Diels-Alder product

C, b.p. 170 C (decomp.), has a characteristic odour. It is the Diels-Alder product of cyclopentadiene reacting with itself, the exo-form being formed most rapidly but the endo-form is thermodynamically favoured. At temperatures above ISO C a retro-Diels-Alder reaction occurs and cyclopentadiene monomer is regenerated see diene reactions. 

Note that the reaction time in water is considerably shorter than that in organic solvents, despite the fact that the concentration of diene used for the reaction in water was less than one third of that for the reaction in the organic solvents. Contrary to the organic solvents, the reaction mixture in water is heterogeneous. It might well be that the low solubility of the Diels-Alder product (3.10c) in this solution reduces inhibition of the reaction by this compound. Consequently, product inlribition is likely to be more pronounced in the organic media. 

Since the Diels-Alder reaction is so good ifs worth going to some trouble to get back to a recognisable Diels-Alder product Take TM 225 for example. The first D-A disconnection is obvious, but can you find your way back to a second ... 

This looks a Diels-Alder product, but the stereochemistry is wrong. However, the centre next to the C=0 can be epimerised in base so ... 

No doubt we could continue with B by disconnecting the a,p-unsaturated carbonyl groups, but intermediate A should be recognisable as a Diels-Alder product, and this is the shorter route ... 

Benzyne is a reactive dienophile and gives Diels-Alder products when generated m the presence of dienes In these cases it is convenient to form benzyne by dissociation of the Grignard reagent of o bromofluoro benzene... 

Hexafluoro-2-butyne adds to the 14,16-diene-20-one (62) at 120° to form the Diels-Alder product, for which structure (63) is proposed. ... 

In the case of 1,3-diphenylisoindole (29), Diels-Alder addition with maleic anhydride is readily reversible, and the position of equilibrium is found to be markedly dependent on the solvent. In ether, for example, the expected adduet (117) is formed in 72% yield, whereas in aeetonitrile solution the adduet is almost completely dissociated to its components. Similarly, the addition product (118) of maleic anhydride and l,3-diphenyl-2-methjdi.soindole is found to be completely dissociated on warming in methanol. The Diels-Alder products (119 and 120) formed by the addition of dimethyl acetylene-dicarboxylate and benzyne respectively to 1,3-diphcnylisoindole, show no tendency to revert to starting materials. An attempt to extrude carbethoxynitrene by thermal and photochemical methods from (121), prepared from the adduct (120) by treatment with butyl-lithium followed by ethyl chloroform ate, was unsuccessful. 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

Furthermore highly strained compounds such as bicyclo[3.2.1]oct-l-ene 11, containing a double bond to a bridgehead carbon atom, have been prepared however this strained olefin could be identified only as its Diels-Alder product from subsequent reaction with an added diene." ... 

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

CoCl2 6H20 [149] or TMSOTf 20 [150-152] in acetonitrile afford Diels-Alder adducts in yields of up to 85%. The dienals 607 are converted by bis(trimethyl-silyl)thiane 601 or bis(trimethylsilyl)selenide 604 and catalytic amounts of BuLi, via 609, to the intramolecular Diels-Alder products 610 in up to 70% yield [153, 154]. 

In the presence of catalytic amounts of Bp3.0Et2 aromatic aldehydes such as benzaldehyde are converted by bis(trimethylsilyl)selenide 604 into hexamethyldi-siloxane 7 and the corresponding trimers, for example 611 in up to 90% yield. On heating with 1,3-dienes such as 2,3-dimethylbutadiene trimers such as 611 react to give the Diels-Alder product 612 [155] (Scheme 5.49). 

Release and Reactivity of tf-o-QMs Although the r 2-o-QM Os complexes 11 are stable when exposed to air or dissolved in water, the quinone methide moiety can be released upon oxidation (Scheme 3.8).16 For example, reaction of the Os-based o-QM 12 with 1.5 equivalents of CAN (ceric ammonium nitrate) in the presence of an excess of 3,4-dihydropyran led to elimination of free o-QM and its immediate trapping as the Diels-Alder product tetrahydropyranochromene, 14. Notably, in the absence of the oxidizing agent, complex 12 is completely unreactive with both electron-rich (dihydropyran) and electron-deficient (A-methylmaleimide) dienes. 

Scheme 43) [92]. Reaction of dienophiles such as 4-nitrobenzaldehyde with linker 80 at high temperature gave Diels-Alder products. Dihydro-pyrans were released from the support by Bronsted or Lewis acid-nucleo-phile combinations in moderate to good yield with stereoselectivity for the anti isomer. 

The formation of the hetero-Diels-Alder product 3 is remarkable, since the Si=N bond in iminosilanes does not yield analogous adducts. 

Aza-Diels-Alder reaction between the lactim ether 49, as azadiene, and 3-methyleneoxindole, as dienophile, resulted in an isomeric mixture of the aza-Diels-Alder products 55 and 56 (Equation 4) <20030L3205>. 

Compounds 575, obtained by the Stille coupling reaction, react with PTAD to give high yields of the Diels-Alder products 576 obtained with good to excellent asymmetric induction (Equation 81) <1995SL1264>. 

Enantiomerically pure 1-sulfinyl-l,3-butadienes 577 are efficient chiral dienes providing the corresponding Diels-Alder products with high stereoselectivity. However, their use in asymmetric synthesis is limited to highly reactive... 

Complexes 17-19 can be written in one valence structure as a, /3-unsaturated carbonyl compounds in which the carbonyl oxygen atom is coordinated to a BF2(OR) Lewis acid. The C=C double bonds of such organic systems are activated toward certain reactions, like Diels-Alder additions, and complexes 17-19 show similar chemistry. Complexes 17 and 18 undergo Diels-Alder additions with isoprene, 2,3-dimethyl-1,3-butadiene, tram-2-methyl-l,3-pentadiene, and cyclopentadiene to give Diels-Alder products 20-23 as shown in Scheme 1 for complex 17 (32). Compounds 20-23 are prepared in crude product yields of 75-98% and are isolated as analytically pure solids in yields of 16-66%. The X-ray structure of the isoprene product 20 has been determined and the ORTEP diagram (shown in Fig. 3) reveals the regiochemistry of the Diels-Alder addition. The C-14=C-15 double bond distance is 1.327(4) A, and the... 

Diacylmethylene)cyclopropanes (34) generated from the corresponding aminocyclopropanes 33 and acetylchloride (Scheme 6) are highly reactive intermediates and can be trapped by dienes such as 2,3-dimethylbutadiene (35), pentadiene 36 and isoprene (37) yielding the Diels-Alder products 38-40 [14]... 

Other sporadic examples of [2 + 2] cycloadditions of olefins on the exo double bond of structurally more complex MCPs, such as methylenecyclo-propenes, allylidene-, and alkenylidenecyclopropanes, have been reported. Thus, dicyclopropylideneethane (2) reacted with TCNE (131) to give the [2 + 2] adduct 164 as a minor product, together with the prevalent [4 + 2] adduct 163 (Scheme 76) [39], The same reaction in a different solvent had been previously reported to furnish exclusively the Diels-Alder product (see Sect. 2.1.2) [5]. 

The C=N double bond is easily reduced, e.g., by refluxing with tetraline (71TL1621). As expected, the imine double bond is also very reactive toward cycloadditions. /3-Lactam structure 55 is formed by 1,2-cycloaddition of f-butylcyanoketene to 38 (71TL1621). As with azabenzoquinones, the 1,4-addition of 1,3-dienes to 38 provides the Diels-Alder products, e.g., 56 and 57, in good yields (Scheme 15) (70JHC615 75JA1681). 

McClure, C.K., Herzog, K.J., and Bruch, M.D., Structure determination of the Diels-Alder product of a ketovinylphosphonate with E-l-acetoxy-1,3-butadiene, Tetrahedron Lett., 37, 2153, 1996. 

A novel use of Buchwald s titanium-based Alder-ene protocol is the cycloisomerization of dienynes to allenes (Equation (47)). Somewhat surprisingly, the Diels-Alder product was observed in trace amounts only in the cycloisomerization of amine 76. 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

Whereas the normal AA]1 reaction (pathway (ii)) in CH3CN/10% H O would yield labeled Diels-Alder product 60, reaction of 27b under these conditions gave 180 labeled benzyl alcohol 59 and unlabelled 53. Benzyl cation 58 is lost in the... 

Monoiodination of a zirconacyclopentadiene with one equivalent of iodine followed by the addition of one equivalent of CuCl gives the dimer of the cyclobutadiene and the Diels—Alder product in the presence of methyl maleate. This indicates the formation of a l-iodo-l,3-dienyl copper compound and the subsequent elimination of Cul to give a cyclobutadiene equivalent. Direct reductive elimination of zirconacydopentadienes affording cyclobutadienes has not yet been observed. 

Hydrolysis of the Diels-Alder products, particularly those formed from hindered imides, is best effected with lithium hydroxide and excess 30% H202 in aqueous THF at room temperature. 

Apart from cydopentadiene 309a, furan [151, 165, 321-323, 327, 329] and pyrrole derivatives [158, 325] 309b and 309c, respectively, are also often used as dienes. Recently, the synthetic applications of furan Diels-Alder chemistry were reviewed comprehensively [330]. In the case of a,/3-unsaturated hydrazones 312, isomerization and elimination of dimethylamine convert the Diels-Alder products 314, which... 

The Diels-Alder product 324 resulting from the diene 322 and the allenyl sulfone 323 can be used together with potassium tert-butoxidc directly in a Ramberg-Back-lund reaction [333]. In this case, a diene permanently in the cisoid conformation is regenerated to make the polycyclic compounds 326 and 327 available by the same Diels-Alder/Ramberg-Backlund sequence. 

Particularly good yields of the cydoadduct 329 are obtained if R1 = R2 = H is valid for the allenyl ketone 328 [165]. The Diels-Alder products 329 can undergo many chemical transformations, for example to the oximes 330, which yield the modified allenes 331 after a subsequent flash vacuum pyrolysis. The oximes 331 generated by retro-Diels-Alder reaction are not available from ketones 328 and hydroxylamine hydrochloride directly [122] (see also Scheme 7.19). 

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