Imino Diels-Alder reactions: synthesis

Imino Diels-Alder reactions synthesis of pyridine and quinoline derivatives... 

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

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

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... 

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. 

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 (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... 

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. ... 

Weinreb, S. M., Levin, J. I. Synthesis of nitrogen-containing heterocycles by the imino Diels-Alder reaction. Heterocycles 979,12, 949-975. 

Birkinshaw, T. N., Tabor, A. B., Holmes, A. B., Kaye, P., Mayne, P. M., Raithby, P. R. The products of an imino Diels-Alder reaction with 2-(trimethylsiloxy)cyclohexadiene synthesis, x-ray crystal structures, and mechanistic implications. J. Chem. Soc., Chem. Common. 1988, 1599-1601. 

The same group has applied this imino Diels-Alder reaction in an enantiosel-ective total synthesis of the alkaloid (-)-cannabisativine (Scheme 33) [70b]. An initial Sharpless epoxidation of allylic alcohol 183 provided enantiomerically pure compound 184, which could be converted in four steps to alcohol 185. This compound could then be relayed into the requisite diene 186. Imino Diels-Alder reaction of 186 led to a single cycloadduct 188, presumably via a transition state like 187. It was then possible to homologate the ester functionality of 188 via the corresponding aldehyde to acetal 189. This intermediate could be converted in several steps into 190. Another key step in the strategy was epimeriza-tion via a retro Michael reaction leading to aldehyde 191, which could be transformed in five steps into (-)-cannabisativine. 

Oppolzer et al. devised a clever total synthesis of lysergic acid (40) that has as its key step an intramolecular imino Diels-Alder reaction (Scheme... 

An intramolecular imino Diels-Alder reaction has also been used as the key step in a total synthesis of the neurotoxic fungal metabolite slaframine (49) 91 [4 2] cycloaddition of an ( , )-diene was used to establish... 

Oppolzer et al. devised a clever total synthesis of lysergic acid (40) that has as its key step an intramolecular imino Diels-Alder reaction (Scheme 2-XIII). A thermal retro-Diels-Alder reaction of 39 liberating cyclopen-tadiene was used to afford a diene oxime ether which cyclized to give a tetracyclic indole as a 3 2 mixture of diastereomers. Three additional steps served to convert this adduct to ( )-lysergic acid (40). Of particular interest here is the fact that simple oximino compounds are not normally reactive dienophUes, and the intramolecularity of the conversion is apparently crucial to the success of this transformation. 

Grieco PA, Kaufman MD (1999) Intramolecular imino Diels-Alder reaction of a 3-vinyl indole application to a total synthesis of (+-)-ebumamonine. J Org Chem... 

Tan Y-J, Zhang Z, Wang F-J, Wu H-H, Li Q-H. Mechanochemical milling promoted solvent-free imino Diels-Alder reaction catalyzed by FeCl3 diastereoselective synthesis of cA-2,4-diphenyl-l,2,3,4-tetrahydroquinolines. RSC Adv 2014 4 35635-8. 

The methodology based on nitroso DieIs-alder reaction that proved useful in the synthesis of tropane alkaloids also seemed to open an attractive route to some other alkaloids. Compared to the intramolecular imino Diels-Alder reaction (ref. Ic) the intramolecular variant of the nitroso Diels-Alder reaction has received far less attention (refs. 6b 12), despite the enormous potential it holds for alkaloid synthesis. With this in mind we proceeded to examine the application of the intramolecular nitroso Diels-Alder cycloaddition in the synthesis of alkaloids possessing saturated nitrogen heterocyclic ring systems. 

Aznar, et al. reported a proline-catalyzed imino-Diels-Alder reactions of acyclic a,p-unsaturated ketones 96 with imines 92 for the synthesis of mc50-2,5-diaryl-4-piperidones 98, Scheme 3.35 [50], The 2-amino-1,3-butadiene was generated in situ by the reaction of a,p-unsaturated ketones 96 with L-proline, followed by Diels-Alder cycloaddition with imine 92 to provide tetrahydropyridine adduct which was then hydrolyzed to the 4-piperidone 98. 

Method 10. An ingenious recent synthesis employs an imino Diels-Alder reaction to form rings D and E of tylophorine simultaneously (82). 

The Povarov reaction is related to the previous examples in that it can be defined as the formal imino Diels-Alder reaction between aromatic imines and electron-rich olefins. It is one of the most popular methods for the synthesis of tetrahydro-quinolines [40], and two examples of Povarov reactions in water are summarized in Scheme 1.27. In an eaily example of the use of ceric ammonium nitrate as a catalyst in synthesis [41], Perumal reported a few examples of a CAN-catalyzed Povarov reaction of aldehydes, amines and N-viitylpyrroUdin-2-ones as the olefin component in water for the synthesis of heteroaiyl-substituted tetrahydroquinolines 54 [42]. Using a different approach, Vaultier later described an onium salt-supported Povarov three-component reaction in water at room temperature affording tricyclic compounds 55. In this study, either the aldehyde or the amine components were linked to a side chain containing an onium salt, which confers solubility to the reactant [43]. 

Ramesh E, SreeVidhya TK, Raghunathan R (2008) Indium chloride/silica gel supported synthesis of pyrano/thiopyranoquinolines through intramolecular imino Diels-Alder reaction using microwave irradiation. Tetrahedron Lett 49 2810-2814... 

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