Oxygen and Sulfur as Nucleophiles

FIGURE 9.45 Substitution of allylic halides by oxygen nucleophiles. 

All the halide anions can act as nucleophiles Iodide is the best, fluoride the ieast good. 

In order for alcohols to be converted to halides, the OH group has to be converted into a good leaving group. This may involve protonation, reaction with PX3, PX5, or SOCij, or conversion to a sulfonate. 

Alkoxide anions are used in 5 2 reactions with halides to prepare ethers in the Williamson synthesis. Neutral alcohols are preferred In S l processes. 

Thioethers are prepared similarly, but the reaction Is easier, and there is less competing elimination. 

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Oxygen and sulfur as nucleophiles ethers, esters, thioethers, epoxides... 

OXYGEN AND SULFUR AS NUCLEOPHILES ESTERS AND CARBOXYLIC ACIDS... 

Cephachlor (35) became accessible when methods for the preparation of C-3 methylenecephalosporins became convenient. The allylic C-3-acetoxyl residue characteristic of the natural cephalosporins is activated toward displacement by a number of oxygen- and sulfur-containing nucleophiles. Molecules such as can therefore be prepared readily. Subsequent reduction with chromium(II) salts leads to the desired C-3... 

Starting from vescalagin (34), all of the condensation reactions we performed using various carbon-, oxygen-, and sulfur-based nucleophiles occurred with retention of configuration at C-1, that is, the newly formed bond is still (3-oriented (see Section 4.3). As these chemical reactions produce ellagitannin derivatives with the same Cj-configuration as that of... 

Di Valentin, C. Freccero, M. Zanaletti, C. Sarzi-Amade, M. o-Quinone methide as alkylating agent of nitrogen, oxygen, and sulfur nucleophiles. The role of H-bonding and solvent effects on the reactivity through a DFT computational study, j. Am. Chem. Soc. 2001, 123, 8366-8377. 

The benzo[fc]thiophene sulfoxides, such as (142), generated from the parent benzo-thiophene on the H202-TFA-mediated oxidation, undergoes Michael-type nucleophilic addition of oxygen and sulfur nucleophiles in acidic media to produce 3-substituted benzo[fc]thiophenes (143). This method provides an easy two-step functionalization of 2-acylbenzo[fc]thiophene derivatives. ... 

There is a rich synthetic potential for enamines in heterocyclic synthesis. Enamines can react as electrophiles or nucleophiles and as new partners in cycloaddition reactions. Various derivatives of nitrogen-, oxygen-, and sulfur-containing heterocycles have been prepared, and these, in turn, are of interest as starting materials for additional syntheses. They represent potential synthons for the development of various new directions in organic chemistry. 

Oxazinium and -thiazinium cations are 67r-aromatic systems which readily react with nucleophiles at C-6. Ring opening is normally followed by recyclization so that a variety of heterocyclic systems are then formed. The behaviour of the oxygen and sulfur compounds are almost identical and so, as the latter are usually prepared from the former, it is not surprising that most attention has focussed on the reactions of 1,3-oxazinium species (72S333). These versatile synthons react with ammonia, for example, to give pyrimidines, while hydrazines afford pyrazoles and hydroxylamine produces isoxazoles (Scheme 20). 

With tetrahexylammonium as the cation of choice and 5 as ligand, the established conditions for the alkylation with carbon nucleophiles has been successfully applied to asymmetric introduction of heteroatoms such as nitrogen, oxygen, and sulfur (Eq. 8E.7), As shown in Table 8E.8, excellent enantioselectivities are observed independent of the counterion of the heteroatom nucleophiles and the ring size. 

Bisulfide and Polvsulfide as Nucleophiles. Hydrogen sulfide (H2S) and bisulfide ion (HS ) are probably the primary sulfur nucleophiles (i.e. species with a lone pair of electrons on sulfur) in reducing sediments. However, several environmental factors such as diffusion of oxygen, the presence of Fe(III) may cause incomplete oxidation of sulfide to form polysulfide ions (S,2-, where n>l) (21)-... 

Nitrogen nucleophiles, in a similar manner to oxygen- and sulfur-based functionality, undergo transition metal-catalyzed cross-coupling with halopyridines. The use of palladium(O) catalysts is most effective in combination with chelating bis-(phosphine) ligands such as BINAP that prevent the formation of pyridine-palladium complexes that... 

As would be expected, nucleophilic attack on the derivatives (84) leads to ring-opening reactions with alcoholic sodium hydroxide to give the selenadiazole (85) and with amines to give compounds (86) (66BP1610). There appears to be no tendency to recyclize, as in the case of the corresponding oxygen and sulfur heterocycles (Scheme 4). 

C-Sn [148] and C-Si [121, 149] bond cleavage has developed into a versatile synthetic method for adding functionality a to nitrogen, oxygen and sulfur centers. C-Si bond cleavage is known to be induced by nucleophiles such as pyridine [150] and methanol, and stereoselectivities have been interpreted as indicating that C-Si bonds can even be attacked by a double bond system [151]. 

Nucleophilic displacement of the nitro group of nitrobenzenes substituted with a variety of electron-withdrawing groups is readily possible at 25°C with HMPA as solvent.1 8 Carbon, oxygen, and sulfur nucleophiles have been used with excellent yields reported. 

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