Nucleophilic addition intermolecular

Three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin also could lead to polysubstituted indole derivatives in moderate to good yields with CuBr catalyst. The reaction conditions are extremely mild and various polysubstituted indoles were obtained successfully. Initially, a triazole intermediate was formed from alkyne and sulfonyl azide in the presence of CuBr and triethy-lamine. It could convert into reactive ketenimine by the ring-opening rearrangement. Subsequently intramolecular nucleophilic addition, intermolecular Michael addition, and tautomerization could lead to the desired polysubstituted indoles [49] (Scheme 8.20). 

The mechanism for the formation of ( )-169 is explained in terms of an intermolecular nucleophilic dimerization. Nucleophilic addition of C-3 of 19 to the 3 position of the initially generated cation 168 gives an imine-nitrone... 

The proposed reaction mechanism involves intermolecular nucleophilic addition of the amido ligand to the olefin to produce a zwitterionic intermediate, followed by proton transfer to form a new copper amido complex. Reaction with additional amine (presnmably via coordination to Cn) yields the hydroamination prodnct and regenerates the original copper catalyst (Scheme 2.15). In addition to the NHC complexes 94 and 95, copper amido complexes with the chelating diphosphine l,2-bis-(di-tert-bntylphosphino)-ethane also catalyse the reaction [81, 82]. 

Jug and co-workers investigated the mechanism of cycloaddition reactions of indolizines to give substituted cycl[3,2,2]azines <1998JPO201>. Intermediates in this reaction are not isolated, giving evidence for a concerted [8+2] cycloaddition, which was consistent with results of previous theoretical calculations <1984CHEC(4)443>. Calculations were performed for a number of substituted ethenes <1998JPO201>. For methyl acrylate, acrylonitrile, and ethene, the concerted [8+2] mechanism seems favored. However, from both ab initio and semi-empirical calculations of transition states they concluded that reaction with nitroethene proceeded via a two-step intermolecular electrophilic addition/cyclization route, and dimethylaminoethene via an unprecedented two-step nucleophilic addition/cyclization mechanism (Equation 1). 

The vinyl metal intermediate arising from intermolecular nucleophilic addition of an oxygen nucleophile to a metal-alkyne complex has been harnessed for further transformations prior to protonation. An example is the ruthenium-catalyzed benzannulation of 1,5-enedyines that occurs through a tandem sequence involving hydroalk-oxylation, carbometallation, and protonation (Equation (82)).293... 

In this chapter, both intermolecular and intramolecular electrophilic [1] and nucleophilic additions [2, 3] to allenes will be discussed. For electrophilic addition, the regio- and stereoselectivity depend on the steric and electronic effects of the substituents on the allenes and the nature of the electrophiles. However, nucleophilic addition usually occurs at the central carbon atom with very limited exceptions. 

Structure can be described as a four-membered ring (TS in Scheme 8). The inclusion of a second equivalent of CHsMgCl, corresponding to an intermolecular mechanism, decreases the barrier height, and the process can be considered as an assisted intermolecular mechanism the first equivalent forms the chelate structure and the second CHsMgCl carries out the nucleophilic addition to the carbonyl group. The most favorable pathway corresponds to an intermolecular mechanism via an anti attack. Analysis of the results reveals that... 

One of the first examples of addition of a zinc enolate to an alkyne was a report dealing with the zinc or cadmium stearate-catalyzed addition of substituted malonates to acetylene under pressure250. Later, Schultze described the intermolecular nucleophilic addition of the zinc enolate derived from diethyl bromomalonate to phenylacetylene in refluxing xylene leading to the alkylidene malonate 392 (equation 171)251. 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

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. 

Intermolecular anodic cyclizations often involve initial coupling of radical-cations followed by a chemical cyclization reaction. An alternative is cyclization by internal nucleophilic addition of some reactant to an intermediate derived by anodic oxidation. 

Palladium(II) salts, in the form of organic solvent soluble complexes such as PdCl2(RCN)2, Pd(OAc>2 or Li2PdCU, are by far the most extensively utilized transition metal complexes to activate simple (unactivated) alkenes towards nucleophilic attack (Scheme 1). Alkenes rapidly and reversibly complex to pal-ladium(II) species in solution, readily generating alkenepalladium(II) species (1) in situ. Terminal monoalkenes are most strongly complexed, followed by internal cis and trans (respectively) alkenes. Geminally disubstituted, trisubstituted and tetrasubstituted alkenes are only weakly bound, if at all, and intermolecular nucleophilic additions to these alkenes are rare. 

Intermolecular addition of carbon nucleophiles to the ri2-pyrrolium complexes has shown limited success because of the decreased reactivity of the iminium moiety coupled with the acidity (pKa 18-20) of the ammine ligands on the osmium, the latter of which prohibits the use of robust nucleophiles. Addition of cyanide ion to the l-methyl-2//-pyr-rolium complex 32 occurs to give the 2-cyano-substituted 3-pyrroline complex 75 as one diastereomer (Figure 15). In contrast, the 1-methyl-3//-pyrrolium species 28, which possesses an acidic C-3-proton in an anti orientation, results in a significant (-30%) amount of deprotonation in addition to the 2-pyrroline complex 78 under the same reaction conditions. Uncharacteristically, 78 is isolated as a 3 2 ratio of isomers, presumably via epimerization at C-2.17 Other potential nucleophiles such as the conjugate base of malononitrile, potassium acetoacetate, and the silyl ketene acetal 2-methoxy-l-methyl-2-(trimethylsiloxy)-l-propene either do not react or result in deprotonation under ambient conditions. 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Enamine catalysis using proline or related catalysts has now been applied to both intermolecular and intramolecular nucleophilic addition reactions with a variety of electrophiles. In addition to carbonyl compounds (C = O), these include imines (C = N) in Mannich reactions (List 2000 List et al. 2002 Hayashi et al. 2003a Cordova et al. 2002c ... 

The sulfinyl group is a useful temporary chiral auxiliary for the activation of a carbon carbon double bond towards nucleophilic addition as both enantiomers of a,//-unsaturated vinyl sulfoxides are available in enantiomerically pure form91. Both intermolecular and intramolecular conjugate additions of V-nucleophiles have been investigated. 

This photochemical umpolung is useful from the perspective of chemoselectivity in synthetic transformations. In addition, oxetane-containing products, prepared regioselectively, can be valuable synthetic intermediates. Both oxetane and vinyloxetane derivatives react with nucleophiles in intermolecular and intramolecular condensations and with transition metals and carbenoids. A second feature of oxetane-containing photoproducts, which has important implications, is that they can act as vehicles for subsequent manipulations and stereocontrolled synthesis. For example, the oxetane photoproduct (6)... 

Computational studies suggest that the mechanism of the proline catalyzed aldol cyclization is best described by the nucleophilic addition of the neutral enamine to the carbonyl group together with hydrogen transfer from the proline carboxylic acid moiety to the developing alkoxide. A metal-free partial Zimmerman-Traxler-type transition state involving a chair-like arrangement of enamine and carbonyl atoms and the participation of only one proline molecule has been established [118,119]. On the basis of density functional theory (DFT) calculations Cordova and co-workers [120,121] have studied the primary amino acid intermolecular aldol reaction mechanism. They demonstrated that only one amino acid molecule is involved in the... 

Cyclic sulfides (episulfides) are known and may be prepared by reaction of an epoxide (14) with potassium thiocyanate to give the episulfide (15), or by reaction of sodium sulfide with 1,4-or 1,5-dihalides for example, (16) yields the episulfide (17) (Scheme 11). The mechanism of the first reaction in Scheme 11 involves initial nucleophilic addition of the thiocyanate anion to the epoxide (14) followed by nucleophilic substitution to yield the episulfide (15) (Scheme 12). The second reaction is an intermolecular followed by an intramolecular nucleophilic substitution... 

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. 

In contrast to Hg(II), Ag(I) does not normally induce intermolecular nucleophilic addition to alkenes. However, internal nucleophiles can sometimes be captured, leading to cyclization reactions. 

---