Intra/intermolecular nucleophilic addition

In a recent report, Shi et al. developed a valuable tool for the synthesis of 2,6-trans substituted morpholines by addition of water and alcohol to epoxy alkynes [109]. The procedure involved a domino three-membered ring opening, 6-exo-cycloisomerization, and subsequent intra-or intermolecular nucleophilic addition or a double-bond sequence. 

The product of the palladation reaction exists as an active intermediate and cannot be isolated in general. However, the product of palladation was isolated as a stable compound in the reaction of cyclooctadiene palladium complex with carbanions such as malonate or alcoholate. Further reaction of the complex with base to give bicyclo (6,1,0) nonene and bicyclo (3,3,0) octane systems was reported by Takahashi and Tsuji 108>. The reactions are understood as intra-and intermolecular nucleophilic addition reactions. 

Alcohols are not only source of ketyl radicals generated by hydrogen abstraction from the a-C-H position (Eq. (7), Table 1). Oxidation of alcohols with Pb(OAc)4, PhI(OAc)2, and S2082 with Ag(I) as catalyst produces alkoxy radicals (RO-) which may further undergo /3-scission (Eq. 13), intramolecular hydrogen abstraction, or intra- and intermolecular addition to alkenes, generating a nucleophilic carbon-centered radical useful for heteroaromatic substitution (Scheme 6) [2]. 

Electron-rich arenes are suitable nucleophiles for this reaction as well. Thus, the addition of arenes to imines has been described in both intra- (equation 121) and intermolecular (equation 122) fashion catalyzed by AuCb/AgOTf The yields were increased in the intramolecular version by acylation of the amide intermediate to give acylamides. In... 

If anions R" are oxidized in the presence of olefins, additive dimers 87 and substituted monomers 89 are obtained (Eq. (11), Table 8, and [la]). The products can be rationalized by the following pathway the radical R obtained by a le oxidation from the anion R adds to the alkene to give the primary adduct 88, which dimerizes to give the additive dimer 87 with regiospecific head-to-head connection of the two olefins, or couples with R to give the additive monomer 89. If the substituent Y in the olefin can stabilize a carbenium ion, 88 is oxidized to the cation 90, which reacts intra- or intermolecularly with nucleophiles to give 91 or 92. 

The development of new procedures for the creation of C-C bonds is of major importance in organic synthesis. In this respect, gold catalysis has emerged as a very efficient synthetic tool, allowing the generally easy and efficient formation of such bonds by addition of various carbone nucleophiles onto alkynes, allenes, and alkenes. These transformations, which can be performed in an intra- or intermolecular manner, are extremely varied. It should however be noted that tlie cycloisomerization of ene-ynes, diene-ynes, or ene-allenes remains the most frequently encountered. A very short selection of such transformations is presented in Scheme 16.16 [15g,k, 20]. 

Iridium monohydrides may be prepared by the reaction of suitable iridium precursors with dihydrogcn via heterolytic splitting mediated intra- or intermolecularly by an external base or by oxidative addition of hydrogenated substrates (HX) to a low-valent iridium complex. Nucleophilic attack by hydride anion and / -elimination from coordinated ligand may also result in the formation of Ir-H bonds. 

---