Dienophiles reactions with dienes

Cycloaddition reactions of (E)-l-acetoxybutadiene (18a) and (E)-l-methoxy-butadiene (18b) with the acrylic and crotonic dienophiles 19 were studied under high pressure conditions [9] (Table 5.1). Whereas the reactions of 18a with acrylic dienophiles regioselectively and stereoselectively afforded only ortho-enJo-adducts 20 in fair to good yields, those with crotonic dienophiles did not work. Similar results were obtained in the reactions with diene 18b. The loss of reactivity of the crotonic dienophiles has been ascribed to the combination of steric and electronic effects due to the methyl group at the )S-carbon of the olefinic double bond. 

The fact that these adducts were diastereoisomerically pure (deduced from the reported melting points and NMR spectra) suggests that these reactions took place with a complete control of the diastereoselectivity. Bearing this in mind, in 1989 Waldner [64] synthesized optically pure sulfoxide 55 (by MCPBA oxidation of the corresponding chiral thioether and further separation from the epimeric mixture so obtained) and studied its reactions with dienes and aza-dienes (Scheme 29). A high 7r-facial selectivity (almost complete with cyclopen-tadiene and azadienes) was observed in all cases, the approach of the diene from the dienophilic face supporting the lone pair of electrons at sulfur being favored. In the case of the reaction with cyclopentadiene, the endo-selectivity was complete as well. 

The strong Lewis acids HC(py)3M (NO)2 (M = Mo, W) (see also Section 14.3.1), with Lewis acidities comparable with that of BF3, were shown by Faller et al. to coordinate and activate a,/8-unsaturated carbonyl compounds via formation of an M-O a-bond. These complexes, in nitromethane, catalyze Diels-Alder reactions with dienes (e.g. butadiene). They also readily polymerize butadiene when a less basic dienophile com-... 

A more readily available Fe-complex for asymmetric Diels-Alder reaction is from chiral hydrobenzoin.Dienophiles derived from f7/ ,61 )-l-pivaloyloxyspiro[4.4]nonan-6-ol 5 give chiral adducts on reaction with dienes. A representative of axially chiral dienophiles is 65 which gives Diels-Alder reactions with high endo- and diastereoselectivity. An access to dihydropyranyl ethers by the hetero-Diels-Alder reaction, C2-syiiunetric Cu(II) complexes such as and yttrium tri[(7 )-l,l -binaphth-2,2 -diyl]phosphonate are... 

Danishefsky has exploited his widely utilized silyloxydiene chemistry to complete a formal total synthesis of 90 (Scheme 1.20). By employing the appropriate oxidation levels for both the diene and dienophile, a resorcinyl ester possessing the required differentiation of the phenolic groups was obtained without further oxidative manipulation. To this end, the dianion of propiolic acid was alkylated with l-bromo-7-octene to give acid 98 in 68% yield. Further alkylation with methyl iodide then gave the ester 99. A Diels-Alder reaction with diene 100, a derivative of methyl acetoacetate, and alkyne 99 then furnished an initial phenolic intermediate which was protected as the benzyl ether to afford... 

Pyrone reacts readily as a diene in Diels-Alder additions, but the initial adduct often loses carbon dioxide, generating a second diene that then adds a second mole of the dienophile reaction with maleic anhydride, shown below, is typical - a monoadduct can be isolated, which under more vigorous conditions loses carbon dioxide and undergoes a second addition. When the dienophile is an alkyne, methyl propiolate for example, benzenoid products result from the expulsion of carbon dioxide. Primary adducts, which have not lost carbon dioxide, can be obtained from reactions conducted at lower temperatures under very high pressure or in the presence of lanthanide catalysts. A useful example is the reaction of 2-pyrone and substituted derivatives with alkynyl boronates leading to aryl boronates 2-pyrone itself reacts in 86% yield with trimethylsilylethynyl boronate. ... 

In the catalyzed inverse electron demand Diels-Alder reaction of dienophile 1 with diene 2, a d.r. of 98 2 is observed. The adduct 3 is converted into the key synthon of la,25-dihydroxy-vitamin D382. 

Of the four possible pathways, it has been empirically determined that vinylnitroso compounds bearing (3 substituents participate as 2ir dienophile components in Diels-Alder reactions with dienes [Eq. (37), path b]6 78 whereas vinylnitroso compounds lacking (3 substitutents participate as 47t diene components in their Diels-Alder reactions with dienes [Eq. (37), path a].6-76 The potential that the observed 47t participation of vinylnitroso compounds in Diels-Alder reactions with dienes [Eq. (37), path c] may arise from a sequence initiated by the all-carbon Diels-Alder reaction [Eq. (37), path d] followed by a [3,3]-sigmatropic rearrangement to the observed oxazine product [Eq. (38)]... 

Disubstituted quinolines of type 21 were obtained from acetylenic ketones 2 as a result of a condensation reaction with 2-amino thiophenol 19 followed by sulfur extrusion (entry f). Acetylenic ketones have also been employed as dienophiles in Carbonyl-Alkyne-Exchange (CAE) reactions with dienes 22 (derived from 2,2-dialkyl-2,3-dihydro-4//-pyran-4-ones )(entry g) or 24 (entry h) to yield aromatic compounds 23 and 25 in a highly regioselective way. 

In behavior unlike that known for phosphole oxides, phosphole sulfides also act as dienophiles in reaction with dienes, thereby giving valuable cycloadducts such as (169) and (170) (Scheme 35) <76T2427>. The latter is a member of a rare class of phosphorus heterocycles describable as phosphasteroids. 

Cycloaddition of nitroalkenes Although nitrostyrene reacts as a dienophile in thermal reactions with dienes, it and other nitroalkenes undergo SnCla-catalyzed reactions with dienes to form syn- and an/i-ring-fiised nitronates with some syn preference (equation I). Nitronates are also obtained by SnCU-calalyzed reaction with cycloalkenes (equation II). But in the latter reaction only anti-adducts are formed. Nitroalkenes also undergo SnCU-catalyzed intramolecular [4-l-2]cycloaddition to form syn ring-fused adducts (equation III). 

By analogy with classical systems, the new systems allow the possibility of topochemical reaction (Fig. 5). But their functional groups also permit them to take part in other reactions such as oxidative coupling (chem. or electrochem.) or as dienophiles in addition reactions with dienes, e.g. polyacetylenes and condensed hydrocarbons such as perylene (mono- or disubstituted) ... 

When 2-pyrone acts as a diene in a Diels-Alder a ddition the initial adduct often loses carbon dioxide, generating a second diene which then adds a second mol of the dienophile reaction with maleic anhydride is typical - a monoadduct can... 

The use of 3-(2-pyridylsulfinyl)acrylates as enantiomerically pure dienophiles of enhanced reactivity in Diels-Alder reactions with dienes of low reactivity such as furan suffer from the following disadvantages ... 

Danishefsky also investigated the development of a trans Diels-Alder reaction in seeming violation of the inherent stereoselectivity of the reaction mechanism. The key to this process was the use of 1-nitrocyclohexene (80) as the dienophile. After a standard intermolecular Diels-Alder reaction with diene 79, cis cycloadduct 81 could be transformed preferentially into trans-fused product 82 upon radical denitration and enol ether hydrolysis. ... 

Carreno reported a similar strategy for the production of tram Diels-Alder products. Instead of nitro-substituted dienophiles, he employed quinones substituted with boronic acids. Reaction of boronic acid dienophile 82 with diene 83 yields the expected cycloadduct as an unstable intermediate that is selectively protonated and then loses boron to yield the ultimate trans fused product 84. ... 

Cyclobutenylideneammonium salts, and hence cyclobutenones, are formed by the [2 + 2] addition of ketenimmonium salts to acetylenes. The reaction of dimethylketenimmonium tetrafluoroborate with the acetylenes gives the salts (205) in good yield, but the reaction is not highly regioselective. The salts are, themselves, excellent dienophiles, and may be used directly in reactions with dienes. The salt (206) gives the adducts (207) and (208) with butadiene or cyclopentadiene. Dimethyl-cyclobutenone (209) has also been prepared by the adcfition of dimethylketen to methyl vinyl sulphide, followed by methylation at sulphur and elimination of dimethyl sulphide. The ketone itself is a useful dienophile, but is less reactive than its imminium salt. The cyclobutenone (209) is functionally equivalent to terelactone which is an extremely reluctant dienophile. 

After 72 h at 150 °C, the reaction of methyl 5-nitrothiophene-2-carboxylate (45c) with isoprene afforded pyrrolyl-thiophene 55. This dienophile yielded the pyrrolyl-thiophene 56 when reacted with diene 6, and in the reactions with diene 7 afforded the benzothiophene derivative 57, in both cases with good yield. (Figure 14)... 

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. 

Much of the reactivity of hexafluorobicycIo[2,2,0]hexa-2,5-diene is associated with the strained double bonds. This is further exemplified by its reactions with dienes and 1,3-dipoles. It is a reactive dienophile in the Diels-Alder reaction, giving with buta-1,3-diene and its 2-methyl and 2,3-dimethyl derivatives, mono- and, more slowly, di-adducts of the type (133) and (134),... 

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

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