Imino Diels-Alder reaction

Lanthanide triflates are catalysts for a powerful imino-Diels-Alder reaction for building N-containing six-membered heterocycles. 

The yields again depend upon the choice of the lanthanide triflate. In a study of the reaction  

Another one-pot synthesis uses reaction of an aldehyde, an amine, and an alkene to give pyridine and quinoline derivatives via the imino-Diels-Alder route. 

Extensions of the triflate catalyst include the use of versions with fluorinated ponytails such as [Sc C(S02C8Fi7)3 3] for use in fluorous phase Diels-Alder reactions (fluorinated solvent.) 

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Imino Diels-Alder reactions catalyzed by indium trichloride (InCIs). Facile synthesis of quinoline and phenanthridinone derivatives [106]... 

In contrast LP-DE gives disappointing results for intramolecular imino Diels-Alder reactions, even in the presence of CSA. This is due to the fact that weak acids become strong acids in highly polar media such as 5.0m LP-DE and the protonation of diene, with concomitant diene isomerization, competes with cycloaddition [42]. This observation was supported by using trifluoroacetic acid (TEA). The imine 33 (Scheme 6.21) in LP-DE at room temperature in the presence of TEA gave a 1 1 mixture of cycloadduct 34 and the isomerized diene 35 within the unreacted imine 33. No Diels-Alder cycloadduct 36 was detected. 

Catalysts such as Fe(BuEtCHC02)3 have been d eloped that are effective for the heteroatom Diels-Alder reaction. Indium trichloride (InCls) is a good catalyst for imino-Diels-Alder reactions. Hetero-Diels-Alder reactions involving carbonyls have been done in water. Ultrasound has been used to promote the Diels-Alder reactions of 1-azadienes. ... 

Oppolzer, W., Francotte, E., Battig, K. (1981) Total Synthesis of ( )-Lysergic Acid by an Intramolecular Imino-Diels-Alder Reaction. Helvetica ChimicaActa, 64, 478 81. 

On the other hand, novel diastereomeric p-amino thiol ligands possessing an isoquinuclidine skeleton have been readily prepared by Hongo et al. via imino-Diels-Alder reactions.As shown in Scheme 3.15, when applied to the enantioselective addition of ZnEt2 to various aldehydes, one of these ligands afforded the products with high enantioselectivities of up to 94% ee. 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

Selective cyclization of an alkenyl imine is catalyzed by trimethylsilyl triflate (Scheme 76).329 /-Butyldimethylsilyl triflate ( BuN SiOTf) catalyzes imino Diels-Alder reactions of TV-phenyl-aromatic aldimines to afford exo adducts preferentially.330 When A1C13 is used instead of Bufv SiOTf, endo adducts are obtained predominantly. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Imidates, rearrangement of, 14, 1 Imines, additions of allyl, allenyl, propargyl stannanes, 64, 1 additions of cyanide, 70, 1 as dienophiles, 65, 2 synthesis, 70, 1 Iminium ions, 39, 2 65, 2 Imino Diels-Alder reactions, 65, 2 Indoles, by Nenitzescu reaction, 20, 3 by reaction with TosMIC, 57, 3 Ionic hydrogenation, 71, 1 Isocyanides, in the Passerini reaction, 65, 1... 

Babu G, Perumal PT (1998) Indium trichloride (InCl3) catalyzed imino Diels-Alder reactions an efficient synthesis of cyclopentaquinolines, azabicyclooctanones and azabicyclo-nonanones. Tetrahedron 54 1627-1638... 

Imino Diels-Alder reactions.1 The cycloaddition of dihydro-p-carbolines with... 

Imino Diels-Alder reactions. The neurotoxic fungal toxin slaframine (2) has been synthesized by an intramolecular imino Diels-Alder reaction. The substrate is obtained from the amide 1 via a methylol derivative. These derivatives are best prepared by reaction of the amide with Cs2C03 and paraformaldehyde in dry THF (equation I). When heated they lose acetic acid and undergo cyclization. 

IMINO DIELS-ALDER REACTIONS Cesium carbonate. 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

Nitrosonium terafluoroborate initiates the cation radical-mediated imino-Diels-Alder reaction of IV-arylimines with IV-vinylpyrrolidinones to give cw-4-(2-oxopyr- (g) rolidin-l-yl)tetrahydroquinolines.175 Also, 2,4,6-triphenylpyrylium tetrafluoroborate catalyses the Diels-Alder addition of IV-arylimines with IV-vinylpyrrolidinone and IV-vinylcarbazole to yield the corresponding 2-oxopyrrolidin-l-yl- and carbazole-9-yl-tetrahydroquinolines.176 The tricyclic core (151) of the batzelladine alkaloids has been prepared by a diastereoselective 4 + 2-annelation of the vinylcarbodiimide (150)... 

A novel route to optically active piperidines is the imino Diels-Alder reaction between the chiral 2//-azirine 49 and trans-1,3 - p c n t a d i c n c (Scheme 115) <20020L655>. The resulting strained intermediate was a single diastereomer and subsequent halogenation produced the 2,6-disubstituted piperidine. 

Intermolecular cycloaddition reactions constitute an important and convergent route to piperidines and related compounds. The research group of Franklin Davis at Temple University published a novel route to optically active piperidines that proceeded through an imino Diels-Alder reaction with enantiomerically enriched compound 84 (Scheme 16) <02OL655>. On reaction with ftww-l,3-pentadiene, intermediate 85 was produced as a single diastereomer in 89% yield. Hydrogenation of this strained intermediate yielded the 2,6-disubstituted piperidine 86 in 75% yield. 

In an alternative approach to this group of alkaloids, ( )-elaeokanine A (9) has been made by an intramolecular imino-Diels-Alder reaction. Pyrolysis of (15) in toluene solution yielded a mixture of the diastereoisomers (16), which, by a sequence of reactions, were converted into ( )-elaeokanine A (9).5 The possible derivation of the Elaeocarpus alkaloids from a common biosynthetic intermediate 3-(l-pyrrolinium)propionaldehyde (17), and the use of (17) in a synthetic approach to these alkaloids, have been discussed.6... 

The use of lanthanide triflates as catalysts for imino-Diels-Alder reactions has been described very recently in a feature article Kobayashi S, Ishitani H, Nagayama S (1995) Synthesis 1195... 

Kouznetsov VV, Puentes CO, Bohorquez APP et al (2006) A straightforward synthetic approach to antitumoral pyridinyl substituted 7H-indeno[2, l-c]quinoline derivatives via three-component imino Diels-Alder reaction. Lett Org Chem 3 300-304... 

Kouznetsov VV (2009) Recent synthetic developments in a powerful imino Diels-Alder reaction (Povarov reaction) application to the synthesis of V-polyheterocycles and related alkaloids. Tetrahedron 65 2721-2750... 

The initial report of an imine acting as a heterodienophile was briefly mentioned by Alder almost five decades ago. Since that time an ever increasing number of examples of this type of cycloaddition have appeared. The large preponderance of imino Diels-Alder reactions have utilized electron-deficient im-ines, although a few cases of inverse electron demand cyclizations exist. Detailed reviews of this subject have previously been published. ... 

Recently, a few examples of imino Diels-Alder reactions using azetinones as dienophiles have been described in work aimed at synthesis of carbapenems. In one sequence of reactions, acetate (34) was treated with a Lewis acid in the presence of a siloxy diene to afford adduct (36) (equation ll). This transformation presumably involves imine (35) which reacts both regio- and stereo-selectively with the diene. Adduct (36) was converted in a few steps to carbapenem (37). 

Over the past ten years, intramolecular imino Diels-Alder reactions have become a useful tool for alkaloid synthesis. This subject has been thoroughly reviewed ° ° and the discussion below is intended to exemplify various important aspects of the methodology. ... 

The la-promoted imino Diels-Alder reaction is highly susceptible to the Lewis acid employed and to the structure of substrates. iV-Phenyl aromatic aldimine 34 readily cyclizes with the silyl enol ether of 35 under the influence of 10 mol % Ic to give exo adduct 36 exclusively (Sch. 26), whereas up to 98 % endo selectivity is observed when AICI3 is used at 20 °C [55a]. 

Imines are also potential dienophiles in hetero-Diels-Alder reactions. Jprgensen et al. have evaluated Cu(I) Lewis acids in enantioselective imino Diels-Alder reactions (Sch. 52) [98]. 

Nafion is another choice of polymer support for Sc-based Lewis acids. Nafion-Sc catalyst is readily prepared by treatment of Nafion with ScCb 6H2O in acetonitrile under reflux [116]. Nafion-Sc catalyst has been found to be effective in several synthetic reactions including allylation of carbonyl compounds with tetraallyltin, Diels-Alder reaction, Friedel-Crafts acylation, and imino Diels-Alder reactions. The use of Nafion-Sc in flow systems has also been tested. 

N-Methyldihydro-j3-carboUne (29) was subjected to the imino Diels-Alder reaction in the presence of methyl pentadienoate (31) to give a mixture of adducts 32,34, and 36 (total yield 71 %). The mixture of adducts was alkylated, affording compound 38 as a single diastereomer. 

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