Heteroatom-based nucleophile reactions

Hydroxymethylaziridine 67 undergoes ring opening in the presence of either carbon- or heteroatom-based nucleophiles upon treatment with 2 equiv of potassium hydride to provide the t)7aminoalcohol derivative 69. The key step of the reaction is considered to be an aza-Payne rearrangement of the deprotonated aziridine methanol to the... 

Carbohydrates are excellent substrates to test nucleophilic displacement reactions with a variety of heteroatom-based nucleophiles. These reactions can be tried on primary and secondary hydroxyl groups at different sites of the sugar ring, and with different steric or stereoelectronic dispositions [1]. 

In principle, the nucleophilic attack at alkene or alkyne ligand can be a reversible process, like the reaction of carbonyl ligand. The reversibility often has been confirmed in the reaction of heteroatom-based nucleophiles, but carbon nucleophiles rarely undergo the reversible ahack at alkenes and alkynes [30]. Occurrence of an equilibrium reaction was observed between the combination of alkene-metal complex with amine on one hand, and zwiher ionic adduct made from the former combination on the other (Eq. 8.6) [31,32]. The isolation of the latter adduct was also realized in some cases as described later. It was demonstrated that this type of reversible adduct formation did not accompany E-Z isomerization of the alkene, meaning stereospecihc nature of the C-N bond formation and its reverse. A closely related stereochemical analysis demonstrated that the ahack of the amine at the coordinated alkene takes place from the side opposite to the metal atom, as will be discussed later in more detail. 

In the last few years, the use of NHC-Cu complexes in catalysis has grown exponentially, particularly for the transfer of carbon and heteroatom-based nucleophiles to various electrophilic substrates. Copper-catalyzed boron and silicon transfers have recently been reported, thus expanding the scope of NHC-copper-catalyzed reactions. Notably, the design of new chiral NHC ligands has enabled the successful development of efficient C-C and C-H bond forming enantioselective reactions. 

Most of the reactions which will be discussed lead to carbonyl compounds with a stereogenic center in the 3-position. This is illustrated in Scheme 1 a substrate molecule (1 X = heteroatom or heteroatom-based functional group), having an electron-deficient double bond, is attacked by a nucleophilic reagent (possibly in the presence of a coordinating ligand or a catalyst) to form an anionic intermediate (2), which is then converted to the product (3) on hydrolytic work-up. 

The construction of complex intermediates from simple and readily available starting materials has been accomplished using the electrocyclic ring-opening reaction of halocyclopropanes. This is typically achieved through interception of the cationic haloallyl intermediate by solvent, the silver(I) counteranion, or some alternate tethered heteroatom or carbon-based nucleophile. Examples of these processes are described below. 

Systemization of experimental data on the syntheses of heterocyclic compounds with perfluoroalkyl groups from perfluoroolefins is based on reactions with various 1,1-, 1,2-, 1,3-, and 1,4-binucleophilic reagents. While the main features of nucleophilic reactions are preserved, further transformations of the primary products (or adducts, or the products of substitution of the functional groups at the internal multiple bond) occur under the influence of the added functional group containing a heteroatom. Here one can expect dramatic differences in the effect of the nature of the nucleophilic reagent between cyclizations by new nucleophilic centers and centers already available in the molecule. Another important aspect is isomerization of the primary internal olefin into the terminal olefin or internal olefin with a different structure under the action of the nucleophilic agent. This may be critical to the structure of the heterocycle formed. 

Organometallics react with this sink by addition to the multiple bond (path Ad r). The more covalent, less reactive organometallics, like R2Cd, react very slowly with almost all of these sinks, whereas organomagnesiums, RMgX, and organolithiums react quickly. Complexation of the metal ion to the Y heteroatom catalyzes this reaction. Organometallics react much faster as nucleophiles with polarized multiple bonds than as bases with the adjacent C-H bonds, (carbon-acid, carbon-base proton transfer is slow). C=Y example ... 

Palladium-catalyzed reactions have been widely investigated and have become an indispensable synthetic tool for constructing carbon-carbon and carbon-heteroatom bonds in organic synthesis. Especially, the Tsuji-Trost reaction and palladium(II)-catalyzed cyclization reaction are representative of palladium-catalyzed reactions. These reactions are based on the electrophilic nature of palladium intermediates, such as n-allylpalladium and (Ti-alkyne)palladium complexes. Recently, it has been revealed that certain palladium intermediates, such as bis-7i-allylpalladium, vinylpalladium, and arylpalladium, act as a nucleophile and react with electron-deficient carbon-heteroatom and carbon-carbon multiple bonds [1]. Palladium-catalyzed nucleophilic reactions are classified into three categories as shown in Scheme 1 (a) nucleophilic and amphiphilic reactions of bis-n-allylpalladium, (b) nucleophilic reactions of allylmetals, which are catalytically generated from n-allylpalladium, with carbon-heteroatom double bonds, and (c) nucleophilic reaction of vinyl- and arylpalladium with carbon-heteroatom multiple bonds. According to this classification, recent developments of palladium-catalyzed nucleophilic reactions are described in this chapter. 

Heteroatom nucleophiles were described less often. Ye and coworkers published a phospha-Michael addition catalysed by prolinol silyl ether catalyst. Another method for constructing a new C-N bond is the aza-Michael addition, that is the addition of nitrogen-based nucleophiles to a,(3-unsaturated aldehydes. Several groups published these type of reactions using diatylprolinol silyl ether as catalyst. " Fustero and coworkers used this reaction as a key step in the synthesis of biologically active chiral heterocycles. Recently, the authors showed the synthesis of quinolizidine alkaloids, such as (-l-)-myrtine, (-)-lupine and (-l-)-epiquinamide. Vicario applied 5-mercaptotetrazoles as nucleophiles towards a range of unsaturated aldehydes. The reaction proceeded via the iminium activation. The... 

A simple variant of the Smiles rearrangement is the Truce-Smiles modification, a reaction that has been little used in recent times, despite it arguably being more synthetically useful due to the selective formation of carbon-carbon bonds (Scheme 18.2) [7]. As shown, a carbon-based nucleophile replaces that of the heteroatom nucleophile (Y, in Scheme 18.1). 

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