Substitution with strong nucleophile

Sodium/alcohol Nucleophilic substitution with strong nucleophiles Thioethers from halides... 

The chemistry of metalated aziridines is far less developed than the chemistry of metalated epoxides, although from what is known [lb], it is obvious that their chemistry is similar. Like metalated epoxides, metalated aziridines can act as classical nucleophiles with a variety of electrophiles to give more highly substituted aziridines (Scheme 5.56, Path A). A small amount is known about how they can act as electrophiles with strong nucleophiles to undergo reductive alkylation (Path B), and undergo C-H insertion reactions (Path C). 

The extent to which 151 phosphorylates the aromatic amine in the phenyl ring is highly dependent upon the solvent. For instance, aromatic substitution of N-methylaniline is largely suppressed in the presence of dioxane or acetonitrile while pho.sphoramidate formation shows a pronounced concomitant increase. The presence of a fourfold excess (v/v) or pyridine, acetonitrile, dioxane, or 1,2-di-methoxyethane likewise suppresses aromatic substitution of N,N-diethylaniline below the detection limit. It appears reasonable to assume that 151 forms complexes of type 173 and 174 with these solvents — resembling the stable dioxane-S03 adduct 175 — which in turn represent phosphorylating reagents. They are, however, weaker than monomeric metaphosphate 151 and can only react with strong nucleophiles. 

At one time, benzenol was made industrially by sulfonating or chlorinating benzene and then introducing the hydroxyl group by nucleophilic substitution with strong alkali ... 

Extensive use of Pd-catalyzed reactions was included in the synthesis of 2,6,8-trisubstituted purines (Fig. II).33 The synthesis started by anchoring dichloropurine to Rink resin via N9 linkage. Polymer-bound 2,6-dichloropurine (63) was selectively substituted at C6 via acid-catalyzed SNAr substitutions. In the absence of Pd catalysis, the substitution on C2 could be performed only with strongly nucleophilic amines. To expand the scope of C2 substitution, catalytic amounts of Pd were used. Under these reaction conditions arylboronic acids and amines successfully substituted the chloro atom on C2 to afford C2-C and C2-N bonds. Subsequently, the C8 position was brominated with a bromine-lutidine complex33 (66) to give resin 67. 

By treating fluoronanotubes with strong nucleophiles such as Grignard reagents, alkyl- and aryllithium reagents, metal alkoxides, acyl peroxides, amines and diamines, the fluorine atoms can be replaced through substitution [29, 47-50]. 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

For the recombination of a-phenylethyl cations with strong nucleophiles, Richard and Jencks (1984a,b,c) obtained good Y-T correlations with the same r value of 1.15 as observed for the solvolysis (Fig. 35). The p value of -2.7 for the bimolecular substitution reaction of azide ion with 1-phenylethyl derivatives is significantly more positive than the value of p = -5.7 for the solvolysis reaction. This shows that there is a smaller development of positive charge in the transition state for the reaction of azide ion than for solvolysis. It is consistent with a coupled concerted reaction with a transition state in which positive charge development at the benzylic carbon is neutralized by bonding to azide ion. 

S j2 substitution with nonbasic nucleophiles E2 elimination with strong bases... 

Because alkyl tosylates have good leaving groups, they undergo both nucleophilic substitution and P elimination, exactly as alkyl halides do. Generally, alkyl tosylates are treated with strong nucleophiles and bases, so that the mechanism of substitution is Sn2 and the mechanism of elimination is E2. 

Sx2 substitution with nonbasic nucleophiles K2 oliininalion with strong bases Mostly E2 elimination (SmI substitution and El elimination in nonbasic solvents) ... 

The sulfonium fluorosulfonates 45 are very useful precursors for functionalized cyclopropyl sulfides. The reaction of these salts with aliphatic alcohols gave mixed acetals (e.g. 47) in quantitative yield, while phenol reacted as both an oxygen and carbon nucleophile. Benzenethiol and potassium fluoride provide the expected substitution products (e. g. 50 and 51, respectively), however, these are accompanied by side products such as methylated reagent [(methylsul-fanyl)benzene] or l,l-bis(methylsulfanyl)cyclopropane. Quite surprisingly, these substitution reactions fail with strong nucleophiles such as alkoxides, thiolates and azide. 

Halocyclopropyl sulfides undergo smooth substitution of the halide with strong nucleophiles such as sodium iodide, lithium azide or lithium aluminum hydrideX Sodium formate also readily substitutes such bromides, but the reaction is assisted by the presence of formic acid. 

A variety of solvents can been used ranging from benzene and dichlorometh-ane to more polar media hke THF or DMF. Sometimes the solvent strongly influences the rate and ee,but there are also reactions that are quite insensitive to the nature of the solvent. In allyhc substitutions with anionic nucleophiles, the counter ion can have a strong effect on the enantioselectivity. In the reaction of... 

This chapter will discuss methods for the preparation of esters, acid chlorides, anhydrides, and amides from carboxylic acids, based on acyl substitution reactions. Acyl substitution reactions of carboxylic acid derivatives will include hydrolysis, interconversion of one acid derivative into another, and reactions with strong nucleophiles such as organometallic reagents. In addition, the chemistry of dicarboxylic acid derivatives will be discussed, as well as cyclic esters, amides, and anhydrides. Sulfonic acid derivatives will be introduced as well as sulfate esters and phosphate esters. Finally, nitriles will be shown to be acid derivatives by virtue of their reactivity. 

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