Lithium halides, chelated

The alkylthiazoline (600) can be prepared readily from the corresponding alkyl halide and commercially available 2-mercaptothiazoline (71TL4359). Treatment of (601) with n-butyllithium yielded the chelated lithium derivative which reacted with various alkyl iodides and bromides to afford the a-alkylated thiazolines (602) in moderate yield (Scheme 132). 

The high reactivity of chelated lithium alkyl compounds severely limits structural study of pure compounds, particularly in aromatic solvents. Most of our more recent work on chelated lithium alkyl systems used H and 7Li NMR to observe various metalation reactions like the self-metalation or aging reaction of TMED LiBu in heptane (I, 2). Much of our current insight into the structural features of chelated alkali metal systems comes from careful quantitative study of systems with relatively stable anions like resonance stabilized carbanions (5) and the systems described in this paper. We discuss magnetic resonance experiments on two systems (a) chelated lithium halides Chel LiX, examples of the recently discovered inorganic salt chelates (6), and (b)... 

The unusual properties of polytertiaryamine chelated lithium salts have been noted (6). The high solubility and conductivity of chelated lithium halides in benzene raise a number of important and interesting questions concerning the role of the aromatic solvent since these chelated... 

The transition state in this instance is envisioned as involving the chelated lithium ion, which acts as a Lewis acid toward the halide, facilitating a specific direction of approach. The range of enantiomeric excess observed for this procedure is 70%-90%. ... 

The mechanism of the asymmetric alkylation of chiral oxazolines is believed to occur through initial metalation of the oxazoline to afford a rapidly interconverting mixture of 12 and 13 with the methoxy group forming a chelate with the lithium cation." Alkylation of the lithiooxazoline occurs on the less hindered face of the oxazoline 13 (opposite the bulky phenyl substituent) to provide 14 the alkylation may proceed via complexation of the halide to the lithium cation. The fact that decreased enantioselectivity is observed with chiral oxazoline derivatives bearing substituents smaller than the phenyl group of 3 is consistent with this hypothesis. Intermediate 13 is believed to react faster than 12 because the approach of the electrophile is impeded by the alkyl group in 12. 

A procedure for enantioselective synthesis of carboxylic acids is based on sequential alkylation of the oxazoline 8 via its lithium salt. Chelation by the methoxy group leads preferentially to the transition state in which the lithium is located as shown. The lithium acts as a Lewis acid in directing the approach of the alkyl halide. This is reinforced by a steric effect from the phenyl substituent. As a result, alkylation occurs predominantly from the lower face of the anion. The sequence in which the groups R and R are introduced... 

Lithium halide complexes with ethylenediamine, en, LiXen2, provide a nice illustration of both chelation and bridging by this ligand (26), resulting in a tetrahedral environment for the cation with Li—N, 2.07 A. 

A number of monomeric adducts between alkylzinc halide compounds and chelating hgands (see Chelating Ligands) have been isolated and stmcturaUy characterized (Table 7). For example, the reaction between the TMEDA adduct of lithium-phenyl(trimethylsilyl)methanide and ZnCh directly led to the formation of the TMEDA... 

The lithium derivative of 153 can equilibrate to the chelated isomer Z-154 that reacts cleanly in the y-position with alkyl and allyl halides to give, after hydrolysis of the initially formed enamine 155, the ketones 156 with generally good enantiomeric excess. Structure Z-154a shows the chelation in the lithiated intermediate best. 

The use of lanthanide metal enolates in the aldol reaction has, to date, only been developed to a synthetically useful level in the case of cerium (Scheme S and Table 7). Stereoselectivities are no better than those of lithium enolates, but the cerium enolates of ketones woik well in crossed aldol additions to ketones (Table 7, entries 1-7) and sterically hindered aldehydes (Table 7, entries 9 and 10). Such crossed aldol reactions do not often work well with lithium enolates as enolate equilibration, retroaldolization and steric retardation of addition occur. Imamoto et al. have shown that cerium enolates (44), formed from anhydrous CeCb (1.2 equiv.) and the preformed lithium enolates of ketones in THF at -78 C, undergo such aldol reactions to give the corresponding p-hydroxy ketones (46), usually in high yield. The cerium suppresses the retroaldol reaction by efficient chelation of the aldolate (45). A similar effect is known for zinc halide mediated aldol reactions (Volume 2, (Chapter 1.8). The stereoselectivity of the... 

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