Cycloaddition, High-pressure

Whereas tropones usually act as dienes in cycloaddition reactions (Section 5.4), tricarbonyl (tropone) iron 59 displays a reactivity that is almost identical to that of a normal enone. High pressure cycloadditions of 59 with 1-oxygen substituted dienes 60 gave the desired cycloadducts 61 in good to excellent yields (Equation 5.9). The subsequent decomplexation of the cycloadducts has been accomplished by treatment with CAN [20]. 

The study of high pressure cycloaddition reactions of tropone (125) with maleic anhydride and norbornene allowed the reaction activation volumes to be measured and showed that they are large, negative and solvent-dependent (Scheme 5.17) [43a]. 

Another versatile two-step synthesis of homobarrelenones [45] is based on the high pressure cycloaddition of tropone (125) and its 2-methoxy-, 2-hydroxy- and 2-chloro-derivatives with 2,3-bis(methoxycarbonyl)-7-oxabicyclo[2.2. l]hepta 2,5-diene (133) followed by thermolysis of the cycloadducts at 130 °C with the... 

High pressure cycloaddition of cytraconic anhydride (140) with 2-substituted furans 142 afforded, cxo-diastereoselectively but unregioselectively, bicyclic cycloadducts 143 and 144 that have been used in straightforward routes to CD-ring fragment of paclitaxel [55] (Scheme 5.22). The cycloadducts were then... 

High-pressure cycloaddition reactions of 3-bromo-1,5-azulenequinone and 3-bromo-1,7-azulenequinone with dienophiles [68]... 

Takeshita H., Mori A., Tian G. R. Carbon-Carbon Double Bond Formation by Means of High-Pressure Cycloaddition-Retro-Diels-Alder Reaction Between 2,3-Bis(Methoxycarbonyl)-7-Oxanorbornadiene and Dienes Yuki Gosei Kagaku Kyo-kaishi 1990 48 132-143... 

Diels-Alder reactions have been conducted on solid phase, with either the dieno-phile or the diene linked to the support [156]. The reaction conditions and the regio-and stereoselectivities observed are similar to those in solution [58,157,158]. Illustrative examples of Diels-Alder reactions leading to support-bound cyclohexenes are listed in Table 5.10. Further examples include the cycloaddition of polystyrene-bound 2-sulfonyl-l,3-butadiene and V-phenylmaIcimidc [51], the high-pressure cycloaddition of 1,3-butadienes to resin-bound 1 -nitroacrylates [95], and the intramolecular Diels-Alder reaction of styrenes with acrylates [159]. 

The kinetics of high-pressure cycloaddition reactions of tropone with dienophiles and enophiles have been reviewed.254 The Diels-Alder reaction of 9,10-dimethylanthracene with acrylonitrile has been investigated at high pressure in acetonitrile and in ethereal solutions of lithium perchlorate.255 The combination of high pressure and a solution of lithium perchlorate in diethyl ether is an excellent reaction rate accelerator in 4 + 2-cycloaddition reactions.256... 

J. Jurczak, T. Bauer, and S. Jarosz, Stereospecific synthesis of 5,6-dihydro-2//-pyran system. High-pressure cycloaddition of l,2 3,4-di-0-isopropylidene a-D-galactopyranose-6-ulose to 1-methoxybuta-l,3-diene, Tetrahedron Lett., 25 (1984) 4809—4812. 

Cantharidin (24) [31] represents the simplest known inhibitor of the ser-ine/threonine protein phosphatases 1 and 2A, and can be isolated from dried beetles (Cantharis vesycatoria). The simplest synthesis of 24 from furan and dimethylmaleic anhydride met with failure, even at pressures as high as 6.0 GPa either at rt or at temperatures of up to 350 °C, presumably due to the thermodynamic instability of the adduct at normal pressure, e.g., when pressure is released [32], However, if this reaction could be carried out in the presence of Pd/C and H2,24 might be obtained in one step. Nevertheless, high-pressure cycloaddition turned out to be very useful for the synthesis of cantharidin and its derivatives [31-33]. For instance, ( )-palasonin was synthesized from furan and citraconic anhydride (21) at 0.8 GPa for 138 h, followed by hydrogenation over Pd/C. Neither high temperatures nor... 

The high-pressure cycloaddition of 2-vinylbenzothiophene 848 with 3-nitro-2-cyclohexen-l-one gives adduct 849, which is treated with l,5-diazabicyclo[4.3.0]non-5-ene (DBN) to afford benzothiophene 850. The reaction with indenone affords the thiophene 852 via oxidation of 851 with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) (Scheme 130) <2001T4959>. 

Another application of high-pressure cycloaddition is the one-pot preparation" of 3,4-dihydro-l-(2/7)-anthracenone (18), a useful intermediate in the synthesis of phenacenes. Compound 18 can be obtained by reacting a,a,a, cx -tetrabromo-o-xylene (16) and 2-cyclohexenen-l-one (17) at 0.9 GPa no... 

Dienes 19 and 20 only react with A-phenylmaleimide (21) when the reactions are activated by high pressure cycloadditions with the more reactive dienophile 1 also occur under thermal conditions, but in lower yield. The reactions are totally a ft-(with respect to the unsubstituted benzene ring of the para-cyclophane unit ) enc/o-diastereoselective. DDQ oxidation of cycloadduct 24 led to the aromatized compound 26 while the aromatization of 23 and 25 failed. Interestingly, the cycloaddition between 1 and 19 led to the aromatized compound 22 this clearly indicates that 1,4-benzoquinone also acts as an oxidant. 

High pressure cycloaddition of (f )-menthyl glyoxylate (la) and symmetric 1,3-dienes 2,3-dimethyl-1,3-butadiene (7) and 1.3-cyclohexadiene (10) has been studied1S. Diastereoselectivi-ties higher than those for 1-methoxy-1,3-butadiene (2a) are obtained, but are still below a d.r. of 62.5 37.5. Obviously, the [4 + 2] cycloaddition of glyoxylates requires a very efficient chiral auxiliary (see Section 1.6.1.1.3.2.2.). 

Diels-Alder reactions. 2-Pyrone can undergo thermal Diels-Alder reactions but generally requires such high temperatures (100-200°) that the adducts lose C02. High-pressure cycloadditions have also been effected, but the products are usually unstable. In contrast, this 3-substituted derivative 1 can undergo thermal Diels-Alder reactions with electrophilic dienophiles at 24-90° to give mainly enrfo-adducts that are stable to chromatography. 

The reaction pathway can lead either to the expected Diels-Alder cycloadducts A or the monoadduct B or bisadduct C resulting from a Michael-type addition (Scheme 10.22), In the case of catalysis, with the exception of LPDE and Znl2, the acidic character of Yb(OTf)3 or BiCh diverts the reaction along both pathways or favors the exlusive formation of Michael-type products. Such chemical behavior is not uncommon in catalyzed furan reactions [106]. At variance with this is the uncatalyzed high pressure cycloaddition and the reaction carried out in solvophobic media at atmospheric pressure which are particularly selective and afford the Diels-Alder cycloadduct A in nearly similar yields. Interestingly, the reaction also proceeds chemoselectively in water-like solvents at ambient pressure but not in hydrocarbon solvents and methanol. In water-like solvents the reactivity cannot be ascribed to polarity effects only, since methanol and glycol have similar values. Solvophobic interactions are very probably mostly responsible for the enhanced reactivity. This is supported by the similar values of the endoiexo ratio. 

A new cathodic cyclodimerisation of 4-pyrones yields either (90) or (91) depending on conditions,88 2-Benzopyran-3-one has been isolated at low temperature and intercepted by NPM as the adduct (92) 88 high-pressure cycloaddition reactions of 2H-pyran-3-ones with a variety of dienophiles have been recorded.88 Cycloaddition reactions of furans and isobenzofurans continue to dominate this section. Dienophiles whose reactions with furan have been studied recently include phenylsulphonylpropadiene (giving predominantly the endo-adduct (93) 8b. benzynes (derived from aryloxazoli nesJ.8 and... 

It is noteworthy that the high pressure cycloaddition of 2-pyrone with fullerene CgQ, which yields isolable bicyclic lactone adducts in the absence of Lewis acid, has recently been reported. ... 

High-pressure cycloaddition of 2,3- -isopropylidene-D-glycer-aldehyde (9) and diene (10) gave the unsaturated derivatives (11) as the major products (65%), accompanied by their C-5 epimers (13%), ... 

High-Pressure Cycloaddition Reactions in the Synthesis of Biologically Relevant Heterocycles... 

HIGH-PRESSURE CYCLOADDITION REACTIONS IN THE SYNTHESIS OF BIOLOGICALLY RELEVANT HETEROCYCLES... 

Jurczak has shown that 3,4-dimethoxyfuran 35 is a more active diene tiran furan, and employed in the synthesis of dimethoxycantharidin 41 [24]. Its higher reactivity overcomes the low reactivity of dimethyl maleic anhydride and high pressure cycloaddition with 35 could be achieved under 22kbar at room temperature (Scheme 10). Reactions performed at lower pressures, e.g., lOkbar, neither at room temperature nor at 60°C afforded (even after 16h of pressurization) the cycloadduct. Reaction was stereospecific, since no endo-adduct could be detected. Hydrogenation of the adduct 40 in the presence of 10% Pd/C gave 41. 

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