Benzyl anion

Benzylic anions, ArCHj, are of little importance in the construction of carbon skeletons, and allylic anions, R C—CR—CR", are discussed in the d -synthons section below. 

The search for opioid analgesics which show reduced addiction liability ha.s centered largely on benzomorphan and morphinan derivatives. Some research has, however, been devoted to derivatives of the structurally simpler meperidine series. The preparation of one such compound, picenadol (59), starts with the reaction of N-methyl-4-piperidone with the lithium derivative from m-methoxybromobenzene. Dehydration of the first formed carbinol 51 gives the intermediate 52. Deprotonation by means of butyl lithium gives an anion which can be depicted in the ambident form 53. In the event, treatment of the anion with propyl bromide gives the product 54 from reaction of the benzylic anion. Treatment of that product, which now contains an eneamine function. 

Florio et al. demonstrated that the lithiation/electrophile trapping of enantio-pure styrene oxide, as well as the (3-substituted styrene oxides 180 and 182, is totally stereoselective (Scheme 5.42) [66]. These results demonstrate that the intermediate benzylic anions are configurationally stable within the timescale of depro-tonation/electrophile trapping. 

The carbonyl addition reactions of benzylmetals, compared to the allylic counterparts, have found few applications in stereoselective synthesis, apparently for the following reasons The carbonyl addition of alkali metal salts (M = Li, Na, K, Cs) of benzyl anions, with few exceptions, usually proceeds with low levels of simple diastereoselectivity affording mixtures of syn- or <7 / -diastereomers (see Section 1.3.2.3.1.). 

Although the ion pairs of a-substituted benzyl anions and the corresponding cations are chiral species, which, in addition, often bear a pyramidal and hence stereogenic carbon atom, in most cases rapid racemization of the alkali and alkaline earth metal derivatives occurs in solution... 

Hetero-benzylic anionic reagents, derived from 2-alkyl-l,3-oxazoles, -1,3-thiazoles and -imidazoles and related compounds, are not covered in this section because these resemble metallo 1-azaenolates in their reactivity (Section D.l.3.5.). 

In most cases, the addition of prostereogenic benzyl anion reagents with prostereogenic aldehydes (or ketones) proceeds with low stereoselectivity. Some notable exceptions are reviewed later. 

In addition reactions to chiral carbonyl compounds, the stereochemical course taken by resonance-stabilized alkali metals or magnesium benzyl anions resembles that taken by localized carbanions of similar bulk. Thus, conditions can be delineated which lead to either the steric approach or chelation control the following serve as examples. 

Because allyltrimethylsilane 82 or benzyltrimethylsilane 83 can be regarded as combinations of the hard trimethylsilyl cation and the soff allyl or benzyl anions, pyridine N-oxide 860 reacts with excess 82 or 83 in the presence of catalytic amounts of tetrabutylammonium fluoride di- or trihydrate in THF to give 2-allyl-or 2-benzylpyridines 948 and 950 [60]. The general reaction of silicon reagents such as 82 and 83 or of trimethylsilyl cyanide 18 with fluoride to generate allyl or... 

An alternative synthesis of a thermally stable cyclopentadienyl functionalized polymer involved ring bromination of poly(oxy-2,6-diphenyl-l,4-phenylene), followed by lithiation with butyl lithium to produce an aryllithium polymer. Arylation of 2-norbornen-7-one with the metalated polymer yielded the corresponding 2-norbornen-7-ol derivative. Conversion of the 7-ol to 7-chloro followed by treatment with butyl lithium generated the benzyl anion which undergoes a retro Diels-Alder reaction with the evolution of ethylene to produce the desired aryl cyclopentadiene polymer, 6. 

Reaction of a Dithioacetal Derived from Indoxyl with Allyl and Stabilized Benzyl Anions... 

Similarly the stabilized benzyl anions from 68 and 70 also reacted with 6.40 following Type IV (4b) reactivity patterns to afford the corresponding 3,4-annulated carbazoles 69 and 71 respectively in moderate yields <99T11563>. 

Reaction of Ar-Benzenesulfonyl-3-[bis(methyIthio)methyIenel-2r3-dihydro-l/F-quinoline-4-one 6.36 with Allyl and Benzyl Anions A New Regiospecific Synthesis of Phenanthridines and Benzo[/]phenanthridines... 

The reaction of 6.36 with allyl and benzyl anions was examined with a view to develop an efficient method for the synthesis of phenanthridines and their benzo[/]-derivatives. The dithioacetal 6.36 when reacted with allyl anions yielded the corresponding... 

FIGURE 3.3 Deprotection of functional groups by reduction. Hydrogenolysis of benzyl-based protectors.1 Attack by electrons liberates the protector as the benzyl anion because the latter is stabilized by resonance. This is a simplified presentation of the reaction. 

The benzyl anion of l-benzyloxy-2,2,4,4-tetramethylpentan-3-ones undergoes intramolecular nucleophilic addition to the carbonyl group without competing Wittig rearrangement or decomposition the stereoselectivity observed is consistent with avoidance of interaction between aryl and r-butyl groups. 

In a novel kinetic approach, Dorfman et al. developed methods for rapidly generating very reactive carbanions such as the benzyl anion in solvent mixtures containing water and alcohols. With pulsed radiolysis techniques, they have been able to study the fast and very exothermic reactions of carbanions with these solvents. The studies have shown that despite the high exothermicity, the protonation is not diffusion controlled and depends on the nature of the carbanion s counterion. 

Some protonation of the benzyl carbanion by the starting ether (selfprotonation reaction) and other side reactions, such as hydrolysis caused by in situ generation of OH (through protonation of the benzyl anion by traces of water), can be avoided by addition of a suitable acid. Under these conditions, electrolysis leads to an effective conversion of the ether into toluene and phenoxide ion with an electron consumption of 2 F/mol. 

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