Imines heterocyclic synthesis

Dipolar cycloaddition of azides with olefins provides a convenient access to triazolines, cyclic imines, and aziridines and hence is a valuable technique in heterocyclic synthesis. For instance, tricyclic -lactams 273 - 276 have been synthesized using the intramolecular azide-olefin cycloaddition (lAOC) methodology (Scheme 30) [71]. 

Quinone imine ketals have also been recognized to be quite useful for heterocycle synthesis. In a series of quinone mono- and bis-ketal chemistry, Swenton and coworkers carried out anodic oxidation of trifluoroacetamido-substituted p-methoxyphenols . For example, the readily available p-methoxyphenol derivative 88 underwent constant current electrolysis (60 mA) in 2% LiC104 in methanol, followed by hydrolysis with 5% aqueous KOH to afford quinone imine ketal 89 in 82% overall yield, through quinone monoketal 90 (Scheme 17). Furthermore, acid treatment of 89 with TsOH provided 5-methoxyindole (91). 

In another example of heterocyclic synthesis, Shamma et al. have prepared 2-pyridone (95) by condensing diethyl glutaconate (91) with imine (92 Scheme 18). The initial adduct (93) cannot be isolated, as... 

Figure 3 Solid-ph e synthesis of heterocycles from amino acids and peptides through imine formation. Synthesis of (a) isoquinolines 2, (b) thiazolidinones 3 and methathiazanones 4, (c) j8-carbolines 5, (d) -lactams 6, (e) pyrrolidines 7, (f) thia-zolidines 8, and (g) quinolinones 9.

Kel in AV, Sromek AW, Gevorgyan V (2001) A novel Cu-assisted cycloisomerization of alkynyl imines efficient synthesis of pyrroles and pyrrole-containing heterocycles. J Am Chem Soc 9 2074-2075... 

High yields of the mixture of products that is illustrated here are obtained, and many examples are given to demonstrate the synthetic utility and to show how the formation of the reduced non-cyclized products can be avoided. The potential of the imine function in heterocyclic synthesis is widely appreciated, and the thermal generation of imines has been known for some time. A new report of their formation by flash vacuum pyrolysis and subsequent intramolecular trapping constitutes a novel retro-ene-Diels-Alder sequence, e.g. (140) -> (141). Although the yields are not good, improvements will no doubt be developed. 

Ruthenium-Catalyzed Heterocyclic Synthesis via Carbonyiative C-H Activation 473 Table 15.5 Selected examples for the preparation of indenones from aromatic imines . ... 

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

Reactions offluorinated dipoles. In recent years, much effort has been devoted to the preparation of tnfluoromethyl-substituted 1,3-dipoles with the goal of using them to introduce trifluoromethyl groups into five-membered nng heterocycles Fluorinated diazoalkanes were the first such 1,3-dipoles to be prepared and used in synthesis A number of reports of cycloadditions of mono- and bis(tnfluo-romethyl)diazomethane appeared prior to 1972 [9] Other types of fluonne-substi-tuted 1,3-dipoles were virtually unknown until only recently However, largely because of the efforts of Tanaka s group, a broad knowledge of the chemistry of tnfluoromethyl-substituted nitrile oxides, nitnle imines, nitnle ylides, and nitrones has been accumulated recently... 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

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