Imines in 1,3-dipolar cycloadditions

P. Caramella and P. Griinanger, Nitrile Oxides and Imines in 1,3-Dipolar Cycloaddition Chemistry, A. Padwa, ed., Wiley, New York, 1984, pp. 291-393. 

Nitrile ylides and nitrile imines in 1,3-dipolar cycloaddition reactions 02HC(59)473. 

H(65)1889, 2005EJO3553>. Starting dihydro[l,2,4]triazolo[3, 4-4]benzo[l,2,4]triazines 482 readily react with aromatic aldehydes to yield iminium salts 483. These salts treated with a base (e.g., triethylamine) are deprotonated to reactive 1,3-dipolar azomethine imines 484. In contrast to related five-membered heterocycles, these compounds are relatively unstable on storage in the solid form and particularly in solution. Fortunately, this obstacle can be easily circumvented by their in situ preparation and subsequent 1,3-dipolar cycloaddition. These compounds can participate in 1,3-dipolar cycloadditions with both symmetric and nonsymmetric dipolarophiles to give the expected 1,3-cycloadducts in stereoselective manner. Selected examples are given in Scheme 82. 

Grigg and co-workers (383) found that chiral cobalt and manganese complexes are capable of inducing enantioselectivity in 1,3-dipolar cycloadditions of azomethine ylides derived from arylidene imines of glycine (Scheme 12.91). This work was published in 1991 and is the first example of a metal-catalyzed asymmetric 1,3-dipolar cycloaddition. The reaction of the azomethine yhde 284a with methyl acrylate 285 required a stoichiometric amount of cobalt and 2 equiv of the chiral ephedrine ligand. Up to 96% ee was obtained for the 1,3-dipolar cycloaddition product 286a. 

Mesoionic compounds have been known for many years and have been extensively utilized as substrates in 1,3-dipolar cycloadditions.158-160 Of the known mesoionic heterocycles, munchnones and sydnones have generated the most interest in recent years. These heterocyclic dipoles contain a mesoionic aromatic system i.e. 206) which can only be depicted with polar resonance structures.158 Although sydnones were extensively investigated after their initial discoveiy in 1935,160 their 1,3-dipolar character was not recognized until the azomethine imine system was spotted in the middle structure of (206). C-Methyl-N-phenylsydnone (206) combines with ethyl phenylpropiolate to give the tetrasub-... 

Whereas nitrile ylides, nitrile imines and nitrile oxides have all been utilized frequently in 1,3-dipolar cycloaddition reactions to form heterocycles (63AG(E)565), nitrile sulfides were... 

The double bonds of the thiophene skeleton can be exploited as a 2-component in 1,3-dipolar cycloaddition reactions. The first examples of an intramolecular addition of nitrile imines 73 to give products 74 and 75 are shown in Scheme 7 <1998J(P1)4103>. 

Using rw-chloroalkenes (e.g., 42) in 1,3-dipolar cycloaddition reactions, Pearson et al. described the synthesis of several alkaloids [20-22]. The reaction proceeds by an intramolecular cycloaddition of an azide onto an alkene, producing an intermediate triazohne. Fragmentation of the triazoUne and rearrangement to a monocyclic imine occurs, which is internally N-alkylated by the alkyl chloride, resulting in iminium ion 43. Reduction with sodium borohydride leads to the racemic lycorane (44). 

Tennant [204], Smalley et al. [205], and Jones et al. [206]. For example, l,2,3-triazolo[l,5-a]qninazolines 70 were obtained in moderate yields by base-catalyzed cycloaddition/condensation reaction (Scheme 14) [205]. Synthesis of 4(3H)-qninazolinones and -imines via 1,3-dipolar cycloaddition has been reported also [207,208]. Novel formation of quinazoUnes via thermal ring contraction of 3H-1,4-benzodiazepines is found by Sashida et al. [209]. Synthesis of quinazoline alkaloids by cycloadditions is discussed in Sect. 3. 

From the cycloaddition reaction standpoint, the photo-generated reactive species suitable for both 1,3-dipolar cycloaddition reactions and Diels-Alder reactions have been studied in the literature. In this review, we will focus our discussion on four cycloaddition reactions (1) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile imines (2) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile ylides (3) photoinduced hetero Diels-Alder reactions and (4) photoinduced strain promoted azide-alkyne cycloaddition (Scheme 3). It is... 

A number of recent examples have served to expand the scope of chiral Cu(II) catalysts and substrates applicable in 1,3-dipolar cycloadditions of nitrones to electron-deficient alkenes. Saito and coworkers demonstrated Cu(OTf)2/bis(imine) (310) to be an efficient catalyst for highly endo and enantioselective cycloaddition of nitrones (309) with (253) [100]. Interestingly, the substitution of the aromatic imine subunit of the bis(imine) ligands (314a-c) was found to have a dramatic effect on chemical yields and the levels of enantioselectivity observed (Scheme 17.69). 

In contrast to the exo-selectivity of the cycloadditions catalyzed by a,a-bis[3,5-di(trifluoromethyl)phenyl]prolinol (10mol%) and trifluoroacetic acid (TFA, 10mol%) as an organocatalyst, only enrio-cycloadducts were obtained with high enantioselectivities in 1,3-dipolar cycloaddition reactions between N,N -cyc ic azomethine imines and cyclic enones employing the 6 -hydroxy derivative of 9-amino-9-... 

An example of 1,3-dipolar cycloaddition involving a thiazole dioxide derivative was described (99T(55)201). A-Benzoyl-(R)-thiazolidin-4-carboxylic acid 5,5-dioxide 120 was cyclized to the bicylic mesoionic thiazolo-oxazolium 5,5-dioxide with Ac O and reacted with the imine 121 in DMF... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utihzed to obtain highly substituted pyrroHdines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine yhdes 100,... 

Dipolar cycloaddition of azides with olefins provides a convenient access to triazolines, cyclic imines, and aziridines and hence is a valuable technique in heterocyclic synthesis. For instance, tricyclic -lactams 273 - 276 have been synthesized using the intramolecular azide-olefin cycloaddition (lAOC) methodology (Scheme 30) [71]. 

In 2007, a novel C2-symmetric diphenylthiophosphoramide ligand was found to be a fairly efficient chiral ligand for the Cu(I)-promoted 1,3-dipolar cycloaddition of imines and pyrrole-2,5-dione derivatives to give the corresponding adducts in moderate to good enantioselectivities and good yields (Scheme 10.14). ... 

The other reactant in a dipolar cycloaddition, usually an alkene or alkyne, is referred to as the dipolarophile. Other multiply bonded functional groups such as imine, azo, and nitroso can also act as dipolarophiles. The 1,3-dipolar cycloadditions involve four it electrons from the 1,3-dipole and two from the dipolarophile. As in the D-A reaction, the reactants approach one another in parallel planes to permit interaction between the tt and tt orbitals. 

It is well known that azomethine ylides, which are usually formed in situ, are very good substrates for 1,3-dipolar cycloadditions. The group of Novikov and Khlebnikov [328] generated such a 1,3-dipol by reaction of difluorocarbene formed from CBr2F2 (2-626) with the imine 2-627. Cycloaddition of the obtained 2-629 with an ac-... 

Another option is the in situ reaction of the obtained enones in a 1,3-dipolar cycloaddition using nitrones or azomethineylides formed from the corresponding imines with DBU in the reaction mixture [153],... 

Dipolar cycloaddition reaction of suitable dipolarophiles to azomethine imines is a well-known method leading to the pyrazolo[l,2-tf]pyrazole ring system and the methodology was duly reviewed in CHEC-II(1996) <1996CHEC-II(8)747>. During the covered period, some new applications have appeared. 

A second category of silene reactions involves interactions with tt-bonded reagents which may include homonuclear species such as 1,3-dienes, alkynes, alkenes, and azo compounds as well as heteronuclear reagents such as carbonyl compounds, imines, and nitriles. Four modes of reaction have been observed nominal [2 + 2] cycloaddition (thermally forbidden on the basis of orbital symmetry considerations), [2 + 4] cycloadditions accompanied in some cases by the products of apparent ene reactions (both thermally allowed), and some cases of (allowed) 1,3-dipolar cycloadditions. 

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