Lithium ion, chelation

A LAH complex (54) prepared from 2.28 equiv. of the amino diol (19) reduces acetophenone and pro-piophenone to the corresponding (f )-alcohols with 82% ee and 77% ee, respectively. The key feature of this carbinolamine-modified LAH reagent is a lithium ion chelate. 

Isatins have served as valuable precursors for the preparation of oxindoles bearing amino functionality at stereodefined C3. In a report from the Emiua group, isatin derived oxime 91 (Scheme 25) was transformed to the urea derivative 92 which underwent a diastereoselective alkylation at C3 to afford the /-menthol adduct 93 (94 6 dr) [59]. Lithium counterions proved to be more effective than potassium ions for achieving diastereocontrol of the enolate alkylation a mechanism has been suggested involving lithium ion chelation between the oxindole enolate of 92, the carbonyl of the urea fimctionality at C3, and the carbonyl of the menthyl ester electrophile. 

The [2,3]-Wittig-Still rearrangement of the phenyl sulfide 51 (n = 0) afforded a mixture of 52 and 53 from a and p approach in 8 92 ratio fScheme 17.9T From the corresponding sulfone 51 (n = 2), use of 2 equiv. n-BuLi selectively yielded 54 in 65% yield with the a stereochemistry, resulting from lithium-ion chelation with the sulfonyl methyl and oxymethyl lithium (51a). The synthesis was continued to attach the side chain, and alkylative macrocyclization gave diol 57 (Scheme 17.9). ... 

TMED, (CH3)2NCH2CH2N(CH3)2. B.p. 122 C a hygroscopic base which forms a hydrocarbon-soluble stable chelate with lithium ions and promotes enhanced reactivity of compounds of lithium, e.g. LiAlH4, UC4H9, due to enhanced kinetic basicity of the chelate. Used in polymerization catalysts, tetramethyl lead, TML 5 lead tetramethyl. 

In readily available (see p. 22f.) cyclic imidoesters (e.g. 2-oxazolines) the ot-carbon atom, is metallated by LDA or butyllithium. The heterocycle may be regarded as a masked formyl or carboxyl group (see p. 22f.), and the alkyl substituent represents the carbon chain. The lithium ion is mainly localized on the nitrogen. Suitable chiral oxazolines form chiral chelates with the lithium ion, which are stable at —78°C (A.I. Meyers, 1976 see p. 22f.). 

The important features of this transition structure are (1) the chelation of the methoxy group with the lithium ion, which establishes a rigid structure (2) the interaction of the lithium ion with the bromide leaving group, and (3) the steric effect of the benzyl group, which makes the underside the preferred direction of approach for the alkylating agent. 

This regiospecificity has been shown to depend on the stereochemistry of the C=N bond in the starting hydrazone. There is evidently a strong preference for abstracting the proton syn to the arenesulfonyl group, probably because this permits chelation with the lithium ion. 

The sequential treatment of tris(/ r/-butylimido)sulfonate with methyllithium and dimethylzinc (Scheme 32) produced an unusual dimethylzinc adduct of hthium-Y-methyl-tri(/< 7/-butylimido)sulfonate 35, shown in Figure 15.80 Here, two imido-nitrogen atoms chelate the lithium ion, while the third one functions as a neutral... 

Macrocyclic compounds with ion-chelating properties occur naturally and often function as ionophores, translocating ions across biological membranes many of these compounds are small cyclic polypeptides. Some natural carboxylic polyethers are selective for Li+ and are, therefore, ionophores for Li+. Monensin, shown in Figure Id, is a natural ionophore for Na+ but it will also complex with Li+ and it has been shown to mediate the transport of Li+ across phospholipid bilayers [21]. It has been proposed that synthetic Li+-specific ionophores have a potential role as adjuvants in lithium therapy, the aim being to reduce the amount of... 

The stereochemistry of this reaction is determined by the preference of an Re side attack and chelation of the lithium ion to the oxygen atom of the nitrone group in the transition state (Fig. 2.31a) (703). 

Evans and Takacs23 demonstrated a diastereoselective alkylation based on metal ion chelation of a lithium enolate derived from a prolinol-type chiral auxiliary. This method can provide effective syntheses of a-substituted carbox-... 

Phosphorus ylides have been reviewed and an intermediate betaine lithium salt adduct (stabilized by complexation with lithium ions and by the chelating effect of pyridyl ligands) has been observed spectroscopically for the first time during the course of a Wittig reaction. ... 

Diastereoselective [2,3]-sigmatropic rearrangement of lithium O-allyl-A-benzylhy-droxylamides (195) bearing a stereogenic center adjacent to the migration terminus was reported 3" 3 (equation 57). When the (E) and (Z)-iV-benzyl-0-(4-methoxy-4-phenylbut-2-enyl)hydroxylamines (194) rearrange, a chelation by the lithium ion occurs and the (Z)-(lR5, 2R5 )-l-phenyl-l-methoxy-3-iV-benzylaminobut-3-ene (196) is the major product... 

Enantioselective alkylation of ketones. Chiral imines prepared from cyclic ketones and 1 on metalation and alkylation are converted to chiral 2-alkyleyclo-alkanones in 87-100% enantiomeric purity.1 The high cnantioselectivity is dependent on chelation of the lithium ion in the anion by the methoxyl group, which results in a rigid structure. 

The reactions of allyltrialkylstannanes with dialdose derivatives proceed similarly, with a high di-astereofacial selectivity in 5.0 M LPDE via chelation-controlled catalysis by the lithium ion. For example, the galactose derivative (4) (1.0 M in ether) reacts with 1.5 equivalents of allyltri-n-butyltin in 5.0 M LPDE, giving rise after 1 h to 96% yield of 5 and 6 in a ratio 25 1, respectively (Scheme 6.3.3). Exposure of (4) to allyltrimethyltin in 5.0 M LPDE proceeded with a high diastereofacial selectivity >25 1. In contrast, treatment of (4) with allyltrimethyltin in 2.0 M LPDE at ambient temperature proceeded with reduced diastereofacial selectivity, giving rise to a 12 1 ratio of (5) and (6), respectively, in only 66% yield. 

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