Alkenes as dienophiles

The domino carbonylation and Diels-Alder reaction proceed only as an intramolecular version. Attempted carbonylation and intermolecular Diels-Alder reaction of conjugated 2-yne-4-enyl carbonates 101 in the presence of various alkenes as dienophiles give entirely different carbocyclization products without undergoing the intermolecular Diels-Alder reaction. The 5-alkylidene-2-cyclopenten-4-onecarboxy-lates 102 were obtained unexpectedly by the incorporation of two molecules of CO in 82% yield from 101 at 50 °C under 1 atm [25], The use of bidentate ligands such as DPPP or DPPE is important. The following mechanism of the carbocyclization of 103 has been proposed. The formation of palladacyclopentene 105 from 104 (oxidative cyclization) is proposed as an intermediate of 108. Then CO insertion to the palladacycle 105 generates acylpalladium 106. Subsequent reductive elimination affords the cyclopentenone 107, which isomerizes to the cyclopentenone 108 as the final product. 

Reactions of 5-membered heterocycles with l,2-bis-(arylsulfonyl)alkenes as dienophiles 910PP571. 

Electron-rich alkenes as dienophiles in the cation radical Diels-Alder reaction... 

Cycloaddition reactions of the chiral exocyclic methylene compounds A and B derived from menthone and of related chiral 1-oxa-l,3-dienes (C) with alkenes as dienophiles, e.g. ketene acetals, proceed smoothly and are highly stereoselective. ... 

Although one trifluoromethyl group activates an alkene as a dienophile, two or more can actually inhibit dienophilic reactivity, as evidenced by the fact that... 

V-Acyliminium ions act as dienophiles in [4 + 2] cycloaddition reactions with conjugated dienes13, while A-acylimimum ions that (can) adopt an x-cis conformation are able to act as heterodienes in an inverse electron demand Diels-Alder process with alkenes or alkynes3 (see Section D. 1.6.1.1.). 

Vinyl sulfones are reactive as dienophiles. The sulfonyl group can be removed reductively with sodium amalgam (see Section 5.6.2). In this two-step reaction sequence, the vinyl sulfone functions as an ethylene equivalent. The sulfonyl group also permits alkylation of the adduct, via the carbanion. This three-step sequence permits the vinyl sulfone to serve as the synthetic equivalent of a terminal alkene.68... 

In 1996, the first successful combination of an enzymatic with a nonenzymatic transformation within a domino process was reported by Waldmann and coworkers [6]. These authors described a reaction in which functionalized bicy-clo[2.2.2]octenediones were produced by a tyrosinase (from Agaricus bisporus) -catalyzed oxidation of para-substituted phenols, followed by a Diels-Alder reaction with an alkene or enol ether as dienophile. Hence, treatment of phenols such as 8-1 and an electron-rich alkene 8-4 in chloroform with tyrosinase in the presence of oxygen led to the bicyclic cycloadducts 8-5 and 8-6 in moderate to good yield (Scheme 8.1). It can be assumed that, in the first step, the phenol 8-1 is hydroxylated by tyrosinase, generating the catechol intermediate 8-2, which is then again oxidized enzy-... 

Hetero Diels-Alder reactions using nitroalkenes followed by 1,3-dipolar cycloadditions provide a useful strategy for the construction of polycyclic heterocycles, which are found in natural products. Denmark has coined the term tandem [4+2]/[3+2] cycloaddition of nitroalkenes for this type of reaction. The tandem [4+2]/[3+2] cycloaddition can be classified into four families as shown in Scheme 8.31, where A and D mean an electron acceptor and electron donor, respectively.149 In general, electron-rich alkenes are favored as dienophiles in [4+2] cycloadditions, whereas electron-deficient alkenes are preferred as dipolarophiles in [3+2] cycloadditions. 

DFT calculations have been used to study the mechanistic pathway of the intramolecular Diels-Alder cycloaddition involved in the biosynthesis of natural products paraherquamide A and VM55599. The cycloaddition involves a dihydropyrolo[l,2- ]pyrazine as the azadiene and a standard alkene as the dienophile (Scheme 1). Analysis of the results reveals that these cycloadditions take place through concerted transition structures associated with [4+2]... 

A number of electrocyclic reactions under PET conditions have been reported. In this way, A-benzyl-2.3-diphcnylaziridinc (40) underwent a 3 + 2-cycloaddition with alkene and alkyne dipolarophiles to afford substituted pyrrole cycloadducts (41) via the radical cation intermediate (42) see Scheme 7.80 Elsewhere, novel arylallenes have been used as dienophiles in a radical cation-catalysed Diels-Alder cycloaddition reaction with 1,2,3,4,5-pentafluromethylcyclopentadiene, which often occurred with peri-, chemo-, facial- and stereo-selectivity.81... 

The uncoordinated portion of the 3-vinylpyrrole complexes described above resembles an electron-rich diene, and undergoes a Diels-Alder reaction under mild conditions with electron-deficient alkenes and al-kynes to give functionalized 5,6,7,7a-tetrahydroindole complexes 122 and 149-164 in moderate to excellent yields (Table 10). In most cases, only one stereoisomer is observed even though up to four new stereocenters are formed. For tetrahydroindole complexes 122 and 150, relative stereochemistry has been assigned and is consistent with cycloaddition occurring through an endo-transition state as well as dienophile attack occurring anti to metal coordination. Furthermore, no isomerization occurs to the 4,5,6,7-tetrahydroindole system, which predominates for uncoordinated tetrahydroindoles.23... 

A cyanosulfine [242] and an oxosulfine [162] were trapped with 2,3-dimethyl-1,3-butadiene (Table 6, entries 2 and 3). Capozzi and his group have extended their phthalimido-sulfenyl chemistry to the synthesis of a-oxosulfines, and have observed a dichotomic behaviour towards cycloaddition. With 1,3-dienes, these sulfines act [243, 244] as dienophiles through their C=S bond (Table 6, entry 4) to afford dihydro-2H-thiapyran S-oxides. With alkenes (Table 7), such as 2,3-dimethyl-2-butene (entry 1) or vinyl-ethers (entry 2), they behave as dienes to give dihydro-1,4-oxathiin S-oxides [243-245]. 

Cycloadditions are called Diels-Alder reactions in honor of Otto Diels and Kurt Alder, the chemists who carried out the first such reaction. The substrate that reacts with the diene in these cycloadditions is called the dienophile. As you saw in Figure 12.1, the simplest Diels-Alder reactions, i.e., the ones between ethene and butadiene and between acetylene and butadiene, respectively, occur only under drastic conditions. Well-designed Diels-Alder reactions, on the other hand, occur much more readily. In the vast majority of those cases acceptor-substituted alkenes serve as dienophiles. In the present section we will be concerned only with such Diels-Alder reactions (see Figures 12.16,12.17, and 12.22 for exceptions). 

Alkynic esters participate as dipolarophiles in 1,3-dipolar cycloadditions and as dienophiles in Diels-Alder additions. They participate in [2+2] cycloadditions with alkenes, and they also undergo facile addition reactions with several nucleophiles to give (5,5)-fused heterocyclic ring systems (76AHC(19)279). 

In addition, also spiro compounds can be synthesized using alkylidene-cyclo-alkenes as a dienophile moiety [56]. Finally, as an immense enlargement of the scope of this protocol, the domino Knoevenagel hetero Diels-Alder reaction can be run as a three component transformation mixing an aldehyde such as 2-99, a... 

Vinyl and ethynyl groups attached to an imidazole ring can be catalytically reduced to the saturated (or less unsaturated) species and cleaved by oxidation. The corresponding 4-carbaldehyde is formed in 71% yield when l-methyl-2,5-diphenyl-4-styrylimidazole is oxidized with osmium tetroxide. However, they may not react like aliphatic alkenes and alkynes not all addition reactions occur normally, Michael additions are known, and the compounds can act as dienophiles in DielsAlder reactions (e.g., Scheme 132). 

Notably, it is not just heteroatom-functionalized alkenes that can behave as dienophiles with metal-bound phospholes. It has been demonstrated that reaction of 2equiv of 3,4-dimethyl-l-phenylphosphole with a cationic platinum(n) complex of an enantiomerically pure cyclometallated A, A -dimethyl-l-(l-naphthyl)ethylamine ligand affords, following decomplexation with cyanide, the novel optically pure diphosphine (-f)-267 quantitatively as an air-sensitive oil (Scheme 93) <2000CC167>. The high-frequency chemical shift of one of the phosphoms centers (5 4.9 and 104.2 ppm (7pp = 43.9 Hz)) is indicative of rwt>-jy -stereochemistry. Similar reactivity has been... 

Alkene- and alkyne-substituted Fischer carbenes participate as dienophiles in Diels-Alder reactions. The conditions are usually mild and the reaction proceeds smoothly at room temperature. Similar isomeric ratio and rate acceleration is observed to that of Lewis acid-promoted Diels-Alder reactions between methyl acrylates and dienes when compared to the uncatalyzed reactions. The reactions are endo-selective. Asymmetric Diels-Alder reactions are... 

Based on the additions described above, alkenyldichloroboranes were used as dienophiles, equivalents of 1-alkenes. The organoboranes were conveniently prepared by monohydroboration of 1-alkynes with dichloroborane, generated in situ19... 

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