach, chiral auxiliaries have been widely used in Reissert-type chemistry to provide practical access to enantiopure addition adducts. For example, the stereoselective addition of cyanide to isoquinoline or quinoline with a modified... 

Incidentally, although in a different context, this Reissert-type chemistry has also been done on solid phase. In this regard, Munoz loaded a 4-hydroxypyridine... 

Alternative reaction pathways exploring different synthetic possibilities have been studied. For instance, electron-rich dihydroazines also react with isocyanides in the presence of an electrophile, generating reactive iminium species that can then be trapped by the isocyanide. In this case, coordination of the electrophile with the isocyanide must be kinetically bypassed or reversible, to enable productive processes. Examples of this chemistry include the hydro-, halo- and seleno-carba-moylation of the DHPs 270, as well as analogous reactions of cyclic enol ethers (Scheme 42a) [223, 224]. p-Toluenesulfonic acid (as proton source), bromine and phenylselenyl chloride have reacted as electrophilic inputs, with DHPs and isocyanides to prepare the corresponding a-carbamoyl-(3-substituted tetrahydro-pyridines 272-274 (Scheme 42b). Wanner has recently, implemented a related and useful process that exploits M-silyl DHPs (275) to promote interesting MCRs. These substrates are reacted with a carboxylic acid and an isocyanide in an Ugi-Reissert-type reaction, that forms the polysubstituted tetrahydropyridines 276 with good diasteroselectivity (Scheme 42c) [225]. The mechanism involves initial protiodesilylation to form the dihydropyridinum salt S, which is then attacked by the isocyanide, en route to the final adducts. 

The chemistry of iV-acyldihydroquinaldonitriles (1) and N-acyldihydroisoquinaldonitriles (2) (Reissert compounds) was the subject of an excellent review in 1955. The purpose of the present... 

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