Diels-Alder reaction bicyclic products

Another stereochemical feature of the Diels-Alder reaction is that the diene and dienophile partners orient so that the endo product, rather than the alternative exo product, is formed. The words endo and exo are used to indicate relative stereochemistry when referring to bicyclic structures like substituted norbornanes (Section 4.9). A substituent on one bridge is said to be exo if it is anti (trans) to the larger of the other two bridges and is said to be endo if it is syn (cis) to the larger of the other two bridges. 

Due to the two electron-donating groups in the bicyclic product 150 and the unhydrolyzed precursor of 148, they should be quite reactive dienes in Diels-Alder reactions. However, such [4+2] cycloadditions were observed only for the cyclohexane-annelated cyclopentadienes 151b, which equilibrate with the more reactive isomers 154 by 1,5-hydrogen shifts (Scheme 33). The [4+2] cycload-... 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

Intramolecular versions of the Diels-Alder reaction are well known, and this is a powerful method for the synthesis of mono- and polycyclic compounds.There are many examples and variations. One interesting internal Diels-Alder reaction links the diene and dienophile by a C—O—SiR2—or a C—O—SiR2—O—C linkage. Internal cyclization to give a bicyclic product is followed by cleavage of the O-Si unit to give a monocyclic alcohol. 

The Diels-Alder reaction of isopyrazoles 365 with MTAD gives azoalkanes 366. Direct as well as triplet-sensitized (benzophenone) photolysis of these compounds leads to the corresponding housanes (bicyclo[2.1.0]pentanes) 367. Under acidic conditions, the housanes rearrange to the corresponding bicyclic products 368 <1995JOC308,... 

The reactions include an unusual Diels-Alder reaction and a very useful synthetic method, the dechlorination of polychlorinated compounds. At the present time this procedure is the best one available for the removal of chlorine from an organic molecule. The end product, 7,7-dimethoxybicyclo[2.2.1]heptene, is an interesting and useful intermediate in bicyclic chemistry it has a reactive double bond and a protected carbonyl group in the 7-position. 

The use of vinylallenes as the diene component in Diels-Alder reactions is very common, thus resulting in their ubiquitous use in natural product synthesis. A vinylal-lene has even been proposed by Schreiber and Kiessling [10] as a biogenetic intermediate in the synthesis of the skeleton of esperamicin A (32 —> 33). Their synthetic approach to esperamicin A (34) was modeled after this biogenetic proposal in which a Type II intramolecular Diels-Alder cycloaddition was used to gain access to the highly unsaturated bicyclic core of 34 (Scheme 19.8) [10]. 

Both enantiomers of the bicyclic enone 78 and their derivatives have been proved to be useful chiral building blocks for the synthesis of natural products [29], among them y-butyrolactones. 78 is readily available in either enantiomeric form by a Diels-Alder reaction of furan with a-acetoxyacry-lonitrile and subsequent hydrolysis, followed by a resolution of the racemate... 

In this type of hetero-Diels-Alder reaction ethylene-bridged bissulfoximines 55 were also applied as ligands, giving bicyclic products with up to 99% ee [59, 60]. It is noteworthy that these results compared very well with those obtained using the well-established Cu(II)/BOX-based systems, which were investigated by j0r-gensen and afforded cycloaddition products with up to 97% ee [61]. 

At 150 °C, the analogous 2-methylenetricyclo[4.1.0.01,3]heptane (34) equilibrated with 35 and 36 as products of a methylenecyclopropane rearrangement and a subsequent retro-Diels Alder reaction, respectively, until at 180 °C an irreversible rearrangement to bicyclo[4.2.0]octa-l,5-diene and 3,4-dimethylenehexa-l,5-diene (39) via diradical 37 took place.223,224 Increasing pressure favored the formation of the bicyclic system 38 (50% yield at lOOTorr).223... 

Myicene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-methyl-3-pentene-2-one with a catalytic amount of A1C13 gives an intermediate monocyclic ketone, which when cydized with 85% phosphoric acid produces the bicyclic ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

Because the bicyclic product arising from 1,2-cycloaddition contains a cyclohexa-1,3-diene unit, a second molecule of maleic anhydride is incorporated in the isolated product 13.471 as a result of a Diels-Alder reaction with the initial photoproduct. 1,2-Cycloaddition is also the observed mode of reaction with mostalkynes, and this leads by way of ring-opening in the initial adduct to a cyclo-octatetraene (3.481. 

The first product of the reaction of 1,2,4,5-tetrazines (39) with alkenes (142) is the bicyclic compound (143), which has never been isolated since it loses nitrogen immediately by a retro-Diels-Alder reaction to give 4,5-dihydropyridazine (144). These compounds have been isolated in a few cases but usually a product is obtained which is formed from (144) in one of four different ways ... 

Diorganylsilyl ethers of sorbyl alcohol (34) undergo a smooth intramolecular Diels-Alder reaction to give a mixture of bicyclic products 35 and 36 (equation 18)114. The endo/exo selectivity depends upon the steric influence resulting from the substituent on silicon atom. 

Linear tricyclic systems have been obtained from intramolecular photocyclization of l,2-dihydropyridin-2-one to give an olefinic bicyclic product and subsequent Diels-Alder reaction with an acyclic dienophile to give the tricyclic compound. Reactions of this type have been mentioned in Sections 2.04.6.3 and 2.04.7.2. 

Simple diastereoselectivity may also occur in Diels-Alder reactions between electron-poor dienophiles and cyclopentadiene (Figure 15.30). Acrylic acid esters or fraus-crotonic acid esters react with cyclopentadiene in the presence or absence of A1C13 with substantial selectivity to afford the so-called emfo-adducts. When the bicyclic skeleton of the main product is viewed as a roof the prefix endo indicates that the ester group is below this roof, rather than outside (exo). However, methacrylic acid esters add to cyclopentadiene without any exo.endo-selectivity regardless whether the reaction is carried out with or without added A1C13 (Figure 15.30, bottom). 

---