Other Cyclization Reactions

1 Alder-Ene Reactions. An ene-iminium one-pot cyclization proceeds smoothly in a mixture of water-THE (Eq. 12.66). The reactivity of the ene-iminium substrates is highly dependent on the substitution pattern of the ethylenic double bond. This methodology can be used to form homochiral pipecolic acid derivatives. 

3-Dipolar Cycloaddition Reactions. The 1,3-dipolar cyclization of nitrile oxide with dipolarophiles generates structurally important heterocycles. As shown by Lee, the reaction can be carried out in an aqueous-organic biphasic system in which the nitrile oxide substrates can be generated from oximes or hydrazones in situ. The method provides a convenient one-pot procedure for generating a variety of heterocyclic products. 

The kinetics of 1,3-dipolar cycloaddition of phenyl azide to nor-bornene in aqueous solutions was studied (Eq. 12.67). As shown in Table 12.1, when the reaction was performed in organic solvents, the reaction showed very small effects of the solvent, while in highly aqueous media, significant accelerations were observed. 

An intermolecular 1,3-dipolar cycloaddition of diazocarbonyl compounds with alkynes was developed by using an InCls-catalyzed cycloaddition in water. The reaction was found to proceed by a domino 1,3-dipolar cycloaddition-hydrogen (alkyl or aryl) migration (Eq. 12.68). The reaction is applicable to various a-diazocarbonyl compounds and alkynes with a carbonyl group at the neighboring position, and the success of the reaction was rationalized by decreasing the HOMO-LUMO of the reaction. 

The one-pot reaction of ethyl acetoacetate, benzaldehyde and urea under acidic condition, termed the Biginelli reaction, is a useful procedure for the expeditious 

Prajapati et al. reported the reaction between enone oximes and 1,3-dicarbonyl compounds that generated tetra-substituted pyridines in good yields using InCl3 as catalyst without any solvent [216]. The authors proposed that the reaction proceeds via an initial Michael-type addition of the 1,3-dicarbonyl compound to 

Yadav et al. reported a InCl3 catalyzed formation of chiral 2,4-disubstituted tetrahydroquinolines, bicyclic adducts of y-hydroxy-a,P-unsaturated aldehydes and aryl amines [219]. The authors proposed a tandem reaction sequence consisting 

Bose et al. reported that InCl3 catalyzed the von Pechmann condensation of phenols with P-ketoesters to form coumarins, a milder catalyst than those in 

Based on the broad-spectrum of activity of PtCl2 in the cycloisomerization of enynes, Fiirstner et al studied the PtCl2-catalyzed cycloisomerization of biaryls bearing an 0-substituted alkyne [227]. The authors found that PtCl2, although efficacious for the synthesis of phenanthrenes from O-alkynylated biphenyls, was not effective for the synthesis of polycyclic heterocycles from the corresponding 

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As in other cyclization reactions, the parent benzo[/]isoindolinediimine as well as substituted derivatives may be employed. 

Note One or more alkyl groups on quinoxaline may become involved in annulation or other cyclization reactions. 

Asymmetric Diels-Alder and Other Cyclization Reactions... 

ASYMMETRIC DIELS-ALDER AND OTHER CYCLIZATION REACTIONS... 

Sulfur-containing acyclic and cyclic compounds have been prepared from allenyl sulfides in numerous transformations such as substitutions, additions, cydoaddi-tions and other cyclization reactions. Like the other donor-substituted allenes, allenyl sulfides are suitable substrates for regioselective lithiation and substitutions as exemplified in Scheme 8.86 [168, 169,175]. 

Several workers have studied other cyclization reactions involving various leaving groups. Thus, compounds 138 have been shown to cyclize to 1,3-thiazines (139) under acidic or alkaline conditions. The earliest recorded reaction of this type is that of Kahan,273 who in 1897... 

HydroxycarbazoIes react with citral to form either pyrano[3,2-a]carbazoles (132) or pyrano[2,3]carbazoles (133), whilst 1-hydroxycarbazoles produce pyrano[2,3-a]-carbazoles (81SC823, 81H(16)1445). Other cyclization reactions involving substituted pyrroles or indoles and aldehydes or ketones in which the substituent becomes part of the new ring system are discussed under the relevant sections relating to the reactivity of the substituent. 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

Other cyclization reactions also require a metal cation. For example, the preparation of the following cyclic Schiff base was possible only with a metal ion template (Jackets et al., 1972). Formation of the same ring system but with benzyl substituents rather than methyls also required a template ion. In... 

Synthesis by Other Cyclization Reactions. Rearrangement of intermediates generated by photolysis of azides has provided an important route from 1-azidoadamantane to aza-homoadamantanes. Now full details have been given... 

The Diels-Alder is an excellent example of forming rings via reaction of two acyclic precursors. Other cyclization reactions generate rings and will be discussed in this section. 

Many other cyclization reactions with palladium catalysts have been reported [188,224-227]. 

A variety of other cyclization reactions are also observed with many of the carbon cumulenes. Especially, allenes and ketenes undergo many of these reactions and gold catalysis has achieved a new dimension in selectivity. From bis-allenes, complex natural products, such as 18,19 norsteroids, are generated in one step. 

Polymerization of a series of dienes of formula [106] has been studied (/i, 16, 93). The polymers that were obtained consisted of both soluble and cross-linked, insoluble fractions. Quantitative infrared and bromination experiments indicated that the soluble polymers possessed cyclic as well as open-chain structures. The percent of cyclization depended on the size of the incipient cycle and corresponded roughly to what is obtained in other cyclization reactions. The results are summarized in the accompanying table. A similar effect of ring size versus tendency toward cyclopolymerization was observed for monomers of structures [107] (92). 

Highly enantioselective ylide-type covalent catalysis has been achieved with sulfides, phosphines, tertiary amines, selenides, and teUurides, and the reported reaction types include epoxidation, aziridination, cyclopropanation, and other cyclization reactions. So far, the sulfur ylide-mediated reactions are the best... 

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