Reactions 1,3-dipolar cydoaddition

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... 

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 behaviour that is typical of a 1,3-dipolar cydoaddition reaction, OSO4 reacts almost as well with electron-poor as with electron-rich alkenes. OSO4 simply chooses to attack the alkene HOMO... 

The ionic liquid grafted benzaldehydes prepared for the 1,3-dipolar cydoaddition reactions have also been used successfully as substrates for Knoevenagel reactions using microwave irradiation (Scheme 7.16). One equivalent of different malonate derivatives with a variety of electron-withdrawing groups was added to the ionic liquid phase and piperidine was used as catalyst. Reaction times varied from 15-60 min. The product was cleaved from the ionic liquid phase by using the NaOMe... 

The 1,3-dipolar cycloaddition reaction between nitrones and unsaturated systems under the action of microwave irradiation has been shown to be a powerful method for the synthesis of a wide variety of novel five-membered heterocycles. In 2002, several nitrone-mediated 1,3-dipolar cydoaddition reactions were reported by de la Hoz in the original edition of this book [3jj. Most of the examples provided had been described between 1995 and 2001 [9a, 13b, 84, 92]. 

Microwave-induced 1,3-dipolar cydoaddition reactions involving azomethine ylides have been widely reported in the literature. In 2002 many examples were described in a book chapter by de la Hoz [3j], which provides extensive coverage of the subject. The objective of this section is to highlight some of the most recent applications and trends in microwave synthesis, and to discuss the impact of this technology. Highly stereoselective intramolecular cycloadditions of azomethine ylides have been performed under solvent-free microwave conditions. 

As described above, 1,3-dipolar cydoaddition reactions of nitrile oxides have also been used for preparation of fullerene derivatives. Theoretical calculations per-ormed for this type of reaction with SWNTs predict that the 1,3-dipolar cydoaddition reaction of nitrile oxides to the sidewall of the nanotubes is possible but not as... 

In Part A, Chapter 10, the relationship of 1,3-dipolar cydoaddition reactions to the general topic of concerted cydoaddition reactions was discussed briefly. It is useful to discuss this reaction in somewhat more detail at this point, since it constitutes a quite general method for the synthesis of heterocyclic rings. Scheme 6.3 lists some of the groups of molecules that are capable of dipolar cydoaddition. These... 

Scheme 18 Trimethylsilyl-directed 1,3-dipolar cydoaddition reactions in the solid-phase synthesis of 1,2,3-triazoles [57]...

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

Z.N. Tisseh, M. Dabiri, M. Nobahar, H.R. Khavasi, A. Bazgir, Catalyst-free, aqueous and highly diastereoselective synthesis of new 5-substituted IH-tetrazoles via a multi-component domino Knoevenagel condensation/1,3 dipolar cydoaddition reaction. Tetrahedron 68... 

S.M. Rajesh, B.D. Bala, S. Perumal, Multi-component, 1,3-dipolar cydoaddition reactions for the chemo-, regio- and stereoselective synthesis of novel hybrid spiroheterocycles in ionic hquid. Tetrahedron Lett. 53 (2012) 5367-5371. 

In recent years, synthesis of pyrroles has drawn the attention of chemists. Traditional methods used for pyrrole synthesis include the Hantzsch reaction [45] and the Paal-Knorr condensation reaction [46,47], The latter is the most widely used method, which involves the cyclocondensation reaction of 1,4-dicarbonyl compounds with primary amines to produce substituted pyrroles. In addition, there are several methods such as 1,3-dipolar cydoaddition reaction, aza-Wittig reaction, reductive coupling, and titanium-catalyzed hydroamination of diynes. Scheme 1 shows several catalysts used in this type of reaction [44]. 

Further appUcations of this catalyst class as Br0nsted acids were shown by Maruoka and coworkers in various enantioselective reactions, such as addition of aza-enamines and vinylogous aza-enamines to imines (178,179), addition of diazo compounds to in situ generated acyclic azomethine imines (Scheme 10.72) [180], and 1,3-dipolar cydoaddition reactions of cyclic azomethine imines with enol ethers and vinylogous aza-enamines (Scheme 10.73) (181). 

Kano, T., Hashimoto, T, and Maruoka, K. (2006) Enantioselective 1,3-dipolar cydoaddition reaction between diazoacetates and a-substituted acroleins total synthesis of manzaddin A. J. Am. Chem. Soc., 128, 2174-2175. 

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