Intermolecular cationic cycloaddition

Substituted 1,2,3,4-tetrahydroquinolines (e.g., 61) are formed with high regio- and stereoselectivity in high yield by intermolecular [A+2] cycloadditions of cationic 2-aza-butadienes and various dienophiles <95CC2137,96SL34>. 

Although cycloaddition reactions have yet to be observed for alkene radical cations generated by the fragmentation method, there is a very substantial literature covering this aspect of alkene radical cation chemistry when obtained by one-electron oxidation of alkenes [2-16,18-26,28-31]. Rate constants have been measured for cycloadditions of alkene and diene radical cations, generated oxidatively, in both the intra- and intermolecular modes and some examples are given in Table 4 [91,92]. 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

A problem with DFT that is not restricted to intermolecular complexes is what might be called overdelocalization . In part because of problems in correcting for the classical self-interaction energy, many functionals overstabilize systems having more highly delocalized densities over more localized alternatives. Such an imbalance can lead to erroneous predictions of higher symmetry structures being preferred over lower symmetry ones, as has been observed, for instance, for phosphoranyl radical structures (Lim et al. 1996), transition-state structures for cationic [4-1-3] cycloadditions (Cramer and Barrows 1998), and in the comparison of cumulenes to poly-ynes (Woodcock, Schaefer, and Schreiner 2002). It can... 

Aziridines. The synthesis of aziridines has been covered in several major reviews <2003CRV2905, 2004T2701, B-2006MI1 >. The intermolecular cycloaddition of an electron-deficient species such as a nitrene, a nitrenium cation, or a carbene (or their formal equivalents) to the -bond of an alkene, alkyne, imine, or nitrile is a significant approach to aziridines and azirines (Scheme 5). These reactions are often named aziridinations. 

The [4+3] cycloaddition between furan and amino-stabilized allyl cations has not been as actively studied. An intramolecular cycloaddition between a furan and a 2-aminoallyl cation, generated from methyleneaziridine under Lewis acid-promoted conditions, is shown in Equation (50) <2004AGE6517>. An AgBF4-promoted asymmetric intermolecular [4+3] cycloaddition of 2-aminoallyl cations, derived from chiral a-chloroimines, with furan to give cycloadducts of up to 60% ee was also reported <1997TL3353>. 

Since their original discovery [362] pericyclic radical cation reactions have been developed for various synthetic formats. The methodology nowadays is most advanced for intra- [363] and intermolecular Diels-Alder cycloadditions [364], and... 

These reactions can lead to carbon-carbon or carbon-heteroatom bonds, and their course can be intermolecular or intramolecular. Furthermore, cycloadditions can be initiated by anodic generation of the dienophile or by inducing a chain reaction with a radical cation as dienophile. 

A formal total synthesis of racemic spatol was accomplished by M. Harmata et al. using an intermolecular [4+3] cycloaddition of a haiogenated cyclopentenyl cation with cyclopentadiene followed by a quasi-Favorskii rearrangement as the key steps. ... 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

Recently, Lautens, Aspiotis and Colucci extended the [4+3] cycloaddition methodology to include the diastereoselective intermolecular cycloaddition between an oxyallyl cation and a chiral furan [45]. The best results were obtained employing furan 26 bearing a free hydroxyl group in the 2-position, reacting with excess 1,3-dibromopentanone in the presence of diethyl zinc. Under the optimized conditions, up to 80% yield of the crystalline oxabicyclo[3.2.1]octene 27 was obtained with a diastereoselectivity of a 19 1. The other product was the minor diastereomer 28, Eq. 17. 

A related intermolecular [4-1-3] cycloaddition of a furan with 2-aminoallyl cations, generated from methyleneaziridines under Lewis acid conditions, was also developed. A representative example is shown below <04AG(E)6517>. 

The intramolecular mode of 4+3 cycloaddition reactions between allylic cations and dienes has been comprehensively summarized in several reviews. Nevertheless, the intramolecular 4+3 cycloaddition reactions are not as well established as the intermolecular ones. One of the very first examples of this reaction was reported in 1979 by Noyori and co-workers, who had previously studied the intermolecular reaction between polyhalogenated ketones and dienes. For instance, treatment of dibromoketones 27 or 28 with diiron nonacarbonyl in refluxing benzene provided cycloadducts 29 or 30 in 41% and 38% yields, respectively (Scheme 9). Although the stereoselectivities of these reactions were high, the lachrymatory nature of dibromoketones and the difficulty associated with the synthesis of dibromoketones limited the development of this process. Thus, no other examples of the intramolecular 4+3 cycloaddition using Noyori s methodology have been reported. 

Cycloaddition of allyl cations to conjugated dienes provides a route to seven-membered carbocycles. One of several methods can be used to generate the allyl cation, such as from an allyl halide and silver trifluoroacetate, or from an allyl alcohol by way of its trifluoroacetate or sulfonate. Cycloaddition of the allyl cation proceeds best with a cyclic diene, particularly for intermolecular reactions. Thus, cyclohexadiene and methylallyl cation gave the bicyclo[3.2.2]nonadiene 187 (3.125). Many intramolecular examples are known, such as the formation of the... 

Hoffmann also made pioneering contributions to the field of [4+3] cycloadditions. These contributions include the development of processes for both intra- and intermolecular cycloadditions and of a variety of methods for generating allyl cations (Eq. 39). ... 

In a highly polar medium such as 3.0 M lithium perchlorate-ethyl acetate, TMSOTf is an effective reagent for promoting intermolecular or intramolecular all-carbon cationic [5 + 2] cycloaddition reactions (eq 75). 

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