Alkenes dienophile

In its simplest form the Diels-Alder reaction is a cycloaddition reaction between a conjugated diene and alkene (dienophile). 

Diels-Alder Reaction The reaction of an alkene (dienophile) with a conjugated diene to generate a six-membered ring. 

A synthesis of the antitumor agent elliptidne has utilized the indolyl-substituted oxazole (351) as a key intermediate (77JOC2039). Diels-Alder reaction of (351) with acrylonitrile in acetic acid afforded a pyridinecarbonitrile (352) which was reacted with methyllithium, and the ketimine salt was hydrolyzed and cyclized to ellipticine (353 Scheme 76). Other Diels-Alder reactions of this type, particularly intramolecular cycloadditions of oxazoles with alkenic dienophiles should provide rapid access to a variety of alkaloid systems. 

In Chapter 13 we encountered the Diels-Alder reaction, which involves addition of a reactive alkene (dienophile) to the 1,4 positions of a conjugated diene. Neither benzene nor naphthalene reacts significantly with dienophiles on simple heating, but anthracene does react. Cycloaddition occurs between the 9,10 positions ... 

The c/s-alkene dienophile gives stereospecific addition—in each product the CC Me is cis to the alkyl chain (and therefore trans to the H atom). But we get about a 50 50 mixture of endo and exo products. This does not seem to be because there is anything wrong with the transition state for endo addition, which leads in this case to cis-fused rings. 

The alkene (dienophile) component has two electrons in a Tt-bond thus, the FMO theory identifies both HOMO and LUMO (Fig. 8.16). Likewise, the diene which has four electrons in conjugated TT-system can have its HOMO and LUMO (Fig, 8,16), The most common situation finds electron-withdrawing substituents (X) on the dienophilic double bond and electron-donating substituents (R) on the diene. The bonding interaction in a normal electron demand will therefore have electrons flowing from the HOMO of the diene ( F2) to the LUMO of the dienophile (tt ). Various possible ways for the [4+2]-cycloaddition reaction to occur are shown in Fig. 8.27. 

Another reaction unique to conjugated dienes is the Diels-Alder cycloaddition. Conjugated dienes react with electron-poor alkenes (dienophiles) in a single step through a cyclic transition state to yield a cyclohexene product. The reaction is stereospecific, meaning that only a single product stereoisomer is formed, and can occur only if the diene is able to adopt an s-cis conformation. 

Vinyl sulfone 347 easily forms adducts like 348. The sulfone group can be reductively cleaved to give 349. As an alternative, 348 can be alkylated first then cleaved to give 350. In these cases, 348 plays the role of a synthetic equivalent to ethylene or terminal alkene dienophiles. j The importance of the utilization of 347 stems from the fact that unactivated alkenes are poor dienophiles and their reactions with even the most active dienes, such as cyclopentadiene, require drastic conditions and are generally impractical. 

Electron-deficient azoalkenes, 1,2-diaza-1,3-butadienes, participate as 4ir components in regiospecific LUMOdiene-controlled [4 + 2] cycloaddition reactions with selected dienes or electron-rich and selected simple alkene dienophiles. The reactions studied in detail exhibit no rate dependency on the solvent polarity, proceed predominantly through an endo transition state, and have been suggested to represent concerted [4 + 2] cycloaddition reactions. Table 12 sununarizes representative examples of the inter- and intra-molecular [4 + 2] cycloaddition reactions of 1,2-diaza-1,3-butadienes. 

Oxazoles represent the most widely recognized heteroaromatic azadiene capable of [4 + 2] cycloaddition reactions. The course of the oxazole Diels-Alder reaction and the facility with which it proceeds are dependent upon the dienophile structure (alkene, alkyne), the oxazole and dienophile substitution, and the reaction conditions. Alkene dienophiles provide pyridine products derived from fragmentation of the [4 + 2] cycloadducts which subsequently aromatize through a variety of reaction pathways to provide the substituted pyridines (Scheme 14). In comparison, alkyne dienophiles provide substituted fiirans that arise from the retro Diels-Alder reaction with loss of R CN from the initial [4 + 2] cycloadduct (Scheme 15,206 Representative applications of the [4 + 2] cycloaddition reactions of oxazoles are summarized in Table 14. Selected examples of additional five-membered heteroaromatic azadienes participatiitg in [4 + 2] cycloaddition reactions have been detailed and include the Diels-Alder reactions of thiazoles, - 1,3,4-oxadiazoles, isoxazoles, pyrroles and imidazoles. ... 

Just and his group have pioneered the use of 7-oxabicyclo[2.2.1]hept-2-enes as starting materials in the synthesis of carbohydrates and analogs [396,397,398,399,400], These bicyclic systems have the advantage to undergo highly face selective reactions. They are obtained simply by Diels-Alder addition of furan to alkene dienophiles [401,402,403,404,405,407],... 

The second reaction unique to conjugated dienes is Diels-AIder cyclo-addition. Conjugated dienes react with electron-poor alkenes (dienophiles)... 

The s -cis (or cisoid) conformation of the diene is required, and the reaction is stereospecific (i.e. only syn- addition). Groups that are cis in the (alkene) dienophile will therefore be cis in the product. Conversely, groups that are trans in the dienophile will be trans in the product. 

Oxazole cycloadditions have been reported with alkyne dienophiles (tandem Diels-Alder addition and retro Diels-Alder loss of a nitrile leads on to furans), benzyne (the primary adduct can be isolated), and with typical alkene dienophiles and the adducts can be transformed into pyridines (8.14.1.4). 

In the present review, [4+2] cycloadditions with alkenic dienophiles are classified for convenience into six categories according to the structures of the final products. 

Cycloaddition of thiophene dioxides with alkenic dienophiles often directly leads to the formation of a benzene ring. This can be attained by extrusion of sulfur dioxide from the initial adducts, followed by 1) elimination of a small molecule, 2) an intramolecular hydrogen transfer, and 3) (accidental) oxidative dehydrogenation under applied conditions. 

Thus, pyridines 21 condensed at the c face are obtained when 1,2,4-triazines are reacted with cyclic dienophiles.386,387 405,437 Starting from condensed 1,2,4-triazines and alkene dienophiles, pyridines 22 condensed at the b face are synthesized and pyridines 23 condensed at the b and rfface are isolated when a condensed 1,2,4-triazine is reacted with a cyclic dienophile.403... 

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