Nucleophilic cycloaddition

Scheme 1.25. Cationic [4+3]-cycloaddition/nucleophilic trapping domino reaction in the synthesis of halocycloheptynes.

Carbonyl or cyano groups, of proven value in Diels-Alder reactions and 1,3-dipolar cycloadditions, are unsuitable for anionic cycloadditions owing to the pronounced nucleophilic and basic character of the anionic reagents. Instead of cycloaddition nucleophilic attack of these groups or deprotonation of the substrates would occur. This means that aromatic residues are indispensible which are practically unremovable after the cycloaddition and, unlike the carbonyl group, hardly unsuitable for subsequent synthetic steps. 

A statement made in an earlier review (5), that the synthetic potential of cycloadditions of diazo compounds with heterocumulenes does not appear to have been extensively probed, is still valid. This may be due in part to the complexity of the reaction. Instead of a concerted [3 + 2] cycloaddition, nucleophilic addition of the diazo compound at the heterocumulene can lead to a diazonium betaine from which several different products can arise with or without conservation of the azo moiety. 

Several reports appear in the more recent literature of syntheses using electrochemical or PIET oxidation of compounds containing >C=N— bonds. These fall into three categories based upon a mechanism or presumed mechanism Cycloadditions, nucleophilic attack on >C=N— + cation radicals and radical annulations. The latter will not be reviewed here179 as none of the annulations appears to involve >C=N— + cation radicals. It should be pointed out that it is by no means certain that the electronic structure of >C=N— + is that of a 7r-cation radical rather than of an iminium cation radical (Figure 5). As will be seen below, reactivity appears sometimes in one guise and sometimes in the other. 

Major types of cyclization reactions used for the synthesis of aromatic heterocycles containing fluoroaUcyl group include (but, not limited to) cycloadditions, nucleophilic, and electrophilic cyclizations. 

There have been numerous and varied methods presented in the literature for the preparation of saturated azaphos-phinanes and diphosphinanes. These avenues include cycloaddition, nucleophilic displacement, amide formation, and Michael addition. Many of these reactions are common across the ring systems but, nevertheless, are discussed individually for ease of reference. 

V. Nair, R.S. Menon, A.T. Biju, K.G. Abhilash, 1,2-Benzoquinones in Diels—Alder reactions, dipolar cycloadditions, nucleophilic additions, multicomponent reactions and more, Chem. Soc. Rev. 41 (2012) 1050—1059. 

In view of the presence of unsaturated -electrons in CNTs, Smalley and coworkers and Holzinger et al. have functionalized the sidewall of SWCNTs directly by fluorination and azide-thermolysis, respectively. Direct addition of functionalities to the CNTs was enabled by nitrene cycloaddition, nucleophilic carbine addition, and radical addition. 

As in the previous volume, this chapter reviews kinetic and mechanistic studies of the stoichiometric reactions of coordinated hydrocarbons with nucleophiles and electrophiles, together with some related processes such as cycloadditions. Nucleophilic addition and substitution, in particular, continue to attract considerable interest, especially with dienyl- and arene-metal substrates. Even here, however, quantitative studies still lag far behind the extensive synthetic literature. However, fundamental reactivity patterns and parameters are beginning to emerge from the mechanistic studies which should assist in the design of rational syntheses. 

C-N bond cleavage, Cycloaddition Nucleophilic ring-opening, Oxidative addition... 

During the past 15 years since Qo became available in macroscopic quantities in 1990 [1], a wide variety of its derivatives have been synthesized as part of the explosive development of the study of its chemistry [2). Various organic reactions have been reported, most of which are cycloadditions, nucleophilic additions, and radical additions. Fullerenes, as represented by Qo, are now commonly accepted to behave as electron-deficient olefins, hence there have been numerous studies on their anions. This has led to a situation where the other equally important species, the fullerene cations, have been left unexplored for nearly a decade in spite of their significance in both fundamental and application studies. Clearly, a systematic study of this class of species is needed. 

The chemistry of ketenes is dominated by their high reactivity most of them are not stable under normal conditions, many exist only as transient Species. Nucleophilic attack at the j -carbon, [2 + 2] cycloadditions, and ketene iasertion iato single bonds are the most important and widely used reactions of such compounds. 

Chemical Properties. The chemistry of ketenes is dominated by the strongly electrophilic j/)-hybridi2ed carbon atom and alow energy lowest unoccupied molecular orbital (LUMO). Therefore, ketenes are especially prone to nucleophilic attack at Cl and to [2 + 2] cycloadditions. Less frequent reactions are the so-called ketene iasertion, a special case of addition to substances with strongly polarized or polarizable single bonds (37), and the addition of electrophiles at C2. For a review of addition reactions of ketenes see Reference 8. 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

Aminomethylindoles are particularly important synthetic intermediates. 3-Dimethyl-aminomethylindole (gramine) (153) and especially its quaternary salts readily undergo displacement reactions with nucleophiles (Scheme 60). Indole-2,3-quinodimethanes, generated from 2-methylgramine as shown in Scheme 61, undergo intermolecular cycloaddition reactions with dienophiles to yield carbazole derivatives (82T2745). 

Nitrile A-oxides, under reaction conditions used for the synthesis of isoxazoles, display four types of reactivity 1,3-cycloaddition 1,3-addition nucleophilic addition and dimerization. The first can give isoxazolines and isoxazoles directly. The second involves the nucleophilic addition of substrates to nitrile A-oxides and can give isoxazolines and isoxazoles indirectly. The third is the nucleophilic addition of undesirable nucleophiles to nitrile A-oxides and can be minimized or even eliminated by the proper selection of substrates and reaction conditions. The fourth is an undesirable side reaction which can often be avoided by generating the nitrile A-oxide in situ and by keeping its concentration low and by using a reactive acceptor (70E1169). 

The chemistry of benzazetidin-2-ones (251) can also be explained in terms of facile ring opening to the iminoketenes (252) which dimerize, rearrange or can be intercepted by nucleophiles or in cycloadditions depending on the conditions. Indeed, this ring opening precludes their isolation in all but exceptional cases (Section 5.09.4.3.5) (76AHC(19)215). 

Extrapolation from the known reactivity of cyclobutadiene would suggest that azetes should be highly reactive towards dimerization and as dienes and dienophiles in cycloaddition reactions and the presence of a polar C=N should impart additional reactivity towards attack by nucleophiles. Isolation of formal dimers of azetes has been claimed as evidence for the intermediacy of such species, but no clear reports of their interception in inter-molecular cycloaddition reactions or by nucleophiles have yet appeared. 

Oxepin, 2-acetoxy-2,3,4,5-tetrahydro-thermal reactions, 7, 559 Oxepin, 3-chloro-synthesis, 3, 725 Oxepin, 2,3-dihydro-cycloaddition reactions, 7, 563 nucleophilic reactions, 7, 562 reduction, 7, 563 Oxepin, 2,5-dihydro-synthesis, 7, 578, 580 Oxepin, 4,5-dihydro-formation, 7, 579 reduction, 7, 563 synthesis, 7, 579 Oxepin, 2,7-dimethyl-NMR, 7, 552... 

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