Cycloadditions with ethene

Photocycloadditions of naphthalene derivatives to alkcnes have been recently reviewed.60 Examples of such reactions are the photocycloaddition of naphthalene to 2,3-dihy-drofuran,61 of 4-methoxy-l-naphthonitrile to acrylonitrile62 and of 2-trimethylsiloxynaph-thalene to methyl acrylate.63 2-Naphthols undergo cycloaddition with ethene in the presence of aluminum trihalides only.64 Other bicyclic aromatic compounds, e.g. A-acylindoles65-67 and /V-methylphenanthrene-9,10-dicarboximide,68 have also been studied in detail. Irradiation of 5/f-dibenzo[u,i7]cyclohepten-5-one (21) and dimethyl 2-methylfumarate (22) in dioxane gives the cyclobutane adduct 23 in 73% yield.69... 

Several 1-substituted 2(177)-pyrazinones (85) undergo [4 -I- 2] cycloaddition with ethene in toluene at 110°C to form bicyclic intermediates (86), the formation of which is more easy when the substituent X is a chloro, cyano, or thiocyanate group (Scheme 21). The adducts having an alkyl or aryl group as the substituent X are sensitive to moist air. Hydrolysis of the iminochloride... 

Diels-Alder reactions with nitroethene offer a method to carry out the equivalent of cycloaddition with ethene, such as in a synthesis of frondosin B, below. Draw the stmcture of the Diels-Alder adduct 1. 

The organotitanium compounds produced by desulfurization of the diphenyl thioacetals of aldehydes 28 with the titanocene(II) species Cp2Ti[P(OEt)3]2 29 react with carbon—carbon double bonds to form the olefin metathesis-type products. Thioacetals 28 may be transformed into terminal olefins by desulfurization with 29 under an ethene atmosphere (Scheme 14.15) [27]. This reaction is believed to proceed through a titanacyclobutane intermediate, formed by cycloaddition of the titanocene-alkylidene with ethene. 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

As can be seen in the intramolecular cycloaddition (Section 8.03.5.1), the intermolecular Diels-Alder reactions between functionalized 2(l/f)-pyrazinones 83 and dimethyl acetylenedicarboxylate (DMAD) forming bicyclo adducts 84 has been shown to be significantly rate enhanced and increased in yields by using controlled microwave irradiation compared to the conventional thermal protocols (Scheme 21) <2002JOC7904>. The microwave-assisted Diels-Alder reactions of substituted 2(l//)-pyrazinones with ethene are significantly more effective utilizing prepressurized (up to 10 bar) reaction vessels <20040BC154>. 

Photochemical cycloaddition of ethene with racemic 4-/er -butyl-2-cyclohexenone yields three racemic diastereomers107. For configurational assignment, see pp 463 and 472. 

Another reactive alkene which undergoes cycloaddition with nonactivated ethenes is hexafluo-ropropene 12.22 Again these cycloadditions give mixtures of stereoisomeric cyclobutanes. It is interesting to note that regiospecificity is observed in these cyclodimerizations with head-to-head dimers being formed exclusively. 

One of the most reactive electrophilic alkenes is l,l-dicyano-2,2-bis(trifluoromethyl)ethene which undergoes cycloadditions with enol ethers, thioenol ethers, ketene acetals and thioacetals even at temperatures as low as — 78 °C. The cyclobutancs are formed as the sole products of the reaction.37-38 The reactions arc regiospecific and highly stereoselective even though evidence for zwitterionic intermediates have been obtained. 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

Cycloaddition with activated alkenes Reaction between 3-substi-tuted imidazole 1-oxides 228 and 2,2-bis(trifluoromethyl)ethene-l,l-di-carbonitrile leads to 2-(l,3-dihydro-2H-imidazol-2-ylidene)malononitriles 304 (2006HCA1304). 

The formation and cleavage of cyclobutane systems have been discussed in Sect. 3.1 and 4.4. The structure of the intermediates is of major interest. The cyclobutane radical cation has been calculated by several groups. Bauld and coworkers [342] modeled the cycloaddition of ethene radical cation to ethene by the MNDO method. At this level of theory an unsymmetrical structure with one long one-electron C—C o-bond is of lowest energy (Scheme 10, type Q. 

We dealt with [4+2]-cycloadditions very briefly in Section 3.3.1. As you saw there, a [4+2]-cycloaddition requires two different substrates one of these is an alkene—or an alkyne—and the other is 1,3-butadiene or a derivative thereof. The reaction product, in this context also called the cycloadduct, is a six-membered ring with one or two double bonds. Some hetero analogs of alkenes, alkynes, and 1,3-butadiene also undergo analogous [4+2]-cycloadditions. In a [2+2]-cycloaddition an alkene or an alkyne reacts with ethene or an ethene derivative to form a four-membered ring. Again, hetero analogs may be substrates in these cycloadditions allenes and some heterocumulenes also are suitable substrates. 

The computed transition state of the [4+2]-cycloaddition between ethene and butadiene is shown in Figure 15.2 (top), along with the computed transition state of the [4+2]-cycloaddi-tion between acetylene and butadiene. It is characteristic of the stereochemistry of these transition states that ethene or acetylene, respectively, approaches the cw-conformer of butadiene from a face (and not in-plane). Figure 15.2 also shows that the respective cycloadducts— cyclohexene or 1,4-cyclohexadiene—initially result in the twist-boat conformation. 

The last factor often is the one that determines the reaction rates of [4+2]-cycloadditions. This factor allows one to understand, for example, why the cycloadditions of ethene or acetylene with butadiene (cf. Figure 15.1) occur only under rather drastic conditions, while the analogous cycloadditions of tetracyanoethene or acetylenedicarboxylic acid esters are relatively rapid. As will be seen, a simple orbital interaction between the reagents at the sites where the new a bonds are formed is responsible for this advantageous reduction of the activation energies of the latter two reactions. 

Why do the Diels-Alder reactions with both normal and inverse electron demand occur under relatively mild conditions And, in contrast, why can [4+2]-cycloadditions between ethene or acetylene, respectively, and butadiene be realized only under extremely harsh conditions (Figure 15.1) Equation 15.2 described the amount of transition state stabilization of [4+2]-cycloadditions as the result of HOMO/LUMO interactions between the 7T-MOs of the diene and the dienophile. Equation 15.3 is derived from Equation 15.2 and presents a simplified estimate of the magnitude of the stabilization. This equation features a sum of two simple terms, and it highlights the essence better than Equation 15.2. 

Do the transition states of the 1,3-dipolar cycloadditions with diazomethane benefit from a stabilizing frontier orbital interaction Yes Computations show that the HOMOdia zomethm/LUMOethene interaction (orbital energy difference, -229 kcal/mol) stabilizes the transition state of the 1,3-dipolar cycloaddition to ethene (Figure 15.37) by about 11 kcal/mol. Moreover, computations also show that the HOMOethene/LUMOdjazomethane interaction (orbital energy difference, -273 kcal/mol ) contributes a further stabilization of 7 kcal/mol. 

Diazomethane is an electron-rich 1,3-dipole, and it therefore engages in Sustmann type I 1,3-dipolar cycloadditions. In other words, diazomethane reacts with acceptor-substituted alkenes or alkynes (e. g., acrylic acid esters and their derivatives) much faster than with ethene or acetylene (Figure 15.36). Diazomethane often reacts with unsymmetrical electron-deficient... 

These thoughts do not only count for the 1-oxa-1,3-butadiene, but also for the dienophile. Thus, in an intermolecular cycloaddition with a benzylidenepyrazo-lone, ethyl vinyl ether reacts about 50 times faster than (Z)-l,2-dimethoxyethe-ne and 1,1-diethoxyethene about 2000 times faster than 1,1,2,2-tetramethoxy-ethene, 3000 times faster than ( )-l,2-diethoxyethene, and 5000 times faster than (Z)-diethoxyethene [119]. 

Ess and Houk applied this model to 1,3-dipolar cycloadditions to ethene and ethyne. B3LYP/6-31G(d) and CBS-QB3 computations were carried out for the reactions of nine 1,3-dipoles shown in Scheme 4.3. The activation energies of these 18 reactions do not correlate with the reaction energies thus, there is no correlation to the effect that the more exothermic is the reaction, the lower will be its activation barrier. Rather, the activation energies correlate extremely well with the distortion energy (r = 0.97). Ess and Houk argue that the TS is achieved when the t-orbitals of the dipole align well with the jc-orbitals of the dipolarophile. This... 

The photochemical cycloaddition of ethene to the bis-butenolides (20) has been examined in an attempt to establish the influence of the ether-protecting groups of the diol system. Generally only two adducts are formed as can be seen from the results shown for the appropriate structures. The most effective ether protecting group is the trimethylsilyl function and here the facial selectivity yields predominantly the anti,anti adduct (21). With the unprotected systems (20, R = H), there is virtually no selectivity and in this case the three adducts (21), (22) and (23) are formed. Irradiation of the butenolides (20a) and (20b) in the absence of ethene leads to intramolecular hydrogen abstraction (a Norrish Type II process) with the formation of the products (24a) and (24b) in 79% and 76%, respectively. 

Heating the diethanolamine or bis(2-chloroethyl)amine hydrochlorides with aniline derivatives gave 1-arylpiperazine derivatives. The 1-substituted piperazines were deuteromethylated. 1,4-Dithiocarbonyl piperazine was obtained from reaction of benzaldehyde with piperazine and sulfur. l,4-Diacetylpiperazine-2,5-dione were reacted with aldehydes to give the monoarylidene products and then 73. 4-Benzylpiperazine-2,5-dione was reacted with bromobenzene to give 74. Diels-Alder cycloaddition of pyrazinone with ethene gave 75 . ... 

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