Unsaturated compounds, nucleophilic addition

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

Because of their relative instabiUty, primary phosphine oxides caimot be isolated and must be converted direcdy to derivatives. Primary and secondary phosphine oxides undergo reactions characteristic of the presence of P—H bonds, eg, the base-cataly2ed nucleophilic addition to unsaturated compounds such as olefins, ketones, and isocyanates (95). 

Etherification. The accessible, available hydroxyl groups on the 2, 3, and 6 positions of the anhydroglucose residue are quite reactive (40) and provide sites for much of the current modification of cotton ceUulose to impart special or value-added properties. The two most common classes into which modifications fall include etherification and esterification of the cotton ceUulose hydroxyls as weU as addition reactions with certain unsaturated compounds to produce ceUulose ethers (see Cellulose, ethers). One large class of ceUulose-reactive dyestuffs in commercial use attaches to the ceUulose through an alkaH-catalyzed etherification by nucleophilic attack of the chlorotriazine moiety of the dyestuff ... 

The direction of addition, verified by acetylene oxidation into a known acid, proves that the nitiilimine carbon atom adds to the terminal atom of the enyne system, which is inconsistent with the assumed polarization of the unsaturated compound H2C=CH—C=C—R from the vinyl group towardR. The authors explain this by a possible transfer of the reaction center in nitrilimine as a particle with a nucleophilic center on a carbon Ph—C=N" —N —Ph Ph—C =N =N—Ph (63ZOB3558). 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

This aldol condensation is assumed to proceed via nucleophilic addition of a ruthenium enolate intermediate to the corresponding carbonyl compound, followed by protonation of the resultant alkoxide with the G-H acidic starting nitrile, hence regenerating the catalyst and releasing the aldol adduct, which can easily dehydrate to afford the desired a,/3-unsaturated nitriles 157 in almost quantitative yields. Another example of this reaction type was reported by Lin and co-workers,352 whereas an application to solid-phase synthesis with polymer-supported nitriles has been published only recently.353... 

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

Friedman, M., Cavins, I.F., and Wall, l.S. Relative nucleophilic reactivities of amino groups and mercaptide ions in addition reactions with a.p-unsaturated compounds, J. Am. Chem. Soc., 87(16) 3672-3682,1965. 

If the potential leaving group is attached to unsaturated carbon, as in vinyl chloride or phenyl chloride, attack by nucleophiles is also extremely difficult, and these compounds are very unreactive in Sn2 reactions compared with simple alkyl halides. In these cases, the reason is not so much steric but electrostatic, in that the nucleophile is repelled by the electrons of the unsaturated system. In addition, since the halide is attached to carbon through an 5p -hybridized bond, the electrons in the bond are considerably closer to carbon than in an 5/ -hybridized bond of an alkyl halide (see Section 2.6.2). Lastly, resonance stabilization in the halide gives some double bond character to the C-Hal bond. This effectively strengthens the bond and makes it harder to break. This lack of reactivity is also tme for SnI reactions (see Section 6.2). 

A specific example involving aflatoxins is shown in Box 6.8. We shall see other examples of glutathione reacting as a nucleophile in detoxification reactions, where conjugation is not the result of nucleophilic substitution. For example, it might be nucleophilic addition to an electrophile such as an unsaturated carbonyl compound (see Box 10.20). 

The Michael reaction is the nucleophilic addition of a carbanion to ot,p-unsaturated carbonyl compounds. It is a useful way to make C-C and C-hetero atom bonds. Karodia s group studied the use of the ionic liquid ethyltri- -butylphosphonium tosylate ( -Bu3PEtOTs) as a solvent for... 

When a new carbon-carbon bond is produced by nucleophilic addition to conjugated systems, the process is called Michael addition. The generalised process involves an a, b-unsaturated compound and a compound containing an active hydrogen attached to a carbon atom (e.g., malonic ester, acetoacetic ester, nitrocompounds, aldehydes, ketones etc.) These are condensed in the presence of a base. The overall reaction and its mechanism can be represented as follows ... 

Nucleophilic Addition to Carbonyl Compounds and -Unsaturated Carbonyl Compounds.—Although the reactions of 17-oxo-steroids with various carbanion reagents are reported to have varying success/ the use of alcohols or DMF as solvents appears to facilitate the Wittig-Horner reaction/ For example, the ketone (97) was converted with (Et0)2P0CHC02Et into the E-ethyl ester (98) in... 

Recall that the LUMO shows which regions of a molecule are most electron deficient, and hence most subject to nucleophilic attack. One such region is over the carbonyl carbon, consistent with the observation that carbonyl compounds undergo nucleophilic addition at the carbonyl carbon. Another region is over the P carbon, again consistent with the known chemistry of a,P-unsaturated carbonyl compounds, in this case conjugate or Michael addition. 

---