Heterocycles, acylation Diels-Alder reactions

Diels-Alder reactions, 4, 842 flash vapour phase pyrolysis, 4, 846 reactions with 6-dimethylaminofuKenov, 4, 844 reactions with JV,n-diphenylnitrone, 4, 841 reactions with mesitonitrile oxide, 4, 841 structure, 4, 715, 725 synthesis, 4, 725, 767-769, 930 theoretical methods, 4, 3 tricarbonyl iron complexes, 4, 847 dipole moments, 4, 716 n-directing effect, 4, 44 2,5-disubstituted synthesis, 4, 116-117 from l,3-dithiolylium-4-olates, 6, 826 electrocyclization, 4, 748-750 electron bombardment, 4, 739 electronic deformation, 4, 722-723 electronic structure, 4, 715 electrophilic substitution, 4, 43, 44, 717-719, 751 directing effects, 4, 752-753 fluorescence spectra, 4, 735-736 fluorinated derivatives, 4, 679 H NMR, 4, 731 Friedel-Crafts acylation, 4, 777 with fused six-membered heterocyclic rings, 4, 973-1036 fused small rings structure, 4, 720-721 gas phase UV spectrum, 4, 734 H NMR, 4, 7, 728-731, 939 solvent effects, 4, 730 substituent constants, 4, 731 halo... 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted important interest thanks to there various applications in different synthetic transformations. These simple structures, directly related to the well-documented Evans oxazolidinones, have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations (7V-enoyl derivatives), but mainly in condensation of their 7V-acyl derivatives on aldehydes. Those have shown interesting characteristics in anti-selective aldol reactions or combined asymmetric addition. Normally, the use of chiral auxiliaries which can accomplish chirality transfer with a predictable stereochemistry on new generated stereogenic centers, are indispensable in asymmetric synthesis. The use of OZTs as chiral copula has proven efficient and especially useful for a large number of stereoselective reactions. In addition, OZT heterocycles are helpful synthons that can be specifically functionalized. 

The 1,2,4-triazine core is a synthetically important scaffold because it could be readily transformed into a range of different heterocyclic systems such as pyridines (Sect. 3.1) via intramolecular Diels-Alder reactions with acetylenes. 1,2,4-Triazines have been synthesized by the condensation of 1,2-diketones with acid hydrazides in the presence of NH4OH in acetic acid for up to 24 h at reflux temperature. Microwave dielectric heating in closed vessels allowed the reaction to be performed at 180 °C (60 °C above the boiling point of acetic acid). As a result, the reaction time was reduced to merely 5 minutes. Subsequently, a 48-membered library of 1,2,4-triazines was generated from diverse acyl hydrazides and a-diketones [139]. Two thirds of the desired heterocycles precipitated from the reaction mixture upon cooling with > 75% purity, while the remaining part of the library was purified by preparative LCMS (Scheme 56). 

Weinreb, S. M., Scola, P. M. N-acyl imines and related hetero dienes in [4+2]-cycloaddition reactions. Chem. Rev. 1989, 89,1525-1534. Marcelis, A. T. M., van der Plas, H. C. Diels-Alder reactions of diazines and pyridines. Trends Heterocycl. Chem. 1990, 1,111-123. 

These solid-acid catalysts are, in principle, applicable to a plethora of acid-catalyzed processes in organic synthesis [18]. These include various electrophilic aromatic substitutions, e.g. nitrations, halogenations, and Fiiedel-Crafts alkylations and acylations, and numerous rearrangement reactions such as the Beckmann and Fries rearrangements. Other examples include a variety of cyclization reactions such as Diels-Alder reactions and the synthesis of pyridines and other heterocycles. 

C.iii. Nitroso-Type Compounds. Nitroso compounds (R—N=0) show reactivity as dienophiles in Diels-Alder reactions, giving heterocyclic rings. In Kibayashi s synthesis of fasicularin, " for example, hydroxamic acid 180 was treated with tetrapropylammonium periodate in the presence of 9,10-dimethyl-anthracene to give transient acylnitroso compound 181, and the resultant Diels Alder product 182 was formed in 84% yield. In this particular example, the Diels-Alder adduct essentially "protected" the acyl nitroso unit, which was used in a subsequent reaction. 

In Scheme 10, examples of eaiantioseleetive cycloadditions with formation of three-, four-, five-, and six-membered carbocyclic or heterocyclic rings are presented, to demonstrate the use of Ti-TADDOLates as Lewis acids. The Diels-Alder reaction has, so far, been studied most extensively, and many protocols have been proposed for the preparation of the Ti catalyst, of which as little as 5 mol-% and as much as several equivalents were employed (more often than not, Lewis acids bind strongly to the products of reactions they have mediated cf. the classical Friedel-Crafts acylation with AICI3 ). 

Stajer and co-workers reported a new series of tricyclic heterocycles 178 containing the phthalazine moiety <01JCS(P1)558>. This pyrimido[2,l-fl)phthala7.ine was synthesized by first treating acyl hydrazide 175 with 2-aroylbenzoic acids 176 to give 177. Then, 177 was converted into 178 upon refluxing in toluene by a retro Diels-Alder reaction eliminating cyclopentadiene. 

Wenkert, E., Moeller, P.D., Piettre, S.R. (1988). Five-membered aromatic heterocycles as dienophiles in Diels-Alder reactions. Furan, pyrrole and indole Journal of the American Chemical Society, 110, 21, 7188-7194, ISSN 0002-7863 Wenkert, E., Piettre, S.R. (1988). Reaction of a-and 3-acylated furans with conjugated dienes. Journal of Organic Chemistry, 53,5850-5853, ISSN 0022-3263 Wilkes, J.S. (2002). A short history of ionic liquids - From molten salts to neoteric solvents. Green Chemistry, 4, 73-80, ISSN 1463-9270... 

Nevertheless, such reactions catalyzed by zeolites have been discussed in the review of 2001 (1) isomerization (double-bond shift, isomerization of tricyclic molecules, like synthesis of adamantane, isomerization of terpenes, diverse rearrangements, conversion of aldehydes into ketones), (2) electrophilic substitution in arenes (alkylation of aromatics, including the synthesis of linear alkylbenzenes, alkylation and acylation of phenols, heteroarenes and amines, aromatics nitration and halogenation), (3) cyclization, including the formation of heterocycles, Diels-Alder reaction, (4) nucleophilic substitution and addition,... 

Isoquinoline alkaloids. The regioselective allylation of N-acyl heterocycles (13, 10) can be used for synthesis of isoquinoline alkaloids. Thus simultaneous reaction of the dihydroisoquinoline (1) with a diunsaturated acyl chloride (2) and allyltributyltin affords the 1,2-adduct (3), which undergoes a Diels-Alder cyclization... 

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