Nucleophilic reactions Abstraction

The A1-piperideines, in contrast to the A2- and A3-isomers, are usually very reactive toward nucleophilic reagents. Depending upon the nature of the nucleophile, two reaction pathways are possible (equation 48). The nucleophile can add to the inline carbon or the nucleophile can abstract the a-hydrogen. Since both of the resulting anions can undergo further reactions, A1-piperideines have potential for the synthesis of complex six-membered ring heterocycles. 

The complexes are reactive towards nucleophilic as well as electrophilic attack. Attack by alkyl halides yields thioalkylated compounds. Mostly an alkylation at one sulfur atom takes place, but examples of alkylation at both sulfur atoms are known (reactions 1 and 2). The facile sulfur abstraction with PPh3 yielding a thiocarbonyl complex is a nucleophilic reaction (reaction 3). 

The trimethylsilyl group is exchanged for a hydrogen atom using PfSA in acetonitrile, a reaction referred to as a protodesilylation Protonation of vinylsilane 7 leads in the process first to cation 25, which is stabilized by the p-effect of silicon.10 A nucleophile subsequently abstracts the TMS group, producing olefin 8. Vinylsi-lanes can be transformed into olefins not onl> with acid.10 but also with fluoride1011 or with catalytic amounts of iodine m the presence of water... 

Also remember that elimination reactions can accompany berth SX1 and reactions. Elimination occurs when the nucleophile behaves as a base rather than a nucleophile it abstracts a proton rather than attacking a carbon. Elimination reactions always result in a carbon-carbon double bond. El and E2 kinetics are similar to V1 and Ss2 respectively. 

The reaction can be rationalized by assuming the mechanism which involves 0x0-ruthenium complex (Scheme 3.9). Hydrogen abstraction with oxo-ruthenium species gives phenoxyl radical 73, which undergoes fast electron transfer to the ruthenium to give a cationic intermediate 74. Nucleophilic reaction with the second molecule of t-BuOOH gives the product 72. 

The simple thietes are unstable with respect to treatment with strong bases or nucleophiles. Proton abstraction from thiete was observed via deuterium-proton exchange with CH3OD-CH3O it appeared to be faster than exchange with allyl sulfide, but slower than that with phenylacetylene. " The thiete, however, could not be recovered from the reaction mixture. Treatment of thiete with potassium t-butoxide did not result in incorporation of deuterium when the reaction was quenched with D2O treatment with potassium 1-methylcyclohexoxide resulted in the rapid disappearance of the nmr absorption of the protons of the thiete. ... 

Among the principal reactions which cation radicals undergo are electron transfer, reaction with nucleophiles, reaction with aromatics and olefins, dimerization, and hydrogen abstraction (e.g. the Hoffmann-Loeffler reaction). Reactions in the gas phase are also being explored with increasing interest by mass spectrometry and ion-cyclotron resonance. 

Radicals are very unstable and reactive, and these bromine radicals may simply recombine or they may react with other compounds. You already know that bromide anions are good nucleophiles in Sfj2 reactions, but bromine radicals do two quite different reactions abstraction and addition. The Br radical may abstract a hydrogen atom from the alkene or it may add to the tc bond. Notice that each reaction produces a new carbon-centred radical and, in the first case, a molecule of HBr. Whereas the Br—Br bond is weak, the H—Br bond is much stronger (366 kj mol" ) and, unlike ionic reactions, radical reactions are dominated by bond strength. 

An analogous ambiguity holds for nucleophilic reactions. We have already seen one facet of this problem in the oxidative addition of alkyl halides to metals (Section 6.3), which can go either by an electrophilic addition to the metal, the Sn2 process, or by SET and the intermediacy of radicals. The two processes can often give the same products. Other related cases we have s n are the promotion of migratory insertion and nucleophilic abstraction by SET oxidation of the metal (Sec. 7.1), and electrophilic abstraction of alkyl groups by halogen (Section 8.5). 

A possible reaction path for the NHPI-catalyzed hydroacylation of alkenes with aldehydes is shown in Scheme 6.20. The reaction may be initiated by a hydrogen atom abstraction from the aldehyde by the radical initiator (In ), giving an acyl radical (C) which then adds to an alkene to afford a (i-oxocarbon radical (D). The resulting radical (D), having a nucleophilic character, abstracts the hydrogen atom from NHPI leading to ketone and PINO. The abstraction of the hydrogen atom from aldehyde by the PINO forms the acyl radical C and NHPI. An alternative formation of PINO from NHPI and radical initiator (In ) may also be possible. 

In conclusion of this review of the nucleophilic properties of O2, the versatile nature of this unique anion radical should be emphasized. This chapter attempted to cover only the main features of the nucleophilic reactions of O2 with well-defined chemical substrates no attempt was made to treat any of the biochemical reactions. Moreover, in addition to nucleophilic properties, O2" is capable of reacting as a free radical as well as an electron transfer agent or electron acceptor. Thus, the understanding of this ubiquitous anion radical is probably only in its late infancy even though a computer search of the 1972-mid 1977 Chemical Abstracts revealed 850 references to super-oxide". 

Instead, it is more likely that the N-X-bond is cleaved heterolytically, resulting in an equilibrium with the adduct [Nu-X]" (Scheme 12, right Nu=nucleophilic activator). The latter then reacts with the nucleophilic compound to be halogenated. As the N-X bond is likely broken, these reactions are not directly relevant in the specific context introduced above, and only a few illustrative cases will be mentioned (for recent events [122]). One impressive example is the enantioselective halocyclization of polyprenoids which is carried out under addition of 1 equiv. of a chiral nucleophilic phosphoramidite. This nucleophilic phosphoramidite abstracts halenium ions from NIS or NBS via the phosphor atom to form a tight ion pair which then initiates the cyclization reaction by coordination to a double bond in the substrate [123]. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Thiazolium derivatives unsubstituted at the 2-position (35) are potentially interesting precursors of A-4-thiazoline-2-thiones and A-4-thiazoline-2-ones. Compound 35 in basic medium undergoes proton abstraction leading to the very active nucleophilic species 36a and 36b (Scheme 16) (43-46). Special interest has been focused upon the reactivity of 36a and 36b because they are considered as the reactive species of the thiamine action in some biochemical reaction, and as catalysts for several condensation reactions (47-50). 

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