Cydoaddition reactions

A remarkable change in reaction course is notable when changing the metal from aluminum to titanium for cydoaddition reactions using BINOL as the chiral ligand. When the chiral aluminum(III) catalyst is applied the cydoaddition product is the major product, whereas for the chiral titanium(IV) catalyst, the ene product is the major product. The reason for this significant change in reaction course is not fully understood. Maybe the glyoxylate coordinates to the former Le-... 

I 6 Asymmetric Metal-catalyzed 1,3-Dipolar Cydoaddition Reactions... 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

A new type of rigid polymer of 1,1-binaphthols was developed recently [41-43]. The 3,3 -crosslinked polymeric binaphthol ligand 18 in combination with AlMe3 was applied as the catalyst for the 1,3-dipolar cydoaddition (Scheme 6.16) [44]. Very high selectivities were obtained when the aluminum catalyst of 18 (20 mol%) was applied to the 1,3-dipolar cydoaddition reaction between nitrone la and al-kene 8a. The only observable diastereomer resulting from the reactions was exo-9a... 

Absolute configurations of the isoxazolidines obtained in the nitrone cydoaddition reactions described in Schemes 7.21 and 7.22 were determined to be 3S,41 ,5S structure by comparison of the optical rotations as well as retention times in a chiral HPLC analysis with those of the authentic samples. Selection of the si face at C/ position of 3-crotonoyl-2-oxazolidinone in nitrone cydoadditions was the same as that observed in the Diels-Alder reactions of cyclopentadiene with 3-croto-noyl-2-oxazolidinone in the presence of the J ,J -DBF0X/Ph-Ni(C104)2-3H20 complex (Scheme 7.7), and this indicates that the s-cis conformation of the dipolaro-phile has participated in the reaction. 

Nitrones are a rather polarized 1,3-dipoles so that the transition structure of their cydoaddition reactions to alkenes activated by an electron-withdrawing substituent would involve some asynchronous nature with respect to the newly forming bonds, especially so in the Lewis acid-catalyzed reactions. Therefore, the transition structures for the catalyzed nitrone cydoaddition reactions were estimated on the basis of ab-initio calculations using the 3-21G basis set. A model reaction indudes the interaction between CH2=NH(0) and acrolein in the presence or absence of BH3 as an acid catalyst (Scheme 7.30). Both the catalyzed and uncatalyzed reactions have only one transition state in each case, indicating that the reactions are both concerted. However, the synchronous nature between the newly forming 01-C5 and C3-C4 bonds in the transition structure TS-J of the catalyzed reaction is rather different from that in the uncatalyzed reaction TS-K. For example, the bond lengths and bond orders in the uncatalyzed reaction are 1.93 A and 0.37 for the 01-C5 bond and 2.47 A and 0.19 for the C3-C4 bond, while those in... 

Cydoaddition Reactions in Organic Synthesis. Edited by S. Kobayashi and K. A. Jorgensen Copyright 2001 Wiley-VCH Verlag GmbH ISBNs 3-527-30159-3 (Hardcover) 3-527-60025-6 (Electronic)... 

Although beyond the scope of the present discussion, another key realization that has shaped the definition of click chemistry in recent years was that while olefins, through their selective oxidative functionalization, provide convenient access to reactive modules, the assembly of these energetic blocks into the final structures is best achieved through cydoaddition reactions involving carbon-het-eroatom bond formation, such as [l,3]-dipolar cydoadditions and hetero-Diels-Al-der reactions. The copper(i)-catalyzed cydoaddition of azides and terminal alkynes [5] is arguably the most powerful and reliable way to date to stitch a broad variety... 

Zheng, X.X., Luo, S.Z., Zhang, L. and Cheng, J.P. (2009) Magnetic nanoparticle supported ionic liquid catalysts for CO2 cydoaddition reactions. Green Chemistry, 11 (4), 455 158. 

Diels-Alder cycloaddition of 5-bromo-2-pyrone with the electron-rich tert-butyldi-methylsilyl (TBS) enol ether of acetaldehyde, using superheated dichloromethane as solvent, has been investigated by Joullie and coworkers (Scheme 6.90) [188]. While the reaction in a sealed tube at 95 °C required 5 days to reach completion, the anticipated oxabicyclo[2.2.2]octenone core was obtained within 6 h by microwave irradiation at 100 °C. The endo adduct was obtained as the main product. Similar results and selectivities were also obtained with a more elaborate bis-olefin, although the desired product was obtained in diminished yield. Related cydoaddition reactions involving 2-pyrones have been discussed in Section 2.5.3 (see Scheme 2.4) [189]. 

Yu and coworkers have reported a recyclable organotungsten Lewis acid as a catalyst for Diels-Alder cydoaddition reactions performed in water or ionic liquids... 

An alternative strategy for generating 4,5-dihydropyrazoles is to perform 1,3-dipo-lar cydoaddition reactions of nitrile imines and alkenes. Langa and coworkers have... 

In contrast with the results of Langa et al. on the cydoaddition reaction to C70, MW irradiation had no effect on the regioselectivity of the reactions in polar solvents, but a substantial effect was observed both in the nonpolar solvent, xylene and under solvent-free conditions. In polar solvents (pentanol and DMF) the ratio of products 64, 65, and 66 was 95 5 0 under both MW and conventional heating. In xylene and in the absence of solvent the ratio of isomers changed from 32 28 40 (xylene) and 36 27 27 (no solvent) under conventional heating to 100 0 0, i. e. totally regioselec-tive, under MW activation. 

Cycloaddition reactions often require the use of harsh conditions such as high temperatures and long reaction times. These conditions are not compatible with sensitive reagents or products such as natural products. The applicability of Diels-Alder cycloadditions is, moreover, limited by the reversibility of the reaction when a long reaction time is required. The short reaction times associated with microwave activation avoid the decomposition of reagents and products and this prevents polymerization of the diene or dienophile. All these problems have been conveniently solved by the rapid heating induced by microwave irradiation, a situation not accessible in most classical methods. With the aid of microwave irradiation, cydoaddition reactions have been performed with great success [9, 10]. 

Several reactions have been performed by use of this methodology, including [4+2] and [2+2] cydoadditions reaction time was significantly reduced and yields improved. 

Dimethylamino)allene is so reactive that [2 + 2]-cydoaddition reactions with acrylonitrile and methyl acrylate are complete only in 30 min at -20 to 0 °C [24],... 

Cydoaddition reactions of electron-deficient allenes are also known. In the presence of A1C13, ethyl 2,3-butadienoate (32) reacts with alkenes to give cyclobutyl-ideneacetic esters at room temperature [28]. 

An intramolecular [3 + 2]-cydoaddition reaction occurred at either the terminal or internal C=C bond in the following examples [77, 78] ... 

Hetero-Diels-Alder-type cydoaddition reactions of the vinylallenes with aldehydes proceeded in the presence of BF3 OEt2 (l.lequiv.) at 0°C to give the adducts in a moderate endo exo ratio. The cydoaddition took place from the less hindered face of the vinylallene [168]. 

The 1,3-dipolar cydoaddition reactions ([3-1-2]) are often used to synthesize five member aza- or azoxaheterocycles. Depending on the nature of the 1,3-dipoles employed in the transformation, different types of heterocycles such as isoxaza-zoles [270], isoxazolines (Scheme 3.22) [110], hydantoins [271], pyrrolidines [272], indolizines [273] or pyrazoles [274] are obtained. 

In addition to these reactions, less common cydoaddition reaction types like [2-1-2] [275] or [6-1-3] [276] cydoaddition have been employed for the ring formation on solid supports. 

Cydoaddition reactions of allenylidene ligands with alkynes have also been described. Thus, heating a toluene solution of the neutral osmium complex 43 in the presence of dimethylacetylenedicarboxylate leads selectively to the allenyl-vinyli-dene 4S (Scheme 2.18) [31c[. The formal insertion of the alkyne into the Co =Cp... 

The theoretical studies showed that the [2 4-2] cydoaddition reactions with alkenes or alkynes were almost barrierless and very exothermic. The exothermicity for alkynes (—42.8 kcal mol ) was found to be greater than that for alkenes (—21.3 kcal mol ). Scheme 4.21b shows the calculated [2 4- 2] cydoaddition with polar unsaturated molecules, formaldehyde and FICN. The barriers (3.6kcalmol for formaldehyde and 9.0 kcal mol for HCN) are slightly higher than those in the reactions with alkenes and alkynes. The exothermicity is also significant (—26.5 for formaldehyde and —37.4 for HCN). 

Polymerization by Cycloaddition. Bisimides and oligoimides capped with reactive unsaturations such as maleimide, acetylene, and xylylene groups, can be chain-extended by a cydoaddition reaction with proper bisdienes. 

Tellurophene, 2-methylmercapto-conformation, 4, 944 Tellurophene, 2-phenyl-irradiation, 4, 946 mass spectra, 4, 942 photolysis, 4, 42 Tellurophene, tetrachloro-synthesis, 4, 118, 963 Tellurophene, tetradeutero-synthesis, 4, 964 Tellurophene, tetrahydro-conformation, 4, 938, 944 IR spectra, 4, 942 mass spectra, 4, 24, 943 PE spectroscopy, 4, 26 reactions, 4, 88, 958 ring strain, 4, 28 synthesis, 4, 118, 962, 963 Tellurophene, tetraphenyl-cydoaddition reactions, 4, 951... 

Isocyanates are liquids or solids which are highly reactive and undeigo addition reactions across the C=N double bond of the NCO group. Reactions with alcohols, carboxylic acids, and amines have been widely exploited in developing a variety of commercial products. Cydoaddition reactions involving both the C=N and the C=0 double bond of the NCO group have been extensively studied and used for product development (1—9). 

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