Indoles reactions with «,/?-unsaturated

This particular experimental fact allowed Kost [164] to speculate that carbon atoms were more preferable endocyclic reaction centers in reactions with unsaturated ketones than nitrogens. But applying this generalization to other ami-noazoles is not correct because of a dramatic difference of the nucleophilicity of the pyrrole-type nitrogen of indole and pyrimidine-type poly azoles. Indeed, the... 

Unsaturated compounds activated by electron-attracting groups can also effect alkylation at the 3-position. An important example is the reaction with nitroethylene to form 3-(2-nitroethyl)indole [31731-23-4] (14). 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Scheme 10 Mechanistic spectrum of the reactions of indoles with unsaturated acceptors...

Thus, the unsubstituted starting compound 69 was treated with resorcinol in the presence of trifluoroacetic acid (TFA) to yield 70. Then, reaction of 69 with the cyclic a,/3-unsaturated ketone in the presence of lithium hydride gave the 7-substituted heteroaromatic compound 71, and ethyl cyanoacetate afforded the cross-conjugated product 72, whereas reaction with pyrimidine-2,4,6-trione in the presence of triethylamine yielded the addition product 73. Indole also been reacted with 69, and heating of the dichloromethane solution for 90 min in the presence of TFA yielded the addition product 74 in excellent yield (95%) <1998ZOR450> (Scheme 12). 

Unsaturated 5(4//)-oxazolones derived from aromatic and heterocyclic aldehydes including phthalic anhydride/ antipyrine/ " chromone/ indoles/ pyridines/" ° quinolines/" diazines/" benzoxazoles/" and benzimidazoles " " have been prepared. Reaction with nitrogen nucleophiles and subsequent cycliza-tion leads to the expected 5(477)-imidazolones. 

These equations are appeahng, but suffer from the debits that both pyridine and benzalani-line have the imine group flanked by unsaturated carbon on both sides while 3H -indole is better described as a cyclic N-alkylbenzaldimine with unsaturated carbon only on one side of the imine functionality. In that the following reaction is thermoneutral to 2 kJmol-1 ... 

Simple bis(oxazoline) ligands, especially azabis(oxazolines), can catalyse the addition of indoles to benzylidene malonates in up to 99% ee, provided that excess of the chiral ligand is avoided.166 The paradigm followed in many asymmetric catalytic reactions that an excess of the chiral ligand with respect to the metal should improve enantioselectivity because the background reaction catalysed by a free metal is suppressed, was shown not to be applicable here,166 which might call for revisiting some of the many copper(II)-bis(oxazoline)-catalysed processes known. Enantioselective additions of pyrroles and indoles to ,/9-unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(III) triflate complex have been accomplished.167... 

Several iodine-catalyzed organic transformations have been reported. Iodine-catalyzed reactions are acid-induced processes. Molecular iodine has received considerable attention because it is an inexpensive, nontoxic and readily available catalyst for various organic transformations under mild and convenient conditions. Michael additions of indoles with unsaturated ketones were achieved in the presence of catalytic amounts of iodine under both solvent-free conditions and in anhydrous EtOH (Scheme 19) [85,86]. l2-catalyzed Michael addition of indole and pyrrole to nitroolefins was also reported (Scheme 20) [87]. 

An intramolecular cycloaddition reaction is also a vital feature of Oppolzer s synthesis (Scheme 5).336 Here the cycloaddition reaction occurs on an unsaturated nitrone ester (39) (not isolated). Again, the aldehyde derived from oxidation of the diol (40) gave entirely the ( )-olefin on reaction with crystalline a-methoxy-carbonylethylidenetriphenylphosphorane, which allowed the synthesis of (+)-chanoclavine I (34) to be completed in an overall yield of 14% from indole-4-aldehyde. In contrast, the Horner-Emmons reaction on the aldehyde from... 

Chiral 2-(3-oxoalkyl)pyrroles and 3-(3-oxoalkyl)indoles can also be accessed by reaction in the presence of 10 mol% of chiral bis(oxazoline)/metal complexes in CH2C12 in very high yields and with ee values over 90% <2005JA4154>. Alkylation of pyrrole and of substituted indoles with, -unsaturated acyl phosphonates <2003JA10780> or 2-acyl N-methylimidazoles catalyzed by a chiral bis(oxazolinyl)pyridine (pybox)/scandium(III) triflate complex also exhibits good enantioselectivity over a broad range of substrates <2005JA8942>. 

Enantioselective Michael-type indole Friedel-Crafts reaction with a,P-unsaturated acyl thiazole has been disclosed <07JA10029>. Reaction of indole 127 and 128 in the presence of 10% mol of bis(oxazolinyl)pyridine-scandium(III) triflate complex 129 in acetonitrile at -40 °C affords 130 with high level of enantioselectivity. 

Very simple and efficient Michael reaction of indoles 449 with cyclic and acyclic unsaturated ketones has been accomplished in the presence of only 1 mol% of iodine as catalyst at room temperature under solvent-free conditions (Equation 106) <2005TL2479>. 

Reagents of type 251 (Fig. 94) are aldehydes or phosphoranes which, by reaction with kctonic and indolic Mannich bases, allow the production of p-diketones 252 or phosphoranes 253, respectively. In the former case, the conversion of aldehyde to ketone is thus made possible, - - and in the latter, the formation of unsaturated derivatives by subsequent reaction of the PPh3 residue with carbonyl compounds is allowed. - ... 

Friedel-Crafts Alkylation Reactions. The activation of glyoxylate esters,trifluoromethyl pyruvate esters, and unsaturated a-ketoesters by catalyst 2 converts these materials into effective electrophiles for asymmetric Friedel-Crafts alkylation reactions with activated arenes (eqs 16 and 17). In fact, bis(triflate) (2) is far superior to tbe bis(hexafluoroantimonate) complex at catalyzing the enantioselective alkylation of benzene derivatives. Aniline and anisole derivatives both give the reaction, as do heterocyclic aromatic compounds such as indole and furan. 

Reactions with otP-Unsaturated Ketones, Nitriles and Nitro-Compomds Such reactions are usually effected using acid (see below), or one of a number of mild Lewis acids, such as scandium iodide (with microwave heating), indium bromide " or hafnium triflate, and can be looked on as an extension of the reactions discussed in 20.1.1.6. In the simplest situation, indole reacts with methyl vinyl ketone in a conjugate fashion in acetic acid/acetic anhydride. ... 

The investigated supported complexes 22 and 23, outlined in Fig. 8, were used for hydrogenations of alkenes, nitriles and a,jS-unsaturated ketones. Furthermore, 23 was used in the reduction of different heterocycles like benzoth-iophene, quinoline, indole, dibenzothiophene and acridine. The supported chiral Rh complexes, depicted in Fig. 9, were used for hydrogenation reactions with prochiral olefins. 

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