Heterocyclic synthesis nitrile imine cycloadditions

Over the last 25 years both nitrile ylides and nitrile imines have continued to provide fascinating and synthetically useful chemistry. In both cases, the exploitation of [3 + 2]-cycloaddition chemistry with an increasing range of dipolarophiles has continued as a key route to five-membered heterocycles. The major development of new chemistry, however, has been in the extensive exploration of intramolecular reactions both in cycloaddition chemistry and in the electrocycliza-tion of 1,3-dipoles with extended conjugation. Such chemistry harnesses the unique reactivity of 1,3-dipoles in the synthesis of relatively elaborate structures but does require the design and preparation of quite complex reactants containing both the 1,3-dipole precursor and the dipolarophilic component. However, access to this chemistry is becoming much easier via the application of new synthetic procedures... 

The intermolecular 1,3-dipolar cycloaddition route to bicyclic heterocycles has received considerable attention since 1983. Diazoalkanes, N-oxides, nitrile imines, and nitrile oxides have all been used as the 1,3-dipole component in the synthesis of these heterocycles. 

Dipolar cycloaddition of azomethine imine or nitrile imine-type dipoles with alkenes or alkynes yields nitrogen heterocycles containing two nitrogen atoms in the ring. MeOPEG resin was applied in the solid-phase synthesis of pyrazolines (Scheme 11.13). Resin-bound... 

Reactions offluorinated dipoles. In recent years, much effort has been devoted to the preparation of tnfluoromethyl-substituted 1,3-dipoles with the goal of using them to introduce trifluoromethyl groups into five-membered nng heterocycles Fluorinated diazoalkanes were the first such 1,3-dipoles to be prepared and used in synthesis A number of reports of cycloadditions of mono- and bis(tnfluo-romethyl)diazomethane appeared prior to 1972 [9] Other types of fluonne-substi-tuted 1,3-dipoles were virtually unknown until only recently However, largely because of the efforts of Tanaka s group, a broad knowledge of the chemistry of tnfluoromethyl-substituted nitrile oxides, nitnle imines, nitnle ylides, and nitrones has been accumulated recently... 

The synthesis of nitrogen containing heterocyclic systems by photocylo-addition processes is virtually limited to examples involving [ 2 + 2] cycloaddition of imines, nitriles, and azo compounds. Successful additions are few in number and the requirements for success uncertain. The reactions do not proceed with the facility with which carbonyl containing compounds undergo photocycloaddition to alkenes to give oxetans, and various explanations have been advanced to account for this observed lack of reactivity.226... 

Hetero-Diels-Alder reactions performed with trifluoromethyl-substituted heterodienes or with trifluoromethyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imines, nitriles, and their parent x./J-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and. depending on the partners, with [2+ 2]-cycloaddition reactions. 

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