Nucleophilic addition of organometallic

A different approach to chiral oc-hydroxy acids 4 is the nucleophilic addition of organometallic reagents to chiral oc-oxo 4,5-dihydrooxazoles 2, which can be synthesized by oxidation of the corresponding 2-alkyl-4,5-dihydrooxazoles l17,19. 

Nucleophilic addition of organometalic reagents occurs when the nitrone form is in equilibrium with the hydroxylamine form, for instance, in the case of N -benzyl-/V-glycosyl hydroxylamines (Scheme 2.130) (213). 

The hemiacetals obtained by nucleophilic addition of organometallic reagents to the carbonyl group of aldonolactones may be reduced to the corresponding C-glycosyl compounds. For example, treatment of 2,3,4,6-tetra-... 

Other additions, such as addition of alkyl halides and carbonyl compounds, are discussed in Chapter 5, whereas Chapter 7 covers addition reactions involving carbon monoxide (hydroformylation, carboxylations). Hydrogen addition is discussed in Chapter 11. The nucleophilic addition of organometallics to multiple bonds is of great significance in the anionic polymerization of alkenes and dienes and is treated in Chapter 13. 

The first results of anionic polymerization (the polymerization of 1,3-butadiene and isoprene induced by sodium and potassium) appeared in the literature in the early twentieth century.168,169 It was not until the pioneering work of Ziegler170 and Szwarc,171 however, that the real nature of the reaction was understood. Styrene derivatives and conjugated dienes are the most suitable unsaturated hydrocarbons for anionic polymerization. They are sufficiently electrophilic toward carbanionic centers and able to form stable carbanions on initiation. Simple alkenes (ethylene, propylene) do not undergo anionic polymerization and form only oligomers. Initiation is achieved by nucleophilic addition of organometallic compounds or via electron transfer reactions. Hydrocarbons (cylohexane, benzene) and ethers (diethyl ether, THF) are usually applied as the solvent in anionic polymerizations. 

The nucleophilic addition of organometallic reagents to imines provides an attractive route to amines [4]. Recendy, however, some completely different approaches to the synthesis of a-aryl amine were reported. Hayashi and Ishigeda-ni found a new catalytic system for the asymmetric addition of arylstannanes to imines derived from aromatic aldehydes (Scheme 11) [20]. 

The theoretical study by Khan et al. [13] on the stereochemistry of nucleophilic addition of organometallics to unsaturated substrates can also be applied to conjugated systems. Of the three major factors affecting the orientation of the nucleophile to the substrate (see Chapter 16), the ability of the substrate to discriminate between the nucleophilic and electrophilic character of the Grignard reagent is the one most susceptible to influence by conjugation with an adjacent 7r-system. They concluded that the accessible electrophilic site (the metal) is the source of the stereochemical preference for the electron-rich olefin face. 

Nucleophilic addition remains the most utilized reaction of pyridinium salts. Addition generally occurs at the 2- or 4-position giving rise to 2- or 4-dihydropyridines, respectively. Charette et al. observed nucleophilic addition of organometallic reagents to the 2-position of N-amidine pyridinium salts <050L5401>. This chemistry is illustrated in Scheme 19 with amide 71. 

Synthetic ways to dihydropyridines can be classified into ring-forming processes and ring transformations, liie first general approach is best represented by the versatile Hantzsch synthesis. This method conveniently affords 1,4-dihydro- or 3,4-dihydro-, but not 1,2-dihydro-pyridines. The second approach may be illustrated by partial reduction of pyridines or pyridinium salts and nucleophilic addition of organometallic reagents to pyridines and pyridinium salts leading to 1,2- or l,4-dihydropyridines . 

Anionic initiation has been accomplished in a variety of solvents, both polar and nonpolar. Typically, initiation can proceed by electron transfer reactions from alkali or alkaline earth metals, polycyclic aromatic radical anions, or alkali and magnesium ketyls. The other possibility includes the nucleophilic addition of organometallic compounds to the monomers. Related monofunctional initiators comprise alkyl derivatives of alkali metals or organomagnesium compounds such as Grignard reagents. Difunctional species are alkali derivatives of a-methylstyrene tetramer or the dimer of 1,1-diphenylethylene. An overview of the initiation process in carbanionic polymerization is given in Ref. [159]. 

Katrl997 Katritzky, A.R., Xie, L., Zhang, G., Griffith, M., Watson, K. and Kiely, J.S., Synthesis of Primary Amines via Nucleophilic Addition of Organometallic Reagents to Aldimines on Solid Support, Tetrahedron Lett., 38 (1997) 7011-7014. 

Scheme 1-111. Nucleophilic addition of organometallics onto diphenylacetylene followed or not by or//jo-metalation.

Numerous examples of additions to carbonyl compounds incorporating a stereogenic center at Ca exist that yield products with impressive diastereo-selectivity, in accordance with the Felkin-Anh transition state model (Scheme 2.2) [51]. In a demonstration of the importance of the metal counterion, Reetz found that nucleophilic addition of organometallic species to (R)-2-phenylpropanal (19) occurs with Felkin-Anh selectivity. The diastereo-selectivity was much more pronounced when organotitanium reagents were... 

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