Addition intermolecular reactions

2 Intermolecular Addition-Indole Cyclization Cascade Reactions 

Radical cascade reactions have received considerable synthetic attention as they represent a notable improvement of synthetic efficiency 01AGE2224 . In this context, complex targets have been constructed using cascade reactions of acyl radicals 90JA4003 99CRV1991 06OL1867 . 

2-Indolylacyl radicals participate in a productive cascade reaction featuring an intermolecular alkene addition-indole cyclization sequence to give the cyclopenta[ ]indole 

Some mechanistic aspects of the above cascade reaction deserve comment. Thus, after the intermolecular addition of the nucleophilic acyl radical to the alkene, the electrophilic radical adduct A, instead of undergoing reduction, reacts intramolecularly at the indole 3-position (formally a 5-endo cyclization) to give a new stabilized captodative radical B, which is oxidized to the fully aromatic system. (For a discussion of this oxidative step, see Section 1.5.) 

In the literature there are few reports of similar cascades ending with the cyclization of an electrophilic radical upon an aromatic system 95TL4307 95CC977 96CPB2020 00TL10181 . In fact, most examples involve cyclization of nucleophilic radicals, which are generated under oxidative conditions by the addition of an electrophilic radical to an alkene 

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Malacria has reported the use of epoxysilanes for intermolecular addition reactions to acrylates, acrylonitrile and vinylsulfones [56]. 

Although it is possible to trap the silanethione 40 by intermolecular addition reactions at —78°C (Scheme 12), the combination of Tbt and Mes groups is not efficient enough to stabilize the silathiocarbonyl unit as stable compounds at ambient temperature. 

Redox and homolytic substitution reactions almost never directly form C—C, C—N and C—O bonds. Such bonds are generated in radical addition reactions (Scheme 14). Intermolecular addition reactions are presented in this chapter. Cyclization reactions have important similarities with, and differences from, bimolecular additions, and they are presented in Chapter 4.2 of this volume. Falling under the umbrella of addition reactions are radical eliminations (the reverse of addition) and radical migrations (which are usually, but not always, comprised of an addition and an elimination). 

The PTOC protocol for the preparation of nitrogen centered radicals is also compatible with a variety of Lewis acids that apparently complex with the aminyl radicals to give reactive, electrophilic species. Lewis acids offer potentially milder reaction conditions than protic acids for sensitive compounds. Efficient intermolecular addition reactions have... 

Intermolecular addition reaction is important. Generally, alkyl radicals derived from O-acyl esters (2) are nucleophilic, so treatment with electron-deficient olefins such as... 

Intermolecular Addition Reactions onto C—C Multiple Bonds... 

According to this equation, the product is indeed produced by an SN reaction because the nucleophile displaces an oxyanion as a leaving group from the attacked C atom. Nonetheless this oxyanion is still a part of the reaction product. In this respect this reaction can also be considered to be an addition reaction. An intermolecular addition reaction is one that involves the combination of two molecules to form one new molecule. An intramolecular addition reaction is one that involves the combination of two moieties within a molecule to form one new molecule. 

Metal complexes of heterocyclic compounds display reactivities changed greatly from those of the uncomplexed parent systems. All of the -electron system(s) of the parent heterocycle can be tied up in the complex formation, or part can be left to take part in alkenic reactions. The system may be greatly stabilized in the complex, so that reactions, on a heteroatom, for example, can be performed which the parent compound itself would not survive. Orbital energy levels may be split and symmetries changed, allowing hitherto forbidden reactions to occur. In short, a multitude of new reaction modes can be made possible by using complexes dimerization of azirines with a palladium catalyst serves as a typical example (Scheme 81). A variety of other insertion reactions, dimerizations, intramolecular cyclizations, and intermolecular addition reactions of azirines are promoted by transition metals. 

The contents of this chapter have been organized into two main sections. Section 2, describes the photosensitized electron transfer reaction where either acceptor or donor molecule is regenerated after the initial PET processes. This includes reaction originating both from radical cations and radical anions. Section 3, deals with the intermolecular addition reaction between donor-acceptor pairs. 

The vast majority of radical cascades initiated by addition of higher main group (VI)-centered radicals to alkynes focus predominantly on S-centered radicals, mainly thiyl radicals, whereas considerably fewer intermolecular addition reactions involving radicals with the unpaired electron located on selenium or even tellurium are known. 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

This section is subdivided into Intermolecular Addition Reactions (Section 4.7.1.2.1.) and Intramolecular Addition Reactions (Section 4.7.1.2.2.). Further categorization does not seem necessary because... 

Oxygen-based nucleophiles 1.03.3.2.2(1) Intermolecular addition reactions... 

Usefiil levels of stereoselectivity were obtained in intermolecular addition reactions of C(3)-sub-stituted allylsilanes to chiral aldehydes. Lewis acids that are citable of chelating to heteroatoms have been used to direct the stereochemical course of allylsilane additions to a-alkoxy and a,p-dialkoxy carbonyl compounds. The allylation of a-benzyloxy iddehyde (94) in the presence of TiG4 and SnOt furnished products with high levels of syn stereoselection (syn-9. In contrast, under nonchelation-controlled reaction conditions (BF3-OEt2) allyltrimethylsilane reacted to form predonunantly the anti-1,2-diol product (anti-95), as shown in Scheme 45. 

Scheme 4.6 Intermolecular addition reaction using the mercuration-demercuration reaction.

Scheme 6.4 Intermolecular addition reactions through iodine atom transfer.

Intramolecular transition metal-catalyzed hydro acylation reactions have opened up a new area of synthesizing cyclic ketones. This reaction can also be extended to intermolecular addition reactions. Miller et al. found the first example of an intermolecular hydroacylation of an aldehyde with an olefin giving ketones, when they were studying the mechanism of the rhodium-catalyzed intramolecular cyclization of 4-pentenal using ethylene-saturated chloroform as the solvent (Eqs.46,50) [112]. 

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