Dienophiles quinones

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Ghosez and co-workers used standard electron-poor dienophiles (quinone, acrylonitrile, methyl acrylate, maleic anhydride) for their experiments, hence the choice of donor substituents to increase the electron density of the azadiene (Alder s rule). However, the intrinsically electron-deficient diene can only be made sufficiently nucleophilic by the presence of exceptionally good donors. The oxygen lone pair is relatively low-lying (a+ 2/3), so it does not confer sufficient reactivity for the oxime to react. AMI calculations validate this qualitative reasoning the oxime B HOMO lies at -9.47 eV versus -8.56 eV for A s HOMO. 

Exposure of I to another efficient dienophile, quinone II, yielded the abnormal product III. This compound shows signs of C- and O-alkylation processes that call for the operation of a mechanism other than the normal [2+4] cycloaddition. 1,4-Benzoquinone is not only susceptible to Diels-Alder operations but also to Michael-type 1,4 additions. In this case the required nucleophile would be the vinyl ether portion of I while the alkyl dithiane group would remain unaltered throughout the sequence. Its role would be limited to provide substantial stabilization to the carbenium ion in V. The second C-alkylation step that would lead to four- and six-membered ring structures VI and IV, respectively, is overcome by proton transfer and D-alkylation to yield III (see Scheme 13.2). 

Some electron deficient dienophiles are quinones, maleic ahydride, nitroalkenes, a,p-unsaturated ketones, esters and nitriles. 

Aromatic fluoro-compounds have been prepared by thermal cycloaddition of fluorinated 1,3-butadienes 10-12 (Figure 2.1) with several dienophiles. Fluorophenols were obtained by cycloaddition of diene 10 with quinones [11]... 

Scheme 2.7). The phenols were formed during isolation (chromatography on silica gel) from the corresponding cycloadducts. In the reaction with p-benzoquinone, a product was unexpectedly obtained from a hetero-T>ie s-Alder reaction with the quinone acting as a carbonyl dienophile. 

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. 

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. 

Quinone-mono-ketals 46 and 47 are also low reactive dienophiles and are sensitive to Lewis-acid catalysts. The use of high pressure overcomes this limitation [17]. As shown in Equation 5.7, cycloadditions with a variety of substituted 1,3-butadienes 48 occur regioselectively and c This approach provides access to a variety of annulated benzenes and naphthalenes after aromatization of adducts 49. 

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). 

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]. 

Entry 7 features a quinone dienophile. The reaction exhibits the expected selectivity for the more electrophilic quinone double bond (see p. 506). The reaction is also regioselective with respect to the diene, with the methyl group acting as a donor substituent. The enantioselectivity is 80%. 

The related l-methyl-2-t-butyldimethylsilyloxy allylidenecyclopropane (129) reacted with activated dienophiles at ambient temperature or even below (Table 13, entries 2-4) to give moderate to good yields of the corresponding [4 + 2] cycloadducts 133-135. Only dimethyl acetylenedicarboxylate (113) required heating to 110 ° to give good yields of the adduct 132 (Table 13, entry 1) [32]. Adduct 135 from p-quinone (entry 4) tends to oxidize by purification on silica gel in the air. 

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... 

The reaction products depend on the ring substituents of the thione and the dienophile. If the dienophile is 2,5-norbornadiene,107 4 affords a new ben-zothiopyran by reaction with a further molecule of 4, 4,4 -dimethylthiobenzo-phenone yields a [4+2] cycloadduct, and 4,4 -dimethoxythiobenzophenone, a quinone derivative via the [4+2] cycloadduct. 

The generation and trapping of 5,6-bis(trimethylsilyl)benzo[c]furan 126 was reported by Wong utilizing Warrener s s-tetrazine methodology. The trapping of the silylated isobenzofuran with A-phenylmaleimide is illustrated below. A number of other dienophiles such as dimethyl acetylenedicarboxylate, benzoquinone, naphthoquinone and anthra-l,4-quinone have also been used <00TL5957>. 

Waldmann et al. used tyrosinase which is obtained from Agaricus bisporus for the oxidation of phenols to give ortho-quinones via the corresponding catechols in the presence of oxygen (scheme 33).1881 A combination of this enzymatic-initiated domino process with a Diels-Alder reaction yields the functionalized bicyclic components 164 and 165 as a 33 1 mixture starting from simple p-methyl-phenol 160 in the presence of ethyl vinyl ether 163 as an electron rich dienophile via the intermediates 161 and 162 in an overall yield of 77%. 

Quinone sesquiterpenes, 21 252-253 Quinone stabilizers, 20 105-106 Quinonoid compounds, 21 237 Quinonoid dienophiles, Diels-Alder cycloaddition of, 21 254... 

In the presence of electron-deficient dienophiles such as tetracyanoethylene (TCNE), however, vinylallene 198 acts as a diene to afford cross [4+2]-cycloadducts. In the case of 1,4-naphthoquinone, the adduct 199 was converted to 1-methylanthra-quinone 200 in the presence of charcoal [163],... 

The electrochemical oxidation of phenols produces quinones that can be used as dienophiles for the Diels-Alder reaction. A typical example is shown in Scheme 14, where a lithium perchlorate/nitromethane system and an electrode coated with a PTFE [poly-(tetrafluoroethylene)] fiber, to create a hydrophobic reaction layer. 

In a rather elegant approach towards colombiasin A (36) Flynn et al. [47] would access the tetracyclic carbon skeleton through an enantioselective intermolecular Diels-Alder sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence between double-diene 166 and quinone 167 (Scheme 26). A key element of the proposed approach would be the chiral sulfoxy group in 167 which controls both the regio and facial selectivity of the intermolecular Diels-Alder reaction and eliminates generation of the dienophile for the IMDA reaction. 

A number of side products can arise with this quinone. They include Diels-Alder adducts (DDQ is a powerful dienophile) and Michael adducts derived from the hydroquinone. 

Many quinones derived from aromatic compounds are used as dienophiles in the Diels-Alder reaction, and functionalized hydroxyquinones are extensively used as anti-oxidants in the photo industry and as polymeric materials. 

In subsequent studies, methyl vinyl ketone (2.0 mmole) was chosen as the dienophile so as to determine the combined effect of the ionic liquid (2 mL) and the Lewis acids (0.2 and 0.5 wt%) upon the yield and selectivity. Without the Lewis acid catalyst, this system demonstrated a 52% conversion of the cyclopentadiene (2.2 mmol) in 1 h with the endojexo selectivity being 85/15. The cerium triflate-catalyzed reaction was quantitative in 5 min and the endo. exo selectivity was very good for this experiment as well (94 6, endo. exo). Also with the scandium or yttrium salts tested, reactions came to completion in a short time with high stereo-selection. Cerium, scandium and yttrium triflates are strong Lewis acids known to be quite effective catalysts in the cycloadditions of cyclopentadiene with acyclic aldehydes, ketones, quinones and cycloalkenones. These compounds are expected to act as strong Lewis acids because of their hard character and the electron-withdrawing triflate group. On the other hand, reaction times of 1 hour were required for... 

Very useful building blocks have been generated by silylation of succinic anhydrides to afford 2,5-bis(trimethylsiloxy)furans (80TL3423). These compounds react with various dienophiles to give p-quinones and hydroquinones. The bis(silyloxy)furan thus functions as an equivalent of the inaccessible diketene (38). With an unsymmetrical dienophile, the regioisomer derived from para orientation predominates (Scheme 8). 

---