Cycloaddition reactions carbon-nitrogen bond formation

Scheme 192. Reaction of Alkenyl Epoxides and Aziridines Producing Heterocycles via Carbon-Heteroatom Bond Formation by (a) Intramolecular Allylation of Oxygen and Nitrogen Nucleophiles and (b) Intermolecular [3 + 2]-Cycloaddition with Heterocumulenes...

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

The 1,3-dipolar cycloaddition of nitrones to alkenes has been shown to be very useful in the field of synthesis of alkaloids. The reaction is normally efficient and the inherent features of carbon-carbon bond formation, oxygen transfer and nitrogen incorporation have been joined by high regioselectivity and even stereoselectivity (79ACR396). The... 

This reaction was intensely investigated by Mloston et al. In a classical, but not general reaction, they observed that heating aromatic or aliphatic thioketones [251, 252], thionoesters [253] and dithioesters [252, 253] with aryl-or benzylazides led to the formation of a carbon-nitrogen double bond. A [3+2] cycloaddition was assumed, with successive elimination of nitrogen and sulfur. 

Formation of aminocyclopropanes in a carbene cycloaddition to a carbon-carbon double bond containing no nitrogen function requires an amino-substituted carbene as counterpart. Such a type of reaction was observed with special nitrile ylides possessing a suitable double bond within the molecule Thus, nitrile ylides (193) generated from the precursors 191 or 192, underwent intramolecular [2-f-l] or [2-I-3]cycloaddition yielding 194 and 195 respectively (Scheme 4). 195 was easily hydrolyzed to aminocyclo-propane (196). The preferential direction of the cycloaddition was influenced by the nature... 

The [3+2] cycloaddition of allylsilanes is applicable to imines and iminium salts [419, 484, 485], Highly substituted pyrrolidines can be synthesized with high diastereo and enantio control by reaction of homochiral crotylsilanes with carbon-nitrogen double bond generated in situ from acetals and methyl carbamate (Scheme 10.174) [419]. The cycloaddition to N-tosylaldimines of aromatic aldehydes proceeds with excellent 2,4-ds selectivity whereas the stereoselectivity with aliphatic aldimines is rather low [484]. With N-tosylaldimines, fhe formation of [2+2] adducts is not observed (vide infra). 

The formation of 111 (Scheme 32) has been rationalized as a [2-1-2] cycloaddition of one of the two carbon-nitrogen double bonds of the dicyclohexylcarbodiimide to the Cp-C. double bond of the allenylidene of 43 to give the intermediate 113, which rapidly evolves into 114, by an Alder-ene reaction, where the C -Cp double bond of 113 acts as an enophile. The presence... 

Tethering the alkene to the carbon atom of the nitrone allows the preparation of cw-l,2-disubstituted cycloalkanes such as 212. Examples in which the alkene is tethered to the nitrogen atom of the nitrone are also common. Thus, addition of formaldehyde to the hydroxylamine 213 promoted formation of the intermediate nitrone and hence the cycloadduct 214 (3.140). " Subsequent transformations led to the alkaloid luciduline. This synthesis illustrates a useful feature of the 1,3-dipolar cycloaddition reaction of nitrones, in that it provides an alternative to the Mannich reaction as a route to (3-amino-ketones, via reductive cleavage of the N-0 bond in the isoxazolidine and oxidation of the 1,3-amino-alcohol product. In another example of such an intramolecular cycloaddition reaction, the bridged bicyclic product 217, used in a synthesis of indolizidine 209B, was formed by addition of an aldehyde to the hydroxylamine 215, followed by heating the intermediate nitrone 216 (3.141).142... 

Utility of Enol and Aryl Triflates. Enol and aryl triflates are extensively used for cross-coupling reactions, the formation of carbon-carbon, carbon-tin, carbon-nitrogen, carbon-sulfur, carbon-phosphorus, and carbon-halogen bonds, and reduction/ deoxygenation. In recent examples, they were used to form enamines or enamides or were eliminated to cyclooctynes for copper-free cycloadditions in biological systems. 

Erba et al. (102) observed a novel formation of pyrrole imines 181 from the 1,3-dipolar cycloaddition of mtinchnones 179 and 5-amino-l-aryl-4,5-dihydro-4-methylene-1,2,3-triazoles 180 (Table 10.4). Treatment with benzaldehyde yielded 3-formylpyrroles (182). The reaction presumably involves loss of carbon dioxide, nitrogen, and morpholine from the initial cycloadduct. Unsymmetrical mtinchnones behave regioselectively and furnish products derived from bonding between C(2) of... 

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