Diels-Alder reaction trapping

The equilibrium between oxepin and benzene oxide created interest in performing Diels-Alder reactions trapping one or both isomeric structures.1 The reaction of maleic anhydride or maleic imide with oxepin and substituted derivatives gives products 1 derived from the addition of the dienophile to the benzene oxide structure.2-l4-126 14 9 156 158 228 231-259... 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

The Boekelheide reaction has found utility in other synthetic methodology. An approach to 2,3-pyridynes made use of this chemistry in the preparation of the key intermediate 30. Treatment of 28 with acetic anhydride produced the desired pyridone 29. Lithiation was followed by trapping with trimethylsilyl chloride and exposure to triflic anhydride gave the pyridyne precursor 30. Fluoride initiated the cascade of reactions that resulted in the formation of 2,3-pyridyne 31 that could be trapped with appropriate dienes in Diels-Alder reactions. 

Compound 5 can be trapped through a Diels-Alder reaction with maleic anhydride and thus be shown to be an intermediate. Further evidence for a mechanism involving two subsequent allyl conversions has been provided by experiments with " C-labeled substrates. 

Further mechanistic evidence comes from trapping experiments. When bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction (Section 14.5) occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene. Ben-zyne is too reactive to be isolated as a pure compound but, in the presence of water, addition occurs to give the phenol, in the presence of a diene, Diels-Alder cycloaddition takes place. 

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

A carbon-selenium bond can also be formed [106] by Diels-Alder reaction of the transient selenonitroso species 106 generated by phenylsulfinylselenylchlor-ide reacting with amines or trimethylsilylated amines. Selenonitroso compounds 106 were trapped with 2,3-dimethylbutadiene to afford 1,2-selenazine derivatives 107 (Scheme 2.44) in low yield. 1,2- Selenazines are interesting compounds which are quite unstable (2-3 h), except for the one having an... 

Chiral heterocyclic compounds containing vicinal oxygen and nitrogen atoms were achieved by an asymmetric Diels-Alder reaction [111] of chiral acylnitroso dienophiles 111. The latter were prepared in situ from alcohols 110, both antipodes of which are available from camphor, and trapped with dienes (Scheme 2.46). Both the yield (65-94 %i) and diastereoisomeric excess (91-96%) were high. 

Photo-induced Diels Alder reaction occurs either by direct photo activation of a diene or dienophile or by irradiation of a photosensitizer (Rose Bengal, Methylene Blue, hematoporphyrin, tetraphenylporphyrin) that interacts with diene or dienophile. These processes produce an electronically excited reagent (energy transfer) or a radical cation (electron transfer) or a radical (hydrogen abstraction) that is subsequently trapped by the other reagent. 

Acetylchloride is a trapping agent that allows the reaction to go completion, transforming the product into a less oxidizable compound.The results of other reactions between indole (57) and substituted cyclohexa-1,3-dienes show that the photo-induced Diels-Alder reaction is almost completely regioselective. In the absence of 59 the cycloaddition did not occur the presence of [2+2] adducts was never detected. Experimental data support the mechanism illustrated in Scheme 4.14. The intermediate 57a, originated from bond formation between the indole cation radical and 58, undergoes a back-electron transfer to form the adduct 60 trapped by acetyl chloride. 

The nitroso moiety of the N-acylnitroso function is a powerful dienophile and therefore N-acylnitroso compounds are trapped rapidly, especially in an intramolecular reaction, with a diene allowing the Diels Alder reaction to occur also in water, although N-acylnitroso compounds are short-lived in aqueous medium. 

Species such as 5 and 6 are called benzynes (sometimes dehydrobenzenes), or more generally, arynes, and the mechanism is known as the benzyne mechanism. Benzynes are very reactive. Neither benzyne nor any other aryne has yet been isolated under ordinary conditions, but benzyne has been isolated in an argon matrix at 8 where its IR spectrum could be observed. In addition, benzynes can be trapped for example, they undergo the Diels-Alder reaction (see 15-58). It should be noted that the extra pair of electrons does not affect the aromaticity. The... 

SsO may also function as a precursor for S2O units. However, it should be noticed that free S2O has never been detected directly in liquid solutions and that the isolated products most probably arise from a reaction of the S2O precursor with the trapping reagent since the reaction temperature is always 20 °C (e.g., by a transition-metal-induced retro-Diels-Alder reaction) [52, 53]. An exception may be the thermal decomposition of the substituted tetrathiolane-2,3-dioxide shown in Scheme 2 this compound evidently... 

With application of reasonable values for trapping parameters and AS2, it was possible to bracket the enthalpy and entropy of activation for isomerization of cyclobutadiene. Hence, A/Zj was estimated to fall between 1.6 and lOkcal/mol, where the upper limit was consistent with theoretical predictions for square-planar cyclobutadiene. Most surprising, though, was the conclusion that AS for automeriza-tion must lie between -17 and -32cal/(molK), based on the AS values normally observed for Diels-Alder reactions as a model for AS2. ... 

On the other hand, numerous examples are already known in which monomeric metaphosphoric esters are generated by thermolysis reactions. Most worthy of mention in this context is the gas phase pyrolysis of the cyclic phosphonate 150 which leads via a retro-Diels-Alder reaction to butadiene and monomeric methyl metaphosphate (151) 108,109, no). While most of the phosphorus appears as pyrophosphate and trimeric and polymeric metaphosphate, a low percentage (<5%) of products 152 and 153 is also found on condensation of the pyrolyzate in a cold trap containing diethylaniline or N,N,N, N,-tetraethyl-m-phenylene-diamine. The... 

Further confirmation of the two-fold shift, and of the double inversion of the position of the 14C label, is provided by trapping (cf. p. 50) the first dienone intermediate (55a) with maleic anhydride in a Diels-Alder reaction. An exactly analogous rearrangement is found to occur in allyl ethers of aliphatic enols, e.g (58) ... 

Two reactions have come to be extensively used with silenes, arising from the need to trap the short-lived species cleanly and in high yield, as evidence either of their formation or of the extent of their formation. These are the addition of alcohols, usually methanol, across the double bond to yield an alkoxysilane, and the Diels-Alder reaction with a diene, often 2,3-dimethylbutadiene. Each is an example of the two different types of addition to the Si=C double bond. 

Apparently, 3 undergoes [4 + 2] cycloadditions with inverse electron demand more readily than normal Diels-Alder reactions (see Sect. 2.1.1). This is in accord with the high lying HOMO of bicyclopropylidene [12]. Several attempts to trap the monomeric 173, which should be in equilibrium with 174 [42], as a cycloadduct with a second molecule of 3 were unsuccessful even at elevated temperatures in chloroform (70 °C) or toluene-d8 (150°C) [13b]. 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

Novel pyrazine-containing cydoadducts 80a-c were synthesized by Diels-Alder reaction of [60]fullerene with the corresponding 2,3-bis(bromomethyl)pyrazine derivatives 79a-c (Scheme 9.23) [73] the 2,3-pyrazinoquinodimethanes were trapped as the Diels-Alder adducts by reaction with [60]fullerene under reflux in o-dichloroben-zene (ODCB) as solvent with classical heating and under the action of microwave ir-... 

Introduction of trimethylsilyl substituents attached directly to the ot-carbon atom of a-(benzotriazol-l-yl)alkyl thioethers provide new opportunities. Thus, treatment of lithiated monosubstituted a-(benzotriazol-l-yl)alkyl thioethers with chlorotrimethylsilane produces a-(trimethylsilyl)alkyl thioethers 837. In reactions with hexamethyl-disilathiane and cobalt dichloride, thioethers 837 are converted to thioacylsilanes 838 that can be trapped in a Diels-Alder reaction with 2,3-dimethylbutadiene to form 2-alkyl-4,5-dimethyl-2-trimethylsilyl-3,6-dihydro-27/-thiopyrans 839 (Scheme 133) <2000JOC9206>. 

The irradiation of ortho tolyl ketones affords dienols 413) via an analogous intramolecular H-abstraction. The dienols formed usually tautomerize back to starting material, but they can also be trapped by dienophiles in inter-414a) (4.12) and intramolecular414b) (4.13) Diels-Alder reactions. This latter... 

Radialenes 86 were obtained when bis(l-diazo-2-oxoalkyl)silanes 84 were decomposed with copper or palladium catalysts60,61. The assumption, that the heterocyclic [3]cumulene 85 is the immediate precursor of 86, is corroborated by its trapping in a Diels-Alder reaction with furan. 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

If X = AcO, intermediate SENA can be trapped by methyl acrylate in the [3+ 2]-cycloaddition reaction (isoxazolidine (416)). If X=C1, attempts to trap silyl nitronate failed however, nitroethylene was detected in a Diels-Alder reaction. By contrast, SENAs, in which X=OSiMe3 or NHPh, are quite stable. Therefore, the substituents X can be arranged in the following series of increasing elimination rates of SiX Cl > AcO > > PhNH. 

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