Diels-Alder type syntheses

When aldehyde containing an electron-withdrawing group is employed, or when a Lewis acid promoter is present, C=0 double bonds can readily undergo Diels-Alder-type reactions. This process is referred to as the oxo Diels-Alder reaction, and it has been explored by Danishefsky and DeNinno35 for the synthesis of a wide range of saccharide derivatives. 

Soon thereafter, the Yamamoto group reported an extension of this work to the highly diastereo- and enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamines in the presence of the BINOL derivative 44 (Scheme 5.61) [115]. This reaction was thought to proceed through a sequential N-NA/ hetero-Michael reaction mechanism. Support for this mechanism was provided from an experiment employing bulkyl 4,4-diphenyl dienamine where the N-NA... 

B. R. Bear, S. M. Sparks, K. J. Shea, The Type 2 Intramolecular Diels-Alder Reaction Synthesis and Chemistry of Bridgehead Alkenes Angew. Chem. Int. Ed. Engl. 2001, 40, 820-849. 

Tetracyclization. The Heathcock group1 has described a remarkably short and efficient synthesis of the skeleton of Daphniphyllum alkaloids (2) by reaction of the dialdehyde 1 with gaseous ammonia and then dissolution in acetic acid at 70°. The yield is 77%, based on the diol precursor to 1. The azadiene a and the imine b have both been isolated and identified. The conversion of a to b is an intramolecular Diels-Alder type reaction. The tetracyclization may well be involved in the biosynthesis of alkaloids such as Daphnilactone A (3). 

The chemistry of the l,3-dithiole-2,4,5-trithione oligomer system 374 derived from monomers 375 and 376 (Scheme 49) has been the subject of a review <2006CHE423>. This system easily depolymerized (heat or UV irradiation at 253 nm) and was effective in Diels-Alder-type cycloadditions. Reactions with unsaturated compounds constituted an efficient method for synthesis of functionalized l,3-dithiole-2-thiones containing substituted 1,4-dithiin rings and are examples of reactivity of thione or sulfenyl substituents (stmctures 374-376) attached to the 1,3-dithiole ring carbon atom. 

An ingenious synthesis of coniine has been obtained by an adaptation of the Diels-Alder type of reaction thus the reaction of pyridine with methyl acetylene dicarboxylate in ether gives rise to methyl quinolizine-1 2 3 4-tetracarboxylate (CII), m.p. 187-188°, and this, on oxidation either... 

There are two types of electrocyclic process which are of considerable value for heterocyclic ring synthesis one of these is 1,3-dipolar cycloaddition, and the second involves a Diels-Alder type addition using some type of azadiene the latter does not in general produce aromatic heterocycles and, important though it is, will not be dealt with here. 

It was originally suggested by Swindell that acylation of baccatin III with protected N-benzoyl-3-phenylisoserine proceeds through an oxazinone intermediate (286). He then developed a synthesis of the side chain methyl ester by hydrolysis of a protected oxazinone intermediate 7.6.3, which was itself prepared in 70% yield by a Diels-Alder type reaction between the imine 7.6.1 and the chiral ketene acetal 7.6.2. Hydrolysis of 7.6.3 and removal of protecting groups gave the side chain methyl ester in 93% yield (287). 

Stephanidou-Stephanatou and co-workers reported a 4-picoline-catalyzed het-ero-Diels-Alder type cycloadditions of chromone-3-carboxaldehydes 124 with acetylenedicarboxylates 125, providing an one-pot synthesis of pyrano[4,3-c] chrotnenesl27, Scheme 3.42 [57],... 

Compared to the relatively young history of the pure metal, aluminium compounds have been known for ages from the above-cited alum class to the more exclusive transition metal-doped aluminium oxides like ruby and sapphire (corundum varieties with chromium for the former and titanium and iron impurities for the latter) or aluminosilicate-like emeralds (a beryl type with chromium and vanadium impurities). However, to the synthetic chemist, aluminium chloride, is de facto one of the first jewels of the aluminium family. Aluminium trichloride (together with titanium tetrachloride, tin tetrachloride and boron trifluoride) is an exemplary Lewis acid that finds many applications in organic synthesis It is extensively used for instance in Friedel-Crafts alkylations and acylations, in Diels-Alder-type cycloadditions and polymerisation reactions. Its involvement in a wide range of reactions has been documented in many reviews and book chapters. ... 

Treatment of M(C0)5[C(0Me)(CsCPh)] (M = Cr, W) with CpH modifies the carbene by Diels-Alder type addition of the alkyne across CpH. " Carbenes Cr(CO)5(carbene) react with 1-alkynols to form hydroquinone and/or vinyl lactone derivatives via vinyl ketene intermediates. Annulation reactions of Cr carbene complexes with 3-carbomethoxy-5-hexynoate and CO form part of a new regiospecific route relevant to the synthesis of... 

Diels-Alder-type Reactions. The Diels-Alder reaction has long been recognized and employed as a highly important transformation for the synthesis of carbocycles and heterocycles. Following the Yb(OTf)3-catalyzed Povarov (imino variant of the Diels-Alder reaction) reaction of cyclopentadiene or dihydrofuran with in situ formed imines, other RE(OTf)3 catalysts have been employed to study this transformation. One example is the three-component coupling of anilines, formaldehyde, and electron-rich... 

The reaction of l-vinylpyrrolidinone-2-one 124 or l-vinylazepan-2-one with aromatic amines 125 on refluxing in water leads to a diastereoselective synthesis of 2-methyl-4-amino-l,2,3,4-tetrahydroquinolines 126 in moderate to good yields (Scheme 42) [95]. No catalyst or any other additive is required for the reaction. The formation of products has been explained by an equilibrium between l-vinylpyrrolidinone-2-one 124 and its corresponding iminium ion 127 in water under reflux (Scheme 43). The active iminium ion could be easily attacked by anilines to form another intermediate 128, which subsequently be transformed into imine 129 with elimination of 2-pyrrolidinone. Finally, imine 129 xmdergoes an aza-Diels-Alder type cycloaddition with another molecule of l-vinylpyrrolidin-2-one forming the desired products. The reaction of a representative 128 with 1-vinylpyr-rolidin-2-one under similar conditions affords the 1,2,3,4-tetrahydroquinoline, which supports the proposed mechanism. 

A synthesis of A- -cyclopentenones from 1,3-dienes has been developed by Corey" (Scheme 11). This is exemplified by Diels-Alder type addition of isoprene to (315) (from dithian and trityl fluoroborate) to give adduct (316) in 95% yield. On treatment with 1 equivalent of n-butyl-lithium at — 78°C in THF, (316) formed ylide (317) which, following attainment of room temperature and evaporative distillation at 80 °C, gave the rearranged product (318) in a yield of 96%. This vinylcyclopropane underwent rearrangement at 200 °C in benzene for 4 h to give (319), in 97 % yield the thioketal was readily converted into (320). The same reaction sequence was successfully applied to prepare both (321) and (322). 

Recently, a synthesis of ( )-oseltamivir featuring a novel asymmetric Diels-Alder—type reaction catalyzed by a barium/F2-FujiCAPO complex was reported by Shibasaki et al. (Scheme 16.3). Diene 16 and dienophile 17 were selected for this transformation however, the diene 16 has never been used before in Lewis acid-catalyzed asymmetric Diels-Alder reactions because of its lability under acidic conditions. Thus, a conceptually distinct catalytic asymmetric Diels-Alder reaction that was not dependent on an acid catalyst was examined by testing metal alkoxides that may activate the siloxy-diene through the formation of a hyper-valent silicate or transmetalation. 

Yamatsugu K, Yin L, Kamijo S, Kimura Y, Kanai M, Shibasaki M. A synthesis of tamiflu by using a barium-catalyzed asymmetric Diels-Alder-type reaction. Angew. Chem. Int. Ed. 2009 48 1070-1076. 

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