Nitrones indoles

The intramolecular cycloaddition of nitrones derived from iV-allyl-2-indolecarbaldehyde was used to an entry to pyrrolo- and pyrido[ 1,2-a]indole skeletons . For instance, the cinnamyl-substituted aldehyde 157 upon treatment with benzylhydroxylamine affords to the nitrone 158, which upon heating in refluxing toluene leads to mainly the cycloadduct 159. 

Pheny 1-3-pheny 1 imino-3-// -indole N -oxide (an indolic nitrone) reacts with triethyl and triisopropyl phosphite in refluxing xylene and fert-butylbenzene to give 2-phenylimino-3// -indole (indolenine) in very good yield (505). 

In contrast to this, it has been concluded that the formation of spin adducts on ultraviolet irradiation or mild oxidation of indole nitrones, in the presence of a N -heleroaromatic base, proceeds according to the Forrester-Hepburn mechanism (522). 

Addition of Indoles Pictet-Spengler intramolecular reaction of nitrones (419), synthesized from A -hydroxytryptamine with aldehydes, gave the... 

The reaction of nitrones with indoles in the presence of HC1 gives indolyl N-hydroxylamines. In the presence of Me SiCl symmetrical diindolylalkanes are formed (Scheme 2.193) (679, 680). 

Nitrone cycloaddition reactions with alkynes have been widely used for the synthesis of imidazolidine nitroxides (736) and (737), containing chelating enam-ino ketone groups (821). Different heterocyclic systems were obtained, such as 3-(2-oxygenated alkyl)piperazin-2-ones (738) (822), also compounds containing the isoxazolo[3,2-i]indole ring system (739) (823) and a new class of ene-hydroxylamino ketones- (l )-2-( 1-hydroxy-4,4,5,5-tetraalkylimidazolidin-2-ylidene)ethanones (740) (824) (Fig. 2.46). 

Depending on the nature of the substituents X1, X2, and X3, the reactions produced nitrones (148) (as indole derivatives) or annelated isoxazolines (149). The authors performed a series of experiments (including one with the use of a deuterium label) and suggested a mechanistic scheme for the interpretation... 

The reactions of nitrones with indoles have been applied to die formation of several A -hydroxylamines and symmetrical and unsymmetrical diindolylalkanes.56 Chiral auxiliaries, alcohols derived from (15)-(—)-/ -pinene (R OH), lead to an enantio-selective synthesis when R acetoacetate reacts with 3-(2-hydroxyethyl)mdole in the presence of, for example, BF3.Et20, forming (27).57 Methyl migration follows Friedel-Crafts reaction of (CH3)3SiCCl3 with benzene in the present of A1C13 and (28) is formed.58... 

As indicated from computational studies, the catalyst-activated iminium ion MM3-2 was expected to form with only the (E)-conformation to avoid nonbonding interactions between the substrate double bond and the gem-dimethyl substituents on the catalyst framework. In addition, the benzyl group of the imidazolidinone moiety should effectively shield the iminium-ion Si-face, leaving the Re-face exposed for enantioselective bond formation. The efficiency of chiral amine 1 in iminium catalysis was demonstrated by its successful application in several transformations such as enantioselective Diels-Alder reactions [6], nitrone additions [12], and Friedel-Crafts alkylations of pyrrole nucleophiles [13]. However, diminished reactivity was observed when indole and furan heteroaromatics where used for similar conjugate additions, causing the MacMillan group to embark upon studies to identify a more reactive and versatile amine catalyst. This led ultimately to the discovery of the second-generation imidazolidinone catalyst 3 (Fig. 3.1, bottom) [14],... 

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... 

Trifluoromethyl-substituted alkynes can also react with nitrones, leading to rearranged cycloadducts. The cycloaddition of ethyl 4,4,4-trifluorobut-2-ynoate and hexafluorobut-2-yne " with C,A -diphenyl nitrone is a route to trifluoromethyl-substituted indoles. 

The stereochemical outcome can be explained by assuming a model in which the oxygen of the nitrone is coordinated to the boron of BLA, as shown in Fig. 21. The proposed transition state model, which shows re face approach of the indole nucleus to a C=N double bond, would be preferred. 

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