Diels-Alder quinone reaction

Engler and colleagues256 demonstrated that the way in which catalyst 406 is prepared has a strong effect on the regioselectivity and enantioselectivity of quinone Diels-Alder reactions. The most effective catalyst was prepared from a 1 1 1 mixture of titanium tetrachloride, titanium tetraisopropoxide and chiral diol 416. The cycloadditions of 2-methoxy-l,4-benzoquinones such as 414 with simple dienes to give adducts like 415 proceeded with high yields and enantioselectivities of up to 80% ee using this catalytic system (equation 123). 

Scheme 3 Enantioselective, rare earth-catalyzed quinone Diels Alder reactions...

Despite remarkable progress in catalytic asymmetric Diels-Alder reactions using various chiral Lewis acid catalysts [51], only a limited number of chiral catalysts effectively mediate quinone Diels-Alder reactions with moderate to good enantioselectivity [56]. Evans et al. reported that Sm(OTf)3- and Gd(OTf)3-PyBOX... 

Table 13.20 Catalytic asymmetric quinone Diels-Alder reaction promoted by Gd and Sm PyBOX complexes...

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

The Diels-Alder reaction between two moles of butadiene and one mole of quinone [106-51-4] produces tetrahydroanthraquinone [28758-94-3]... 

The first examples of macrocyclization by enyne RCM were used in Shair s impressive biomimetic total synthesis of the cytotoxic marine natural product longithorone A (429) [180]. This unique compound features an unusual hep-tacyclic structure which, in addition to the stereogenic centers in rings A-E, is also chiral by atropisomerism arising from hindered rotation of quinone ring G through macrocycle F (Scheme 85). It was assumed that biosynthesis of 429 could occur via an intermolecular Diels-Alder reaction between [12]paracy-... 

The ortho-quinone methides are difficult to isolate due to their high reactivity, which leads to rapid Diels-Alder dimerization or trimerization (Fig. 7.26). At 150°C, a partial retro-Diels-Alder reaction of the trimer can occur to form ortho-quinone methide and bis(2-hydroxy-3,5-dimethylphenyl) ethane (dimer).51... 

The use of ultrasonic (US) radiation (typical range 20 to 850 kHz) to accelerate Diels-Alder reactions is undergoing continuous expansion. There is a parallelism between the ultrasonic and high pressure-assisted reactions. Ultrasonic radiations induce cavitation, that is, the formation and the collapse of microbubbles inside the liquid phase which is accompanied by the local generation of high temperature and high pressure [29]. Snyder and coworkers [30] published the first ultrasound-assisted Diels-Alder reactions that involved the cycloadditions of o-quinone 37 with appropriate dienes 38 to synthesize abietanoid diterpenes A-C (Scheme 4.7) isolated from the traditional Chinese medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge. 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

The cycloadditions of cyclopentadiene 1 and its spiro-derivatives 109 and 110 with quinones 52, 111 and 112 (Scheme 4.20), carried out in water at 30 °C in the presence of 0.5% mol. of cetyltrimethylammonium bromide (CTAB), gave the endo adduct in about 3 h with good yield [72b]. With respect to the thermal Diels-Alder reaction, the great reaction rate enhancement in micellar medium (Scheme 4.20) can be ascribed to the increased concentration of the reactants in the micellar pseudophase where they are also more ordered. 

An interesting combination of enzymatic with non-enzymatic transformation in a one-pot three-step multiple sequence was reported by Waldmann and coworkers [82]. Phenols 125 in the presence of oxygen and enzyme tyrosinase are hydroxylated to catechols 126 which are then oxidized in situ to ortho quinones 127. These intermediates subsequently undergo a Diels-Alder reaction with inverse electron demand by reaction with different dienophiles (Table 4.19) to give endo bicyclic 1,2-diketones 128 and 129 in good yields. 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

Azulene quinones [49b] are compounds related to the family of tropones and are considered to possess great biological and physiological potential. Several polycyclic compounds have been prepared by high pressure (3kbar, PhCl, 130°C, 15h) Diels-Alder reaction of 3-bromo-l,5-azulene quinone (137) and 3-bromo-l,7-azulene quinone (138) with several dienophiles. The cycloadditions were regioselective and afforded cycloadducts in reasonable to good yields (Scheme 5.20). 

The high pressure Diels-Alder reactions of quinone-mono-ketals [80]... 

Diels-Alder reactions of quinones generated in situ by electrochemical oxidation in lithium perchlorate-nitromethane [105]... 

Mataka and coworkers reported the studies of the Diels-Alder reactions of [3.3] orthoanthracenophanes 96 and 97, of which anthraceno unit, the potential diene, has two nonequivalent faces, inside and outside. The reactions of 96 with dien-ophiles gave the mixtures of inside and outside adducts with the ratios between 1 1 and 1 1.5. However, the ratio changes drastically, in favor of the inside adducts, when 97 reacts with dienophiles such as maleic anhydride, maleimide and naphto-quinone [55] (Scheme 46). Mataka suggested that the Jt-facial selectivity is controlled by an orbital interaction between the electron-poor dienophiles and the Jt-orbital of the facing aromatics, which would lead to a stabilization of the transition state, while Nishio suggested that the selectivity is due to the attractive k/k or CH/jt interaction [53]. 

Evans and Wu have prepared complexes derived from PyBOx ligands and samarium or gadolinium triflates that were efficient for the Diels-Alder reaction between various quinones and dienes [102] (see Scheme 38 for an example). 

Synthetic Applications of the Diels-Alder Reaction. Diels-Alder reactions have long played an important role in synthetic organic chemistry.74 The reaction of a substituted benzoquinone and 1,3-butadiene, for example, was the first step in one of the early syntheses of steroids. The angular methyl group was introduced by the methyl group on the quinone and the other functional groups were used for further elaboration. 

Wang, H. Wang, Y. Han, K.-L. Peng, X.-J. A DFT study of Diels-Alder reactions of o-quinone methides and various substituted ethenes selectivity and reaction mechanism. J. Org. Chem. 2005, 70, 4910-4917. 

The oxidative formation of p-benzoquinones from anilides such as 7-108 was used for the synthesis of the core scaffold of the natural products elisabethin A (7-106) and pseudopterosin A aglycone (7-107) (Scheme 7.30). Exposure of anilide 7-108 to DMP [53] led to the formation of the o-imidoquinone 7-109, which underwent an intramolecular Diels-Alder reaction to give 7-110 in 28% yield after hydration. In a competitive pathway, the p-quinone 7-111 is also formed from 7-108, which on heating in toluene again underwent an intramolecular Diels-Alder reaction to give cycloadduct 7-112 in 25% overall yield. Hydrolysis of 7-112 furnished the carbocyclic skeleton 7-113 of elisabethin A (7-106). 

Inubushi s synthesis of racemic serratinine commences with a Diels-Alder reaction of butadiene with substituted quinone derivative 26 (available in four steps from 25,... 

Ethoxy)-allylidenecyclopropane (136a) readily underwent Diels-Alder reaction with activated dienophiles under mild conditions (Table 14) [33]. Only one regioisomer was formed with unsymmetrically substituted dienophiles such as methyl maleic anhydride (137), and quinones 138-141 (entries 2 and 3-6). AH the cycloadducts 143-147 derive from an endo approach between the two reagents. Two site-isomers were obtained in 96 4 ratio with 3-isopropyl-6-methyl-p-quinone (141) (entry 6) and the high site-selectivity observed in this... 

Condensed benzo[i>]furan molecules can be prepared by inter- or intra-molecular Diels-Alder reactions from furo[3,4-b]benzofurans, and some interesting intermolecular examples are listed below. As can be seen, the furo[3,4-i>]benzofuran 60 underegoes Diels-Alder reactions with naphtho-l,4-quinone in the presence of Znl2 as a Lewis acid to form the aromatized cycloadduct. When the diene precursor reacts with benzo-l,4-quinone in the absence of Znl2, the product is obtained as an endo-exo mixture <00JCS(P1)1387>. 

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