Diels-Alder reactions high pressure promoted

At ambient pressure, 195a did not undergo intramolecular [4 + 2] cycloaddition even at temperatures up to 150°C. The use of Lewis acids to promote the Diels-Alder reactions was of marginal success only. In contrast, on exposing the furan derivatives 195 to high pressure (10kbar) in 0.1-0.5 moll-1 solutions at 60-70°C, a clean cycloaddition took place (Table 18). 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

Hanessian and Compain have also reported a Lewis acid-promoted inverse electron demand hetero-Diels-Alder reaction between dihydrofurans and dihydropyrans with a-keto-/3,7-unsaturated phosphonates to give stmcturally related products <2002T6521>. High-pressure OTr/o-selective hetero-Diels-Alder reactions between a,/3-unsaturated aldehydes and enol ethers in the presence of lanthanide catalysts have also been reported and give 3,4-dihydro-27/-pyrans. Examples include the use of cyclic enol ethers to give 2,3,4,4a,5,8a-hexahydro-277,577-pyrano[2,3-. ]pyrans <1995T8383>. 

The known Diels-Alder reactions of thiophenes depend on one of three strategies to promote adduct formation (i) use of highly reactive dienophiles, (ii) increasing the reactivity of the thiophene by proper choice of substituents, and (iii) carrying out the reaction at very high pressure. 

Scheme 7.29 High-pressure promoted Diels-Alder reaction on solid-phase.

Scheme 10. The molecular LEGO set employed in the synthesis of kohnkene 43 [21, 112]. Both the thermally-promoted and high pressure-promoted Diels-Alder reactions proceed with the same remarkable treble diastereoselectivities. The clock-face shown in the middle of structure 43 provides a convenient frame of reference for the discussion of structural features in the macropolycycle...

Intermolecular [4 + 2] cycloadditions exhibit strongly negative activation volumes and reaction volumes. High pressure, therefore, can be applied to accelerate Diels-Alder reactions and to shift the reaction equilibrium towards the cycloadducts. These effects are of particular advantage to (1) promote odierwise slow [4 + 2] cycloadditions involving heat or Lewis acid sensitive educts or products (2) suppress cycloreversion processes which are eidier thermodynamically favored or would interfere with a kinetically controlled stereochemistry. In view of a recent review (1985) only a few examples are presented here. 

Ultrasound was reported to promote Diels-Alder reactions as well as improve their regioselectivity similarly to high pressure, but much more conveniently (Scheme 56, Table 7). Comparison of entries 2/3 indicates the similarity of the yields and product ratios (242)/(243), obtained at 10 kbar (entry 2) and on sonication (entry 3). The latter were attributed to the implosion of the ultrasound-induced cavities which locally generate high pressures and temperatures (up to 1 kbar and 5000 K). Deacetalization of the major aromatized regioisomer (242) gave the natural product tanshindiol B. 

The enantioselective total synthesis of the Securienega alkaloid (-)-phyllanthine by S.M. Weinreb et al. involved a stereoselective Yb(OTf)3-promoted hetero Diels-Alder reaction between a cyclic imine dienophile and Danishefsky s diene This was the first example of using an unactivated cyclic imine in this type of cycloaddition. Commonly used Lewis acid catalysts (e.g., SnCb, TiCU, etc.) produced only low yields of the desired cycloadduct. However, it was discovered that ytterbium triflate catalyzed the cycloaddition and afforded the product in 84% yield. Later they also found that the cyclization could occur at high pressure and in the absence of the catalyst, although a slightly lower yield (71%) of the product was obtained. 

Furyl derivatives 76, with an allylether or allylamine-type linkage to a methylenecyclopropane framework, readily undergo high pressure-promoted intramolecular cycloaddition" to give spirocyclopropane tricyclic products 77. No cycloaddition reaction occurred at ambient pressure and the products were mostly tar and polymers. Lewis acid catalysis was only marginally successful (Scheme 7.18). At 1.0 GPa and a slightly elevated temperature (60-70 °C) the intramolecular Diels-Alder reaction occurs readily and is exo-diastereo-selective. To quantify the pressure effect on the kinetics the volumes of activation were determined. 

Araki, Y, and Konoike, T, Enantioselective total synthesis of (+)-6- 77i-mevinolin and its analogs. Efficient construction of the hexahydronaphthalene moiety by high pressure-promoted intramolecular Diels-Alder reaction of (7 ,2Z,8 , 10 )-l-[(fert-butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one, 7. Org. Chem., 62, 5299, 1997. 

An additional and exceptionally useful technique for promoting the Diels—Alder reaction of simple a,/3-unsaturated carbonyl compounds with electron-rich or simple olefinic dienophiles employs the use of liquid high pressure techniques [Eqs. (6)-(8)].23 28-30 69>72-73... 

In these cases the size of the activation volumes obviously depends not only on the effective packing probably caused by the restriction of vibrations and rotations in the transition state, but also on the transition-state polarization enhanced by the polar groups leading to a further decrease in volume which is not observed in the less polarized cycloadducts. Blake and Jorgensen [51] have assumed similar effects to explain the acceleration of Diels-Alder reactions in water. Catalytic and solvophobic promotion of high pressure addition reactions will be discussed in Chapter 11. 

Diels-Alder reactions. The cycloaddition of 1,3-cyclohexadiene with electron-deficient dienophiles is promoted by the dihydrate of YbfOTf), under high pressure. Radical cyclization. The dehydroabietane skeleton is readily formed by an oxidative radical cyclization reaction to which a catalytic amount of YbfOTf) dihydrate is also added. 

Hetero Diels-Alder reactions. The Eu(fod)3 complex is a Lewis acid catalyst that. frequently used to promote the condensation of conjugated carbonyl compounds and enol. -.hers. High pressure further favors the reaction. Exclusive endo-selectivity in the reactions olving f )-l-benzenesulfonyl-3-alken-2-ones has been determined. ... 

Diels-Alder reactions may be accelerated and the selectivities enhanced if the cycloaddition reactions are conducted in water or under high pressure or in the presence of a Lewis acid (see Section 3.1.3). In water at room temperature, cyclopentadi-ene reacts with methyl vinyl ketone 700 times faster than in 2,2,4-trimethylpentane and the endo exo selectivity rises from about 4 1 to more than 20 1. This can be ascribed to hydrophobic effects, which promote aggregation of non-polar species. Diels-Alder reactions in water are normally carried out with (at least partially) water-soluble dienes such as sodium salts of dienoic acids. Thus, a key step in a formal synthesis of vitamin D3 involved the cycloaddition of the sodium salt 46 with methacrolein in water, to give the adducts 47 and 48 in high yield and a ratio of 4.7 1 after 16 h (3.43). In contrast, the corresponding methyl ester of the diene in excess neat methacrolein at 55 °C gave only a 10% yield of a 1 1 mixture of isomers after 63... 

High pressure was used to effect [4+2] cycloaddition of 5-raethoxy-carbonyl-2-pyrone with irida-2(7),5-diene 46 as the key step in a synthesis of ( )-shizuka-acoradienol. In this case, thermal conditions alone were unsuccessful in promoting the cycloaddition, and in fact, upon heating at ambient pressure, the cycloadduct undergoes retro-Diels-Alder reaction to give starting materials. 

A variety of other reaction conditions promote the Diels-Alder reaction/ including high pressure, ultrasound, electron transfer, polar... 

S5mthesis of CD-ring of paclitaxel was accomplished by Schereen [26]. In model studies, 2-methylfuran was used as diene in the high-pressure promoted Diels-Alder reaction with citraconic anhydride 31 (Scheme 12). The reaction... 

Paquette s [27] synthetic studies on sesquiterpenes furanoheliangolides such as zexbrevin possessing in their framework a 6,9-epoxycyclodeca[b]furan involve as the key synthetic steps high-pressure-promoted Diels-Alder reaction of 4-methyl-2-[(phenylmethoxy)methyl] furan 58 with 1-cyanovinyl acetate (Scheme 14). To suppress side reactions, hydroquinone was added. Near-quantitative formation of single diastereomeric adduct 59 was achieved at 12 kbar. Its conversion to tricyclic core 61 of furanoheliangolides was achieved after elaboration of the 7-oxabicyclo[2.2.1] heptene moiety and final [3,3] sigmatropic rearrangement of 60. 

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