Indoles with nitrones

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 cyclisation of nitrones derived from tryptamines is a similar process and can be carried out enanti-oselectively using a chiral Lewis acid."° A similar enantioselective intermolecular process is the copper-catalysed reaction of indoles with tosyl-imines of aromatic aldehydes. "... 

In fight of the successful methodology used by Young and Kerr in the ability of activated cyclopropanes to undergo nucleophilic ring-opening/cycloaddition reactions with indoles and nitrones [21], Johnson and coworkers reported the synthesis of tetrahydrofurans via an adaptation of this... 

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). 

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... 

Aromatic nitro-compounds can be made to condense with silyl-enol-ethers using tris(dimethylamino) sulfur (trimethylsilyl)difluoride (TASF) a non-aromatic nitronate intermediate is aromatised by reaction with bromine, without isolation, to provide a 2-(orf/to-nitroaryl)-ketone and thence an indole after nitro group reduction. ... 

Bis(indol)-3-ylalkanes. Nitrones condense with indoles under acidic conditions When Me3SiCl is used as promoter, the adducts serve as alkylating agents. 

X0-derivative (730) of this ring system is formed by Fischer indolization of the JV -methyl-iV -phenylhydrazone of the aldehyde 0CHCHMeCH2C02Et. 2-Methylfuran and C-benzoyl-iV-phenylnitrone, PhCOCH=N(Ph)—O, combine to form a mixture of the cyclo-adducts (731) and (732), together with the condensation product (733)." The iV-acyl-nitrone (734 Ad == 1-adamantyl), generated by oxidation of 7V-adamantane-l-carbonyl-A-methylhydroxylamine with silver sulphate, has been trapped as the 1,3-dipolar cyclo-adduct (735) with... 

Indolenines exemplified by compound (336) can be converted into the related 3/f-indole 1-oxide (338) by a sequence involving reduction to the dihydro compound (337) followed by oxidation with /M-chloroperbenzoic acid. Compound (338) behaves as a typical cyclic nitrone and undergoes cycloaddition with DMAD and methyl propiolate. The initially formed cycloadduct (339) rearranges via an aziridine intermediate to an oxazolo[3,2-a]indole (340) (Scheme 107) <93JCS(Pl)939>. 

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