Quinones, as dienophiles

C.C. Nawrat, C.J. Moody, Quinones as dienophiles in the Diels—Alder reaction history and applications in total synthesis, Angew. Chem. Int. Ed. 53 (2014) 2056—2077. 

The Diels-Alder reaction ([4+2] cycloaddition) [8] provides one of the most powerful methods for the constmc-tion of PAHs because it affords one-step formation of the six-membered ring framework, the basic unit of these derivatives. This chapter, based on the results of our work, will highUght the synthesis of substituted oligoacenes including anthracene (1), tetracene (2), and pentacene (3) cores by Diels-Alder reactions using arynes and quinones as dienophile components and furans, thiophene-1,1-dioxides, and o-quinodimethane as diene components. The synthetic methodology will be accompanied by discussions on molecular and packing stmctures as weU as solid-state optical properties. 

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. 

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. 

The dimerization of o-quinone methides in which one molecule acts as the heterodiene and another as dienophile leads to spiroannelated chromans (equation 12). The driving force for this considerable tendency to dimerize is associated with the ease with which the... 

The reaction has been shown to involve a stereospecific syn-addition with respect to the dienophile. For example, the reaction of 2,3-dimethylbuta-1,3-diene with maleic anhydride gives cis-l,2,3,6-tetrahydro-4,5-dimethylphthalic anhydride (Expt 7.20). An example of the use of a quinone as the dienophile is provided by the synthesis of cis-1,4,4a,9a-tetrahydro-2,3-dimethyl-9,l0-anthra-quinone which upon dehydrogenation (most simply by the action of oxygen upon its solution in alcoholic potassium hydroxide) yields 2,3-dimethylanthra-quinone (Expt 7.21). Tetraphenylcyclopentadienone (tetracyclone) readily undergoes the addition of dienophiles, such as maleic anhydride, to give an adduct, which then extrudes a molecule of carbon monoxide on heating, as in the preparation of 3,4,5,6-tetraphenyldihydrophthalic anhydride (Expt 7.22). 

Discrepancies between different researchers derive from the character inter-or intramolecular of the interactions presumably controlling the reactive conformation. Thus, in most of the cases, the population of the different rotamers in the sulfinylated substrate (only governed by intramolecular interactions) is the only factor considered for explaining the observed 7r-facial selectivity. This explanation (static conformational polarization) was formulated by Koizumi and used by many authors to justify the behavior of vinyl sulfoxides acting as dienophiles and dipolarophiles. A second explanation assumes that the interactions of the two reagents in the transition states determine a different reactivity of the rotamers around the C-S bond. This intermolecular factor can become the most important one in the control of the 7r-facial selectivity of the cycloadditions, and therefore the tendency expected from conformational stability criteria was not observed in those cases where the most reactive conformation is not the most populated one. This dynamic conformational polarization has been used just to explain some of the results obtained for sulfinyl quinones and sulfinyl dienes (unexplainable with the above model) but it can be applied to many other cases. 

Here again, the cycloaddition is endo-selective, with only regioisomers 79 being formed, and, when using 2- and/or 3-substituted furans, only the unsubstituted furan double-bond reacts in these inverse electron-demand Diels-Alder processes [134-136]. Indoles, pyrroles, and thiophenes can also be made to react as dienophiles with ortho-quinone monoketals... 

Thiophenes can act as dienophiles in Diels-Alder reactions with electron-poor dienes such as hexachlorocyclopen-tadiene, tetrazines, or o-quinone monoimines. The masked o-benzoquinone 64 can undergo inverse electron demand cycloadditions with thiophene itself or simple derivatives such as 2-methyl-, 2-methoxy-, and 2,4-dimethylthiophene (Scheme 5) <2001TL7851>. Depending on the substitution pattern on the thiophene skeleton, different cycloadducts can be observed. The basic thiophene skeleton gives rise to a bis-adduct 65. By blocking the second double bond with a methyl or methoxy group, a 1 1 adduct 66 or 67, respectively, is obtainable in moderate yield. 

Benzvalene (95) could be used as dienophile with o-quinones (96) leading to diones 97 which were photolyzed to dienes 98. The unsubstituted compound 98a is yet another member of the (CH)10 family. Irradiation of 97b at 436 nm led to the cyclo-butanedione 55). 

Although it is possible to synthesize anthracene in a number of ways using Friedel-Crafts methodology, the usual routes involve either an adaptation of the Haworth synthesis of naphthalene or a Dicls-Alder reaction using naphtho-l,4-quinone as the dienophile. 

Quinones, typical of unsaturated ketones, undergo base-catalysed epoxidation The epoxy ketone may then rearrange with the formation of a hydroxy quinone. Quinones may also act as dienophiles in the Diels-AIder reaction. This can be a useful way of constructing polycyclic ring systems (Scheme 3.54). 

Despite their high reactivity as dienophiles and the potential utility of the derived cycloadducts, quinones have rarely been utilized in catalytic enantioselec-... 

Diels-Alder reactions. Unhke p-benzoquinones, which are potent dieno-philes in Diels-Alder reactions, o-benzoquinones can function as either dienes or dienophiles. Danishefsky et al. reasoned that 4-methoxy-o-benzoquinones should serve predominantly as dienophiles. Indeed when heated in a sealed tube at 105° for 5 hr. with 1,3-butadiene, the quinone (1) gives (3) in 63% yield. This product is evidently formed by cycloaddition to the 5,6-double bond followed by enolization to the diosphenol. 

Most of the classical dienes are hydrocarbons, like cyclopentadiene. butadiene, anthracene, 9,10-dimethylanthracene, isoprene, 2,3-dimethylbutadiene. For dienes of this kind it is generally true that electrophilic dienophiles are the most reactive, and actually acrylic derivatives, maleic anhydride, p-benzo-quinone and similar compounds have found a large use as dienophiles both for preparative purposes and for kinetic studies. The latter demonstrated quantitatively the importance of electronegative groups on the dienophiles, and conversely of electron-releasing substituents on the diene, in order to accelerate such type of Diels-Alder reaction. It was also realised later that Diels-Alder additions with inverse electron demand , that is between electrophilic dienes and nucleophilic dienophiles, do occur . ... 

Acylindoles act as dienophilic components of a [4 + 2] cycloaddition when treated with an o-quinone monoimide (Equation (85)) <87TL669l>. 

Non-catalyzed Diels-Alder reactions of chiral dienes with the achiral dienophiles compiled below have been widely studied. As dienophiles especially quinones (1), maleic anhydride (2), nitro-substituted alkenes (5) and acrylates (4) have been examined. 

Various cycloaddition reactions can be efficiently catalysed by prolinol silyl ethers.Dienamines generated from a,(3-unsaturated aldehydes participated in the Diels-Alder reaction with quinones. Nitrolefins can also function as dienophiles in organocatalytic Diels-Alder reaction. Reyes, Vicario and coworkers found that unconjugated 2,5-dienals are more reactive substrates than the corresponding conjugated aldehydes (Scheme 8.35). The reaction proceeded with clean p,E-selectivity and the corresponding products were obtained in high diastereomeric and enantiomeric purities. 

Importantly, though. Nature does not have to rely on enzymatic assistance in order to utilize the full range of synthetic power afforded by the Diels—Alder reaction since she can also construct compounds whose unsaturated motifs are disposed to participate spontaneously in this pericyclic reaction on their own accord. For instance, in the previous chapter on longithorone A, we chronicled how a transannular Diels—Alder reaction was initiated under ambient conditions the instant that a quinone-based dienophile was unveiled in a macrocyclic ring bearing a neighboring diene system. Similarly, as described in Chapter 17 of Classics /, heating a small... 

Ketenes participate as dienes as well as dienophiles in [4+2] cycloaddition reactions. For example, several ketenes with a suitable substituent in the a-positions readily participate in [4+2] cycloaddition reactions. The substituents include unsaturated groups, a-oxo, a-thio or a-imino groups. In their role as dienophiles, ketenes participate in the reaction with dienes, azadienes, diimines and o-quinones by addition across the C=C bonds, and sometimes the C=0 bonds. The [2+2+2] adducts obtained in the reaction of ketenes with C=N double-bonded substrates (see Section 4.1.4.2) are another example of [4+2] cycloaddition reactions of ketenes. 

A one-pot technique has been developed to oxidize 1,4-hydroquinones and utilize the quinone products as dienophiles in Diels-Alder reactions (eq 3). Tetrahydrophenanthrene-9,10-quinones have also been prepared by a one-pot double Diels-Alder reaction (eq 4). ... 

The non-prenyl 1,2-naphthoquinones 534 were obtained correspondingly through the Knoevenagel condensation of lawsone (2-hydroxy-1,4-naphthoquinone) with paraformaldehyde (CH20)n leading to a quinone methide intermediate, which undergoes a HDAR with styrene as dienophile (Nair and Treesa 2001). Treatment of lawsone with CAN and styrene (Kobayashi et al. 1996 Sun et al. 1998) also yielded the dihydrofuran-naphthoquinone derivatives via [3 + 2]-lype cycloaddition in a one-pot reaction (Perez-Sacau et al. 2005). 

Et2AlCl has been extensively used as a Lewis acid catalyst for intermolecular and intramolecular Diels-Alder reactions with a,3-unsaturated ketones and esters as dienophiles. It also catalyzes inverse electron demand Diels-Alder reactions of alkenes with quinone methides and Diels-Alder reactions of aldehydes as enophiles. ... 

Stereoselective cycloadditions of quinones and their derivatives have played an important role in the synthesis of natural products. The early example by Woodward (Scheme 17.2) involved direct use of a quinone as the reacting dienophile. An alternative approach with potential added strategic benefits employs appropriate precursors that provide the reactive quinone upon in situ oxidation prior to the Diels-Alder reaction. An example was reported by Corey, who showed that treatment of diene amide 85 with Pb(OAc)4 led to the formation of Diels-Alder adducts 86 and 87 (dr=8 1,... 

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). 

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