Norbornene, cycloaddition with

In spite of the known tendency of norbornene and related systems to undergo rearrangements of the Wagner-Meerwein type during eleetro-philic addition, no such rearrangement was observed when norbornene underwent cycloaddition with the acridizinium or the. A/ -methylenium benzamide cation. As Schmidt correctly pointed out, this lack of rearrangement is an argument for a concerted reaction. Alternatively, if the cycloaddition is nonsynchronous, the time interval between step 1 and step 2 must be very short. 

One of the first examples of ruthenium-catalyzed C-C bond formation afforded the synthesis of cyclobutenes, from norbornene derivatives with dimethyl acetylenedicarboxylate, and was reported by Mitsudo and coworkers [45, 46] by using various catalysts such as RuH2(CO)[P(p-C6H4F)3]3 or RuH2(PPh3)4. More recently, the complex Cp RuCl(COD) has shown to be an excellent catalyst for the [2+2] cycloaddition of norbornenes with various internal alkynes [45] (Eq. 33) and with a variety of substituted norbornenes and norbornadienes [47]. The ruthenacycle intermediate, formed by oxidative coupling, cannot undergo /1-hydride elimination and leads to cyclobutene via a reductive elimination. 

If the silole bears hydrogen atoms in 2,5-positions (e.g., 48), it can undergo cycloaddition with the very weak dienophile 47 to give 7-sila-norbornadiene 49 or with itself during its formation to give 7-sila-norbornenes such as SO <2002ZNB741>. 

A -l,2,3-Triazolines, e.g. (181a), are usually formed by 1,3-dipolar cycloaddition of azides to alkenes (cf. 63AG604, 742, 63AG(E)565, 633,68AG329,68AG(E)32i). The addition always occurs cis and is usually regiospecific. Norbornene condenses with azides to form only the exo... 

On the other hand, trimethyl 3,4,6-pyridazinetricarboxyiate and tetra-methyl 3,4,5,6-pyridazinetetracarboxylate undergo cycloaddition with norbornene and related compounds to give esters of benzenepolycarbox-ylic acids (85LA853). In a similar manner, xanthenes were obtained from allyloxypyridazines (80CPB198). 

The [2 -I- 2] cycloaddition of an alkene and an alkyne is a valuable route leading to cyclobutene derivatives. The ruthenium(0)-catalyzed [2 -1- 2] cycloaddition of a strained cycloalkene, norbornene 40, vith highly electron-deficient DMAD afforded the cyclobutene 74 (Scheme 4.28) [62]. As expected, the reaction took place at the exo face of 40 via the ruthenacyclopentene intermediate 75, that ivas formed by the oxidative cyclization of DMAD and norbornene. In addition to the parent 40, various norbornene derivatives can also be used as alkene components. When the Ru" precatalyst 17 ivas employed, electronically neutral alkynes participated in the [2 -1- 2] cycloaddition with norbornene and its derivatives [63]. A similar [2 -1- 2] cycloaddi-... 

A similar approach to enantiomericaUy pure norbornene derivatives was developed by Nouguier et al. who employed l,3 2,4-di-0-methylene acetals of pentitols as chiral templates [62]. Hence, the 5-(5-acryloyl-D-arabinatol derivative 82 underwent highly stereoselective Lewis acid catalyzed cycloaddition with cyclopentadiene, giving 83 (Scheme 10.28). The stereochemical outcome of the reaction was explained in terms of the chelate complex 84, in which the chair-like dioxane ring and the acrylic moiety are fixed in two parallel planes, forcing the diene to approach the cisoid acrylate from the ii-face. The synthesis and utihty of various methylene protected glycosides have also been reported by this group [63-66]. 

As shown in Section 2.2.2.3.1., bicyclopropylidene (1) is capable of undergoing [2-1-2] cycloadditions with electron-deficient alkenes such as diethyl fumarate under nickel(O) catalysis. The [3 -I- 2] cyclodimer and a cyclotrimer are obtained only as minor products from this reaction. In contrast, exclusive [3 -I- 2] cycloaddition can be achieved with many other substrates when palladium(O) catalysts are employed. These cycloaddition products are also produced with phosphite-modified nickel(O) catalysts, but both yields and selectivities are markedly lowered. The reactions of 1 with norbornadiene and norbornene serve as examples for the reaction with strained hydrocarbons, providing the cyclodimers 2 and 3 in 61% and 66% yield, respectively. ... 

Efforts have been made to stabilize the 2,3-bismethylene-2,3-dihydrothiophene system by introducing suitable substituents. Thus the compound (297) with phenyl groups at the exocyclic double bonds was generated by base-catalyzed elimination of methanol from (296) <91ACS9I9>. However, (297) also dimerized easily and the only isolable product (30%) was the spiro compound (298) (Scheme 55). This corresponds to the exo-addition of the diene system to the 3-methylene bond of another molecule. The cycloaddition appears to be orbital symmetry controlled. Only one isomer was obtained. Similarly, (297) could be trapped by means of norbornene cycloaddition led to the exo-adduct in 40% yield. 

Direct Wittig reaction of Ph PCHCOn,Me with the four unsubstituted D-aldopentoses followed by acetylation provides convenient preparative access to acyclic seven-carbon trans-2.3-unsaturated sugar derivatives. These products served as dienophiles for a detailed comparative study in Diels—Alder cycloaddition with cyclopentadiene. Related syntheses afforded analogous cis-dienophiles. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo, exo ratios, and diastereofacial selectivities of the adducts were determined by NMR spectroscopy and by chemical transformations, supplemented by selected X-ray crystallographic analyses. Different distributions of isomers were encountered when a Lewis acid was used to catalyze the cycloaddition. The reaction can be controlled to provide preparative access to selected isomers and thus constitutes a versatile method for chirality transfer from the precursor sugar to four new asymmetric centers in a carbocyclic framework. 

Fig. 1 Cycloaddition reactions employed in nucleic acid labeling with reporter groups (green star). A Cu -mediated azide-alkyne cycloaddition (CuAAC) of a terminal alkyne with an azide. B Strain-promoted azide-alkyne cycloaddition (SPAAC) of an azide with a cyclooctyne derivative. C Staudinger ligation of an azide with a phosphine derivative (not a cycloaddition reaction, see below). D Norbornene cycloaddition of a nitrile oxide as 1,3-dipole and a norbornene as dipolarophile. E Inverse electron-demand Diels- Alder cycloaddition reaction between a strained double bond (norbornene) and a tetrazine derivative. F Photo-cUck reaction of a push-pull-substituted diaiyltetrazole with an activated double bond (maleimide)...

Bis(c/j-l, 2-perfluoromethylethylene-l, 2-dithiolato)nickel (138) undergoes a kinetically second-order oxidative cycloaddition with norbornene and norbomadiene via a charge-separated transition state to give (139) this is a full report now amplifying the preliminary report (cf. Vol. 1, p. 155). Conjugated dienes mostly react too rapidly for kinetic study, to give, for... 

Norbornene-2-carboxylic acid (8) was obtained in acceptable ee by the use of a chiral auxiliary. Optically active tetrahydropyrimidones 6 underwent Diels-Alder cycloadditions with cyclopentadiene (5) in water at room temperature. Subsequent removal of the auxiliary was achieved by boiling the carboxamide 7 in water (Scheme 5.2). The cycloaddition conversions were at least 90% and the endo adduct was the prevalent diastereoisomer. Using 70% aqueous ethanol as reaction medium, both the endo/exo ratio and ee were lower than in pure water. Since tetrahydropyrimidones 6 can be prepared in water from L-asparagine and a suitable aldehyde and subsequent acylation with acryloyl chloride, the entire synthesis of 8 was performed in water by one-pot procedure. The yield was fair, but the ee of norbornene carboxylic acid 8 was lower than that obtained by using a step-by-step procedure. This result was probably due to some acryloyl chloride being hydrolyzed to acrylic acid, which then reacted with 5 in a non-stereo-biased manner. 

Making use of norbornenes in place of alkynes, Carell and colleagues explored the modification of DNA with a variety of oximes via the in-situ nitrile oxide-norbornene cycloaddition (Gutsmiedl et al, 2009). In this case, complete conversions were obtained at room temperature in 10-20 min, although a 10-fold excess of nitrile oxide with respect to the norbornene moieties was utilized. 

Asymmetric [2-1-2-1-2] cycloadditions of norbornene derivatives with unsymmetrical diynes 2.186 that have ester functional groups in both acetylenic branches were catalyzed by Rh-DIFLUORPHOS (5,5 -bis(diphenylphosphino)-2,2,2, 2 -tetrafluoro-4,4 -di-l,3-benzodioxole) to produce norbomane 2.187 (Scheme 2.65) [61, 116]. These studies focused mainly on the construction of a... 

Early work established that S4N4 forms di-adducts with alkenes such as norbornene or norbomadiene. Subsequently, structural and spectroscopic studies established that cycloaddition occurs in a 1,3-S,S"-fashion. The regiochemistry of addition can be rationalized in frontier orbital terms the interaction of the alkene HOMO with the low-lying LUMO of S4N4 exerts kinetic control. Consistently, only electron-rich alkenes add to S4N4. 

The mechanism of the cycloaddition of phenyl azide to norbornene has been shown to involve a concerted mechanism with a charge imbalance in the transition state (199). In a similar manner the cycloaddition of phenyl azide to enamines apparently proceeds by a concerted mechanism (194, 194a). This is shown by a rather large negative entropy of activation (—36 entropy units for l-(N-morpholino)cyclopentene in benzene solvent at 25°C), indicative of a highly ordered transition state. Varying solvents from those of small dielectric constants to those of large dielectric constants has... 

Optically active norbornene derivatives [26] have been prepared by cycloaddition of hexachlorocyclopentadiene with /-menthylacrylate and /-menthylallyl-ether (Equation 2.9). Low levels of enantiomeric excess have been obtained in the thermal processes, whereas Lewis acid catalyzed reactions (BF3, BBr3, AICI3, SnCU, DCM, 40-80 °C) gave better results. 

The study of high pressure cycloaddition reactions of tropone (125) with maleic anhydride and norbornene allowed the reaction activation volumes to be measured and showed that they are large, negative and solvent-dependent (Scheme 5.17) [43a]. 

The reactions with quadricyclane, shown in Eq. (31), gave products identical to those formed by the same silene reacting in a [2 + 2] manner with norbornene. Mixtures of exo endo isomers were frequently observed. Again, only silenes of the Auner type have been studied with this reagent,51-53,185,188 so it is not known whether the Wiberg- or Brook-type silenes will undergo this mode of cycloaddition. 

Another unprecedented domino cycloaddition process of a chromium complex, namely a [2+2+l]/[2+l] cycloaddition, was observed by Barluenga and coworkers [316]. These authors treated norbornene 6/4-137 with the Fischer alkynyl Cr car-bene 6/4-138 and obtained, as the main product, not the expected cyclopropane derivative 6/4-139, but compound 6/4-140 (Scheme 6/4.35). 

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