Organolithium species

The conjugate addition substrate that we were considering bore an obvious resemblance to Stork s however, it would incorporate a free NH and OH, as well as a more sensitive aldehyde. In this light, an approach involving reactive organolithium species seemed unlikely to be successful, and a few experiments quickly validated this surmise. We therefore sought a precursor that could... 

Lithiation of to form 184 was reported by the Harmata group to be the first example of a sulfoximine-stabilized vinyl carbanion. The resulting organolithium species 184 reacted with various electrophiles to supply structurally diverse benzothiazines <88TL5229>. However, the diastereoselectivity of the reactions with aldehydes was low (Scheme 48). 

As documented in detail for organolithium species, ligand and donor play a key role in determining the degree of aggregation. Methyllithium adopts a hexameric structure in hydrocarbon solvents.13,15 In the presence of monodentate, donors such as THF or diethyl ether tetramers are observed, while the increase in donor denticity to 2 (1,1-Dimethoxyethane (DME), N,N,N, N -Tetramethylethylenediamine (TMEDA)) affords monomeric structures. Further documenting the differences between solution and solid states, [CH3Li]4 adopts a tetrameric structure in the latter.15,15a-15c... 

Similar methods also generate the selenium and oxygen analogues 3370) and 34 71), respectively, as outlined in Eq. 37 and 38. These organolithium species add to carbonyl groups of non-conjugated and conjugated aldehydes and ketones, frequently... 

Due to the high interest in metalation reactions with lithium amide or alkyllithiums, an indicator scale of lithium ion pairs in THF has been developed119. Aggregation studies have indicated that organolithium species exist predominantly, if not exclusively, as monomers in the 10-3-10-4 M concentration range. Particular attention has been devoted to the lithium and caesium ion-pair acidities of diphenylamine in THF120 that, at 25 °C, have been found to be 19.05 and 24.20, respectively. 

A major problem in the development of catalytic asymmetric 1,4-additions of RLi reagents is the high reactivity usually associated with organolithium species. One solution has been found in the stoichiometric formation of the corresponding chiral cuprates ee s of up to 99% have been reported [20]. An impressive example of the use of a substoichiometric quantity (33 mol%) of chiral ligand is to be found in... 

In attempting a systematic analysis of related organolithium species, it would be advantageous to consider all of them in at least one common phase. Our preference is for the gas phase where intermolecular interactions are usually absent, although this may not hold true for organolithium species. Unfortunately, most of the desired phase change enthalpies for organolithiums are not found in the experimental literature. However, where the species of interest is a liquid, we can employ the published CHLP protocol for the estimation of the enthalpy of vaporization. ... 

The general conclusion from this investigation is that even aggregated organolithium species can be studied by solid state C NMR spectroscopy, and that these complexes seem to retain the solid state structure in solution. 

Reactions of organolithium species with epoxides, yielding secondary alcohols, are shown in equations 69 and 75 (Section VI.B.l). 

Carbolithium compounds of moderate reactivity open the O—C bond of cyclic sulfate esters or cyclic sulfamidates to produce new C—C links, as shown, for example, in equation 112 for a chiral cyclic sulfamidinate and 2-lithio-l,3-dithiane (380a). More reactive organolithium species, such as n-BuLi and PhLi, yield mixtures of products, probably due to attack on the S atom of the sulfonamido group too °. 

Although there is a kinetic barrier to the direct deprotonation of tertiary amines, Ahlbrecht and Dollinger showed in 1984 that the Schlosser superbase, i c-BuLi/f-BuOK, can deprotonate A-methylpiperidine selectively on the methyl group (Scheme 3). This superbase probably yields an a-amino-organopotassium species (and f-BuOLi), but treatment with LiBr effects transmetalation to the more nucleophilic, and less basic, a-amino-organolithium species. Electrophilic quench with several aldehydes and ketones gives substitution products in good yields as typified by the example in Scheme 3. Similarly,... 

Ahlbrecht and coworkers showed that tin-lithium exchange can be used to lithiate enamines of 2-methoxymethylpyrrolidine, as shown in Scheme 46. A 50 50 mixture of diastereomers is transmetalated, and the resultant organohthium(s) alkylated to give, after enamine hydrolysis, a 98 2 ratio of ketone enantiomers. In this system, the low barrier to inversion allows equilibration to a single organolithium species, which alkylates by an S 2inv mechanism. 

The r] a-amino-organolithium species shown in Scheme 66 react with several different electrophiles at the y-position relative to the nitrogen atom. With benzyl bromide, electrophilic substitution is invertive, but with enones and ketones, it is retentive (Scheme 67). Reversal of steric course between CO2 (Sg2inv) and ClC02Me (Sg2ret) is also observed in this system (compare Scheme 64). Hydrolysis of the enamine products affords /3-substituted aldehydes that can be further elaborated. " ... 

Transmetallation of allyltributyltin with organolithium species has been used for the generation of allyllithium solutions free of the coupling byproducts which often result from reduction of allylic halides with lithium metal. These solutions may then be used directly for the preparation of Gilman reagents and other reactive modifications of the parent allyllithium. 

In the Suzuki strategy 138 was treated with trityl chloride to afford amine 139 in 84% yield (Scheme 4.29) (Todo et al., 2000). Metal-halogen exchange of 5-bromoisoindoline 139 was achieved using w-butyl lithium at — 65°C to deliver an intermediate organolithium species that was trapped with triisopropylborate to afford the boronic acid upon work-up. Further treatment of the boronic acid with diethanolamine gave diethanolamine boronic ester 140 (Hayashi et al., 2002). Presumably, the diethanolamine boronic ester was formed for stability reasons, as a given diethanolamine boronic ester tends to be less... 

The mixed-metal Li(/x-0)Al-based complex CeHgO (THF)2 LiAl[(R)-binol]2 has been a source of great interest recently by virtue of its ability to catalyse [69, 70] the conjugate addition of organolithium species to a, -unsaturated... 

Related pyrrolidines 149 and 150 are produced from organolithium species which readily undergo cyclization onto suitably positioned alkenes <20030BC2111>. The amino-stannane starting material undergoes tin-lithium exchange at low temperatures followed by cyclization on warming to produce two stereoisomers in a 4 1 ratio (Equation 51). The major product formed was found to be the stereoisomer 149, contrary to expectation from model studies. 

The above comments should not be taken as claims that anisole and diphenyl ether cannot be metallated by organolithium species. For example, alkyllithiums are known (38,39,40) to react with anisole, usually in the ortho position. However, these reactions are generally slow, particularly at ambient temperature and when the ether is diluted with a hydrocarbon solvent. Our results merely indicate that active center deactivation via metallation of these aromatic ethers is not a serious problem during the time span of our measurements with species that are, at least, partially delocalized (33J ... 

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