Lithium complexes alkylation

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. 

In 1991, Kessar and coworkers demonstrated that the kinetic barrier could be lowered by complexing the tertiary amine with BF3, snch that i-BuLi is able to deprotonate the ammoninm compound, which can be added to aldehydes and ketones as shown by the example in Scheme 4a. Note the selectivity of deprotonation over vinyl and allyl sites. A limitation of this methodology is that the ylide intermediate does not react well with alkyl hahde electrophiles. To get aronnd this, a seqnence that begins with the stannylation and decomplexation shown in Scheme 4b was developed. The stannane can be isolated in 94% yield (Scheme 4b) and snbseqnently snbjected to tin-lithium exchange to afford an unstabilized lithiomethylpiperidine that is a very good nucleophile. However, isolation of the stannane is not necessary and a procedure was devised in which the amine is activated with BF3, deprotonated, stannylated, decomplexed from BF3 with CsF, transmetalated back to lithium and alkylated, all in one pot (Scheme 4c). ... 

The chelate formation in lithium complexes 17 or 20 contributes to stabilization. Enhancement of kinetic acidity arises from the formation of pre-complexes 16 and 19, respectively. Here, already a dipole is induced and, in addition, proton exchange can proceed intramolecularly via a five- or six-membered ring. Despite these favourable features, the acidity of alkyl carbamates 15 is lower than those of the 1-proton in butane n-BuLi does not lead to deprotonation. In order to suppress carbonyl attack, a branched amino residue NR2 such as diisopropylamino (in Cb) or 2,2,4,4-tetramethyl-l,3-oxazolidin-3-yl (in Cby) is essential. A study on the carbenoid nature of compounds 17 was undertaken by Boche and coworkers. ... 

Enantiomerically pure glycosyl stannanes gave, after tin-lithium exchange and reaction with oxiranes in the presence of boron trifluoride diethyl ether complex, alkylation products as diastereomers (1 1 -2 1 d.r.) with complete retention at the stereogenic center a to the oxygen atom41. 

Buchachenko (1974) has advanced another theory. He based his reasoning on the absence of the CIDNP signals for the reaction of //-butyl iodide with t-butyl lithium conducted in ether at -70°C. The halogen and metal quickly exchange under these conditions, but the C—C bond does not form. In contrast to the preceding scheme, Buchachenko s theory assumes that the radicals produced form complexes with the alkyl lithium associates. Alkyl... 

Lithium aluminum hydride (LAH) reacts with pyridines and their analogs in aprotic solvents to give dihydro- and tetrahydro-pyridines. In the absence of proton sources dihydropyridines normally predominate, solutions of pyridine and LAH form lithium complexes (32 Scheme 7), which likely consist of both 1,2- and 1,4-dihydropyridlnes. This intermediate has been used as a reducing agent for ketones, and reaction with alkyl halides generates 3-substituted pyridines (33) in good yield. 

If the tetrahydroisoquinoline moiety is connected to a chiral bidentatc complexing group, e.g., 4, then the preformed complex with butyllithium results in rapid removal of the proton from the st-face, forming the lithium complex. In contrast to alkylation, deuteration of this complex by dimethyl sulfoxide-fif6 occurs with retention of configuration (5)11. 

As shown in a model study (Fig. 60), extension of the Barbier procedure to carboxylic acids is unsatisfactory for ketone synthesis. On the other hand, lithium carboxylates and lithium and alkyl chlorides lead to good to excellent yields when sonicated in THF. An application of such a procedure to the preparation of long chain alkyl ketones is given in Ch. 9, p. 361. The use of chlorides is required. The reason seems to be the necessity of a rapid formation of the organometallic (p. 217). When this formation is slow, with bromides or iodides, complex electron transfers take place and imexpected couplings result. 

Homoleptic lithium complexes [Li NNE 2]Cl (E = 0, S), containing Juc-coordinating NNE-donor hgands prepared from bis(3,5-dimethylpyrazol-l-yl)methanewith BuLi and alkyl- or aryl-containing isocyanates or isothiocyanates, have been used to synthesize a series of scandium and yttrium complexes. ... 

Otero A, Lara-Sanchez A, Femandez-Baeza J, et al. New achiral and chiral NNE heteroscorpionate ligands. Synthesis of homoleptic lithium complexes as well as halide and alkyl scandium and yttrium complexes. Dalton Trans. 2010 39 930-940. 

The influence of the coordination of lithium and sodium enolates on the stereochemical outcome of their aldol reactions has been reviewed. The alkylation of the ambident enolates of a methyl glycinate Schiff base with ethyl chloride have been studied at B3LYP and MP2 levels. The transition states for the alkylation of the free ( )/(Z)-enolate with ethyl chloride have energy barriers of 13kcalmol However, with a lithium ion, the ( )-enolate behaves as an ambident enolate and makes a cyclic lithium complex in bidentate pattern, which is more stable by 11-23 kcal mor than the (Z)-enolate-lithium complexes. The results suggest that the alkylation of ambident enolates proceeds with stable cyclic bidentate complexes in the presence of metal ion and solvent. 

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