Secondary benzylic lithium compounds

The rearrangement of an ether 1 when treated with a strong base, e.g. an organo-lithium compound RLi, to give an alcohol 3 via the intermediate a-metallated ether 2, is called the Wittig rearrangement. The product obtained is a secondary or tertiary alcohol. R R can be alkyl, aryl and vinyl. Especially suitable substrates are ethers where the intermediate carbanion can be stabilized by one of the substituents R R e.g. benzyl or allyl ethers. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

Only few types of benzyUithium compounds being configurationally stable in solution at —78°C are known lithium-TMEDA complexes of secondary 0-benzyl Af,Af-dialkyl carbamates, such as 211 or the 2,4,6-triisopropylbenzoate 212 ° , of secondary N-aryl-Af-Boc-benzylamines (213) and the dUithio-(—)-sparteine derivative 214 . ... 

Hydroxy-8,9-methylenedioxyphenanthridine, [10]. The method developed by Kessar et al. [11] for phenanthridines and related compounds was applied to the synthesis [10] of 3-hydroxy-8,9-methylenedioxyphenanthridine (22) (Scheme 5). Thus, the benzylidene aniline 23, prepared from 6-chloropiperonal and 3-benzyloxyaniline, was reduced to the secondary amine 24. Treatment of 24 with excess lithium diisopropylamide furnished, on work-up, the benzyl ethers 25 (22%) and 26 (6%) respectively. Catalytic debenzylation of the former generated 22. 

On the other hand, a-alkoxyorganolithiums are not configurationally stable on a macroscopic timescale when they are secondary and allylic or benzylic. For example, despite the known (see section 5.2.1) stereospecificity of the tin-lithium and lithium-tin exchanges of similar compounds, tin-lithium exchange of 110 with rc-BuLi/TMEDA at -78 °C gives an organolithium 111 which has completely racemised after 10 min stannylation returns racemic stannane 112.55 Similarly, 111 racemises rapidly at -70 °C in pentane/cyclohexane in the... 

Exceptions are the few secondary benzyllithiums which show configurational stability on the microscopic (but not macroscopic) timescale - in other words, they racemise slower than they react with electrophiles, though they still cannot be maintained in stereoisomerically pure form for periods of minutes or more. These are the carbamates 288 and the sulfones 289, discussed in sections 5.1.4 and 5.I.7.6 It is significant that both of these compound classes contain powerful lithium-coordinating oxygen atoms, which may hold the lithium counterion close to one face of the benzylic system.134-120... 

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