Diels-Alder reaction with alkenes

Vinylindote radical-cations, for example that derived from 64, take part in a Diels-Alder reaction with alkenes. Subsequent oxidation of the initial product with loss of two protons and dimethylamine gives the pyrido[l,2a]indoie. Reaction is achieved either by direct electrochemical oxidation or by photochemical electron... 

The Diels-Alder reaction is a well-established synthetic method that allows the creation of two new carbon-carbon bonds and leads to the formation of six-membered rings. Eventually, the photochemical reaction can advantageously compete with the thermal process. For instance, anthracene undergoes thermal and photochemical Diels-Alder reactions with alkenes, but the photoinduced addition of maleic anhydride to the homochiral anthracene, as depicted in Scheme 9.28, is faster than the thermal reaction and occurs with excellent diastereoselectivity (only one diastereoisomer) [42]. 

The photochemical generation of hydroxy-o-quinodimethanes from o-alkylbenz-aldehydes may be followed by a thermal Diels-Alder reaction with alkenes (Scheme 9.33) [54]. This reaction is effective in both intermolecular and intramolecular modes, and has been applied to the synthesis of various natural products [55],... 

Synthesis of 5,6-dihydro-4 H-l,3-oxazines. Acid-catalyzed depolymerization and condensation of the resulting formaldehyde with an amide gives the acyliminium ion, which is capable of undergoing a formal Diels-Alder reaction with alkenes. 

Diels-Alder reactions. Unlike cyclopentadienone, this substance is stable as the monomer, probably because of the bulky substitutents. However, this dienone undergoes Diels-Alder reactions with alkenes, sometimes at room temperature or below. In reactions with 1,3-dienes, it functions as the diene rather than the dienophile, probably because of steric effects. 

Acid-catalyzed condensation of a-phosphonyl dithioate 67 with aromatic bis-morpholino aminal 68 yielded a-phosphonyl a,p-unsaturated dithioate 69 in high yield, which underwent hetero-Diels-Alder reactions with alkenes to give the 3,4-dihydro-2ff-thiopyrans 70 in high yields (Scheme 17) [54]. 

Oxazoles are competent dienes for Diels-Alder reactions with alkenes, alkynes, and singlet oxygen however, the initial cycloadduct is unstable and decomposes to yield different products depending on the nature of the dienophile. 

The chemistry of o-benzoquinones, especially their involvement in cycloadditions, has been the subject of extensive investigations in recent years (Nair and Kumar 1994, 1996a, b). In contrast, their aza analogs, viz., o-quinonediimines, have received only scant attention (Friedrichsen and Bottcher 1981), the available information on their cycloadditions being mainly concerned with their participation in Diels-Alder reactions with alkenes (Friedrichsen and Schmidt 1978). 

Commercial manufacture of this polymer was first announced by CdF Chimie in 1975 following about 10 years of study on the Diels-Alder reactions of alkenes with cyclopentadiene. In 1976 a plant with a capacity of 5000 tonnes per annum was put on stream and product marketed as Norsorex. Manufacturing under licence is now being extended to American Cyanamid whilst CdF Chimie has also signed a marketing agreement with Nippon Zeon. 

The two transition states in Figs 8.5 and 8.6 correspond in principle to a metal-catalyzed carho-Diels-Alder reaction under normal electron-demand reaction conditions and a hetero-Diels-Alder reaction with inverse electron-demand of an en-one with an alkene. The calculations by Houk et al. [6] indicated that with the basis set used there were no significant difference in the reaction course. 

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.). 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

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-... 

Diels-Alder reaction of the 1,3,4-oxadiazole with the pendant olefin and loss of N2, the C2-C3 7t bond participates in a subsequent 1,3-dipolar cycloaddition with the carbonyl ylide to generate complex polycycles such as 45 as single diastereomers with up to six new stereocenters. That the cascade reaction is initiated by a Diels-Alder reaction with the alkene rather than with the indole is supported by the lack of reaction even under forcing conditions with substrate 46, in which a Diels-Alder reaction with the indole C2-C3 n bond would be required [26a]. 

Bistrifluoromethyl-l,3,4-thiadiazole 71 undergoes a Diels-Alder reaction with norbornadiene under high pressure to give the unstable cycloadduct 72 which rapidly loses dinitrogen forming the 1,3-dipolar intermediate 73. The [4+2] cycloaddition of the intermediate 73 with a second alkene affords product 74 in 29% yield (Scheme 5) <1997SL196>. 

Electrochemical oxidation of 2,6-dimethoxy-4-allylphenol in aqueous methanol buffered with sodium hydrogen carbonate gives similar amounts of 2- and 4-methoxy substitution products, fhe 2-methoxylated product readily undergoes a Diels-Alder reaction with itself. The dimer 19, the natural product asatone, is found in some 1 % yield and most of the 2-methoxylated product is lost by addition of the ally alkene bond across the diene system of a second molecule [109]. 

The reactivity of the produced complexes was also examined [30a,b]. Since the benzopyranylidene complex 106 has an electron-deficient diene moiety due to the strong electron-withdrawing nature of W(CO)5 group, 106 is expected to undergo inverse electron-demand Diels-Alder reaction with electron-rich alkenes. In fact, naphthalenes 116 variously substituted at the 1-, 2-, and 3-positions were prepared by the reaction of benzopyranylidene complexes 106 and typical electron-rich alkenes such as vinyl ethers, ketene acetals, and enamines through the Diels-Alder adducts 115, which simultaneously eliminated W(CO)6 and an alcohol or an amine at rt (Scheme 5.35). 

The benzoxazoles 59 and 60 can act as azadienes in Diels-Alder reactions with nucleophilic alkenes such as vinyl ethers <98JCS(P1)3389>. ... 

The related 5-trifluoromethyl-l,3-dioxin-4-ones underwent high pressure Diels-Alder reactions with Danishefsky s diene (Eq. 114), and [2 + 2] photocycloadditions with alkenes [305]. The former reaction failed entirely when attempted in the absence of the fluorine atoms. 

Triazines are reactive electron-deficient dienes in Diels-Alder reactions with inverse electron demand. They react with alkenes, strained double bonds, electron-rich and electron-deficient alkynes and C=N double bonds. In most cases it is found that the dienophile addition occurs across the 3- and 6-positions of the triazine ring, but ynamines can also add across the 2- and 5-positions. The reactions are still under active theoretical and practical investigation. 

In the presence of aluminum chloride, which presumably lowers the energy of the LUMO of the heterodiene by Lewis acid complexation, electron-rich alkenes give dihydropyrans on reaction with acyl cyanides at room temperature (82AG(E)859). Unsaturated esters further extend the range of diene components of value in these Diels-Alder reactions with inverse electron demand (82TL603). 

Review. The varied uses of singlet oxygen in organic syntheses have been reviewed (70 references). The best known are the ene reaction of alkenes, which results in an allylic hydroperoxide, and the Diels-Alder reaction with 1,3-dienes to form 1,4-endoperoxides. 

Diels-Alder reactions with electron-rich alkenes.1 Simple a,(i-unsaturated im-ines (1-aza-1,3-butadienes) do not undergo Diels-Alder reactions with dienophiles. In contrast, the N-phenylsulfonyl imines derived from an aldehyde or ketone undergo Diels-Alder reactions under forcing conditions with electron-rich dienophiles to... 

In contrast to the conventional Diels-Alder reaction with free pyrroles, which requires specialized functionalization on both the pyrrole and dienophile, the [2+3] dipolar cycloadditions described herein allow the use of simple alkenes (i.e., bearing at least one electron-withdrawing group) and pyrroles containing no electron-withdrawing groups. Use of... 

When the diene is acyclic, [4+4] cycloaddition remains the primary reaction pathway even when the result is a highly reactive and unstable trans-alkene product, e.g., 150 and 151 (Sch. 35). With 1,3-butadiene, these intermediates are intercepted by an additional equivalent of the diene, to give the 2 1 adducts 152 and 153. When a diene is used that cannot achieve an s-cis conformation such as 154, Diels-Alder reaction with [4+4] adducts 155 and 156 is impossible and these compounds relieve strain via Cope rearrangement to give cyclobutanes 157 and 158, respectively [98]. An intramolecular version of this reaction has been reported [99]. 

Diels-Alder reactions of the type shown in Table 12.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (fnms-butenedioic acid esters), maleic anhydride, and tetra-cyanoethene—all of which are acceptor-substituted alkenes. Typical dienes are cy-clopentadiene and acyclic 1,3-butadienes with alkyl-, aryl-, alkoxy-, and/or trimethyl-silyloxy substituents—all of which are dienes with a donor substituent. 

If pyrrole would do a similar thermodynamically controlled exo Diels-Alder reaction with a vinyl pyridine, a short route to the interesting analgesic epibatidine could be imagined, with just a simple reduction of the remaining alkene left to do. The reaction looks promising as the pyridine makes the dienophile electron-deficient and pyrrole is an electron-rich diene . 

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