Diels activated 1,3-dienes

Cyclodienes. These are polychlorinated cycHc hydrocarbons with endomethylene-bridged stmctures, prepared by the Diels-Alder diene reaction. The development of these insecticides resulted from the discovery in 1945 of chlordane, the chlorinated adduct of hexachlorocyclopentadiene and cyclopentadiene (qv). The addition of two Cl atoms across the double bond of the ftve-membered ring forms the two isomers of chlordane [12789-03-6] or l,2,4,5,6,7,8,8-octachloro-2,3,3t ,4,7,7t -hexahydro-4,7-methano-lJT-indene, QL-trans (mp 106.5°C) and pt-tis (32) (mp 104.5°C). The p-isomerhas signiftcantiy greater insecticidal activity. Technical chlordane is an amber Hquid (bp 175°C/267 Pa, vp 1.3 mPa at 25°C) which is soluble in water to about 9 fig/L. It has rat LD qS of 335, 430 (oral) and 840, 690 (dermal) mg/kg. Technical chlordane contains about 60% of the isomers and 10—20% of heptachlor. It has been used extensively as a soil insecticide for termite control and as a household insecticide. 

Cyclopentadiene contains conjugated double bonds and an active methylene group and can thus undergo a Diels-Alder diene addition reaction with almost any unsaturated compound, eg, olefins, acetylene, maleic anhydride, etc. The number of its derivatives is extensive only the reactions and derivatives considered most important are discussed. 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

Scandium(lll) perfluorooctanesulfonate [Sc(OPf)3 a novel catalyst for the hetero-Diels-Alder reaction of aldehydes with non-activated dienes [108]... 

Intramolecular Diels—Alder reactions without prior 1,4-addition of oxygen (cf. previous section) have similarly been postulated for a number of [2.2]paracyclophane analogs. When [2](2,5)furano[2](l,4)naphthalen-ophane (42) is heated in excess dimethyl acetylenedicarboxylate at 100 °C, a polycyclic compound of structure 134 is formed. The mechanism of formation of 134 is most probably as follows 101> the furan moiety reacts as active diene component in an intermolecular Diels—Alder reaction to give 135. This is followed by further intramolecular 1,4-addition with the unsubstituted naphthalene ring as diene component to give the product 133, which has been isolated. 

TABLE 7.52. DIELS-ALDER ADDUCTS FROM REACTION OF UNSATURATED 5(47D-OXAZOEONES AND ACTIVATED DIENES... 

Activated dienes such as Danishefsky s diene 112 can also be used in the hetero-Diels-Alder reaction with alkyl glyoxylates. Ghosh and co-workers showed that this reaction proceeded to form cycloadducts 113a,b in yields up to 76% and ee up to 70% using either bu-box 3, phe-box 6 or inda-box ent-9a. The results are summarized in Table 9.18 (Fig. 9.36). 

Scheme 16.12). The bicyclic nature of the intermediate was inferred from the observed Diels-Alder type reactivity with activated dienes. 

An attractive entry to the carbohydrate synthesis is provided by the cycloaddition reaction. Hetero-Diels-Alder reaction, either between an oxa-diene (a,[3-unsaturated aldehyde) and an nucleophilic dienophile, or between activated diene and carbonyl compound (usually an aldehyde), leads to dihydropyrans, which can be subsequently functionalized to sugars in the desired manner (Scheme 3). 

Yamamoto reported an aluminum complex-catalyzed asymmetric hetero Diels-Alder reaction (Scheme 9.19) [36]. Chiral ketone d-3-bromocamphor discriminates (R)-organoaluminum complex 34 from (S)-complex 34 by diastereoselective complexation, whereas the remaining (S)-isomer 34 catalyzes the enantioselective cycloaddition of an activated diene to benzaldehyde. 

Cycloadditions are useful for the preparation of cyclic ompounds. Several thermal and photoactivated cycloadditions, typically [4+2] (Diels-Alder reaction), are known. They proceed with functionalized electronically activated dienes and monenes. However, various cycloaddition reactions of alkenes and alkynes without their electronical activation, either mediated or catalysed by transition metal complexes under milder conditions, are known, offering a useful synthetic route to various cyclic compounds in one step. Transition metal complexes are regarded as templates and the reactions proceed with or without forming metallacycles [49]. 

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

Hetero-Diels-Alder Reactions of Ketones. Ketonic substrates such as ethyl pyruvate (eq 9, R =Me, R = OEt) do not react with simple dienes such as cyclopentadiene or 1,3-cyclohexadiene in the presence of (5, 5)-/-Bu-box and a metal salt as catalyst. However, using activated dienes such as /ranf-l-methoxy-3-[(trimethylsilyl)oxyl]-l,3-butadiene (Danishefsky s diene), a hetero-Diels-Alder reaction with ethyl pyruvate and similar substrates catalyzed by 10 mol% of Cu[(5, 5)-/-Bu-box] (OTf)2 takes place in good yields and enantioselec-tivities (eq 9). Surprisingly, it was even possible to reduce the catalyst loading to only 0.5 mol % without affecting the yield of the product, and in some cases the enantiomeric excess was even improved. 

Hetero Diels-Alder reactions between prochiral aldehydes and activated dienes such as 84 are also known to be catalyzed by Lewis acids (Eq. 26) and catalysis by chiral Lewis acids supported by dimethylpolysiloxane (83a) has been investigated [100]. Enantio-selectivity up to 43 % ee was achieved by use of polymeric Lewis acids. 

Backvall and Juntunen and Fuchs and Braish have developed ( )-2-phenylsuphonyl-1,3-dienes prepared under Julia conditions as versatile synthones for a variety of organic transformations . These dienes undergo facile Diels-Alder reaction and subsequent 1,4-elimination of sulphinic acid by base to generate a new diene (equation 62) . An elegant extension of this method is to use chiral sulhnylmaleate which, on Diels-Alder reaction and elimination of the sulhnyl group, generates an optically active diene for further applications (equation 63) . 

Simonsen, K. B., Svenstrup, N., Roberson, M., Jorgensen, K. A. Development of an unusually highly enantioselective hetero-Diels - Alder reaction of benzaldehyde with activated dienes catalyzed by hyper-coordinating chiral aluminum complexes. Chem.- Eur. J. 2000, 6, 123-128. 

Masked o-benzoquinones (one CO group is acetal- or acylal-protected) as active dienes in Diels-Alder reactions with dienophiles (among them thiophene and pyrrole derivatives) 02ACR856. 

Jurczak has reported an interesting approach to optically active 6-substituted-2-methoxy-5,6-dihydropyrans. The approach is based on a high-pressure catalysed hetero-Diels-Alder reaction of activated diene 49 with non-activated heterodienophile 52 (Scheme 7.13). These authors studied the eifects of catalyst... 

The modified organoaluminum reagent, BINAL, can be used as a chiral Lewis acid catalyst in the asymmetric hetero-Diels-Alder reaction [41]. Reaction of various aldehydes with activated dienes under the influence of catalytic BINAL (5-10 mol%) at -20 °C gave, after exposure of the resulting hetero-Diels-Alder adducts to tri-fluroacetic acid, predominantly c/v-dihydropyrone in high yield with excellent enan-tioselectivity. 

Cycloaddition. 4-Methylene-4,5-dihydroisoxazoles (174) are good dipolarophiles towards a variety of 1,3-dipoles (e.g., arylnitrile oxide (177)) to form a spiral compound (178), which is not easily accessible by other routes. The resulted 1,3-dipolar cycloaddition product (178) is regio- and stereoselective <95SL1208>. The exocyclic double bond of (174) is sluggish towards the diene systems, but with the activated diene, 2,5-dimethyl-3,4-diphenyl-2,4-cyclopoentadienone (179) yielded the Diels-Alder product (180) (Scheme 27) <95SL1208>. 

Since Danishefsky demonstrated that activated dienes, such as siloxydiene (commonly referred to as Danishefsky s diene) react with a wide spectrum of aldehydes to afford 5,6-dihydro-y-pyrones in 1982 [l],the hetero-Diels-Alder reaction has attracted a great deal of attention over the last two decades [2,3]. The use of asymmetric catalysis in these reactions is overwhelmingly associated with heterodienophiles. Especially, the cyclocondensations of activated dienes with aldehydes or their derivatives are of particular importance, providing a multitude of opportunities for the highly efficient regio- and stereoselective construe-... 

J.1.1 Activated Dienes and Their Use in the Diels-Alder Reaction... 

Dienes that contain electron-donating groups (activated dienes) are more reactive in Diels-Alder reactions than unsubstituted or electron-deficient dienes. In molecular orbital formalism, the substituents on the diene perturb the tT-electron density to cause an increase in the energy of the highest occupied molecular orbital (HOMO Figure 1). In a normal-demand Diels-Alder reaction this results in an increase in the interaction between the HOMO of the diene and the LUMO (lowest unoccupied molecular orbital) of the dienophile. This interaction, in turn, lowers the transition state energy of the reaction. Similar arguments have also been used to explain the increased reactivity of activated dienes towards heterodienophiles such as aldehydes. 

Activated dienes are also highly regioselective. This is due to the unsymmetrical polarization of the HOMO that is caused by the placement of substituents on the diene. The use of activated dienes is well documented in classical Diels-Alder reactions. They provide for high reactivity, good regioselectivity and introduce useful functionality into the cycloadducts."... 

Table 7 Lanthanide-catalyzed Hetero Diels-Alder Reaction of Highly Activated Dienes with Unactivated and...

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